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Rheumatoid arthritis is a chronic autoimmune disease characterized by the infiltration of synovial inflammatory cells and progressive joint destruction. Total flavonoids of Bidens pilosa have been used against inflammation in rheumatoid arthritis, but its role in bone destruction remains to be explored. The aim of this paper was to study whether total flavonoids of B. pilosa relieve the severity of collagen-induced arthritis in rats, particularly whether it regulates the production of proinflammatory cytokines and the receptor activator of nuclear factor- κ B/receptor activator of nuclear factor- κ B ligand/osteoprotegerin signaling pathway. In this research, a collagen-induced disease model was induced in adult rats by subcutaneous injection of collagen II. Total flavonoids of B. pilosa at different doses (40, 80, and 160 mg/kg/d) were administered intragastrically, while methotrexate (1 mg/kg/w) was injected intraperitoneally as a positive control. Paw swelling, arthritis score, and body weight were assessed and evaluated. The severity of joint damage was determined using X-ray and confirmed by histopathology. The expression levels of receptor activator of nuclear factor- κ B ligand, osteoprotegerin, IL-1 β , IL-17, and TNF in the serum and tissue were assayed using ELISA and immunohistochemistry. We found that total flavonoids of B. pilosa attenuated collagen-induced arthritis at the macroscopic level, and total flavonoids of B. pilosa -treated rats showed reduced paw swelling, arthritis scores, and X-ray appearance of collagen-induced arthritis in addition to improved histopathological results. These findings were consistent with reduced serum and tissue receptor activator of nuclear factor- κ B ligand, TNF, IL-1 β , and IL-17 levels but increased osteoprotegerin levels. Our data suggest that total flavonoids of B. pilosa attenuate collagen-induced arthritis by suppressing the receptor activator of nuclear factor- κ B ligand/receptor activator of nuclear factor- κ B/osteoprotegerin pathway and the subsequent production of proinflammatory cytokines. In addition, total flavonoids of B. pilosa may be a promising therapeutic candidate for the management of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the gastroprotective activity of the total alkaloids from the bark of Phellodendron amurense and identify their possible mechanism. Total alkaloids were obtained through an alcohol extraction method and were analyzed using LC-MS/MS. Chronic gastric ulcers were induced by acetic acid (0.14 mol/L) filter paper on the gastric serosa. The antiulcer effect of total alkaloids was evaluated using the ulcer area, the ulcer inhibition ratio, and epidermal growth factor. The gastroprotective mechanism of total alkaloids was revealed using the levels of serotonin and noradrenaline. The results showed that oral administration of total alkaloids (30 mg/kg/day) obviously decreased the ulcer area (7.67 ± 2.06 mm²; p<0.01) compared with the model group (15.15 ± 2.34 mm²). The ulcer inhibition ratio of the total alkaloids group (50%) was higher than the omeprazole-treated group (46%), which showed that the antiulcer effect of the total alkaloids may be superior to omeprazole. Besides, the total alkaloids significantly increased the epidermal growth factor level and accelerated the healing of ulcers. Histological examination of gastric tissues also supported the same conclusion. In addition, the total alkaloids significantly elevated the levels of serotonin and noradrenaline (both p<0.01 compared to the model group). Our data indicates that total alkaloids of Cortex Phellodendri exerts a beneficial gastroprotective effect and the involved mechanism is likely neurohumoral regulation. Thus, Cortex Phellodendri may develop into a promising clinical medicinal agent for improving the quality of ulcer healing. [ABSTRACT FROM AUTHOR]

The carrot-made LTB-Syn antigen (cLTB-Syn) is a vaccine candidate against synucleinopathies based on carrot cells expressing the target antigen LTB and syn epitopes. Therefore, the development of an efficient production process is required with media culture optimization to increase the production yields as the main goal. In this study, the effect of two nitrogen sources (urea and glutamate) on callus cultures producing cLTB-Syn was studied, observing that the addition of 17 mM urea to MS medium favored the biomass yield. To optimize the MS media composition, the influence of seven medium components on biomass and cLTB-Syn production was first evaluated by a Plackett–Burman design (PBD). Then, three factors were further analyzed using a central composite design (CCD) and response surface methodology (RSM). The results showed a 1.2-fold improvement in biomass, and a 4.5-fold improvement in cLTB-Syn production was achieved at the shake-flask scale. At the bioreactor scale, there was a 1.5-fold increase in biomass and a 2.8-fold increase in cLTB-Syn yield compared with the standard MS medium. Moreover, the cLTB-Syn vaccine induced humoral responses in BALB/c mice subjected to either oral or subcutaneous immunization. Therefore, cLTB-Syn is a promising vaccine candidate that will aid in developing immunotherapeutic strategies to combat PD and other neurodegenerative diseases without the need for cold storage, making it a financially viable option for massive immunization. [ABSTRACT FROM AUTHOR]

Isocorynoxeine, one of the major alkaloids from Uncaria Hook, shows the effects of lowering blood pressure, vasodilatation, and protection against ischemia-induced neuronal damage. In this paper, the metabolism of isocorynoxeine was investigated in rats. Twelve metabolites and the parent drug were isolated by using solvent extraction and repeated chromatographic methods, and determined by spectroscopic methods including UV, MS, NMR, and CD experiments. Seven new compounds were identified as 11-hydroxyisocorynoxeine, 5-oxoisocorynoxeinic acid-22-O-β-Dglucuronide, 10-hydroxyisocorynoxeine, 17-Odemethyl-16,17-dihydro-5-oxoisocorynoxeine, 5-oxoisocorynoxeinic acid, 21-hydroxy-5-oxoisocorynoxeine, and oxireno[18, 19]-5-oxoisocorynoxeine, together with six known compounds identified as isocorynoxeine, 18,19-dehydrocorynoxinic acid, 18,19-dehydrocorynoxinic acid B, corynoxeine, isocorynoxeine-N-oxide, and corynoxeine-N-oxide. Possible metabolic pathways of isocorynoxeine are proposed. Furthermore, the activity assay for the parent drug and some of its metabolites showed that isocorynoxeine exhibited a significant neuroprotective effect against glutamate-induced HT22 cell death at the maximum concentration. However, little or weak neuroprotective activities were observed for M-3, M-6, M-7, and M-10. Our present study is important to further understand their metabolic fate and disposition in humans. [ABSTRACT FROM AUTHOR]

