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Ethnopharmacological Relevance: Schima wallichii (D.C.) Korth is traditionally used in Manipur, India for treatment of diabetes and hypertension. However, there is no data reported regarding safety profile of this medicinal plant upon repeated per oral administration over a period of time., Aim of the Study: In the current study phytochemical profile, toxicological profile and total phenolic and flavonoid compound content of Schima wallichii leaves extract were evaluated., Materials and Methods: Gas chromatography coupled to mass spectrometry was performed for chemical profiling by using Gas Chromatography-Mass Spectrometry/Mass Spectrometry (GC-MS/MS), Shimadzu, TQ8040 system. A 28 days sub-acute toxicity study was carried out using albino Wistar rats by administering 3 different doses (200, 400 and 800 mg/kg body weight per oral) of methanol leaves extract. Changes in body weights were recorded weekly. Serum biochemical parameters were estimated as well as blood-cell count was done to check the effect of extract on haematopoietic system. Histopathology of vital organs viz. kidney, heart, brain, liver was performed to find any pathological indications. Since, liver is main the site for xenobiotic metabolism, estimation of the level of glutathione, catalase and lipid peroxidation were done. Further, total phenolic and flavonoid compound content estimation was performed for the leaves extract., Results: GC-MS revealed 14 major compounds with area percentage >1% of which quinic acid, n-Hexadecanoic acid, 9,12,15-Octadecatrienoic acid, (Z,Z,Z)-, Octatriacontyl trifluoroacetate, are three major compounds. No mortality was observed after the treatment with extract. Blood-cell count and biochemical parameters didn't show significant deviation as compared to control group. Histopathology study of vital organs viz. (liver, kidney, heart and brain) showed normal cellular construction comparing to control group. There was no sign of membrane lipid peroxidation, depletion of catalase level and glutathione level in liver. The result demonstrates that NOAEL (no-observed-adverse-effect levels) in the sub-acute toxicity was above 800 mg/kg. The leaves extract showed significant total phenol and flavonoid content., Conclusion: The present study revealed that Schima wallichii possessed important bioactive compounds with therapeutic values. The plant was safe for consumption after repeated high doses administration in rats and possesses significant amount of total phenol and flavonoid content., Competing Interests: Declaration of Competing Interest Authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Solanum torvum Sw. (ST) is used to clear heat toxins, promote blood circulation, and alleviate blood stasis. Therefore, this plant has traditionally been used as an ethnomedicine for common cold, chronic gastritis, and tumors., Aim of the Study: This study aimed to elucidate the mechanism by which ST induces ferroptosis in hepatocellular carcinoma (HCC), the combination effect with lenvatinib, and the impact on lenvatinib-resistant cells., Materials and Methods: Cell viability assays were performed using different hepatoma cell lines treated with ST. Lipid peroxidation and iron assays were performed using flow cytometry. Molecules involved in the ferroptosis pathway were detected by Western blotting. Finally, a lenvatinib-resistant cell line was established to evaluate the antiproliferative effects of ST., Results: ST ethanol extract inhibited the growth of various hepatoma cell lines. A significant reduction in glutathione peroxidase 4 (GPX4) expression was observed following ST treatment, which was accompanied by increased lipid peroxidation and Fe 2+ accumulation. ST induced ferroptosis mainly through heme oxygenase-1 (HO-1) expression. HO-1 knockdown reduced ST-induced lipid peroxidation and reversed GPX4 suppression. Acyl-CoA synthetase long-chain family member 4 (ACSL4) also participated in ST-induced ferroptosis. ST and lenvatinib combination showed an additive effect, and ST retained its potential anti-HCC efficacy in a lenvatinib-resistant cell line., Conclusion: This study demonstrated that the ethanol extract of ST inhibits hepatoma cell growth by inducing ferroptosis. ST displayed an additive effect with lenvatinib in Hep 3B cells and showed remarkable anti-HCC activity in lenvatinib-resistant Hep 3B cells. Collectively, the study shows that ST might have the potential to reduce lenvatinib use in clinical practice and salvage cases of lenvatinib resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Cancer is a multistep disease and its management is exceedingly expensive. Nowadays medicinal plants are gaining more attention in drug discovery and approximately 70% of anticancer drugs were developed from natural products or plants. A strong candidate from medicinal plant with anticancer potential should have four major properties: antioxidant, anti-inflammatory, anti-angiogenic, and cytotoxic activities., Aim of the Study: In order to assess Togolese traditional healer's claims about the anticancer potential of medicinal plants and obtain candidate plants for anticancer drug discovery, some species were selected from surveys and evaluated for their antioxidant, anti-inflammatory, anti-angiogenic and cytotoxic activities., Methods: Four species, Cochlospermum planchonii (CP), Piliostigma thonningii (PT), Paullinia pinnata (PP), and Securidaca longipedunculata (SL) were selected and analyzed to detect the phytochemical components. The mentioned bioactivities were evaluated using in vitro, ex vivo and in vivo assays., Results: Relative to SL extract, CP and PT have shown significantly high polyphenols and flavonoids content. The DPPH, FRAP, and TAC of the extracts revealed that CP, PT, and PP have a potent antioxidant effect compared to SL. MDA analysis revealed the same antioxidant activity as CP, PT and PP showed a minor MDA level. The egg albumin denaturation assay showed that IC50 of CP and PP was significantly higher than control (P < 0.05). In contrast, the Bovine Serum Albumin (BSA) results showed a nonsignificant effect (P > 0.05). Notably, SL extract was nonsignificant to control in both Egg Albumin and BSA. Furthermore, angiogenesis assay showed that SL at 50 μg/ml and PP at 100 μg/ml effectively reduced the number of blood vessels than control and showed a potent anti-angiogenic effect (2.7-fold and 2.5-fold, respectively, P < 0.05). No cytotoxicity on PBMC was reported for CP, PP, and PT up to 1000 μg/ml, whereas SL at 1000 μg/ml exhibit benign cytotoxicity (P < 0.0001)., Conclusion: This study provided in vitro evidence supporting further evaluation on cancer cell lines and tumors in vivo., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Niujiaodihuang Detoxify Decoction (NDD) is an integrated traditional Chinese medicine prescription that has been used as a therapeutic agent for the treatment of acute liver failure (ALF). However, the mechanisms underlying its action remain unclear., Aim of the Study: To determine the protective effect of NDD on D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced ALF and explore the underlying mechanisms., Materials and Methods: We characterized the NDD fingerprint by HPLC and established D-GalN/LPS-induced ALF models in Sprague-Dawley rats and LO2 cells. Next, we measured the protective and antiferroptotic effects of NDD in vivo and in vitro. To further investigate the molecular mechanisms underlying the effects of NDD, we performed metabolomic analysis of the liver tissue using LC-MS/MS., Results: Results of serum biochemical analysis, liver histopathology, and cell viability showed that NDD effectively relieved the liver injury. It reduced the accumulation of labile iron and alleviated lipid peroxidation by enhancing GPX4 activity. The mitochondrial morphology indicated that NDD exerted its hepatoprotective effect through an antiferroptotic activity. Metabolomic analysis showed that NDD treatment increased the levels of cysteine, decreased those of glutamate, and ameliorated the D-GalN/LPS-induced reduction in the levels of glutathione (GSH). The results for intracellular levels of reduced (GSH) and oxidized (GSSG) glutathione were consistent with those of metabolomic analysis., Conclusion: Our findings indicate that NDD exerts hepatoprotective activity by evoking the reprogramming of GSH metabolism, and thereby, inhibiting ferroptosis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Elaeagnus conferta Roxb. (Elaeagnaceae) is a subtropical shrub mainly native to India, Vietnam, Malaysia and South China, whose various parts are used for treatment of diabetes, gastric ulcers, pain, oxidative stress and pulmonary disorders. Though the other parts of the plant have been reported for their ethnic use i.e. fruits as astringent locally and for cancer systemically, leaves for body pain and flowers for pain in chest and the seeds are mentioned as edible, there is no report per se on the medicinal use of seeds. Based on the fact that seeds of closely resembling species i.e. Elaeagnus rhamnoides has demonstrated significant anti-gastroulcerative property, the probability of the seeds of E. conferta possessing similar activity seemed quite significant., Aim of the Study: Phytochemical investigation and assessment of pharmacological mechanism(s) involved in anti-ulcer effect of methanolic extract of the seeds of E. conferta., Materials and Methods: Bioactive phytoconstituents were isolated by column chromatography. These were identified by spectroscopic techniques including infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) and mass spectrometry. Methanolic extract (MEC) of the seeds was prepared by cold maceration and its anti-ulcerogenic potential was evaluated using indomethacin (50 mg/kg) and water immersion stress models in male rats. The animals were pre-treated with different doses of MEC (400 and 800 mg/kg) and the therapeutic effect was compared with standard drug i.e. ranitidine (RANT; 50 mg/kg). The ameliorative effects of MEC were investigated on gastric juice pH, total acidity, free acidity and ulcer index. The assays of malionaldehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and pro-inflammatory cytokines i.e. interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were carried out to find out the possible mechanism(s) of protection. Further, histopathological changes were also studied., Results: Chromatography studies and further confirmation by spectroscopic techniques revealed the presence of four different compounds in MEC i.e oleic acid (1), stearic acid (2), ascorbic acid (3) and quercetin (4). MEC exhibited anti-ulcerogenic effect in dose dependent manner which may be attributed to suppression of pro-inflammatory cytokines (IL-6, TNF-α) and MDA (112.7%), and up-regulation of protective factors such as CAT (90.48%), SOD (92.77%) and GSH (90.01%). Ulcer inhibition, reduction in total and free acidity and increase in gastric juice pH were observed in MEC treated rats as compared to disease control animals. Histopathological findings confirmed decreased cell infiltration, less epithelial cell damage and regeneration of gastric mucosa in dose dependent manner., Conclusions: The anti-ulcer effect of MEC may be attributed to its ability to scavenge free radicals and anti-inflammatory property via suppression of TNF-α and IL-6, thus offers a complete and holistic approach for management of peptic ulcer., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Diabetes mellitus (DM), as a multiorgan syndrome, is an endocrine and metabolic disorder that is associated with male reproductive system dysfunction and infertility. Safflower (Carthamus tinctorius L.) as an herbal remedy improves DM and infertility-related disorders. The anti-hypercholesterolemic, anti-inflammatory, and antioxidative properties of this herb have been well documented, but its role in testosterone production, male reproductive system and zinc homeostasis has not been fully illustrated., Aim of the Study: This study aimed to investigate the preventive and therapeutic properties of different doses of safflower seed oil against reproductive damage caused by type II DM by investigating zinc element homeostasis, inflammation and oxidative damage in testis tissue and their relationship with testosterone production and sperm parameters., Materials and Methods: Eighty adult male Sprague-Dawley rats were randomly divided into eight groups and treated daily for 12 and 24 weeks in protective and therapeutic studies, respectively. Type II DM was induced by a High Fat Diet (HFD) in normoglycemic rats for three months. At the end of each study, serum level of glucose, testosterone, gonadotropins, TNF-α, insulin, and leptin were measured. Moreover, antioxidant enzymes activity, lipid peroxidation, zinc and testosterone along with the expression of Nrf-2, NF-κB, TNF-α, StAR, P450scc, and 17βHSD3 genes in the testis were detected., Results: After the intervention, the activity of antioxidant enzymes and the level of testosterone and gonadotropins significantly decreased in the rats with DM in comparison to the others. However, lipid peroxidation and serum level of insulin, leptin and TNF-α increased and the testicular level of zinc significantly changed in the rats with DM compared to the control groups (p < 0.05). The gene expression of NF-κB and TNF-α were also significantly increased and the gene expression of Nrf2, StAR, P450scc and 17βHSD3 were decreased in the testis of diabetic rats (p < 0.05). The results showed that pretreatment and treatment with safflower seed oil could improve these parameters in diabetic rats compared with untreated diabetic rats (p < 0.05)., Conclusion: HFD could impair the production of testosterone and sperm, and reduce gonadotropin by increasing the serum level of leptin and