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Background. Inflammation is a frequent phenomenon in the pathogenesis of hepatic disorders leading to fibrosis and cirrhosis. Phytopharmaceuticals developed from traditional medicine can provide effective therapeutic alternatives to conventional medications. Datura stramonium (DS) has reported traditional uses in inflammatory diseases. In this study, we have tried to validate its potential as a source of anti-inflammatory agents. Methods. Powdered leaf part of DS was extracted using ethyl acetate (EA) to provide the extract (DSL-EA). Lymphocyte and macrophage viability and acute toxicity assays established the safety profile, while nitric oxide (NO) scavenging assay estimated the in vitro anti-inflammatory potential. Noninvasive anti-inflammatory, antidepressant, and antinociceptive activities were monitored using BALB/c mice using low and high doses (150 and 250 mg/kg). Major inflammatory studies were performed on Sprague-Dawley male rats using CCl4-induced liver injury model. Disease induction was initiated by intraperitoneal injections of CCl4 (1 mL/kg of 30% CCl4 in olive oil). The rats were divided into six groups. The anti-inflammatory potential of DSL-EA in low and high doses (150 and 300 mg/kg, respectively) was assessed through hematological, biochemical, liver antioxidant defense, oxidative stress markers, and histological studies as well as the expression of Nrf2 and iNOS. Results. DSL-EA exhibited prominent in vitro NO scavenging (IC50: 7.625 ± 0.51 μg/mL) and in vivo anti-inflammatory activity in paw and anal edema models. In CCl4 model, hematological investigations revealed vasotonic effects. Liver functionality was significantly ( P < 0.001 − 0.05 ) improved in DSL-EA-treated rats. The activity level of endogenous antioxidant enzymes in liver tissues was improved in a manner identical to silymarin. The extract reduced the percent concentration of oxidative stress markers in liver tissues. Furthermore, DSL-EA displayed restorative effects on histological parameters (H and E and Masson’s trichrome staining). Immunohistochemistry studies showed marked decline in Nrf2 expression, while overexpression of iNOS was also observed in disease control rats. The damage was distinctly reversed by the extract.

Ethnopharmacological Relevance. Thymus linearis Benth. in Wall is extensively used and sold in Gilgit Baltistan province of Pakistan for the amelioration of conditions like obesity and diabetes. However, this ethnomedicinal use still lacks any scientific backing. Based upon this traditional use, the present study was designed to scientifically validate its role in the prevention of metabolic syndrome. Materials and Methods. The extract library (n-hexane (NH), ethyl acetate (EA), methanol (M), distilled water (DW), and combined extract (CE)) was standardized using in vitro phytochemical, antioxidant, and α-amylase inhibition assays, after which the protective effect of selected “hit,” i.e., CE against metabolic syndrome, was determined in vivo, using rats fed a high-fat diet supplemented with additional cholesterol administration. CE was administered to Sprague Dawley rats in high dose as 100 mg/kg in carboxymethyl cellulose (CMC) (1 ml; 0.75% in DW) and low-dose group as 50 mg/kg in CMC (0.5 ml; 0.75% in DW). After 10 weeks, the effects of CE on insulin resistance, lipid metabolism, nonalcoholic fatty liver disease (NAFLD), oxidative stress, and genotoxicity were assessed through histological, biochemical, and hematological investigations. Results. Phytochemical analysis including RP-HPLC analysis of the extracts showed that flavonoids and phenolics (myricetin, kaempferol, and apigenin), previously known to be effective against obesity and diabetes, are present in the extracts. Antioxidant studies revealed that the plant possesses a highly significant ( p < 0.05 ) concentration of antioxidants. Satisfactory α-amylase inhibitory activity was also observed in in vitro experiments. In vivo studies showed that CE-administered animals had significantly ( p < 0.05 ) lower weight gain and smaller adipocytes than the control group. Moreover, CE resisted any significant ( p < 0.05 ) change in the organ weights. Analogous to findings from its traditional use, the plant extract had a positive modulatory effect on insulin resistance and hyperglycemia. The study also indicated that CE resisted high-fat diet-induced disturbance in lipid profile and countered any pathological changes in liver enzymes caused by fat-infused diet. Furthermore, a study on endogenous antioxidant levels indicated that CE was effective in maintaining catalase and peroxidase levels within the normal range and resisted the effects of lipid peroxidation of thiobarbituric acid reactive substances. Conclusion. In principle, the current study’s findings scientifically validate the implication of T. linearis in metabolic syndrome and recommend further studies on molecular insights of the observed therapeutic activity.