In this paper, the chemical composition and biological activity of the essential oil of Artemisia absinthium was studied. The aim of this study was to investigate the potential of ethnopharmacological uses of this plant species in the treatment of gastrointestinal diseases and wounds, and as an insect repellent. The aerial part of the plant was hydrodistilled, and the chemical composition of the essential oil was analyzed by gas chromatography and gas chromatography/mass spectrometry. Forty-seven compounds, corresponding to 94.65% of the total oil, were identified, with the main constituents being sabinene (24.49%), sabinyl acetate (13.64%), and α-phellandrene (10.29%). The oil yield was 0.23% (v/w). The antimicrobial activity of the oil was investigated against ten bacterial isolates (from patients wounds and stools) and seven American Type Culture Collection strains using a microwell dilution assay. The minimal inhibitory/bactericidal concentration of the oil ranged from <0.08 to 2.43 mg/mL and from 0.08 to 38.80 mg/mL, respectively. The antioxidant activity of the essential oil was evaluated using 2,2-diphenyl-1-picrylhydrazil and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical-scavenging methods and assessed as significant. Skin irritation potential and acute toxicity of the oil were also investigated. Results of the skin irritant reaction showed that none of the 30 volunteers developed a positive skin irritant reaction to undiluted A. absinthium essential oil. Acute oral exposure to the essential oil did not cause mortality in the treated mice, but it did cause neurological, muscle, and gastrointestinal problems. A subchronic toxicity test on Drosophila melanogaster showed that the essential oil of A. absinthium is toxic for developing insect larvae. Starting with the concentration of 0.38% of essential oil in medium, significant mortality of larvae exposed to the oil was noted when compared to the control. Probit analysis revealed that the LC50 value of A. absinthium essential oil for D. melanogaster larvae after 15 days of exposure was 6.31 % (49 mg/mL). The essential oil also affected the development of D. melanogaster larvae and significantly delayed achievement of the pupa stadium. [ABSTRACT FROM AUTHOR]

Agave applanata is a Mexican agave whose fresh leaves are employed to prepare an ethanol tonic used to relieve diabetes. It is also applied to skin to relieve varicose and diabetic foot ulcers, including wounds, inflammation, and infections. In this study, the chemical composition of this ethanol tonic is established and its association with antihyperglycemic, anti-inflammatory, antimicrobial, and wound healing activities is discussed. The fresh leaves of A. applanata were extracted with ethanol : H2 O (85 : 15). A fraction of this extract was lyophilized, and the remainder was partitioned into CH2 Cl2 , n -BuOH, and water. CH2 Cl2 and n -BuOH fractions were subjected to a successive open column chromatography process. The structure of the isolated compounds was established using nuclear magnetic resonance and mass spectrometry spectra. The antihyperglycemic activity was evaluated through in vivo sucrose and glucose tolerance experiments, as well as ex vivo intestinal absorption and hepatic production of glucose. Wound healing and edema inhibition were assayed in mice. The minimum inhibitory concentrations (MICs) of the hydroalcoholic extract, its fractions, and pure compounds were determined through agar microdilution against the most isolated pathogens from diabetic foot ulcers. Fatty acids, β -sitosterol, stigmasterol, hecogenin (1), N -oleyl-D-glucosamine, β -daucosterol, sucrose, myo -inositol, and hecogenin-3- O - α -L-rhamnopyranosyl-(1 → 3)- β -D-xylopyranosyl-(1 → 2)-[ β -D-xylopyranosyl-(1 → 3)- β -D-glucopyranosyl-(1 → 3)]- β -D-glucopyranosyl-(1 → 4)- β -D-galactopyranoside (2) were characterized. This research provides evidence for the pharmacological importance of A. applanata in maintaining normoglycemia, showing anti-inflammatory activity and antimicrobial effects against the microorganisms frequently found in diabetic foot ulcers. This plant plays an important role in wound healing and accelerated tissue reparation. [ABSTRACT FROM AUTHOR]

Extracellular senile plaques and intraneuronal neurofibrillary tangles are two devastating brain proteinopathies that are indicative of Alzheimerʼs disease, the most prevalent type of dementia. Currently, no effective medications are available to stop or reverse Alzheimerʼs disease. Ginkgo biloba extract, commonly referred to as EGb 761, is a natural product made from the leaves of the G. biloba tree. It has long been demonstrated to have therapeutic benefits in Alzheimerʼs disease. The current study assessed the beneficial effects of EGb 761 against Alzheimerʼs disease in comparison with memantine, a standard treatment for Alzheimerʼs disease. The scopolamine-heavy metals mixture rat Alzheimerʼs disease model is a newly created model to study the effects of EGb 761 oral therapy on cognitive performance and other Alzheimerʼs disease-like changes over a 28-day experimental period. This new Alzheimerʼs disease model provides better criteria for Alzheimerʼs disease hallmarks than the conventional scopolamine model. The EGb 761 reversed memory and learning deficits induced by the scopolamine-heavy metals mixture. These outcomes were linked to a more pronounced inhibitory effect on acetylcholinesterase, caspase-3, hippocampal amyloid-beta protein (A β 1 – 42), phosphorylated tau protein counts, and proinflammatory cytokines (tumor necrosis factor- α and interleukin-1 β) compared to the memantine-treated group. Furthermore, EGb 761 treatment considerably reduced lipid peroxidation (malondialdehyde) and improved reduced glutathione levels compared to memantine. Our results suggest EGb 761′s potential in treating central nervous system disorders. Itʼs a promising candidate for future Alzheimerʼs disease therapeutic exploration. This study also highlights the need for future research to focus on the positive benefits of herbal medicines. [ABSTRACT FROM AUTHOR]

Zingiber zerumbet, a plant native to tropical and subtropical Asia, has a vast range of traditional uses and has been continuously studied for its medicinal properties. However, a systematic methodological approach in evidence synthesis on the plantʼs efficacy is lacking, and there is a need to elicit the current research status of this plant. This scoping review was conducted to systematically explore and collate the available scientific evidence on the efficacy of Z. zerumbet and its main phytoconstituents in various formulations, their biological mechanisms, and their safety. Results included 54 articles consisting of animal studies, while there were no published human studies. Only half of the included studies provided adequate reporting on the quality-related details of Z. zerumbet formulations. Identified pharmacological activities were analgesic, anti-inflammatory, anti-diabetic, anti-hyperlipidemic, anti-neoplastic, immunomodulatory, antioxidant, antipyretic, hepatoprotective, nephroprotective, gastroprotective, and locomotor-reducing activities. Notably, the ethanolic extract of Z. zerumbet was found to be well tolerated for up to 28 days. In conclusion, Z. zerumbet and zerumbone have various pharmacological effects, especially in analgesic and anti-inflammatory models. However, there is still a pressing need for comprehensive safety data to conduct clinical trials. [ABSTRACT FROM AUTHOR]