inducing insulin resistance, oxidative stress and inflammation. However, safflower oil in a dose-dependent manner could improve testosterone level and sperm parameters by improving the level of leptin, zinc and insulin resistance, and the genes expression involved in testosterone synthesis, inflammation and oxidative stress., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Flavonoids interact with multiple targets in Central Nervous System resulting in a broad neuroprotection mediated by complementary processes and synergic interactions. Therefore, flavonoid-based therapies may input positive outcomes in the prevention and early management of neurodegenerative diseases. In Brazilian folk medicine Trichilia catigua is used for its neuroactive properties, such as neurostimulant, antioxidant and anti-neuroinflammatory, while Turnera diffusa is traditionally used as a tonic in neurasthenia. Both species are known to be rich in flavonoids., Aim of the Study: To study aqueous extracts of T. catigua and T. diffusa in terms of their antioxidant and antiglycation effects, inhibition of tyrosinase activity, and interaction with enzymes and pathways engaged in neuroinflammation. Moreover, whenever possible, to establish a relationship between the studied activities and the traditional usage of the species., Materials and Methods: The phenolic profiles of the aqueous extracts were validated by HPLC-DAD. The effect of the extracts over mushroom tyrosinase and 5-lipoxygenase activities, as well as their capacity to impair bovine serum albumin glycation, were assessed by in vitro assays. The anti-neuroinflammatory potential of the same extracts was evaluated by their capacity to mitigate the pro-inflammatory stimulus induced in BV-2 microglia cells by interferon-gamma., Results: T. catigua extract, a rich mixture of phenolic acids, catechins and flavonolignans, excels by its ability to decrease lipid peroxidation (EC 50  = 227.18 ± 9.04 μg/mL), and to work as anti-glycation agent, and inhibitor of both tyrosinase and 5-lipoxigenase (IC 50  = 358.84 ± 19.05 and 56.25 ± 14.53 μg/mL, respectively). However, only T. diffusa extract, mainly composed by luteolin derivatives, is able to lower NO production by BV-2 microglia cells stimulated with interferon-gamma, despite its lower activities in the other assays., Conclusions: Overall, this work highlights the value of medicinal plant extracts as sources of bioactive flavonoid-rich extracts with neuroactive effects. Furthermore, these results support their application as alternative strategies to develop functional foods and therapeutics to fight chronic neurodegenerative disorders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Myrrh, a traditional remedy, is the stem resinous exudate of Commiphora molmol Engler (Burseraceae). The aromatic yellowish-brown oleoresin has a long history in folk and traditional medicine, in Saudi Arabia and the Arab world. Severe universal concern attributable to the high mortality is Myocardial Infarction (MI). Acute administration of Isoproterenol (ISO) is an established animal model to induce myocardial injury., Objective: The existing animal study was outlined to inspect the actions of Myrrh essential oil on cardiac functional, antioxidant status, apoptotic and inflammatory deviations in isoproterenol induced MI., Materials and Methods: Normal and Myrrh control animals were administered normal saline and Myrrh essential oil for thirty days orally, respectively. On the 29th and 30th day, the animals were injected by saline (s.c.). In the ISO control, the animals were administered saline orally for 30 days and then confronted with ISO (85 mg/kg s.c.) on 29th and 30th days. In the Myrrh Groups (IV and V), the animals were treated with Myrrh essential oil (50 and 100 mg/k) respectively for 30 days and injected with ISO (85 mg/kg, s.c.) on 29th and 30th days., Results: Animals experienced MI displayed functional blood pressure deviations, intensification in the heart to body weight ratio, myocytes indicative markers (CK-MB, CPK, LDH, cTnT, cTnI), lipid peroxidation (MDA), protein expression of Nrf2 and HO-1, apoptotic markers (Caspase 3,9), and inflammatory indicators. Conversely, animals pre-treated with Myrrh revealed obliteration of those elevations triggered by ISO induction, diminished elevated biochemical values and improved heart function., Conclusion: Myrrh abstain effective cardio-protective action in MI model through improving the oxidative condition with myocytes and abolishing apoptotic as well as inflammatory responses., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological relevance Processed Nux vomica seed extracts and homeopathic medicinal preparations (HMPs) are widely used in traditional Indian and Chinese medicine for respiratory, digestive, neurological and behavioral disorders. Antioxidant property of Nux vomica is well known and recent investigation has highlighted the anticonvulsant potential of its homeopathic formulation., Aim of the Study: To explore the anticonvulsant and antiepileptogenic potential of Nux vomica HMPs (6CH, 12CH and 30CH potency) in pentylenetetrazole (PTZ) induced acute and chronic experimental seizure models in mice and investigate their effects on cognition, memory, motor activity and oxidative stress markers in kindled animals., Materials and Methods: Acute seizures were induced in the animals through 70 mg/kg (i.p.) administration of PTZ followed by the evaluation of latency and duration of Generalized tonic-clonic seizures (GTCS). Subconvulsive PTZ doses (35 mg/kg, i.p.) induced kindling in 29 days, which was followed by assessment of cognition, memory and motor impairment through validated behavioral techniques. The status of oxidative stress was estimated through measurement of MDA, GSH and SOD., Results: HMPs delayed the latency and reduced the duration of GTCS in acute model signifying possible regulation of GABAergic neurotransmission. Kindling was significantly hindered by the HMPs that justified the ameliorated cognition, memory and motor activity impairment. The HMPs attenuated lipid peroxidation by reducing MDA level and strengthened the antioxidant mechanism by enhancing the GSH and SOD levels in the kindled animals., Conclusions: Nux vomica HMPs showed anticonvulsant and antiepileptogenic potency in acute and chronic models of epilepsy. The test drugs attenuated behavioral impairment and reduced the oxidative stress against PTZ induced kindling owing to which they can be further explored for their cellular and molecular mechanism(s)., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Pfaffia glomerata roots are widely used in Brazil to treat various pathological conditions, particularly psychological disorders. 20-hydroxyecdysone, a phytosteroid present in the plant, can promote greater body resistance against exogenous and endogenous stressors. The objective of this study was to evaluate the possible neuroprotective effect of a 20-hydroxyecdysone-enriched fraction (20E-EF), obtained from P. glomerata roots, in an acute murine stress model., Material and Methods: The 20E-EF was obtained by partitioning the methanol extract from P. glomerata roots with dichloromethane. Mice were treated by gavage with three doses of 20E-EF (3, 10, and 30 mg/kg) and parameters of stress, anxiety, and depression were evaluated. Biomarkers of oxidative stress (enzymes, antioxidant profile, and oxidized molecules) were evaluated in the cortex, striatum (basal ganglia), and hippocampus of animals treated with 30 mg/kg of 20E-EF., Results: Mass spectrometry revealed that 20E was the main compound in the dichloromethane fraction. At a dose of 30 mg/kg, 20E-EF reduced stress, anxiety, and depression, while stimulating antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase), promoting antioxidant activity (antioxidant capacity, sulfhydryl groups, and reduced glutathione), and reducing oxidative markers (lipid peroxidation). In addition, 20E increased the concentration of NO in the striatum, possibly improving memory function and antioxidant activity., Conclusion: A 30 mg/kg dose of 20E-EF was able to reduce stress, anxiety, and depression, in addition to maintaining antioxidant defenses of the cortex and striatum. These findings open new perspectives for understanding the therapeutic properties of P. glomerata and the underlying mechanism(s)., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Hyperplasia, Tumors and cancers are various forms of proliferative disorders affecting humans. Surgery is the main treatment approach while other options are also associated with adverse effects. There is therefore a need for the development of better alternative therapy that is cost effective and readily available with little or no adverse effect. Some bioactive agents in medicinal plants exhibit their anti-proliferative potential by induction of mitochondrial permeability transition pore (mPT) opening. Gloriosa superba, a medicinal plant, is folklorically used in the treatment of tumors and cancers., Aim of the Study: This study therefore aimed at investigating the effect of ethanol leaf extract of Gloriosa superba (EEGS) on mPT and monosodium glutamate-induced proliferative disorder in some specific tissues using rat model., Materials and Methods: Isolated rat liver mitochondria were exposed to different concentrations (10, 30, 50, 70 and 90 μg/ml) of EEGS. The mPT pore opening, cytochrome c release, mitochondrial ATPase activity and lipid peroxidation were assessed spectrophotometrically. Caspases 9 and 3 activities were carried out using ELISA technique. Histological assessment of the liver, prostate and uterus of normal and monosodium glutamate (MSG)-treated rats were carried out., Results: The results showed significant induction of mPT pore opening, release of cytochrome c, enhancement of mitochondrial ATPase activity, inhibition of lipid peroxidation and activation of caspases 9 and 3 activities by EEGS. The histological assessment revealed the presence of MSG-induced hepato-cellular damage, benign prostate hyperplasia and uterine hyperplasia which were ameliorated by EEGS co-administration., Conclusions: These findings suggest that EEGS contains putative agents that can induce apoptosis via induction of mPT pore opening and as well protect against MSG-induced hepato-cellular damage and proliferative disorder in prostate and uterus., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Pilosocereus gounellei (xique-xique) is a popular cactus from Caatinga, traditionally used to counter inflammatory processes and indicated as a hypoglycemic agent. Previous studies have shown that mice treated orally with saline extract of P. gounellei stem (containing flavonoids and sugars) showed decreased serum lipid levels., Aim of the Study: In this work, we evaluated whether this extract would have beneficial effects against hyperglycemia and inflammatory status related to obesity in mice fed a high-fat diet (HFD)., Methods: Obese animals were treated daily per os with the extract (EXT; 125, 250, and 500 mg/kg), metformin (MET; 400 mg/kg), or saline solution (diet-induced obese, DIO) for 21 days. A group of non-obese animals served as the control. We evaluated lipid profile, glucose and insulin tolerance, atherogenic indices, histological alterations, cytokine levels, and oxidative stress in liver, muscle, and adipose tissue., Results: At the end of the experiment, mice from EXT groups showed lower body weight and total cholesterol, LDL-cholesterol, and triglycerides compared with the DIO group; in addition, HDL-cholesterol levels and glucose and insulin tolerance were similar to those of the control group. When compared with the DIO group, the extract-treated mice showed reduction in cardiac risk ratio, atherogenic coefficient, atherogenic index of plasma, and Castelli's Risk Index II; decrease in epididymal fat; reduction in steatosis, collagen deposition, and liver inflammation; lower serum levels of pro-inflammatory cytokines (tumor necrosis factor α, interleukin 6, and monocyte chemoattractant protein-1); inhibited lipid peroxidation; and increased superoxide dismutase levels in liver, muscle, and adipose tissue., Conclusion: The P. gounellei saline extract was able to improve physiological parameters of obese mice, which highlight the potential of this plant as source of compounds with biotechnological relevance for pharmaceutical industry., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Taraxacum officinale (L.), commonly called dandelion has been used for centuries as a natural medicine to treat inflammatory diseases including some metabolic alterations associated with obesity., Aim of the Study: Based on animal experiments this study aims to explore the potential mechanisms of action of T. officinale flower water syrup (TOFS) together with a normal-fat diet in the intervention of obesity., Materials and Methods: Obese male albino-Wistar rats (n = 8) at 25 weeks of age were fed with a normal-fat diet with or without added 27.82% TOFS (w/w) for 4 weeks. The reactivity of thoracic aorta and antioxidant capacity were studied., Results: TOFS delivered daily 926.8 μg of L-chicoric acid, 20.19 μg of luteolin and 3.379 ‬g of sucrose. TOFS showed beneficial effects by regulating blood lipids (HDL, x1.11-fold increase), thereby lowering the risk factors for atherosclerosis (TC/HDL, x0.90-fold). The antioxidant status was improved via an increase in plasma superoxide radical scavenging (SOD, x1.6-fold) and a decrease in lipid peroxidation (MDA, x0.81-fold). Moreover, the following were decreased: Cu (x0.53-fold), Zn (x0.72-fold) and the Cu/Zn molar ratio (x0.60-fold). A marker for liver damage/disease was beneficially decreased (ALP, x0.87-fold). TOFS modulated in a significant way COX-depended relaxation to ACh (p = 0.05) but not to CORM-2 (p = 0.1651) in isolated thoracic arteries, by