Background: Euphorbia nivulia Buch.-Ham (En) is one of the members of Euphorbiaceae family that is rich in phytochemicals including flavonoids, triterpenes and polyphenolics. Purpose: To evaluate hepato-nephronprotective potential of Euphorbia nivulia. Study Design: Sprague Dawley rats were used as animal models in the study. Methods: En hydro alcoholic extract was standardized and managed in high dose (300 mgkg−1 body weight (BW) and low dose (150 mgkg−1 BW) to Sprague Dawley rats, administered with CCl4 (1mlkg−1BW). Silymarin (50 mgkg−1 BW) was taken as positive control. The treatments were given thrice a week. Consequently, blood and hepatic homogenates were collected after 4 weeks of treatment. While the situation of kidney was explored through measurement of serum creatinine, serum urea, sodium and albumin levels. Hepatic and renal samples of rats treated with both 150 and 300 mg/kg of the extract were used for tissue pathological study. Results: En extract revealed dose dependent moderate level of shelter against CCl4 intoxicated hepato-nephrotoxicity as directed from the acquired results. The decrease of the albumin levels by the maximum dose of the extract exceeded similar to that attained with Silymarin, and the protecting effects of the extract against oxidative destruction were evaluated. Examination of serum show significant (p < 0.05) elevation in the level of aspartate transaminase(AST), alkaline phosphatase(ALP), alanine transaminase(ALT), whereas decline were noted for albumin in CCl4 treated rats. Histopathological cuts and damages were seen in hepatic cells and kidney of rats managed by CCl4. But, co-administration of En extract, dose dependently, improved the CCl4-carried hepatic harms in these limits. Conclusion: These effects propose that the phyto-ingredients of En extract with known polyphenols were able to improve the oxidative stress brought along with CCl4 and may be a useful healing mediator to manage oxidative stress related disorders like hepato-nephro toxicity.

Triazoles and their heterocyclic analogues are nitrogen-rich versatile pharmacophores easily synthesized and converted to a range of biologically relevant heterocycles. In this context, the present research reports the synthesis, characterization, in vitro antioxidant, cytotoxic and α-glucosidase inhibitory potential of 4-amino-5-benzyl-2H-1,2,4-triazol-3(4H)-thione (3) and 5-benzyl-4-(benzylideneamino)-2H-1,2,4-triazole-3(4H)-thiones 5(a–g). Consequently, the percent DPPH free radical scavenging ability was found to be in the decreasing order of 5 g > 5e > 3 > 5d > 5b > 5c > 5a > 5f. The most potent derivatives (5 g), (5e) and (3) showed significant dose-dependent scavenging ability with IC50 values of 61.22, 74.06 and 94.87 µg/ml, respectively. The antioxidant derivatives were screened in brine shrimp lethality as well as protein kinase inhibitory assay to unveil their toxic nature. The percent mortality was found to be decreasing in the order of 5b > 5f > 3 > 5a > 5 g > 5d > 5e > 5c at 200 µg/ml in brine shrimp lethality assay. Accordingly, three derivatives (5b), (3) and (5f) showed significant percent mortality with LC50 values of 25.88, 32.94 and 34.87 µg/ml, respectively. Similarly, in protein kinase inhibitory assay, maximum inhibitory potential was observed for the derivatives (5 g), (3) and (5e) with MIC values of 50 µg/disc in each case. Likewise, in α-glucosidase inhibition assay, the screened derivatives (3) and (5e) showed notable percent α-glucosidase inhibition (66.78 and 55.15%) with IC50 value of 36.11 µg/ml and 60.33 µg/ml, respectively. Molecular docking studies of the screened derivatives were performed in order to assess their binding potential and mechanism of their binding with α-glucosidase, α-kinase and β-kinase enzymes. Docking simulation revealed that the molecules stabilize themselves inside the active site by establishing non-covalent interactions with critical residues. Noteworthy were the derivatives (3) and (5e) which anchored themselves through various significant electrostatic interactions with the critical residues.