Boswellia is a traditional medicine for bruises and injuries. Its main active ingredient, acetyl-11-keto-beta-boswellic acid, has antioxidant and antiapoptotic effects. In this experiment, we used Sprague-Dawley rats to make a sciatic nerve injury model to detect the transcription factor NF-E2-related factor 2/heme oxygenase 1 signaling pathway and apoptosis, combined with clinical indicators, for testing whether acetyl-11-keto-beta-boswellic acid can reduce oxidative stress and promote sciatic nerve repair. Our results showed that acetyl-11-keto-beta-boswellic acid administration promoted myelin regeneration and functional recovery in the rat sciatic nerve, reduced lipid peroxidation levels, upregulated the expression of various antioxidant enzymes and enhanced enzyme activity, decreased the expression levels of apoptosis-related proteins, and promoted nuclear translocation of the transcription factor NF-E2-related factor 2 protein. In vitro studies revealed that acetyl-11-keto-beta-boswellic acid reduced H2 O2-induced reactive oxygen species production, restored mitochondrial membrane potential, upregulated the expression of various antioxidant enzymes, and downregulated apoptosis-related indicators in Schwann cells, and these therapeutic effects of acetyl-11-keto-beta-boswellic acid were reversed after ML385 treatment in Schwann cells. In summary, acetyl-11-keto-beta-boswellic acid alleviates oxidative stress and apoptosis caused by sciatic nerve injury in rats by activating the transcription factor NF-E2-related factor 2/heme oxygenase 1 signaling pathway, promotes the recovery of sciatic nerve function in rats, and is a promising therapeutic agent to promote sciatic nerve repair by alleviating excessive oxidative stress. [ABSTRACT FROM AUTHOR]

The aerial parts of Phyllanthus urinaria are used in traditional medicine in West Africa against helminthiasis, but their anthelmintic potential has not been evaluated until now. Within the current study, a hydroacetonic extract (AWE) and fractions and isolated ellagitannins from P. urinaria were, therefore, tested in vitro against Caenorhabditis elegans and the larvae of the animal parasites Toxocara canis, Ascaris suum, Ancylostoma caninum, and Trichuris suis. Compounds 1 – 13 , mainly representing ellagitannins, were isolated using different chromatographic methods, and their structures were elucidated by HR-MS and1 H/13 C-NMR. AWE exerted concentration-dependent lethal effects (LC50 of 2.6 mg/mL) against C. elegans and inhibited larval migration of all animal parasites tested (T. suis L1 IC50 24.3 µg/mL, A. suum L3 IC50 35.7 µg/mL, A. caninum L3 IC50 112.8 µg/mL, T. canis L3 IC50 1513.2 µg/mL). The anthelmintic activity of AWE was mainly related to the polar, tannin-containing fractions. Geraniin 1 , the major ellagitannin in the extract, showed the strongest anthelmintic activity in general (IC50 between 0.6 and 804 µM, depending on parasite species) and was the only compound active against A. caninum (IC50 of 35.0 µM). Furosin 9 was least active despite structural similarities to 1. Among the parasites tested, Trichuris suis L1 larvae turned out to be most sensitive with IC50 of 0.6, 6.4, 4.0, 4.8, and 2.6 µM for geraniin 1 , repandusinic acid A 3 , punicafolin 8 , furosin 9 , and phyllanthusiin A 10 , respectively. [ABSTRACT FROM AUTHOR]

Essential oils are often utilized for therapeutic purposes and are composed of complex structural molecules, including sesquiterpenes, with high molecular weight and potential for stereochemistry. A detailed study on the properties of selected sesquiterpenes was conducted as part of a broader investigation on the effects of sesquiterpenes on the central nervous system. A set of 18 sesquiterpenes, rigorously selected from an original list of 114, was divided into 2 groups i.e., the training and test sets, with each containing 9 compounds. The training set was evaluated for the sedative activity in mice through inhalation, and all compounds were sedatives at any dose in the range of 4 × 10−4 –4 × 10−2 mg/cage, except for curzerene. Molecular determinants of the sedative activities of sesquiterpenes were evaluated using quantitative structure–activity relationship (QSAR) and structure–activity relationship (SAR) analyses. An additional test set of six compounds obtained from the literature was utilized for validating the QSAR model. The parental carbonyl cation and an oxygen-containing groups are possible determinants of sedative activity. The QSAR study using multiple regression models could reasonably predict the sedative activity of sesquiterpenes with statistical parameters such as the correlation coefficient r2 = 0.82 > 0.6 and q2LOO = 0.71 > 0.5 obtained using the leave-one-out cross-validation technique. Molar refractivity and the number of hydrogen bond acceptors were statistically important in predicting the activities. The present study could help predict the sedative activity of additional sesquiterpenes, thus accelerating the process of drug development. [ABSTRACT FROM AUTHOR]

The low amount of metabolites isolated from natural products is one of the challenges preventing their biological evaluation. The modulation of biosynthetic pathways by stimulating stress-induced responses in plants was proven to be a valuable tool for diversification of already known natural products. Recently, we reported the dramatic effect of methyl jasmonate (MeJA) on Vinca minor alkaloids distribution. In this study, three compounds identified as 9-methoxyvincamine, minovincinine, and minovincine are successfully isolated in good yield and subjected to several bioassays based on a network pharmacology study. The extracts and isolated compounds show weak to moderate antimicrobial and cytotoxic activities. Also, they are found to significantly promote wound healing in scratch assay, and transforming growth factor- β (TGF- β) modulation is suggested to be the potential pathway based on bioinformatic analysis. Hence, Western blotting is used to assess the expression of several markers related to this pathway and wound healing. The extracts and isolated compounds are able to increase the expression of Smad3 and Phosphatidylinositol-3-kinase (PI3K), while downregulating the levels of cyclin D1 and the mammalian target of rapamycin (mTOR) except for minovincine, which increases the mTOR expression, inferring that it might act through a different mechanism. Molecular docking is used to give insights on the ability of isolated compounds to bind with different active sites in mTOR. Collectively, the integrated phytochemical, in silico , and molecular biology approach reveal that V. minor and its metabolite could be repurposed for the management of dermatological disorders where these markers are dysregulated, which opens the gate to develop new therapeutics in the future. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a metabolic endocrine disorder caused by decreased insulin concentration or poor insulin response. Muntingia calabura (MC) has been used traditionally to reduce blood glucose levels. This study aims to support the traditional claim of MC as a functional food and blood-glucose-lowering regimen. The antidiabetic potential of MC is tested on a streptozotocin–nicotinamide (STZ-NA)-induced diabetic rat model by using the1 H-NMR-based metabolomic approach. Serum biochemical analyses reveal that treatment with 250 mg/kg body weight (bw) standardized freeze-dried (FD) 50% ethanolic MC extract (MCE 250) shows favorable serum creatinine (37.77 ± 3.53 µM), urea (5.98 ± 0.84 mM) and glucose (7.36 ± 0.57 mM) lowering capacity, which was comparable to the standard drug, metformin. The clear separation between diabetic control (DC) and normal group in principal component analysis indicates the successful induction of diabetes in the STZ-NA-induced type 2 diabetic rat model. A total of nine biomarkers, including allantoin, glucose, methylnicotinamide, lactate, hippurate, creatine, dimethylamine, citrate and pyruvate are identified in ratsʼ urinary profile, discriminating DC and normal groups through orthogonal partial least squares-discriminant analysis. Induction of diabetes by STZ-NA is due to alteration in the tricarboxylic acid (TCA) cycle, gluconeogenesis pathway, pyruvate metabolism and nicotinate and nicotinamide metabolism. Oral treatment with MCE 250 in STZ-NA-induced diabetic rats shows improvement in the altered carbohydrate metabolism, cofactor and vitamin metabolic pathway, as well as purine and homocysteine metabolism. [ABSTRACT FROM AUTHOR]