decreased participation of vasoconstrictor prostanoids. The vascular contraction to prostaglandin F 2α was also decreased (x0.62-fold). We observed no change in the feed intake, body weight, organ-to-body weight ratio, blood glucose, CAT, FRAP, AST, ALT, TBARS/carbonyls (in heart, liver, kidneys, spleen) and carbonyls (in blood plasma, thoracic arteries); as well as F 2 -isoprostanes in urine. Vascular response to the vasodilators ACh, SNP, A23187, CORM-2, pinacidil, NS-1619 and to the vasoconstrictors NA, U-46619, ET-1 as well as hyperpolarizing mechanism(s) were not modified., Conclusions: TOFS possesses beneficial properties by regulating prostanoids and antioxidant status., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Plant materials are commonly used in traditional medicine in order to treat various diseases such as Diabetes mellitus. Some plants, such as Syzygium cumini, have the capability to act controlling oxidative stress and protein glycation besides their potential to decrease hyperglycemia and hyperlipidemia by the inhibition of the catalysis of digestive enzymes. The aim of this study was to evaluate the antioxidant and antiglicant activity of S. cumini leaves fractions, their capacity to inhibit hydrolases and lipase enzymes, as well as the cytotoxicity effects against erythrocytes and comparate these results with isolate quercetin flavonoid., Material and Methods: Ethnobotanical researches, carried out by academic studies at the Federal University of Uberlandia, led us to choose S. cumini as a potential plant for treatment of Diabetes mellitus. Fractions from ethanolic extract of S. cumini (hexane/Hex, dichloromethane/DCM, ethyl acetate/EtOAc, n-butanol/ButOH and water/H 2 O) were used to evaluate their antioxidant (DPPH, ORAC and FRAP) and antiglycant (BSA/fructose, BSA/methylglyoxal and Arginine/Methylglyoxal) activity as well as the inhibitory potential against α-amylase, α-glucosidase and lipase. In addition, identification of the main bioactive compounds of S. cuimini leaves by HPLC-ESIMS/MS analysis was carried out., Results: Our results indicate that all fractions, for exception Hex, present noteworthy antioxidant activity, mainly in EtOAc and ButOH fractions (FRAP 1154.49 ± 67.37 and 1178.27 ± 21.26 μmol trolox eq g -1 , respectively; ORAC 1224.63 ± 58.16 and 1313.53 ± 85.23 μmol trolox eq g -1 , respectively; DPPH IC 50 15.7 ± 2.4 and 23.5 ± 2.7 μg mL -1 , respectively). Regarding the antiglycant activity (BSA/fructose and Arginine/Methylglyoxal models), all fraction, for exception Hex, presented inhibition higher than 85%. All fractions were capable to inhibit 100% of α-amylase and the fractions DCM, EtOAc and ButOH inhibited α-glucosidase more than 50%. Regarding the lipase assay, DCM and Hex had the best activity (31.5 ± 14.3 and 44.3 ± 4.5 μg mL -1 , respectively). Various biomolecules known as potent antioxidants were identified in these fractions, such as quercetin, kaempferol, luteolin and (Epi)catechin., Conclusion: S. cumini fractions and quercetin presented promising antioxidant and antiglycation properties as well as the ability to inhibit digestive enzymes. This study presents new biological activities not yet described for S. cumini which provide new possibilities for further studies in order to assess the antidiabetic potential of S. cumini fractions especially EtOAc and ButOH., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Boesenbergia rotunda (L.) Mansf. Kulturpfl., previously known as Boesenbergia pandurata (Family: Zingiberaceae) is a ginger species, locally known as fingerroot. It is an integral part of Southeast Asian traditional medicine in alleviating many gastrointestinal disorders such as flatulence, carminative, stomach ache, dyspepsia, and peptic ulcer., Aim of the Study: Earlier we have investigated the cytoprotective effect of Boesenbergia rotunda extract. In the present study, we investigated the gastroprotection activity of Boesenbergin A (BA), a chalcone isolated from Boesenbergia rotunda extract in ethanol-induced ulcer model in rats. Besides, the contribution of anti-inflammatory and anti-oxidant ability of BA as probable mechanisms involved in the anti-ulcer activity, also been studied., Materials and Methods: BA was orally administered in rats before ulcer induction with ethanol. The lesions of the gastric mucosa were evaluated macroscopically and histopathologically. The efficiency of BA in mucus production, NO production, PGE 2 synthesis, mucosal nonprotein sulphydryls, glutathione (GSH) level, and lipid peroxidation (MDA) level were studied. The involvement of the anti-inflammatory capacity of BA was analyzed by using the measurement of cytokines such as TNF-α and IL-6. Finally, the expression of biomarkers such as HSP 70 and iNOS was analyzed at the transcriptional and translational levels., Results: We confirmed the protective capacity of BA via the reduction of ulcerated and haemorrhagic areas. It has induced the protection through lowering GSH, MDA and increased NP-SH level. The plasma NO levels were significantly less in BA treated rats. Both cytokines TNF-α and IL-6 were decreased together with elevated PGE 2 . Upregulation of HSP and downregulation of iNOS were determined in immunohistochemical and gene expression studies CONCLUSIONS: The current results suggest that the prophylactic effect found with BA is due to (i) boosting of gastric mucus production and suppression of inflammatory mediators, via pro-inflammatory cytokines and (ii) modulating the oxidative stress response. The usefulness of Boesenbergia rotunda in folk medicine in treating ulcers partially could be due to the presence of this chalcone., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Various traditional texts like Ayurveda and Materia Medica profoundly mentioned the ethnopharmacological use of Terminalia bellirica fruit for its protective effect on heart and various other vital organs. Hence the present research was focussed to scientifically prove the effect of T. bellirica in support of its traditionally claimed use as cardioprotective agent., Aim the Study: The aim and objective of the present study was to investigate the protective effect of T. bellirica (Roxb.) against drugs viz. Doxorubicin (DOX) and Isoproterenol (ISO) induced cardiotoxicity in wistar albino rats., Material and Methods: Cardiotoxicity was induced using DOX (15 mg/kg, i.p.) and ISO (85 mg/kg s.c.) models. Methanolic extract of T. bellirica (METB) was subjected to rats in two different doses (low dose of 250 mg/kg p.o.; and high dose of 500 mg/kg p.o.) for the purpose of investigation of various biochemical markers present in cardiac tissue as well as in blood serum, in order to assess the improvement in drugs induced cardiotoxicity. Also, the histopathological study was carried out in terms of ultrastructural changes occurred in the myocardium during drugs induced cardiomyopathy, to ensure the proposed cardioprotective effect of METB., Result: Biochemical investigation of cardiac tissue using METB showed significant decrease in CK-MB (creatine kinase-muscle/brain) activity and MDA (malondialdehyde) levels and increase in GSH (reduced glutathione) levels. It also increased the activity of SOD (superoxide dismutase) and CAT (catalase). In serum, METB increased the levels of oxidative stress markers like ALP (alkaline phosphatase), UA (uric acid), ALT (alanine transferase), and AST (aspartate transaminase) near to their normal values as in control group. The use of METB also decreased the levels of total cholesterol and TGs (triglycerides) in serum and significantly increased HDL (high density lipoprotein) levels. Treatment with METB also proved a considerable restoration in histopathological findings of myocardium., Conclusion: In the present study it was concluded that T. bellirica fruit has profound potential for the treatment of drugs induced cardiotoxicity suggesting the consumption of T. bellirica for cardiac benefits during routine treatment of cardiotoxicity., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Ziziphus mucronata (ZM) is used traditionally in the treatment of mood and depression. However, no existing scientific data is confirming this traditional claim., Aim of the Study: The present study was planned to investigate the anxiolytic and antidepressant-like effects of this plant in a stressed-induced depression model in rats., Materials and Methods: Depressive-like behaviors were induced by exposing rats to different stress paradigms daily for 30 days. A sucrose preference test was performed to assess anhedonia in rats. Anxiety and depression-related behavior were assessed. The oxidative parameters (lipid peroxidation, SOD and catalase activities) were evaluated. Pindolol and Flumazenil were also used to assess the mechanism of action of ZM extract., Results: The results showed that chronic administration of ZM (150, 300, and 600 mg/kg, p.o., 30 days) and imipramine treatment (20 mg/kg, p.o, 30 days) remarkably (P < 0.05) reversed the UCMS-induced behavioral changes observed in stress vehicle treated rats by reducing sucrose preference, decreased the immobility period in the FST and latency in NSF. Besides, ZM (300 and 600 mg/kg, p.o., 30 days) raised the percentages of time spent and number of open arms entries as well as the number of transitions. Also, ZM (300 mg/kg, (P < 0.05) decreased lipid peroxidation and increased both SOD and catalase activities (300 and 600 mg/kg, (P < 0.05)). These aforementioned behavioral indices were also completely nullified by pindolol a β-adrenoceptors blocker and 5-HT 1A/1B receptor antagonist but not by flumazenil, a benzodiazepine receptors antagonist., Conclusion: ZM improved symptoms of anxiety and depression in behavioral despair paradigm in chronically stressed rats. The observed effects could be due to its capacities to restore the antioxidant status, and probably the modulation of monoamines transmissions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Ephedra foeminea is a member of the Ephedraceae family which is widespread in the eastern Mediterranean area. In Lebanon, Ephedra is a popular remedy in traditional medicine to prevent and/or counteract many stress oxidative-related diseases like inflammation and bacterial infections., Aim of the Study: Oxidative stress leads to endothelial cell dysfunction, and is a major factor contributing to etiology of atherosclerosis and related diseases. This study aims to investigate the antioxidant and cytoprotective potential of extracts from E. foeminea fruits on human endothelial cells exposed to hydrogen peroxide (H 2 O 2 ) to mimic in vitro vascular endothelium dysfunction., Materials and Methods: Different extracts of E. foeminea fruits were prepared using pure ethanol (EE), methanol/water (EMW), pure hexane (Ehex) or ethyl acetate/water (Epoly) as extraction solvents. The phenolome profile of each extract was characterized using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS). Total phenolic and flavonoid content, and radical scavenging properties of the extracts were assessed spectrophotometrically. Then, the effects on human endothelial cells HECV were evaluated., Results: Epoly extract showed the highest phenol and flavonoid content, and the highest radical scavenging capacity. On H 2 O 2 -insulted HECV cells Epoly was able: (i) to counteract the ROS/RNS production and lipid peroxidation; (ii) to rescue the ROS-dependent decrease in the mitochondrial membrane potential; (iii) to counteract the apoptosis induction; (iv) to restore endothelial cell viability and migration., Conclusions: The findings indicated that the polyphenol-enriched extract Epoly from E. foeminea fruits is endowed with in vitro anti-oxidant and anti-apoptotic effects and might be used as nutraceutical for treating ROS-related endothelium dysfunction and inflammation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Juniperus plants are considered important sources of cedar-wood oil which is used widely in folk medicine as antiseptic and in treatment of inflammatory disorders such as, rheumatoid arthritis but there is not enough scientific evidence to support the claimed uses and there is no specification of a certain Juniperus species as the most active., Aim of the Study: The aim of this study is volatiles profiling of three Juniperus species; J. communis, J. horizontalis and J. chinensis in addition to efficacy-directed discrimination of the three studied essential oils based on their antimicrobial, and anti-inflammatory activities in LPS (lipopolysaccharide)-stimulated WBCs (White blood cells) to investigate the inter-specific variability effect on the biological activities of each oil., Materials and Methods: Volatile components profiling of the three studied plants volatile oils was achieved using GC-FID (Gas chromatography - flame ionization detector) and GC-MS (Gas chromatography - mass spectrometry). The antimicrobial activity of the studied essential oils was investigated and the minimum inhibitory concentration (MIC) was determined for oils. The production of the pro-inflammatory cytokines was evaluated by ELISA (Enzyme linked immunosorbent assay). Identification of the biomarkers responsible for each activity was attempted through construction of orthogonal projection to latent structures model using multivariate statistical analysis., Results: Forty five components were identified in the volatile oils of the three studied plants. J. horizontalis oil displayed the highest activity against E. coli while J. communis showed the highest activity against S. aureus. OPLS model biplot showed the in-between class discrimination of J. chinensis oil sample from J. communis and J. horizontalis. The three oils were found to significantly decrease the production of the pro-inflammatory cytokines tumour necrosis factor (TNF)- α, interleukin (IL)-1β, and gamma interferon (INF- γ) in lipopolysaccharide-activated white blood cells. All studied oils were similar in reduction of TNF-α, and INF-γ, while J. chinensis oil possessed the highest potency against IL-1β. The coefficient plots of TNF-α and INF-γ pro-inflammatory mediators showed that 1-terpineol, 4-terpineol, bornyl acetate, dl-limonene and α-pinene positive contributors to both activities while β-thujone, 3-carene and γ-muurolene were the positive contributors to IL-1β inhibitory activity., Conclusion: The differences observed in the volatile profiles among the three studied oils demonstrate the effect of inter-specific variability on the biological activities of the tested oils. It was shown that the tested oils possessed good antibacterial activities against E.coli and S. aureus justifying its folk use as an a topical antiseptic while the observed anti-inflammatory effects in human WBCs is due at least in part to their inhibitory effect on the production of pro-inflammatory cytokines., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Phragmanthera incana (Schum) Balle is a member of the African mistletoes that has been reported to be used in ethnomedicine for the treatment of hypertension., Aim: The aim of this study was to investigate the antihypertensive effect of Phragmanthera incana leaf ethanol extract (PILEE) in NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats., Materials and Methods: Phytochemical analysis of PILEE was determined using the Gas chromatography - Mass spectrophotometry (GC-MS) method. Antihypertensive activity was investigated in rats that received PILEE (50, 100 and 200 mg/kg) or captopril (40 mg/kg) daily for 28 days together with oral administration of L-NAME (40 mg/kg). Blood pressure parameters were measured on day 7, 14, 21 and 28. Blood was obtained for determination of serum nitrite, interleukin-6 (IL-6) and tumor necrosis factor, TNF-α. The heart, liver and kidneys were used to determine oxidative stress indices (malondialdehyde, reduced glutathione and catalase). The cardiac tissue was processed for histopathological changes., Results: The GC-MS profiling of PILEE identified 20 compounds namely fatty acid esters. Administration of PILEE (50, 100 and 200 mg/kg) dose dependently and significantly reduced systolic blood pressure and mean arterial pressure in hypertensive rats. PILEE administration significantly (p < 0.05) reversed elevated IL-6 and TNF-α in hypertensive rats. PILEE demonstrated antioxidant activity by attenuating L-NAME-induced elevated malondialdehyde and depletion of reduced glutathione and catalase activity in rat tissues. PILEE treatment demonstrated cardioprotective effect in L-NAME-induced cardiac hyperplasia and necrosis in rats., Conclusion: It can be concluded that Phragmanthera incana leaf ethanol extract possess antihypertensive, antioxidant and anti-inflammatory properties, suggesting a protective role in cardiovascular diseases., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Tianma Gouteng granules (TG), a clinical prescription of traditional Chinese medicine, has been clinically applied to treat Parkinson's disease (PD) in combination with Madopar, as included in the Chinese Pharmacopoeia (2015). TG has the potential to decrease the susceptibility of PD pharmacologically, however the mechanisms need detailed demonstration., Aim of the Study: To evaluate the pharmacological activities, as well as the possible mechanism of TG in diverse models of PD., Materials and Methods: 6-OHDA-treated rats, MPTP-treated mice, and α-synuclein A53T overexpressed mice, were utilized as PD animal models. Rotarod, locomotor activity, inclined plane and traction tests were used for behavioral assessment. Immunohistochemistry was used for tyrosine hydrolase determination. Western blot were conducted for detection of 4-HNE and 15-lipoxygenase-1 (ALOX15). The interactions of ALOX15 with the components in TG were predicted by molecular docking approach., Results: Lipid peroxidation was involved in dopaminergic neuron damage in 6-OHDA-induced rat models. In MPTP-treated mice, the inhibition of lipid peroxidation improved behavioral and pathological symptoms of PD. The lipid peroxidation-related protein, ALOX15 was found to be the key factor in PD process in diverse PD models including 6-OHDA-treated rats, MPTP-treated mice, and α-synuclein A53T overexpressed mice. TG treatment significantly relieved behavioral and pathological symptoms of MPTP-induced PD mouse models with a potential mechanism of alleviating ALOX15-induced lipid peroxidation. Moreover, the results of molecular docking analysis show that compounds in TG might have interactions with ALOX15., Conclusions: TG effectively improved the behavioral and dopaminergic neuron damage in diverse PD models. The mechanism of this action may be related to the direct inhibition of ALOX15 and the relief of lipid peroxidation., Competing Interests: Declaration of competing interest The authors declared no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Genus Trigonella has a history of folkloric medicinal uses in China, Japan, Egypt and India. There are a variety of therapeutic actions of Trigonella including hypocholesterolemia, hypoglycemia, antibacterial, antiviral, anti-inflammatory activities, antioxidants and appetite stimulant., Aim of the Study: The prevalence of diabetes mellitus is increasing annually. The present study aims at investigating the protective effects of Trigonella stellata against the adverse effects of diabetes mellitus through investigation of the changes in phase I & II drug-metabolizing enzyme activities, protein expression of cytochrome P 450 isoenzymes [CYP2E1 & 3A4], oxidative stress, antioxidant enzymes as well as histopathology of both liver and kidney tissues., Methods: GC-MS and MALDI-TOF were used to analyze the main constituents of the aqueous and the ethanolic extract of Trigonella stellata. Western immunoblotting technique used to show the protein expression of CYP 450 isozymes in different groups. Spectrophotometric- and fluorophotometric techniques were also used for assessment of different hepatic integrity enzymes. Histopathological techniques used to illustrate the changes in the tissues of both livers and kidneys after different treatments., Results: Trigonelline was found to be the main constituent of both aqueous and ethanolic extract of Trigonella stellata. Administration of the aqueous and/or the ethanolic extracts of Trigonella stellata to the diabetic rats was found to decrease the blood glucose level, the biochemical markers of both liver (transaminases activities, Lactate dehydrogenase, gamma-glutamyl transferase) and the renal functions (urea, creatinine and bilirubin) which were increased in diabetic-treated rats relative to their normal levels. Diabetes mellitus potentially induced the oxidative stress, and also activities of dimethylnitrosamine N-demethylase I, cytochrome c-reductase, ethoxyresourfin O-deethylase, and the total hepatic content of cytochrome P 450 . On the other hand, the activity of catalase [CAT], superoxide dismutase [SOD], glutathione S-transferase [GST], glutathione reductase [GR], glutathione peroxidase [GPx] and levels of reduced glutathione [GSH] were potentially inhibited in diabetic rats compared to the control rats. However, treatments of diabetic rats with either aqueous and/or ethanolic extracts of Trigonella stellata restored such changes caused by diabetes almost nearly to their normal levels compared to the control group. Supporting the activity of dimethyl nitrosamine N-demethylase I activity, the protein expression of CYP2E1 was also induced in diabetic rats. However, the aqueous extract of Trigonella stellata was more effective than ethanolic extract in restoring the changes in the protein expression of CYP2E. On the other hand, the protein expression of CYP3A4 was markedly decreased in diabetic rats, and this decrease was partially restored to its normal level after treatment of diabetic rats with aqueous and/or ethanolic extracts. In addition, Trigonella stellata extracts alleviated the histopathological changes in livers and kidneys caused by diabetes mellitus., Conclusion: It is concluded that diabetes mellitus induced changes in oxidative stress, phase I & II drug-metabolizing enzymes, and antioxidant enzymes activities, whereas both extracts of Trigonella stellata alleviated such changes. Alterations in cytochrome P 450 system should be considered when therapeutic drugs are administered to diabetic patients since most of xenobiotic are mainly metabolized by this system., Competing Interests: Declaration of competing interest All authors confirm that there are no conflicts of interest and financial support for this publication that could affect its outcome., (Copyright © 2020. Published by Elsevier B.V.)

Ethnopharmacological Relevance: The Mallotus apelta (Lour.) Muell.Arg. is a well-known traditional Chinese medicine (TCM) used for anti-inflammatory, hemostasis and chronic hepatitis., Aim: The purpose of this study was to explore the antifibrotic effect of total flavonoids of Mallotus apelta leaf (TFM) and its potential mechanism., Methods: Hepatic fibrosis was induced by carbon tetrachloride (CCl 4 ) in rats. The CCl 4 -induced rats received intragastric administration of colchicine (0.2 mg/kg per day), TFM (25, 50, 100 mg/kg per day) and the equal vehicle was given to normal rats. Pathological evaluation in hepatic tissue were examined by hematoxylin and eosin (HE) staining. And the levels of serum biochemical parameters were detected by automatic biochemical analysis. Meanwhile, the collagen deposition in liver was observed by staining with Masson's trichrome. Collagenic parameters and inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA) kits. Additionally, corresponding assay kit was used to estimate the antioxidant enzyme and lipid peroxidation. In order to explore the potential mechanism of anti-fibrotic effects in TFM, the expressions of liver fibrosis related gene and protein were analyzed by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot., Results: The CCl 4 -induced hepatic fibrosis were inhibited dose-dependently in rats by TFM. The results showed that the key hallmarks of liver injury including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin (ALB) and total protein (TP) in the serum were reversed in CCl 4 -induced hepatic fibrosis rats which were treated by TFM. Furthermore, TFM significantly alleviates collagen accumulation and reduces the contents of hydroxyproline (Hyp), Type III precollagen (PC-III), collagen I (Col I), hyaluronic acid (HA) and laminin (LN). RT-PCR and Western blot results showed that TFM markedly inhibits liver fibrosis hallmark factor α-smooth muscle actin (α-SMA) expressions in CCl 4 -induced hepatic fibrosis rats. Moreover, TFM alleviated the oxidative stress and lipid peroxidation in rats induced by CCl 4 . TFM also attenuated the pro-inflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) via inhibiting nuclear factor-κB (NF-κB) activation. Meanwhile, transforming growth factor-β1 (TGF-β1)/Smad signaling pathway was inhibited by TFM treatment., Conclusions: TFM can alleviate CCl 4 -induced hepatic fibrosis in rats, which potential mechanism may be due to its ability of reducing ECM accumulation, improving antioxidant and regulating TGF-β1/Smad signaling pathways and NF-κB-dependent inflammatory response., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Lipid homoeostasis is important for neurodevelopment, cell signaling and neurotransmission. Alteration of lipid metabolism has been demonstrated in many neurological disorders and neurodegenerative diseases. Geissoschizine methyl ether (GM) is an active alkaloid ingredient in the traditional Chinese medicine Uncaria hook. It has been shown that GM has strong potency in neuroprotective activity and GM reduces the production of reactive oxygen species by regulating glucose metabolism, which protects neurons against oxidative stress-induced cell death. However, it is unknown whether GM could regulate neuronal lipid metabolism during oxidative challenge., Aim of the Study: The current study aimed to explore whether GM regulates lipid metabolism in oxidative damaged neurons and to determine the underlying mechanism involved in this neuro-protection., Materials and Methods: Using a glutamate-induced oxidative toxicity model in mouse hippocampal neuronal cell line (HT-22 cells), we investigated the effect of GM on glutamate-induced lipid peroxidation, lipotoxicity and mitochondrial dysfunction. In order to clarify the mechanism underlying the neuroprotection by GM, lipid metabolomics was performed to investigate whether GM prevent oxidative stress-induced lipid metabolism disruption. Furthermore, the expression of lipid metabolism-related genes was measured., Results: The results show the protective effect of GM against oxidative stress through blocking glutamate-induced lipid peroxidation and lipotoxicity. Overall, lipidomics analysis revealed that glutamate treatment resulted in different extents of changes in a wide range of lipid classes such as fatty acids (FA), triacylglycerol (TG), sphingomyelin (SM), cardiolipin (CL), lysophosphatidylcholines (LPC). However, GM treatment can significantly reverse glutamate-induced lipids disorder to the homeostasis level. GM prevented the disruption of lipid metabolism by regulating the expression of lipid homeostasis related genes, which contributes to preserve mitochondrial function under oxidative damage., Conclusion: These findings clearly demonstrated a novel protective mechanism of GM against glutamate-induced oxidative toxicity in neurons via regulating lipid metabolism. GM may provide an effective approach for the prevention and treatment of oxidative damaged neurons., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: In Turkish folk