Sweet potato (Ipomoea batatasL. Lam.), known as “Shakarqandi” in Pakistan, is an imperative root vegetable with large size, traditionally used as aphrodisiac, antiprostatic, anti-inflammatory, antidiabetic, cardiotonic, and anticancer agent. Present study was conducted to gauge aphrodisiac potential ofIpomoea batatasethyl acetate (IPT-EA, IPA-EA) and methanol (IPT-M, IPA-M) extracts from tuber and aerial part, respectively, via behavioral and biochemical tests and their possible protective role in BPA-induced gonadotoxicity at the dose 300 mg/kg in male Sprague Dawley rats. Phytochemical analysis was done qualitatively and quantitatively through total phenolic and flavonoid content (TPC and TFC) and high performance liquid chromatographic (HPLC-DAD) fingerprinting while antioxidant profiling used multimodein vitroassays. To calculate sexual excitement mount latency, intromission latency, mount frequency, intromission frequency, ejaculatory latency, and postejaculatory interval were examined while for biochemical ratification semen characteristics, levels of testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol were measured. Gonadoprotective ability was assessed through comet assay and histomorphological examination of testes. Qualitative analysis ensured the presence of phenols, flavonoids, tannins, anthocyanin, saponins, coumarins, terpenoids, and betacyanin. Quantitatively maximal TPC (304.32±7.20 μg GAE/mg dry extract) and TFC (214.77±4.09 μg QE/mg DE) were estimated in IPA-EA extract. IPT-EA yielded maximum rutin (7.3±0.12) and myricetin (2.7±0.14 μg/mg DE) while IPA-EA and IPA-M yielded maximum caffeic acid (4.05±0.22 and 1.92±0.17 μg/mg DE, respectively) in HPLC-DAD analysis. Extracts enhanced sexual excitement, improved semen quality, levels of testosterone, FSH, LH, and estradiol, and successfully attenuated toxic effects of BPA. Levels of endogenous antioxidant enzymes (CAT, SOD, POD, and GSH) were restored and NO abundance was minimized. Significant stimulation in sexual behavior, amelioration of toxicity symptoms, elevated spermatic production, raised viability, vitalized levels of gonadal hormones, maintained endogenous enzymes, genoprotection, and reformed testicular histology endorsedI. batatasas a better aphrodisiac alternative and gonadoprotective agent.

Widespread applications of nanomaterials in food and health sciences have inevitable toxicological outcomes. Among nanomaterials, copper oxide nanoparticles (CuO NPs) are commonly used in all fields due to its distinctive characteristics. The study was designed to investigate the comparative hepatotoxic effect of green (GNPs) and chemically synthesized (CNPs) CuO NPs on spargue-dawely rats and their offspring. NPs (50 and 100 mg/kg) were orally administered to rats twice a week starting before mating. After birth the parents were continued dosing while pups were only on mother feed. Antioxidant, lipid peroxidation, genotoxicity, and histology were performed on liver tissue. In addition serum biochemistry of parents and offspring was also performed. The levels of catalase, peroxidase, and glutathione were significantly lowered only in CNPs treated parents while lipid peroxidation level was increased in these groups. Maximum genotoxicity (2.3%) in terms of percent tail DNA was observed in parent rats administered with high CNPs dose while other groups did not exhibit significant variation in genetoxic parameters. Gender and dose dependent effects were observed on liver function tests especially ALP and ALT in parents however no obvious differences were observed in offspring. Furthermore, dose dependent dilation and congestion of sinusoids was observed on CNPs administration. In GNPs treated rats and offspring histological alterations were observed. The study concludes that chemically synthesized CuO NPs exhibit dose dependent toxic effects on liver as compared to green synthesized CuO NPs. Furthermore lactation does not play significant role in the hepatotoxicity of offspring though minor oxidative stress was observed only on CNPs administration. The study also shows that pharmacological application of green synthesized NPs can be accomplished due to their biocompatible nature.