Gnaphalium affine is traditionally used to treat hyperuricemia and gout in China. Recently, the hypouricemic and renal protective effects of G. affine extract (GAD) have been deeply evaluated. However, little is known about the pharmacokinetics (PKs) of bioactive constituents in GAD. This study is aimed at investigating the individual and holistic pharmacokinetics of 10 bioactive components (including caffeic acid, caffeoylquinic acids, and flavonoids) in rats after single and multiple administrations of GAD. GAD is orally dosed to normal male rats at doses of 225, 450, or 900 mg/kg/day for 10 consecutive days and also orally administrated to uric acid nephropathy (UAN) rats at a dose of 900 mg/kg/day for 28 consecutive days. Integrated PKs of multiple components are calculated by area under the curve (AUC)-based weighting approach. All the components show a double-peak phenomenon in terms of their plasma concentration-time curves, suggesting that the components undergo enterohepatic circulation. The integrated AUC increases in a good dose-proportional manner with GAD dose. Compared with that in normal rats, the plasma exposure of caffeic acid and caffeoylquinic acids increases by 2.3- to 4.3-fold after 10-day chronic treatment of 900 mg/kg GAD in UAN rats. Modest drug accumulation is observed after 28-day chronic treatment. [ABSTRACT FROM AUTHOR]

Microemulsions are optically nanosized emulsions, isotropic and thermodynamically stable. They represent versatile drug delivery systems with high potential because they can be administered regardless of route. In the present study, we report on the formulation of a microemulsion made with glycerol (2.25%), Labrasol (20.25%) vitamin E acetate (2.50%), and water (75.00%), which was developed using the pseudo-ternary phase diagram. Globules of the microemulsion had PdI less than 0.25 and size of about 17 nm, evaluated by DLS analysis. These values did not change after loading khellin, a natural lipophilic molecule with interesting biological activities, used as a model of lipophilic drug. Carboxymethyl cellulose was selected as gelling polymer to obtain a microemulgel. Viscosity was 22 100.0 ± 1555.6 mPas·s at 21 ± 2 °C, while it was 8916.5 ± 118.1 mPas·s at 35 ± 2 °C, remaining stable over time. Khellin recovery was 93.16 ± 4.39% and was unchanged after 4 weeks of storage (93.23 ± 2.14%). The pH was 6.59 ± 0.19 and it was found to be 6.42 ± 0.34 at the end of the storage lifetime. The diffusion of khellin from the developed formulation was prolonged over an extended period. Based on overall results and due to the dermatological properties of the ingredients of the formulation, the developed microemulgel loaded with khellin is very promising and suitable for skin care applications. [ABSTRACT FROM AUTHOR]

Orthosiphon stamineus leaves (Java tea) extract is traditionally used for the treatment of urinary tract infections. According to recent in vitro data, animal infection studies, and transcriptomic investigations, polymethoxylated flavones from Java tea exert antiadhesive activity against uropathogenic Escherichia coli (UPEC). This antiadhesive activity has been shown to reduce bladder and kidney lesion in a mice infection model. As no data on the antivirulent activity of Java tea intake on humans are available, a biomedical study was performed on 20 healthy volunteers who self-administered Orthosiphon infusion (4 × 3 g per day, orally) for 7 days. The herbal material used for the study conformed to the specification of the European Pharmacopoeia, and ultra high-performance liquid chromatography (UHPLC) of the infusion showed rosmarinic acid, caffeic acid, and cichoric acid to be the main compounds aside from polymethoxylated flavones. Rosmarinic acid was quantified in the tea preparations with 243 ± 22 µg/mL, indicating sufficient reproducibility of the preparation of the infusion. Urine samples were obtained during the biomedical study on day 1 (control urine, prior to Java tea intake), 3, 6 and 8. Antiadhesive activity of the urine samples was quantified by flowcytometric assay using pre-treated UPEC NU14 and human T24 bladder cells. Pooled urine samples indicated significant inhibition of bacterial adhesion on day 3, 6 and 8. The urine samples had no influence on the invasion of UPEC into host cells. Bacterial proliferation was slightly reduced after 24 h incubation with the urine samples. Gene expression analysis (qPCR) revealed strong induction of fitness and motility gene fliC and downregulation of hemin uptake system chuT. These data correlate with previously reported datasets from in vitro transcriptomic analysis. Increased bacterial motility was monitored using a motility assay in soft agar with UPEC UTI89. The intake of Java tea had no effect on the concentration of Tamm-Horsfall Protein in the urine samples. The present study explains the antiadhesive and anti-infective effect of the plant extract by triggering UPEC from a sessile lifestyle into a motile bacterial form, with reduced adhesive capacity. [ABSTRACT FROM AUTHOR]

Radix arnebiae oil (RAO) is a clinically useful traditional Chinese medical formula with outstanding curative effects on burns. However, the mechanism of the effect of RAO on wound healing remains unclear. The present study investigates the molecular mechanisms of the potential curative effect of RAO on wound healing. The concentrations of the main constituents, shikonin, imperatorin, and ferulic acid in RAO detected by HPLC were 24.57, 3.15, and 0.13 mg/mL, respectively. A rat burn model was established, and macroscopic and histopathological studies were performed. RAO significantly accelerated wound closure and repair scarring, increased superoxide dismutase activities, and reduced malondialdehyde. RAO also downregulated interleukin (IL)-6, IL-1 β and tumor necrosis factor- α in wound tissues and increased secretion of vascular endothelial growth factor, epidermal growth factor, and transforming growth factor (TGF)- β 1. RAO increased the gene expression of TGF- β 1, type I and III collagen, and increased the protein expression of TGF- β 1 and phosphorylation of PI3K and Akt. In conclusion, RAO likely promotes wound healing via antioxidant and anti-inflammatory activities and increases re-epithelization. Activation of the TGF- β 1/PI3K/Akt pathway may play an important role in the healing efficacy of RAO. These findings suggest that RAO could be a promising alternative local treatment for burn wound healing. [ABSTRACT FROM AUTHOR]