medicine, leaves of Sorbus domestica are used for the treatment of burns, cough, stomachache, bradyuria, kidney stone. The fruits of this plant are used for diarrhoea., Aim of the Study: This study was carried out to investigate the effect of S. domestica on ulcerative colitis induced by acetic acid in rats., Materials and Methods: The crude methanolic extract of fruits was sequentially fractionated into five subextracts; dichloromethane, diethyl ether, ethyl acetate, n-butanol and aqueous extracts. Effects of the extract, subextracts and fractions were investigated in acetic acid-induced rat colitis model. The colonic interleukin-6 (IL-6), tumor necrosis factor (TNF-α), nitrite, superoxide dismutase (SOD), glutathione (GSH), lipid peroxidation (LPO), catalase (CAT), and malondialdehyde (MDA) levels as well as the caspase-3 and myeloperoxidase (MPO) activities were measured to determine the activity. Histopathological analyzes were also performed on the colon tissue of rats., Results: The methanolic extract and diethylether subextract have led to a noteworthy decrease in MPO, caspase-3, IL-6, TNF-α, MDA, and nitrite levels in the colon tissue and blood. In addition, histopathological analysis results were supported by biochemical parameters. After confirmation of the activity against ulcerative colitis, the diethyl ether subextract was subjected to more chromatographic separation for the isolation of compounds 1, 2 and 3. The structures of these three compounds were elucidated as vanillic acid 4-O-α-L-rhamnopyranoside (1), protocateuic acid anhydrite (2) and trivanilloyl-(1,3,4-trihydroxybenzol) ester (3)., Conclusion: In this study, the potential of S. domestica in the treatment of colitis was investigated. Fruits of this plant were found to have important anti-inflammatory and antioxidant activities. Through isolation techniques, vanillic acid 4-O-α-L-rhamnopyranoside, protocateuic acid anhydrite and trivanilloyl-(1,3,4-trihydroxybenzol) ester were determined as the main active components of the fruits. Consequently, S domestica might be a promising candidate for upcoming use the prevention and treatment of various disorders, such as inflammatory bowel diseases, irritable bowel syndrome and Clostridium difficile infection., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Albizia procera L. (Leguminosae) commonly known as Konda vagai in Tamil, is used for the treatment of stomach and intestinal disorders. A decoction of the bark is prescribed for rheumatism and haemorrhage. Traditionally, literature claims Albizia procera as a drug to have antirheumatic properties and hence used by Tribal for the management of chronic rheumatism. Consequently, the present study has been undertaken to illustrate the beneficial outcome of Albizia procera in adjuvant induced arthritic rat model with respect to its antioxidant and anti-inflammatory activities., Aim of the Study: The present study is aimed to investigate the oxidative stress and the expression of inflammatory markers in arthritic rats treated with ethanolic bark extract of Albizia procera., Materials and Methods: Ethanolic bark extract was characterized by HPTLC analysis. Acute oral toxicity study was performed according to the OECD test guideline 423 - Acute toxic class method. The anti-inflammatory effect of ETBE (100, 200 mg/kg/day/p.o.) was evaluated in complete Freund's adjuvant induced arthritic rats using diclofenac as positive control (0.3 mg/kg/day/p. o.). Plasma levels of interleukins TNF- α, IFN-α, IL-2, IL-6, myeloperoxidase and Cathepsin D levels were measured to assess the inflammatory effect of ETBE extract of Albizia procera. Further, the effect of ETBE on superoxide dismutase (SOD), glutathione peroxidase (GPX), reduced glutathione (GSH) and lipid peroxidation (LPO) were assessed in plasma., Results: HPTLC analysis showed the presence of 0.57% w/w of biochanin-A in ETBE. ETBE did not show any toxic signs up to 2000 mg/kg body weight. It exhibited the significant anti-inflammatory and antioxidant potential and did not show mortality up to 2000 mg/kg body weight. ETBE treatment significantly reduced the levels of TNF- α, IFN-α, IL-2, IL-6 and myeloperoxidase, and increased cathepsin D levels compared to vehicle treated animals. SOD, GSH and GPX levels were significantly restored to normal levels while LPO was significantly reduced at 200 mg/kg b. wt. Treated animals. Histopathological studies showed complete cartilage regeneration and near normal joint in ETBE treated arthritic rats., Conclusion: ETBE demonstrated potent anti-inflammatory activity by modulating the expression of inflammatory cytokines and restoring the antioxidant enzyme levels., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Tinospora sinensis Lour. (Merr.) belongs to the family Menispermaceae and its stem extract have been used traditionally in broad aspects of therapeutic remedies including debility, dyspepsia, fever, jaundice, ulcer, bronchitis, urinary disease, skin disease, liver disease and diabetes., Aim of the Study: The aim of the study was to evaluate the protective effects of methanol extract of stem of Tinospora sinensis (METS) on streptozotocin induced pancreatic islet cell injuries of diabetic rats and its correlation to its phytochemical profiles., Materials and Methods: A high-performance liquid chromatography technique (HPLC) was used to identify and quantify the major phytochemicals present in the METS. Diabetic rats were administered with METS at a dose of (100, 200 and 400 mg/kg respectively orally) and standard drug Metformin (300 mg/kg) was given orally to group serving positive control. Effect of the METS on glucose homeostasis, oxidative stress, antioxidant status, histopathology of pancreas and also on intracellular reactive oxygen species (ROS), mitochondrial membrane potential, apoptosis, cell cycle of pancreatic islet cells were studied in diabetic rats., Results: The major phytochemicals identified and quantified by HPLC in the extract were berberine, caffeic acid, myricetin and ferulic acid. This result showed that methanol extract exhibited good antioxidant effect. The methanol extract of the plant prevented the diabetogenic effect of STZ and significantly lowered the fasting blood glucose level, glycated haemoglobin and increased insulin and C-peptide level in treated rats. METS reduced apoptosis of STZ treated islet cells by significantly decreasing pro-inflammatory cytokines (TNFα, IL6), intracellular ROS generation, lipid peroxidation, nitric oxide (NO) production and increasing mitochondrial membrane potential and sub-G 0 peak area, enzymatic and nonenzymatic antioxidants., Conclusion: The results revealed that the methanol extract of the stem of the plant possesses protective effects against diabetes and associated complications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Zygophyllum album is widely used to treat many cardiovascular diseases (CVDs) and as anti-inflammatory plant., Aim of the Study: This study aimed to investigate the mechanism of the potential protective effects of Zygophyllum album roots extract (ZARE) against myocardial damage and fibrosis induced by a chronic exposure to deltamethrin (DLM) in rats., Materials and Methods: Bioactive compounds present in ZARE were analyzed by HPLC-DAD-ESI-QTOF-MS/MS. In vivo, DLM (4 mg/kg body weight), ZARE (400 mg/kg body weight) and DLM with ZARE were administered to rats orally for 60 days. Biochemical markers (LDH, ALT, CK, CK-MB and cTn-I) were assessed in the plasma by an auto-analyzer. Pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were evaluated by a sandwich ELISA. NF-κB was quantified at mRNA levels by real time PCR. Heart tissue was used to determine cardiac oxidative stress markers (MDA, PC, SOD, CAT, and GPx). Masson's Trichrome (MT) and Sirius Red (SR) stainings were used for explored fibrosis statues., Results: Phytochemical analysis using HPLC-DAD-ESI-QTOF-MS/MS revealed the presence of twenty six molecules including phenolic compounds and saponins. ZARE significantly improved the heart injury markers (LDH, ALT, CK, CK-MB and cTn-I), lipid peroxidation (MDA), protein oxidation (PC), antioxidant capacity (SOD, CAT, and GPx), and DNA structure, which were altered by DLM exposure. Moreover, ZARE cotreatment reduced the expressions of NF-κB, decreased plasmatic pro-inflammatory cytokines concentration (TNF-α, IL-1β and IL-6), and suppressed the myocardial collagen deposition, as observed by Sirius Red and Masson's Trichrome staining., Conclusion: ZARE ameliorated the severity of DLM-induced myocardial injuries through improving the oxidative status and reducing profibrotic cytokines production. The ZARE actions could be mediated by downregulation of NF-κB mRNA., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Pilosocereus gounellei is a plant found in the Brazilian Caatinga and is popular due to its traditional uses in the treatment of inflammation. The present study was conducted to investigate the sub-acute toxicity of the saline extract from the stem of P. gounellei., Aim of the Study: To evaluate the 28-day oral toxicity (through behavioral, biochemical, hematological, and morphological analysis) and the antipyretic activity of the extract in mice., Materials and Methods: A single oral dose (250, 500, and 1000 mg/kg) was administered daily over 28 consecutive days to male and female mice. Body weight, food and water intake, blood biochemical and hematological parameters, and urine composition were recorded. Histopathological examinations of the liver, kidney, spleen, lungs, and heart were performed and oxidative stress in the organs was evaluated by lipid peroxidation, superoxide dismutase (SOD), catalase (CAT), and nitrite analysis. The antipyretic effect of the 500 mg/kg dose was assessed using a yeast-induced pyrexia model., Results: Oral administration of the extract over 28 days did not affect body weight gain, food and water consumption, body temperature, and hematological parameters in male and female mice. Blood glucose, total cholesterol, and triglyceride levels in male and female mice were reduced. Protein in the urine and histological alterations in both the liver and lungs were detected in male and female mice treated with the highest dose of the extract. SOD levels in the liver and the spleen increased significantly in both sexes, whereas lipid peroxidation decreased in the spleen of male mice. The extract also exerted an antipyretic effect after the first 60 min of the evaluation until the end of the observation duration (180 min)., Conclusion: The saline extract from the stem of P. gounellei did not present significant toxic effects over 28 consecutive days and demonstrated antipyretic activity when administered orally. Moreover, the results suggest that the extract has potential hypoglycemic and hypolipidemic effects. Future studies are needed to investigate its pharmacological potential., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Schinopsis brasiliensis is a native plant from Brazil, popularly used in folk medicine to relieve pain and treat inflammation. This study evaluated the antinociceptive and anti-inflammatory activities and antioxidant properties of the hydroethanol extract (HEE) and ethyl acetate fraction (EAF) obtained from S. brasiliensis bark., Materials and Methods: The HEE and EAF of S. brasiliensis bark (10, 30 and 100mg/kg, p.o.) were evaluated using models of analgaesia (formalin-induced licking and hot-plate models) or inflammation (licking response by formalin-induced and carrageenan-induced cell migration into the subcutaneous air pouch). The antioxidant activities of HEE and EAF (50, 100 and 200µg/ml) were evaluated using the lipoperoxidation method induced in egg yolk by 2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and FeSO 4 ., Results: HEE and EAF presented a central antinociceptive effect (at 100mg/kg dose), increasing the baseline and area under the curve in the hot plate model. EAF (100mg/kg) significantly reduced (p< 0.005) the pain response in the first (45%) and second (35%) phases of the formalin-induced licking model, while HEE (100mg/kg) reduced (38%) only the pain response in the second phase. Regarding anti-inflammatory activity, EAF (100mg/kg) also inhibited the inflammatory process induced by subcutaneous carrageenan injection in the SAP model, reducing the amount of the cytokine TNF-α produced., Conclusion: HEE and EAF from S. brasiliensis bark show pharmacological interest because they were able to inhibit the peripheral and central transmission of pain. Our data also suggest that the anti-inflammatory activity caused by EAF exposure occurs through the inhibition of the pro-inflammatory cytokine TNF-α, also reducing the spreading of the inflammatory processes by neutralizing reactive oxygen species, which are by-products in the biosynthesis of pain mediators., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Reichardia picroide is a species mainly used for alimentary purposes, but it is traditionally known to be used as hypoglycemiant, diuretic, depurative, galactagogue and tonic., Aim of the Study: To date, there are no studies corroborating both its safety and antioxidant activities. The objective of the present study, thus, was to assess the safety profile of Reichardia picroide methanolic extract (RPE) and as well as on its antioxidant and antihemolytic activities., Materials and Methods: The acute toxicity of RPE was carried out based on OECD guidelines 425. Signs accompanying toxicity and possible death of animals were monitored for two weeks to ascertain the median lethal dose (LD 50 ) of the RPE. In sub-acute toxicity study, the extract was administered by gavage at the doses of 250, 500 and 1000mg/kg/day for 21 consecutive days. The antioxidant activity of RPE was investigated through various methods both in vitro and in vivo., Results: The admistrated doses did not produce mortality or changes in general behaviors of the tested males and females mice. The LD 50 was found to be superior to 5000mg/kg DW. Moreover, daily administration of RPE at doses ranged from 500 to 1000mg/kg could result in alteration of liver and kidney histology. Significant decrease in liver enzymes (ALT and AST), urea and creatinine levels in female plasma was recorded. The RPE was, in vitro, strong in DPPH scavenging and hemolytic inhibition, benificial in lipid peroxidation inhibition and reducing power. In addition, it exhibited, in vivo, a strong effect on GSH level increasing and lipid peroxidation inhibition in liver and kidney., Conclusions: It can be suggested, based on the results of this study, that the crude extract of Reichardia picroide was non-toxic in acute administration and the use of this extract is safe at doses ≤ 250mg/kg. This study supports the application of Reichardia picroides in alimentary and traditional medicine purposes. Moreover, antioxidant activity results suggested that Reichardia picroide had potent antioxidant activities and could be utilized as new natural antioxidant in food and therapeutics., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Virola oleifera (Schott) A. C. Smith, Myristicaceae has been largely used in traditional folk medicine in Brazil as an anti-inflammatory agent and our previous data indicated the antioxidant properties in other oxidative stress-related models. However, its effects on atherosclerosis (AT) are not yet investigated., Aims of the Study: To evaluate the influence of resin from Virola oleifera (RV) on progression of AT in LDLr -/- mice., Materials and Methods: LDLr -/- mice were divided into 4 groups: 1) The ND group received a normal diet without treatment. 