Background Cancer is a horrific disease relentlessly affecting human population round the globe. Genus Datura encompasses numerous species with reported medicinal uses. However, its potential as a source of natural anticancer agents is yet to be determined. Datura stramonium (DS) and Datura inoxia (DI) are the two species chosen for this study. Methods Total phenolic and flavonoid content (TPC and TFC) as well as antioxidant activity were assessed through colorimetric method. Polyphenolic quantification was done by RP-HPLC. Following extract standardization ethyl acetate leaf extracts of both species (DSL-EA and DIL-EA) were chosen for anticancer studies. In vitro cytotoxicity using various models including cancer cell lines was monitored. Following toxicity studies, benzene (0.2 ml) was used to induce leukemia in Sprague-Dawley rats. Extracts were orally administered to preventive (100 and 200 mg/kg) and treatment (200 mg/kg only) groups. The antileukemic potential of extracts was assessed through haematological, biochemical, endogenous antioxidants and histological parameters. Results Significant TPC and TFC were estimated in DSL-EA and DIL-EA. RP-HPLC quantified (μg/mg extract) rutin (0.89 ± 0.03), gallic acid (0.35 ± 0.07), catechin (0.24 ± 0.02) and apigenin (0.29 ± 0.09) in DSL-EA while rutin (0.036 ± 0.004) and caffeic acid (0.27 ± 0.03) in DIL-EA. Both extracts exhibited significant brine shrimp cytotoxicity (LC50 50 3) /μl), bilirubin (7.56 ± 0.97 mg/dl), Thiobarbituric acid reactive substances (TBARs) (133.75 ± 2.61 nM/min/mg protein), decreased RBCs (4.33 ± 0.065 (× 106)/μl), platelets (344 ± 3.19 (× 103)/μl), total proteins (2.14 ± 0.11 g/dl), Glutathione S-transferases (GST) (81.01 ± 0.44 nM/min/ml), endogenous antioxidant enzymes levels and abnormal liver and kidney functionality in disease control rats. Both species revealed almost identical and significant (p Conclusion Comprehensive screening divulged the tremendous potential of selected species as potent source of natural anticancer agents in a variety of cancers particularly leukemia. Present study might provide useful finger prints in cancer research and mechanistic studies are prerequisite in logical hunt of this goal.

The c-Jun N-terminal kinase (JNK) pathway and neurotrophic factor dysregulation play a critical role in the pathogenesis of neurobehavioral disorders (anxiety and depression). Targeting the JNK pathway and BDNF/VEGF signaling may signify a new avenue for the treatment of neurobehavioral disorders. The present study investigated the effect of matrine (Mat) against anxiety- and depressive-like emotional status in an acute mouse model of burn injury and explores its underlying mechanism. In the mouse model of thermal injury, anxiety- and depression-related behaviors were evaluated using the elevated plus-maze test, the light-dark box test, the open-field test, the forced swimming test, and the tail suspension test. The JNK/caspase-3 and BDNF/VEGF proteins were determined by immunohistochemistry. Additionally, proinflammatory cytokine, antioxidant, nitric oxide, and corticosterone levels were also measured. The results showed that treatment with Mat significantly improves anxiety- and depressive-like behaviors. It remarkably reduced the levels of proinflammatory cytokines, malondialdehyde, and nitric oxide in the hippocampus and prefrontal cortex of a mouse brain. It considerably improved burn-induced alteration in the antioxidant status, corticosterone, and BDNF/VEGF. It also inhibited burn-induced apoptotic signaling by downregulating the expression of JNK/caspase-3. Similarly, it prevented DNA damage and histopathological changes in the dentate gyrus of the hippocampus. Furthermore, molecular docking results showed that Mat possess better binding affinity for JNK/caspase-3 and BDNF/VEGF proteins. These findings provide convincing evidence that Mat improves anxiety- and depressive-like emotional status through modulation of JNK-mediated inflammatory, oxidative stress, apoptotic, and BDNF/VEGF signaling in an acute mouse model of burn injury.

There are numerous extra- and intra-cellular processes involved in the production of reactive oxygen species (ROS). Augmented ROS generation can cause the damage of biomolecules such as proteins, nucleic acid and lipids. ROS act as an intracellular signaling component and is associated with various inflammatory responses, chronic arthropathies, including rheumatoid arthritis (RA). It is well documented that ROS can activate different signaling pathways having a vital importance in the patho-physiology of RA. Hence, understanding of the molecular pathways and their interaction might be advantageous in the development of novel therapeutic approaches for RA.

Cannabis has been used medicinally for centuries and numerous species of this genus are undoubtedly amongst the primeval plant remedies known to humans. Cannabis sativa in particular is the most reported species, due to its substantial therapeutic implications that are owed to the presence of chemically and pharmacologically diverse cannabinoids. These compounds have long been used for the palliative treatment of cancer. Recent advancements in receptor pharmacology research have led to the identification of cannabinoids as effective antitumor agents. This property is accredited for their ability to induce apoptosis, suppress proliferative cell signalling pathways and promote cell growth inhibition. Evolving lines of evidence suggest that cannabinoid analogues, as well as their receptor agonists, may offer a novel strategy to treat various forms of cancer. This review summarizes the historical perspective of C. sativa, its potential mechanism of action, and pharmacokinetic and pharmacodynamic aspects of cannabinoids, with special emphasis on their anticancer potentials.