To further study the aminoalcohol-diterpenoid alkaloids (ADAs) in Fuzi (Aconiti Lateralis Radix Praeparata), a simple and sensitive UFLC-MS/MS method was established and validated for the determination of five ADAs, aconine, mesaconine, hypaconine, deoxyaconine and fuziline, in rat plasma to compare the pharmacokinetic characteristics of pure ADAs and Fuzi decoction. After precipitating protein with methanol, plasma samples were isolated at 0.5 mL/min flow rate on Waters Acquity UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 µm). The mobile phase was composed of 0.1% formic acid-water and methanol with gradient elution. Mass spectrometric inspection was conducted on a 5500 UFLC-MS/MS system with an electrospray ionization source in patterns of positive ion and multiple reaction-monitoring (MRM). All calibration curves were proved to have acceptable linearity (r2 > 0.99) in linear ranges. Intra-day and inter-day precision and the accuracy met the requirements. The matrix effects of all analytes were between 85% and 115% of three concentration levels. This method has been under verification for comparative pharmacokinetic research after oral administration between aqueous extract of Fuzi and single pure ADAs. The results demonstrated that there are evident pharmacokinetic discrepancies between them, and administration in the extract form instead of pure form may contribute to higher absorption. [ABSTRACT FROM AUTHOR]

Oral administration of rich in flavonoids hydroalcoholic extract from Zuccagnia punctata (ZpE) improves lipid profile and prevents vascular dysfunction in hypercholesterolemic rabbits. This study aimed to evaluate the ability of ZpE to prevent metabolic and vascular alterations induced by high fat diet (HFD) on a metabolically obese and normal weight rabbit model. The major components of ZpE were analyzed by HPLC method. Rabbits were separated into six groups: 1-fed on standard chow (CD); 2-fed on HFD; 3, 4, 5- fed on HFD and orally administrated 2.5 mg, 5 mg or 10 mg GAE/day of ZpE, respectively (ZpE- HFD); 6- fed on HFD and orally administered 30 mg orlistat/day (Or-HFD). All diets were administrated by 6 weeks. The major compounds of ZpE identified were chalcones: 2′,4′-dihydroxy-3′-methoxychalcone and 2′,4′-dihydroxychalcone. Oral treatment with ZpE 5 mg GAE/day as well as orlistat prevented the HFD-induced increase of triglycerides, fasting glucose, intraperitoneal glucose test, white cells, and TyG index. Acetylcholine relaxation was reduced in arteries from HFD group and oral administration of ZpE reached this response to CD values. Contractile response to angiotensin II was lower in arteries from rabbits fed on HFD treated with ZpE 5 and 10 mg GAE/day than those of untreated rabbits. Moreover, ZpE could inhibit the activity of pancreatic lipase in vitro and in vivo. In conclusion the ZpE may prevent normal weight obesity by inhibiting the pancreatic lipase. Thus, the use of ZpE as a natural product in the prevention of metabolic syndrome and endothelial dysfunction is very promising. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease is one of the leading causes of liver-related morbidity and mortality worldwide, but effective treatments are still lacking. Honokiol, a lignin-type natural compound isolated from the leaves and bark of Magnolia plants, has been widely studied for its beneficial effects on several chronic diseases. Accumulating studies have revealed that honokiol displays a potential therapeutic effect on alcoholic liver disease. In this study, the protective activity of honokiol on alcoholic liver disease was confirmed due to its significant inhibitory activity on the expression levels of inflammatory cytokines (such as tumor necrosis factor-alpha, interleukin-6, and interleukin-1 β) in EtOH-fed mice and in EtOH-induced AML-12 cells. Meanwhile, the expression of the lipid metabolic parameter sterol regulatory element-binding protein-1c was also reduced. However, peroxisome proliferator-activated receptor α was increased in animal and cell experiments, which indicates that the activity of honokiol was related to its regulated activity on lipid metabolism. The result showed that honokiol significantly inhibited the expression level of p38 α in vivo and in vitro. Blocking p38 α inhibited the expression levels of tumor necrosis factor-alpha, interleukin-6, interleukin-1 β , and sterol regulatory element-binding protein-1c but promoted the expression level of peroxisome proliferator-activated receptor α compared with the honokiol-treated group. Moreover, the forced expression level of p38 α further produced the opposite effect on inflammatory cytokines and lipid metabolism indicators. Furthermore, p38 α has been related to the activation of the nuclear factor kappa B signaling pathway. In our study, honokiol significantly inhibited the activation of the nuclear factor kappa B signaling pathway mediated by p38 α. In conclusion, the results suggest that honokiol might be an effective regulator of p38 α by downregulating the nuclear factor kappa B signaling pathway, thereby reducing the inflammatory response and lipid metabolism disorder in alcoholic liver disease. [ABSTRACT FROM AUTHOR]

Lychnophora is a genus of South American flowering plants in the daisy family, popularly known as "Brazilian arnica". It is used in traditional medicine as an anti-inflammatory and analgesic agent, whose active components are derived from chlorogenic acid (CGA) and C-flavonoids. Since the drugs currently used are ineffective to treat glaucoma, agents with antioxidant and anti-inflammatory properties may represent new alternatives in preventing cellular lesions in retinal ischemia. In this study, we report the neuroprotective effects of CGA and 4,5-di- O -[E]-caffeoylquinic (CQA) acid, isolated from Lychnophora plants, in a rodent glaucoma model. Wistar rats were administered intravitreally with 10 µg CGA or CGA, and then subjected to acute retinal ischemia (ISC) by increasing intraocular pressure (IPO) for 45 minutes followed (or not) by 15 minutes of reperfusion (I/R). Qualitative and quantitative analyses of neurodegeneration were performed using hematoxylin-eosin or Fluoro-Jade C staining protocols. All retinas submitted to ISC or I/R exhibited matrix disorganization, pyknotic nuclei, and pronounced vacuolization of the cytoplasm in the ganglion cell layer (GCL) and inner nuclear layer (INL). Pretreatment with CGA or CQA resulted in the protection of the retinal layers against matrix disorganization and a reduction in the number of vacuolized cells and pyknotic nuclei. Also, pretreatment with CGA or CQA resulted in a significant reduction in neuronal death in the GCL, the INL, and the outer nuclear layer (ONL) after ischemic insult. Our study demonstrated that CGA and CQA exhibit neuroprotective activities in retinas subjected to ISC and I/R induced by IPO in Wistar rats. [ABSTRACT FROM AUTHOR]