2) The HD group received a high-fat diet without treatment. 3) The HD-V50 received a high-fat diet and was orally treated with RV at 50mg/Kg. 4) The HD-V300 received a high-fat diet and was orally treated with RV at 300mg/Kg. After 4 weeks, blood was collected to quantify biochemical parameters and ROS total and the aorta was removed to measure the lipid deposition by en face analysis. The liver was also collected to determine total lipids and lipid and protein oxidation. In order to investigate in more detail the contributions of RV in the vascular structure, we carried out the in vitro tests using four cellular types: macrophages, fibroblasts, vascular smooth muscle and endothelial cells., Results: We showed that the chronic treatment of RV at both doses reduced vascular lipid accumulation (~50%, p<0.05), probably through systemic and hepatic antioxidant effects, independent of dyslipidemia. Moreover, the in vitro assay results demonstrated that RV develops antioxidant properties on the vascular smooth muscle and endothelial cells, reinforcing the protective role of RV in progression of AT. LPS-stimulated macrophages treated with RV resulted in a significant reduction of NO production in a concentration-dependent manner., Conclusions: Chronic treatment with RV diminishes lipid deposition in atherosclerotic mice, which may be justified, at least in part, by antioxidant systemic and local mechanisms, reinforcing the protective role this resin in the setting of vascular lipid deposition, independent of hypercholesterolemia., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Terminalia bellerica Roxb. fruits are rich in a variety of biologically active ingredients. Tharu and Buksa tribes of Udham Singh Nagar, Uttarakhand, India use grilled fruits of Terminalia bellerica as an effective cure for diarrhea AIM OF THE STUDY: We validated the ethnobotanical claim by comparing the antidiarrheal effect of grilled fruits (GF) with dried fruits (DF)., Materials and Methods: The 50% ethanolic extracts of GF and DF were successively fractionated; the antioxidant and bacterial inhibition activity were studied using DPPH free radical scavenging, anti-lipid peroxidation and broth dilution method respectively. Difference in metabolites of ethyl acetate fractions of GF and DF was analyzed using GC-MS, gallic acid content was determined through HPTLC. Further the in-vivo antidiarrheal effect of ethyl acetate fractions of DF and GF was studied on castor oil induced diarrhea model., Results: The ethyl acetate fractions showed potential DPPH free radical scavenging (IC 50 11.13µg/ml in DF and 8.56µg/ml in GF), anti-lipid peroxidation and antibacterial activity. The non-targeted metabolic profiling showed higher content of tartaric acid, valeric acid, gallic acid, succinic acid, oxalic acid, malonic acid, malic acid, 1,2,3 trisbenzene, uridine and 11-eicosenoic acid in GF. The HPTLC results indicated that gallic acid content was 2.8 (±0.14) and 4.92 (±0.28) mg/g while ellagic acid content was 4.7 (±0.32) and 4.45 (±0.45) mg/g dry powder in DF and GF respectively. According to in vivo antidiarrheal activity DF and GF (100mg/kg oral) inhibited diarrhea by 41.87% and 71.72% respectively., Conclusion: Grilling significantly altered the levels of metabolites in T. bellerica fruits which could be responsible for its increased therapeutic potential., (Copyright © 2017. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Centaurium erythraea Rafn (CE) is a traditional medicinal herb in Serbia with antidiabetic, digestive, antipyretic and antiflatulent effects AIM OF THE STUDY: To investigate the potential protective effects of the methanol extract of the aerial parts of CE against glyco-oxidative stress in red blood cells (RBCs) in rats with experimentally induced diabetes., Material and Methods: Diabetes was induced in Wistar rats by intraperitoneal (i.p.) injection of multiple low-dose streptozotocin (STZ) (40mg/kg, for five consecutive days), with the 1st day after the last STZ injection taken as the day of diabetes onset. The methanol extract of CE (100mg/kg) was administered orally and daily, two weeks before the first STZ injection, during the 5-day treatment with STZ, and for four weeks after the STZ injections (pre-treated group) or for four weeks after diabetes onset (post-treated group). The effect of CE extract administration on the redox status of RBCs was evaluated by assessing lipid peroxidation, the ratio of reduced/oxidized glutathione (GSH/GSSG), the level of S-glutathionylated proteins (GSSP) and the enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in RBCs four weeks after diabetes onset. The major biochemical parameters of diabetes, protein glycation/glycosylation of erythrocytes and parameters which correlate with their aggregation and deformability were also evaluated., Results: Daily application of CE extract to STZ-induced diabetic rats provided important antidiabetic effects, observed in both pre-treated and post-treated groups of diabetic rats as elevated serum insulin concentration, reduction of blood glucose and glycated hemoglobin concentrations and an improved lipid profile. Antioxidant effects of CE extract were detected in RBCs of diabetic rats and observed as decreased lipid peroxidation and ameliorated oxidative damage as a result of increased SOD, CAT and GR activities, an improved GSH/GSSG ratio and reduced GSSP levels. Moreover, the CE extract protected RBC proteins from hyperglycemia-induced damage by reducing non-enzymatic glycation and enzymatic glycosylation processes. CE extract was more effective when applied before diabetes induction (pre-treated group)., Conclusions: The results of this study show that the Centaurium erythraea methanol extract protects RBCs in diabetic animals from oxidative damage. They provide additional support for the application of this traditionally used plant in diabetes management., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Dolichandra unguis-cati L. is a native climbing plant of Brazil, popularly known as "unha de gato". It has been traditionally used mainly as an antipyretic, anti-inflammatory and anti-tumor agent, yet little toxicological information is found in the literature., Aim of the Study: To identify the chemical composition of the hydroethanolic extract obtained from the leaves of Dolichandra uniguis-cati and to evaluate the acute and subacute toxicity in male and female rats, in order to assess the safety profile of this plant., Materials and Methods: In the acute study, a single dose (2000mg/kg) of the extract was orally administered to male and female rats. In the subacute study, the extract was orally administered to male and female rats at doses 100, 200 and 400mg/kg for 28 days. Behavioral changes, catalase and tbars evaluations, biochemical, hematological and histopathological analysis were determined. The extract' chemical composition was accessed through UHPLC/MS., Results: Chlorogenic acid, caffeic acid, ferulic acid, vanillinic acid, p-coumaric acid, rosmarinic acid, trans-cinnamic acid, luteolin, apigenin, quercitrin and quercetin were identified in the extract. In the acute treatment, the extract was classified as safe (category 5), according to the OECD guide. In relation to the subacute study, females showed a reduction in AST (100, 200 and 400mg/kg), ALT (200mg/kg) and BUN (100 and 200mg/kg) levels, while male rats 400mg/kg presented an increase in AST levels. The Chol dosage significantly decreased in female rats in a dose-dependent manner, whereas for male rats this parameter showed no statistically significant reductions. No behavioral and histopathological changes were recorded., Conclusions: Our results indicate that the hydroethanolic extract of Dolichandra unguis-cati leaves did not present relevant toxic effects when administered orally to male and female rats. The extract also showed a potential hypocholesterolemic activity., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Various parts of the tropical plant, Morinda citrifolia L. (Noni), have been widely used in traditional medicine in South and Southeast Asia for several centuries. The therapeutic effects of the noni are believed to be mediated through several phytochemicals such as anthraquinones, iridoid, fatty acid glycosides, alcohols, etc., Aim of the Study: The aim of the study is to investigate the effects of Morinda citrifolia fruit juice (noni fruit juice; NFJ) on neural-immune interactions through the involvement of intracellular signaling pathways both in vitro and in vivo in the splenic lymphocytes of young and old male F344 rats., Material and Methods: In the in vitro study, splenocytes from young and old F344 rats were isolated and treated with 0.0001-1% concentrations of NFJ for a period of 24h, while in the in vivo study, old F344 rats were orally administered (5ml/kg body weight) with NFJ (5%, 10% and 20%) twice daily for 60 days. After the treatment period, concanavalin A (Con A)-induced lymphocyte proliferation, cytokines (IL-2, IFN-γ, IL-6, and TNF-α) production, expression of tyrosine hydroxylase (p-TH), nerve growth factor (NGF), m-TOR, IκB-α, p-NF-κB (p50 and p65), p-ERK, p-Akt, p-CREB and lipid peroxidation, protein carbonyl formation, nitric oxide (NO) production were examined in the splenocytes., Results: In vitro NFJ incubation of splenic lymphocytes increased Con A-induced lymphocyte proliferation, IL-2 and IFN-γ production, and expression of p-ERK, p-Akt, and p-CREB in young and old rats. In vivo treatment of old rats with NFJ increased lymphoproliferation, IL-2 and IFN-γ production, the expression of p-TH, NGF, and NO production, and suppressed IL-6 production, lipid peroxidation, protein carbonyl formation, and the expression of IκB-α and p-NF-κB (p50) in the splenocytes., Conclusion: Taken together, these results suggest that Morinda citrifolia fruit juice enhanced neural-immune interactions and cell survival pathways while inhibiting inflammatory processes that may be useful in the treatment of age-associated diseases., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Paederia foetida Linn. (Family: Rubiaceae) is widely used as a natural remedy for diabetes mellitus by the Nepali and Lepcha tribes of Sikkim and Darjeeling Himalayan region. The plant is administered to a diabetic individual in the form of leaf infusion for 2-3 weeks. Therefore, we investigated the effects of methanolic leaf extract of Paederia foetida (MEPF) on alloxan (ALX) induced diabetic renal oxidative stress and NF-kB dependent renoinflammatory events in rat. Method Effects of MEPF on blood glucose, glomerular filtration rate (GFR), serum and oxidative stress markers were evaluated in ALX induced diabetic wistar rats. Enzyme linked immunosorbent assay (ELISA) was carried out to estimate serum IL-6, IL-1β, TNF-α and renal tissue NF-kB p65 levels. MEPF treatment was given to the diabetic rats at a dose of 250 and 500mg/kg body weight (b.w.)