Current study is intended to investigate the antimicrobial and antidiabetic potential of Bombax ceiba L. Antileishmanial potential was assessed via MTT colorimetric method while antifungal activities were found out through disc diffusion method. The antidiabetic potential was investigated by α-amylase inhibition assay. Considerable antifungal activity (in the range of 10-12 mm ZOI) was demonstrated by CH: M extracts of both flower and stem bark, and CH extract of root bark against A. niger Whereas M: EA, AC extracts of leaf, EA extract of stem bark, NH, CH:E, M:EA extracts of root bark and NH extract of root wood exhibited the antifungal potential (ZOI from 10-12 mm) against F. solani. The most potent α-amylase inhibitory activity was shown by EA extract of leaf part with 66.69 ± 0.95% inhibition (IC50 190 ± 4.5 µg/ml). Selected plant is a potential source of antileishmanial, antifungal and antidiabetic agents. This information can be further utilized for the purpose of bioactivity guided isolation of biologically active principles of B. ceiba L.

Background Ipomoea batatas L. Lam. is a functional food and belongs to family Convolvulaceae. It is used as an antiinflammatory, aphrodisiac, antiasthmatic, anticonvalescent, antitumor, antanemic and antidiabetic agent by local communities. This study has been planned to evaluate its antiinflammatory and antiarthritic potentials. Methods Dry powder of I. batatas tuber and roots were extracted with ethyl acetate (IPT-EA, IPR-EA) and methanol (IPT-M, IPR-M), respectively. These extracts were tested for total phenolic and flavonoid contents (TPC and TFC), HPLC finger printing, multidimensional in vitro and in vivo antioxidant potential and albumin denaturation inhibition. Carrageenan-induced paw edema, croton oil-induced ear and anal edema inhibition and Complete Freund’s Adjuvant (CFA)-induced antiarthritic assays were executed at a dose of 300 mg/kg body weight on Sprague-Dawley rats. Serum levels of interleukins IL-1β and IL-6 and nitric oxide (NO) were assessed to measure the inhibition of inflammation. Results Maximal TPC (319.81 ± 14.20 μg GAE/mg dry extract) and TFC (208.77 ± 9.09 μg QE/mg DE) were estimated in IPR-EA extract. IPT-EA and IPR-EA yielded the maximum amounts of rutin (7.3 ± 1.12 and 4.5 ± 0.55), caffeic acid (1.60 ± 0.25 and 2.17 ± 0.26) and myricetin (2.7 ± 0.14 and 1.01 ± 0.08 μg/mg DE), respectively in HPLC-DAD analysis. All extracts showed dose dependent response in in vitro antioxidant assays. Best inhibition (76.92 ± 3.07%) of albumin denaturation was shown by IPT-EA in comparison to ibuprofen (79.48 ± 4.71%). IPR-EA exhibited highest edema inhibition in models of carrageenan-induced paw edema (79.11 ± 5.47%) and croton oil-induced ear and anal edema (72.01 ± 7.80% and 70.80 ± 4.94%, respectively). Significant inhibition of CFA-induced arthritic edema and arthritic score were observed by IPR-EA as compared to ibuprofen. Suppression of pro-inflammatory cytokines (IL-1β, IL-6) and NO levels was shown by IPR-EA and IPT-EA, respectively. Conclusion These results depict that richness of polyphenols and phytoconstituents in I. batatas ameliorates oxidative stress and inflammation of acute and chronic nature. Dose dependent antioxidant potential and inhibition of inflammatory edema, pro-inflammatory cytokines and hematological, biochemical and histological changes prove I. batatas therapeutic potential as an antiinflammatory and antiarthritic agent. Graphical abstract Electronic supplementary material The online version of this article (10.1186/s12906-018-2279-5) contains supplementary material, which is available to authorized users.

Current study was intended to investigate the cytotoxic potential of Bombax ceiba L.by executing a wide range of in vitro assays. Brine shrimp lethality assay showed that stem wood’s chloroform (CH) extract was highly toxic (LC50 42.41 ± 3.40 µg/ml) followed by acetone : ethyl acetate (AC:EA) extract with LC50 value of 72.92 ± 4.41 µg/ml. n-Hexane (NH) extract of root wood part caused 70.95 ± 1.77% inhibition of THP-1 cell line at 20 μg/ml concentration (IC50 15 ± 0.56 µg/ml). NH and CH extracts of stem wood part showed promising results in protein kinase inhibitory assay with 21 ± 1.2 and 29 ± 1 mm bald ZOI (MIC= 50 µg/disc) respectively. The present findings revealed that CH and NH extracts of stem wood as well as root wood part as an enriched source of phytochemicals possessing cytotoxic potential.