Plants of Tabernaemontana species have several pharmacological activities including antimicrobial effects. Amoebiasis continues to be a public health problem, with increasing evidence of resistance to metronidazole. In this study, we assessed the effect of the alkaloid fraction of T. arborea root bark and the alkaloids ibogaine and voacangine on the viability and infectivity of Entamoeba histolytica trophozoites. Cultures were exposed to 0.1 – 10 µg/mL for 24, 48 and 72 h, and viability was then determined using a tetrazolium dye reduction assay and type of cellular death analyzed by flow cytometry. Results showed that the alkaloid fraction, but mainly ibogaine and voacangine alkaloids, exhibited potent dose-dependent anti-amoebic activity at 24 h post-exposure (IC50 4.5 and 8.1 µM, respectively), comparable to metronidazole (IC50 6.8 µM). However, the effect decreased after 48 and 72 h of exposure to concentrations below 10 µg/mL, suggesting that the alkaloids probably were catabolized to less active derivatives by the trophozoites. The treatment of trophozoites with the IC50 s for 24 h induced significant morphological changes in the trophozoites, slight increase in granularity, and death by apoptonecrosis. The capacity of T. arborea alkaloids to inhibit the development of amoebic liver abscesses in hamsters was evaluated. Results showed that even when the treatments reduced the number of amoebic trophozoites in tissue sections of livers, they were unable to limit the formation of abscesses, suggesting their rapid processing to inactive metabolites. This work leaves open the possibility of using Tabernaemontana alkaloids as a new alternative for amoebiasis control. [ABSTRACT FROM AUTHOR]

The liverwort Radula perrottetii contains various bibenzyl derivatives which are known to possess various biological activities, such as anti-inflammatory effects. Mast cells (MC) play crucial roles in allergic and inflammatory diseases; thus, inhibition of MC activation is pivotal for the treatment of allergic and inflammatory disorders. We investigated the effects of perrottetin D (perD), isolated from Radula perrottetii , and perD diacetate (Ac-perD) on antigen-induced activation of MCs. Bone marrow–derived MCs (BMMCs) were generated from C57BL/6 mice. The degranulation ratio, histamine release, and the interleukin (IL)-4 and leukotriene B4 productions on antigen-triggered BMMC were investigated. Additionally, the effects of the bibenzyls on binding of IgE to Fc ε RI were observed by flow cytometry, and signal transduction proteins was examined by Western blot. Furthermore, binding of the bibenzyls to the Fyn kinase domain was calculated. At 10 µM, perD decreased the degranulation ratio (p < 0.01), whereas 10 µM Ac-perD down-regulated IL-4 production (p < 0.05) in addition to decreasing the degranulation ratio (p < 0.01). Both compounds tended to decrease histamine release at a concentration of 10 µM. Although 10 µM perD reduced only Syk phosphorylation, 10 µM Ac-perD diminished phosphorylation of Syk, Gab2, PLC- γ , and p38. PerD appeared to selectively bind Fyn, whereas Ac-perD appeared to act as a weak but broad-spectrum inhibitor of kinases, including Fyn. In conclusion, perD and Ac-perD suppressed the phosphorylation of signal transduction molecules downstream of the Fc ε RI and consequently inhibited degranulation, and/or IL-4 production. These may be beneficial potential lead compounds for the development of novel anti-allergic and anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

The leaves of Echinodorus grandiflorus are traditionally used in Brazil to treat several inflammatory conditions, including arthritis. This study aimed to investigate the antiarthritis activity of the 70% ethanol extract of E. grandiflorus leaves and a standardized flavonoid-rich fraction in an antigen-induced arthritis model in mice. Previously immunized mice were treated per os with saline (control group), 70% ethanol extract (100- 1000 mg/kg), or a flavonoid-rich fraction (0.7- 7.2mg/kg) 40 minutes before and 3 and 6 hours after the challenge with antigen into the knee joint. The administration of the 70% ethanol extract and flavonoid-rich fraction to mice significantly reduced neutrophil recruitment to the joint cavity and in periarticular tissue. The levels of chemokine (C-X‑C motif) ligand 1, tumor necrosis factor-α, and interleukin-1β quantified by the enzyme-linked immunosorbent assay (ELISA) in the periarticular tissuewere also diminished in mice treated with the 70% ethanol extract and flavonoid-rich fraction, as well as mechanical hypernociception. Histological analysis confirmed that both the 70% ethanol extract and flavonoidrich fraction suppressed joint inflammation and inhibited cartilage and bone destruction when compared to the control group. Our results demonstrate, for the first time, that E. grandiflorus has anti-inflammatory activity in an experimental arthritis model and highlights the role of flavonoids in the observed response. [ABSTRACT FROM AUTHOR]

Emodinol, 1β,3β,23-trihydroxyolean-12-en-28-acid, as the main active ingredient firstly extracted from the rhizomes of Elaeagus pungens by our research group, has been demonstrated to exhibit uricosuric activity by our previous study. The aim of this study was to evaluate the uricosuric and nephroprotective effects of emodinol and explore its possible mechanisms in potassium oxonate-induced hyperuricemic mice with renal dysfunction. Mice were orally administrated 250 mg/kg of potassium oxonate once daily for 7 consecutive days to induce hyperuricemia with renal dysfunction. Emodinol was given at doses of 25, 50, and 100 mg/kg on the same day 1 h after oxonate treatment, and allopurinol (10 mg/kg) was given as a positive control. After 1 week, serum uric acid, serum creatinine, urine uric acid, urine creatinine, blood urea nitrogen, and hepatic xanthine oxidase activity were determined. The mRNA and protein levels of urate transporter 1, glucose transporter 9, ATP-binding cassette subfamily G member 2, organic anion transporter 1, oncoprotein-induced transcript 3, and organic cation/carnitine transporters in the kidney were detected by real-time polymerase chain reaction and Western blot analysis. In addition, urinary and renal Tamm-Horsfall glycoprotein concentrations were examined by ELISA assays. Emodinol significantly reduced serum urate levels, increased urinary urate levels and fractional excretion of uric acid, and inhibited hepatic xanthine oxidase activity in hyperuricemic mice. Moreover, potassium oxonate administration led to dys expressions of renal urate transporter 1, glucose transporter 9, ATP-binding cassette subfamily G member 2, organic anion transporter 1, and oncoprotein-induced transcript 3 as well as alternations of uromodulin concentrations, which could be reversed by emodinol. On the other hand, treatment of emodinol caused upregulated expressions of organic cation/carnitine transporters, resulting in an improvement of renal function characterized by decreased serum creatinine and blood urea nitrogen levels. Emodinol exhibited hypouricemic and nephroprotective actions by inhibiting xanthine oxidase activity and regulating renal ion transporters and oncoprotein-induced transcript 3, which may be a potential therapeutic agent in hyperuricemia and renal dysfunction. [ABSTRACT FROM AUTHOR]