., Results & Discussion: MEPF treatment significantly reduced hyperglycaemia, serum creatinine, blood urea nitrogen (BUN), bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides (TRIGs), and total cholesterol (TCHOL) levels in the diabetic rats, whereas it significantly restored GFR and serum albumin level. The activity of enzymatic and non-enzymatic antioxidant machineries was remarkably augmented by MEPF treatment. Likewise, it also significantly lowered lipid peroxidation which was evidenced by decreased concentration of thiobarbituric reactive substances (malondialdehyde, MDA) in the renal tissue of treated diabetic groups. Moreover, MEPF treated animals exhibited low serum concentrations of IL-6, IL-1β and TNF-α compared to the diabetic control rats. It showed a dose dependent inhibition of NF-kB activation in the diabetic kidney, but the effects were more prominent at a dose of 500mg/kg. Histopathological examinations also confirmed its nephroprotective action during diabetes., Conclusion: MEPF treatment mitigates oxidative stress and suppresses renal inflammation via inhibition of NF-kB in diabetic kidney in early progressive diabetic nephropathy., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Huperzia squarrosa (Forst.) Trevis is used in traditional medicine for improving memory deficits. Alkaloids, triterpenoids, flavonoids are main bioactive compounds of Huperzia squarrosa (Forst.) Trevis., Aim of the Study: This study aimed to investigate the antioxidant, AChE inhibitory activities in vitro of differents fraction of Huperzia squarrosa (Forst.) Trevis extract and neuroprotective effects of EtOAc fraction on scopolamine-induced cognitive impairment in mice., Materials and Methods: Antioxidant activity was measured by DPPH assay. AChE inhibitory effect in vitro and detail kinetic inhibition mechanism was evaluated by Ellman's assay. For in vivo assay, mice were administrated orally EtOAc fraction (150 and 300mg/kg) for fourteen days, and injected scopolamine at a dose of 1mg/kg intraperitoneally for four days to induce memory injured. The memory behaviors were evaluated using the Morris water maze. ACh levels were measured in brain tissue. Superoxide dismutase (SOD), glutathione peroxidase (GPx) activities, malondialdehyde and protein thiol groups were also evaluated in the brains., Results: Our data also demonstrated that EtOAc fraction had the strongest antioxidant with an IC 50 value of 9.35±1.68µg/mL and AChE inhibitory activity with an IC 50 value of 23.44±3.14μg/mL in a concentration-dependent manner. Kinetic inhibition analysis indicated that EtOAc fraction was mixed inhibition type with Ki (representing the affinity of the enzyme and inhibitor) was 34.75±1.42µg/mL. Scopolamine significantly increased the escape latency time, reduced the crossings number, and swimming time in the target quadrant, while EtOAc fraction reversed these scopolamine-induced effects. EtOAc fraction significantly increased levels of acetylcholine in the brain. EtOAc fraction also significantly decreased oxidative stress in mice., Conclusion: Our data suggest that EtOAc fraction of Huperzia squarrosa extract exhibited a strong neuroprotective effect on cognitive impairment, and may be a potential candidate for the treatment of Alzheimer., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: The leaves of Syzygium cumini (L.) or Skeels (Myrtaceae) are widely used in Brazilian folk medicine to treat diabetes., Aim of the Study: The present study evaluated the functional capacity, biochemical parameters, oxidative stress and DNA damage from eight weeks of intervention with a crude hydroalcoholic extract of S. cumini leaves (EBH) and continuous aerobic training (TAC) in diabetic (D) rats., Materials and Methods: A hydroalcoholic (50%) extract was prepared by ultrasound and phytochemical parameters (total phenols, total tannins and myricetin content) were analyzed. Thirty-seven male Wistar rats were divided into five groups: normoglycemic controls (CONT), diabetic controls (D-CONT), diabetics treated with extract (D+EBH), trained diabetic (D+TAC) and diabetics treated with extract and trained (D+EBH+TAC). Functional capacity was assessed with a maximum exercise capacity test; biochemical parameters with enzymatic kits; oxidative stress by superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS) and oxidized dichlorofluorescein (DCF), and the DNA damage by the comet assay., Results: The D+TAC and D+EBH+TAC groups showed better functional capacity at the end of interventions. The D+EBH group showed glucose and triglyceride reduction, lowest DNA damage index in the blood, liver, kidney, heart, lung and gastrocnemius muscle, improved SOD levels in the liver, kidney and lung, improved CAT levels in the kidney and lower lipid peroxidation in all tissues studied, compared to the D-CONT group. The exercise (D+TAC) was effective in reducing triglycerides, improving SOD levels in the lung, reducing lipid peroxidation in all tissues studied and reducing the DCF oxidation in the kidney, in addition to protecting against DNA damage in the blood and heart. However, the additive effect of the intervention protocols when combined (EBH+TAC) was observed only in improving the gastrocnemius SOD levels. The phytochemical analyses showed a high content of phenols and the presence of myricetin glycosides., Conclusion: The findings in this study suggest a crude hydroalcoholic extract of S. cumini leaves has potential hypoglycemic, hypolipidemic and protective properties acting against oxidative stress and against DNA damage, probably due to its phenols and myricetin glycoside content and the antioxidant properties of these constituents. Moreover, exercise was suggested to have beneficial effects on diabetes, improving functional capacity, ameliorating blood triglyceride control and decreasing lipid peroxidation, but with no effects on ameliorating blood glucose levels. The association of intervention protocols presented an additive effect on the antioxidant SOD activity in the muscle cells of diabetic rats., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Caesalpinia mimosoides Lam. is one of the important traditional folk medicinal plants in the treatment of skin diseases and wounds used by healers of Uttara Kannada district of Karnataka state (India). However scientific validation of documented traditional knowledge related to medicinal plants is an important path in current scenario to fulfill the increasing demand of herbal medicine., Aim of the Study: The study was carried out to evaluate the claimed uses of Caesalpinia mimosoides using antimicrobial, wound healing and antioxidant activities followed by detection of possible active bio-constituents., Materials and Methods: Extracts prepared by hot percolation method were subjected to preliminary phytochemical analysis followed by antimicrobial activity using MIC assay. In vivo wound healing activity was evaluated by circular excision and linear incision wound models. The extract with significant antimicrobial and wound healing activity was investigated for antioxidant capacity using DPPH, nitric oxide, antilipid peroxidation and total antioxidant activity methods. Total phenolic and flavonoid contents were also determined by Folin-Ciocalteu, Swain and Hillis methods. Possible bio-active constituents were identified by GC-MS technique. RP-UFLC-DAD analysis was carried out to quantify ethyl gallate and gallic acid in the plant extract., Results: Preliminary phytochemical analysis showed positive results for ethanol and aqueous extracts for all the chemical constituents. The ethanol extract proved potent antimicrobial activity against both bacterial and fungal skin pathogens compared to other extracts. The efficacy of topical application of potent ethanol extract and traditionally used aqueous extracts was evidenced by the complete re-epithelization of the epidermal layer with increased percentage of wound contraction in a shorter period. However, aqueous extract failed to perform a consistent effect in the histopathological assessment. Ethanol extract showed effective scavenging activity against DPPH and nitric oxide free radicals with an expressive amount of phenolic and moderate concentration of flavonoid contents. Ethyl gallate and gallic acid were found to be the probable bio-active compounds evidenced by GCMS and RP-UFLC-DAD analysis., Conclusion: The study revealed the significant antimicrobial, wound healing and antioxidant activities of tender parts of C. mimosoides and proved the traditional folklore knowledge., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Dioscoreophyllum cumminsii is widely used in the management and treatment of diabetes and obesity in Nigeria. This study evaluates the effect of aqueous leaf extract of D. cumminsii on high-fructose diet-induced metabolic syndrome., Methods: Seventy male rats were randomized into seven groups. All rats were fed with high-fructose diet for 9 weeks except groups A and C rats, which received control diet. In addition to the diet treatment, groups A and B rats received distilled water for 3 weeks starting from the seventh week of the experimental period. Rats in groups C-F orally received 400, 100, 200 and 400mg/kg body weight of aqueous leaf extract of D. cumminsii respectively, while group G received 300mg/kg bodyweight of metformin for 3 weeks starting from the seventh week., Results: There was significant (p<0.05) reduction in high-fructose diet-mediated increase in body weight, body mass index, abdominal circumference, blood glucose, insulin, leptin and insulin resistance by aqueous leaf extract of D. cumminsii. Conversely, high-fructose diet-mediated decrease in adiponectin was reversed by the extract. Increased levels of cholesterol, triglycerides, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, atherogenic index, cardiac index and coronary artery index were significantly lowered by the extract, while high-fructose diet mediated decrease in high-density lipoprotein cholesterol was increased by the extract. Tumour necrosis factor-α, interleukin-6 and interleukin-8 levels increased significantly in high-fructose diet-fed rats, which were significantly reversed by the extract. High-fructose mediated-decrease in superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose 6-phosphate dehydrogenase and glutathione reduced were significantly reversed by aqueous leaf extract of D. cumminsii. Conversely, elevated levels of malondialdehyde, conjugated dienes, lipid hydroperoxides, protein carbonyl and fragmented DNA were significantly lowered by the extract., Conclusion: Data generated in this study further laid credence to the hypoglycemic activity of aqueous leaf extract of D. cumminsii as evident from the reversal of hyperglycemia, insulin resistance, dyslipidemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome rats., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Amorphophallus paeoniifolius (Dennst.) Nicolson (Family- Araceae) is a crop of south East Asian origin. In India, its tuber is widely used in ethnomedicinal practices by different tribes for the treatment of piles (hemorrhoids)., Aim: The present study evaluated the effect of methanolic and aqueous extract of Amorphophallus paeoniifolius tuber on croton oil induced hemorrhoids in rats., Materials and Methods: The methanolic extract was standardized with the major phenolic compound, betulinic acid, by HPLC. The hemorrhoids were induced by applying 6% croton oil preparation in the ano-rectal region. Rats were orally administered methanolic and aqueous extract at doses of 250 and 500mg/kg, each for 7 days. Pilex (200mg/kg) was used as reference anti-hemorrhoidal drug. Hemorrhoids were assessed on eighth day by measuring hemorrhoidal and biochemical parameters along with histology of ano-rectal tissue., Results: Croton oil application caused induction of hemorrhoids as indicated by significant (p<0.001) increase in plasma exudation of Evans blue in ano-rectal tissue, macroscopic severity score and ano-rectal coefficient as compared to normal rats. It significantly (p<0.001) elevated lactate dehydrogenase and cytokines (TNF-α and IL-6) levels in serum and increased myeloperoxidase activity and lipid peroxidation in ano-rectal tissue along with marked histological damage as compared to normal rats. Treatment with tuber extracts and pilex significantly (p<0.05-p<0.001) ameliorated Evans blue exudation, hemorrhoidal parameters and other biochemical parameters with attenuation of tissue damage compared to hemorrhoid control rats. The results indicate that tuber extracts exhibited curative action on hemorrhoids. The aqueous extract showed more pronounced effect than methanolic extract. The effects may be attributed to anti-inflammatory and antioxidant properties., Conclusion: Results indicate that tuber of Amorphophallus paeoniifolius exhibited curative action on hemorrhoids through anti-inflammatory and antioxidant properties. The study validates the ethnomedicinal use of tuber in hemorrhoids and implicates its therapeutic potential as an anti-hemorrhoidal agent., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Suanzaorenhehuan Formula (SHF) has been used for treating depression-like disorders for many years in China. The saponins part of the SHF (SSHF) extract was the antidepressant effective component., Aim of Study: To investigate the antidepressant-like effect of SSHF and its possible mechanisms., Materials and Methods: Experimental approaches including the forced swim test (FST), the tail suspension test (TST) and unpredictable chronic mild stress (UCMS) were used to evaluate the effects of SSHF. The possible mechanisms were explored by measuring monoamine neurotransmitter in mice frontal cortex and hippocampus, testing monoamine oxidase enzyme (MAO) activities, antioxidant enzyme activities and free radicals levels in the brains of UCMS-exposed mice., Results: The results showed that SSHF (10, 20, 40mg/kg) significantly decreased the immobility period in FST and TST in mice after two-week treatment. Whereas, SSHF had no significant effect on locomotor activity in mice. It was also found that the serotonin (5-HT) and noradrenaline (NE) levels in the hippocampus and frontal cortex were significantly increased only in 40mg/kg SSHF treated mice. In addition, SSHF (10, 20, 40mg/kg) significantly inhibited monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B) after 21-day UCMS exposure. SSHF (10, 20, 40mg/kg) significantly decreased the nitrous oxide (NO) levels, and increased the activities of total antioxidant capability (T-AOC), glutathione peroxidase (GSH-PX), and catalase (CAT) in different degrees in the brains of UCMS-exposed mice., Conclusions: Our results suggested that SSHF may effectively produce an antidepressant-like effect, which appeared to involve the serotonergic, noradrenergic, monoamine oxidase enzyme and antioxidant systems., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: "Zereshk-e-Saghir" (ZES), one of the traditional