Ocimum gratissimum is used in popular medicine to treat painful diseases. The antihypernocicep-tive properties of O. gratissimum essential oil and two of its active components (eugenol and myrcene) were tested in a model of neuropathic pain induced by a chronic constriction injury of the sciatic nerve. In tests to determine chronic antinociception, adult male C57BL/6J mice were treated orally with corn oil (control group), O. gratissimum essential oil at doses of 10, 20, or 40 mg/kg or eugenol or myrcene at doses of 1, 5, or 10 mg/ kg for 14 days after surgery. Pregabalin (20 mg/ kg) was used as a standard in this study. The treatment with 20 and 40 mg/kg of O. gratissimum essential oil and at doses of 5 and 10 mg/kg of the active components were able to promote antihypernociception in both mechanical (von Frey) and thermal (hot plate) tests. The treatment with the essential oil of the plant or eugenol was effective in reducing the levels of interleukin-1β in the sciatic nerve. Our findings demonstrate that O. gratissimum essential oil and its isolated active components possess antihypernociceptive activity in neuropathic pain models. [ABSTRACT FROM AUTHOR]

Lophanthera lactescens is a medicinal plant commonly used in traditional medicine to relieve fever and pain in inflammatory processes. In the present study, the in vivo antinociceptive and anti-inflammatory effects of the methanolic extract from L. lactescens have been investigated. Antinociceptive activity was evaluated through writhing, formalin, and tail flick tests, while the anti-inflammatory activity was evaluated through paw oedema and air pouch tests in mice. A phytochemical analysis was performed. The extract produced significant inhibition on nociception induced by acetic acid-induced abdominal writhing, formalin, and tail flick tests, and on inflammation induced by oedema and air pouch tests. The previous administration of atropine and glibenclamide reduced the antinociceptive effect produced by the methanolic extract from L. lactescens on the tail flick test in 89% and 66%, respectively. The methanolic extract had no significant effect in the open field test. No intoxication symptoms were observed in the animals administered orally at increasing doses up to 2000 mg/kg. The methanolic extract from the stem bark of L. lactescens possesses antinociceptive properties on models of acute pain induced by chemical and thermal stimuli as well as in models of inflammation and further suggests that this anti-inflammatory activity might involve inhibition of the proinflammatory cytokines, and the antinociceptive activity might involve participation of the cholinergic system and adenosine triphosphate-dependent K+ channel. [ABSTRACT FROM AUTHOR]

The dried stem bark of Berberis kansuensis is a commonly used Tibetan herbal medicine for the treatment of diabetes. Its main chemical components are alkaloids, such as berberine, magnoflorine and jatrorrhizine. However, the role of gut microbiota in the in vivo metabolism of these chemical components has not been fully elucidated. In this study, an ultra-high performance liquid chromatography method coupled with Orbitrap mass spectrometry (UHPLC-Orbitrap-MS) technology was applied to detect and identify prototype components and metabolites in rat intestinal contents and serum samples after oral administration of a B. kansuensis extract. A total of 16 prototype components and 40 metabolites were identified. The primary metabolic pathways of the chemical components from B. kansuensis extract were demethylation, desaturation, deglycosylation, reduction, hydroxylation, and other conjugation reactions including sulfation, glucuronidation, glycosidation, and methylation. By comparing the differences of metabolites between diabetic and pseudo-germ-free diabetic rats, we found that the metabolic transformation of some chemical components in B. kansuensis extract such as bufotenin, ferulic acid 4- O - β -D-glucopyranoside, magnoflorine, and 8-oxyberberine, was affected by the gut microbiota. The results revealed that the gut microbiota can affect the metabolic transformation of chemical constituents in B. kansuensis extract. These findings can enhance our understanding of the active ingredients of B. kansuensis extract and the key role of the gut microbiota on them. [ABSTRACT FROM AUTHOR]

Caulis Trachelospermi, the stems with leaves of Trachelospermum jasminoides , is a well-known herbal drug of the Apocynaceae family recorded in the Chinese pharmacopeia and used for the treatment of inflammation-related diseases by ethnic minorities of China. The mechanism of anti-inflammatory activity and responsible constituents of T. jasminoides have not been well elucidated in previous studies. Preliminary investigation showed that both the water and the ethyl ester extracts of T. jasminoides exhibited potent inhibitory activity on nitric oxide (NO) production using lipopolysaccharide (LPS)-stimulated murine macrophages. Phytochemical investigation on these extracts afforded 23 compounds, including three new compounds (1 – 3) identified on the basis of spectroscopic and mass spectrometric data. Anti-inflammatory bioassay showed that compounds 17, 18, 22 , and 23 inhibited significantly the production of NO in a concentration-dependent manner. Further studies indicated that compound 23 inhibited significantly TNF- α and IL-6 produced by LPS-stimulated RAW 264.7 cells with good selectivity, as well as protein expression of iNOS in RAW 264.7 cells. These chemical constituents may contribute to the anti-inflammatory potential of T. jasminoides. [ABSTRACT FROM AUTHOR]

In following up on observed in vitro anti-inflammatory activity of the organic extract of the marine sponge-derived fungus Aspergillus tamarii MCCF102, two new dipyrrolobenzoquinones, terreusinone B and C (1 and 2), were discovered along with the known analogue, terreusinone (3). The structures of 1 – 3 were determined by spectroscopic and spectrometric analyses, along with chemical inter-conversion. In vitro testing on lipopolysaccharide (LPS) stimulated RAW 264.7 murine macrophage cells revealed that 1 – 3 exhibit anti-inflammatory activity by inhibiting nitric oxide production in a dose-dependent manner (IC50 < 1 µM) without any cytotoxicity observed at the same concentrations. Due to this and the UV-A absorptive properties imparted by the highly conjugated structures of these molecules, the potential for using 1 – 3 or related analogues as natural sunscreen components is suggested. Gene sequencing and informatics biosynthetic gene cluster comparisons were insufficient to confidently elucidate the biosynthetic origins of these compounds, possibly suggesting the occurrence of a gene cluster not detected in the initial sequencing or a non-canonical pathway that should be further investigated. [ABSTRACT FROM AUTHOR]

Yiru Tiaojing Granule, a traditional Chinese medicine formula, is used to treat hyperprolactinemia. This study was conducted to evaluate the mechanism of action and pharmacological activity of Yiru Tiaojing Granule on prolactin secretion. The animal model of hyperprolactinemiawas induced by metoclopramide. The dopamine D2 receptor in hyperprolactinemia rat models was analyzed by immunohistochemistry. The biochemical parameters, including a follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, testosterone, and prolactin, were measured by an enzyme-linked immunosorbent assay. Furthermore, the expression of prolactin and the dopamine D2 receptor was analyzed by Western blotting. The components in the Yiru Tiaojing Granule- medicated serum were assayed by liquid chromatography-tandem mass spectrometry. The Yiru Tiaojing Granule significantly decreased the prolactin level in the hyperprolactinemia rat model, and increased the estradiol, luteinizing hormone, and progesterone levels. The high and medium doses of Yiru Tiaojing Granule reduced dopamine D2 receptor expression in the brain (p < 0.001) and produced a similar effect on bromocriptine (p < 0.001). Yiru Tiaojing Granulemedicated serum reduced (p < 0.001) prolactin expression in MMQ cells in a concentration-dependent manner, but had no effects on GH3 cells. The level of the dopamine D2 receptor in MMQ cells was also increased dose-dependently (p < 0.05). In addition, the protein kinase A and cyclic adenosine monophosphate in MMQ cells were significantly attenuated dose-dependently by treatment with a high and medium dose of Yiru Tiaojing Granule-medicated serum (p < 0.05) and bromocriptine-medicated serum (p < 0.01). The results suggested that Yiru Tiaojing Granule was effective against hyperprolactinemia, and the activation of the dopamine D2 receptor, which was related to the second messenger cyclic adenosine monophosphate and protein kinase A, might be the potential mechanism. [ABSTRACT FROM AUTHOR]