herbal medicines in old manuscripts of Persian hakims, has been used for the treatment of liver disorders. This current study is aimed to evaluate ZES effects on animal model to investigate its safety and hepatoprotective activity., Materials and Methods: ZES was prepared according to a traditional method by blending aqueous extracts of Berberis vulgaris L., with fine particles of other plants including Rosa damascene Mill, Cichorium intybus L., Cucumis sativus L., Portulaca oleracea L., Rheum palmatum L., and Nardostachys jatamansi DC.. The lethality of ZES was determined in male NMRI mice. Acute organ toxicity of ZES (750 and 1500mg/kg for 15 days, orally) was evaluated by measuring the cell blood count, liver marker enzymes, creatinine, antioxidant status and histopathological examinations in rats. CCl4-induced liver toxicity was used to examine the hepatoprotective effects of the preparation. The rats were pretreated with 250, 500, 750 and 1500mg/kg ZES by gavage for 15 days. At day 16, the rats were intraperitoneally injected 1ml/kg CCl4 in olive oil. Forty-eight hours after CCl4 injection, the animals were sacrificed and their liver samples and blood were collected for determination of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase (ALT, AST, and ALP), histopathological examinations and antioxidant status., Results: Treatment of the mice with a single dose of ZES up to 2g/kg did not cause mortality. Treatment of the rats with doses of 750 and 1500mg/kg for 15 days showed no significant hematotoxicity and hepatotoxicity. Treatment of the rats with ZES reduced the increased serum levels of ALT, AST, and ALP induced by CCl4 at the doses of 250, 500, and 750mg/kg. This was almost confirmed by histopathological examinations. Pretreatment with ZES also decreased lipid peroxidation and maintained the levels of glutathione and total antioxidant capacity., Conclusions: The present in vivo study revealed that the long term usage of ZES was safe for organs in laboratory animals. Meanwhile, prescribing the traditionally-recommended dose of ZES can be probably used against the liver injuries induced by xenobiotics. Further studies in other models of liver injuries are recommended for finding the exact hepatoprotective mechanism of ZES., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Ayurvedic and Chinese traditional medicine and tribal people use herbal preparations containing Piper nigrum fruits for the treatment of many health disorders like inflammation, fever, asthma and cancer. In Brazil, traditional maroon culture associates the spice Piper nigrum to health recovery and inflammation attenuation., Aims of the Study: The aim of the current work was to evaluate the relationship between reactive oxygen species (ROS) overproduction, DNA fragmentation, cell cycle arrest and apoptosis induced by Piper nigrum ethanolic extract and its antitumor activity., Methods: The plant was macerated in ethanol. Extract constitution was assessed by TLC, UV-vis and ESI-IT-MS/MS spectrometry. The cytotoxicity, proliferation and intracellular ROS generation was evaluated in MCF-7 cells. DNA damage effects were evaluated through intercalation into CT-DNA, plasmid DNA cleavage and oxidative damage in CT-DNA. Tumor growth inhibition, survival time increase, apoptosis, cell cycle arrest and oxidative stress were assessed in Ehrlich ascites carcinoma-bearing mice., Results: Extraction yielded 64mg/g (36% piperine and 4.2% piperyline). Treatments caused DNA damage and reduced cell viability (EC50=27.1±2.0 and 80.5±6.6µg/ml in MCF-7 and HT-29 cells, respectively), inhibiting cell proliferation by 57% and increased ROS generation in MCF-7 cells (65%). Ehrlich carcinoma was inhibited by the extract, which caused reduction of tumor growth (60%), elevated survival time (76%), cell cycle arrest and induced apoptosis. The treatment with extract increased Bax and p53 and inhibited Bcl-xL and cyclin A expression. It also induced an oxidative stress in vivo verified as enhanced lipid peroxidation and carbonyl proteins content and increased activities of glutathione reductase, superoxide dismutase and catalase. GSH concentration was decreased in tumor tissue from mice., Conclusion: The ethanolic extract has cytotoxic and antiproliferative effect on MCF-7 cells and antitumor effect in vivo probably due to ROS overproduction that induced oxidative stress affecting key proteins involved in cell cycle arrest at G1/S and triggering apoptosis. Finally, the overall data from this study are well in line with the traditional claims for the antitumor effect of Piper nigrum fruits., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Dangui-Jakyak-San (DJ) is a traditional Korean medicinal polyherb, prescribed typically in patients with insufficient blood supply in Eastern Asia. The DJ also has been reported to have neuroprotective effects in vitro and in vivo studies., Aim of Study: The therapeutic potential of DJ was examined in stroke rat model, in comparison with donepezil, a reversible acetylcholinesterase inhibitor., Materials and Methods: Ischemic stroke rat model was induced by surgery of permanent occlusion of middle cerebral artery (pMCAO). The model was orally administered with distilled water (pMCAO control), donepezil at 10mg/kg (Donepezil) and DJ at 200, 100 and 50mg/kg (DJ 200, DJ 100 and DJ 50, respectively). Sham had the same surgery excepting for the pMCAO, and it was administered with distilled water (sham control)., Results: After the administration for 28 days, the groups of DJ exhibited dose-dependent reduction in infarct/defect volumes with improvement in sensorimotor and cognitive motor function, comparing to pMCAO control. The DJ treatments seemed to enhance antiapoptotic and antioxidant effects; increases in antiapoptotic expressions (STAT3 and Pim-1) and decreases in lipid peroxidation (MDA) together with increases in contents of endogenous antioxidant (GSH) and activities of antioxidant enzymes (catalase and SOD). The histopathological analyses revealed significant reduction in neuronal apoptosis (caspase-3 and PARP) and neuronal degradation with atrophy and degeneration, in the DJ treatments. Furthermore, the oxidative stresses (nitrotyrosine as an iNOS factor and 4-HNE as a marker of lipid peroxidation) were observed mild. Although the similar neuroprotective effects were observed, the body weight loss was scarcely alleviated in Donepezil comparing to pMCAO control., Conclusion: These suggest that DJ ameliorate the neurological dysfunction of cerebral ischemia through augmentation of antioxidant defense system and up-regulation of STAT3 and Pim-1., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Eclipta alba, also known as Eclipta prostrata, is a weed of the family Asteraceae found in tropical and subtropical regions widely used in herbal medicine, including treatment of renal diseases., Aim of the Study: This study aims to evaluate the protective effect of the methanolic leaf extract of Eclipta alba on gentamicin-induced nephrotoxicity in rats., Materials and Methods: Nephrotoxicity was induced in rats by subcutaneous injection of gentamicin (80mg/kg/day for seven days). Quercetin was used as a positive control. The nephroprotective activity was evaluated by determining blood urea nitrogen, serum creatinine, urinary microprotein, renal catalase and malondialdehyde levels., Results: The extract protected the rat kidneys against gentamicin-induced renal tubular alterations and rises in blood urea nitrogen, serum creatinine, and microprotein levels. Lipid peroxidation and decrement in catalase levels were also ameliorated., Conclusion: The study revealed the protective effect of the methanolic leaf extract of E. alba and suggests that the probable mechanism for the nephroprotection by the extract may be due to its good radical scavenging activity and Fe(3+) ion-reducing ability., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Terminalia arjuna (Roxb. ex DC.) Wight & Arn. (T. arjuna) has been widely used in the traditional ayurvedic system of medicine as a cardioprotectant and for acute and chronic renal diseases supporting its ethnopharmacological use., Aim of the Study: The present study aimed at evaluating the diuretic action of an alcoholic extract of T. arjuna and its possible use as a prophylactic to prevent vascular leakage during acute mountain sickness at high altitude., Materials and Methods: Rats were exposed to hypobaric hypoxia simulated to an altitude of 27,000 ft. in a decompression chamber for 12h. T. arjuna bark extract was administered at a single dose of 150 mg/kg (p.o.) to male Sprague Dawley rats (200 ± 20 g) 30 min prior to exposure. Total urine volume was measured during exposure to hypobaric hypoxia. The animals were then investigated for cerebral vascular leakage and serum concentration of sodium, potassium, renin, angiotensin-II, aldosterone and atrial natriuretic peptide (ANP)., Results: T. arjuna ameliorated acute hypobaric hypoxia induced decrease in glomerular filtration rate (p<0.5), increased total urine output (p<0.5) and prevented cerebral vascular leakage in hypoxic rats. T. arjuna treated animals also showed decrease in serum levels of renin (p<0.001) and angiotensin-II (p<0.5) as compared to placebo treated animals. Administration of T. arjuna attenuated acute hypobaric hypoxia induced oxidative stress, improved aldosterone levels and altered electrolyte balance in animals through ANP dependent mechanism., Conclusion: Results of the present study indicate towards diuretic potential of hydro-alcoholic extract of T. arjuna bark and provide evidence for its novel application as a prophylactic to attenuate acute hypobaric hypoxia induced cerebral vascular leakage through ANP mediated modulation of renin-angiotensin-aldosterone system., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Ribes diacanthum Pall. (Saxifragaceae), a Mongolian folk medicinal plant, was used to treat urinary system diseases. The present work aims to investigate the protective effects of Ribes diacanthum Pall (RDP) against cisplatin-induced nephrotoxicity., Methods: The renal injury was modeled by intraperitoneal injection of cisplatin for 5 consecutive days (5 mg/kg). Nephroprotection of RDP was investigated by oral administration of RDP aqueous extract at a daily dose of 40 mg/kg for 14 consecutive days, starting 7 days prior to cisplatin administration., Results: We demonstrated that pretreatment with RDP aqueous extract protected the mice from death induced by cisplatin administration. RDP treatment also significantly reduced blood urea nitrogen (BUN) and serum creatinine (Cr) levels observed in cisplatin-administrated mice. Histopathological analysis demonstrated that RDP administration protected cisplatin-induced renal tubular cell apoptosis. Further western blotting analysis revealed that RDP significantly reversed cisplatin-increased expression levels of cleaved-Caspase-3, Bax and cisplatin-decreased expression level of Bcl-2 in renal tissue. Finally, RDP markedly enhanced enzyme activities of reduced superoxide dismutase (SOD), Heme oxygenase 1 (HO-1) and catalase (CAT), suppressed lipid peroxidation as well as reactive oxygen species (ROS) production., Conclusion: We concluded that RDP displayed nephroprotective effects against cisplatin-induced renal tubular cell apoptosis, possibly associated with both enhanced antioxidase activity and suppressed ROS generation. Given the major nephrotoxicity of cisplatin cancer chemotherapy, RDP might be a potential candidate for neoadjuvant chemotherapy., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Garcinia brasiliensis, a plant native to the Brazilian Amazon Rainforest, is used in traditional medicine to treat inflammation of the urinary tract, peptic ulcers, arthritis and other conditions., Aim of the Study: The purposes of this study were to analyze the chemical constituents of G. brasiliensis branches and leaves and to evaluate the potential of isolated compounds to act as inhibitors of both the oxidative burst of stimulated neutrophils and oxidative damage in human erythrocyte membranes to verify the antioxidant and anti-inflammatory effects of this plant., Materials and Methods: Neutrophils were isolated from the blood of healthy donors by Ficoll-Paque density gradient centrifugation. Superoxide anion and total reactive oxygen species (ROS) produced by stimulated neutrophils were measured by WST-1 reduction and luminol-enhanced chemiluminescence assays, respectively. Radical-induced lipoperoxidation and hemolysis were performed using erythrocytes from the blood of healthy donors. Compounds were isolated from G. brasiliensis branches and leaves by HPLC microfractionation, and structure elucidation of the isolated compounds was performed based on NMR and HR-MS analyses., Results: The biflavonoids procyanidin, fukugetin, amentoflavone and podocarpusflavone isolated from G. brasiliensis showed potent inhibitory effects on the oxidative burst of human neutrophils, inhibiting ROS production by 50% at 1 μmol L(-1). These biflavonoids also proved to be potent inhibitors of hemolysis (with 88 ± 7% inhibition at 50 µmol L(-1) for procyanidin) and lipid peroxidation in human erythrocytes, with a malondialdehyde level (a biomarker of oxidative stress) of 8.5 ± 0.3 nmol/mg Hb at 50 µmol L(-1) for procyanidin., Conclusions: These findings indicate that the biflavonoids extracted from G. brasiliensis branches and leaves modulate oxidative stress via inhibition of NADPH oxidase and ROS production by stimulated human neutrophils. Furthermore, the biflavonoids exhibited potent inhibition of oxidant hemolysis and lipid peroxidation induced by AAPH in human erythrocytes. Therefore, these studies suggest the use of G. brasiliensis extract as an antioxidant and anti-inflammatory agent., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)