The monoterpene gamma-terpinene is a natural compound present in essential oils of a wide variety of plants, including the Eucalyptus genus, which has been reported to possess anti-inflammatory activity. The goal of this studywas to evaluate the effect of gamma-terpinene on several in vivo experimental models of acute inflammation. Swiss mice were pretreated with gamma-terpinene and subjected to protocols of paw edema with different phlogistic agents such as carrageenan, prostaglandin-E2, histamine, or bradykinin. The microvascular permeability was measured by intraperitoneal injection of acetic acid and measuring the amount of protein extravasation. Carrageenan-induced peritonitis was used to analyze the effect of gamma-terpinene on inflammatory cell migration and cytokine production. We also developed an acute lung injury protocol to define the anti-inflammatory effect of gamma-terpinene. Mice pretreated with gammaterpinene displayed reduced paw edema induced by carrageenan from 1-24 h after challenge. A similar reduction was observed when gammaterpinene was administered after stimulation with PGE2, bradykinin, and histamine. Treatment with gamma-terpinene also inhibited fluid extravasation in the acetic acid model of microvascular permeability. In a carrageenan-induced peritonitis model, gamma-terpinene treatment reduced neutrophilmigration as well as the production of interleukin-1β and tumor necrosis factor- α when compared to nontreated animals, and in the acute lung injury protocol, gamma-terpinene diminished the neutrophil migration into lung tissue independently of the total protein extravasation in the lung. These data demonstrate that, in different models of inflammation, treatment with gamma-terpinene alleviated inflammatory parameters such as edema and pro-inflammatory cytokine production, as well as cell migration into the inflamed site, and that this monoterpene has anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

The aqueous infusions of the aerial parts of Artemisia herba-alba Asso and Ajuga iva Schreber, prepared in accordance with the traditional procedure used in the local folk medicine, have been analysed for their composition and content of phytochemical constituents and examined for their antidiabetic effectiveness in alloxan-in-duced diabetic rats. Oral administration of A. herba-alba and A. iva infusions was studied in normal and alloxan-induced diabetic rats, which were randomly divided into nine groups, each group consisting of six animals. The drug preparations (100,200, and 300 mg/kg b. w.) of each plant were given orally to the rats of each group twice daily for 15 days. Compositional analysis of the aqueous infusions revealed the presence of several polyphenols as main components. A. herba-alba infusion was characterised by mono- and di-cinnamoylquinic acids, with 5-caffeoylquinic (chlorogenic) acid being the main compound, followed by 3,5-dicaffeoylquinic acid. Vicenin-2 (apigenin 6,8-di-C-glucoside) appeared to be the most abundant among flavonoids. On the other hand, A. iva showed the exclusive presence of flavonoids, with the flavanone naringin present in relatively high levels together with several apigenin (flavone) derivatives. Oral administration of 300mg/kg b.w. of the aqueous infusions of A. herba-alba and A. iva exhibited a significant reduction in blood glucose content, showing a much more efficient antidiabetic activity compared to glibenclamide, the oral hypoglycaemic agent used as a positive control in this study. These results suggest that A. herba-alba and A. iva possess significant antidiabetic activity, as they were able to improve the biochemical damage in alloxan-induced diabetes in rats. [ABSTRACT FROM AUTHOR]

The most common conventional therapy for inflammatory bowel disease in clinical practice involves the use of nonsteroidal anti-inflammatory drugs, such as 5-amino salicylic acid. However, a high dose of 5-amino salicylic acid may bring about severe side effects. Chinese people have used Rheum tanguticum as a folk remedy for gastrointestinal disease for two thousand years. Our group has isolated R. tanguticum polysaccharide 1 from R. tanguticum and verified that it can attenuate 2,4,6-trinitrobenzene sulfonic acid-induced colitis in murines/rats. The present study aims to evaluate whether the addition of R. tanguticum polysaccharide 1 can improve efficacy and limit subsequent side effects of conventional treatment (5-amino salicylic acid) in rats with 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Sixty Sprague-Dawley male rats were randomized into five groups and treated with (1) saline (saline, 0.2mL/day x 5, p.o.), (2) 2,4,6-trinitrobenzene sulfonic acid alone (saline, 0.2 mL/ day x 5, p.o.), (3) 2,4,6-trinitrobenzene sulfonic acid + 5-amino salicylic acid (5-amino salicylic acid, 75 mg/kg/day x 5, p.o), (4) 2,4,6-trinitrobenzene sulfonic acid + R. tanguticum polysaccharide 1 (R. tanguticum polysaccharide 1,200 mg/kg/day x 5, p.o.), and (5) 2,4,6-trinitrobenzene sulfonic acid + 5-amino salicylic acid + R. tanguticum polysaccharide 1 (5-amino salicylic acid, 25 mg/kg/day x 5, p.o; R. tanguticum polysaccharide 1, 200 mg/kg/day x 5, p.o.). All the rats were sacrificed on the 6th day after treatment using an overdose of anesthesia. A histological assessment was performed using semiquantitative scores; nuclear factor-kappa B and tumor necrosis factor-α were measured with Western blot, cycloox-ygenase 1 and cyclooxygenase 2 protein expressions were investigated by RT-polymerase chain reaction, and prostoglandin E2 and inducible nitric oxide synthase productions were investigated by ELISA. The extent and severity of histological signs were attenuated significantly in the 2,4,6-trinitrobenzene sulfonic acid + 5-amino salicylic acid + R. tanguticum polysaccharide 1 group. Treatment with R. tanguticum polysaccharide 1 plus 5-amino salicylic acid markedly decreased nuclear factor-kappa Bp65 and tumor necrosis factor-α protein expressions. R. tanguticum polysaccharide 1 and 5-amino salicylic acid had no effect on cyclooxygenase 1 protein expression, but inhibited the overexpression of the cyclooxygenase 2 protein. After treatment with 5-amino salicylic acid and R. tanguticum polysaccharide 1, the prostoglandin E2 level increased significantly and the inducible nitric oxide synthase level decreased considerably in the 2,4,6-trinitrobenzene sulfonic acid + 5-amino salicylic acid + R. tanguticum polysaccharide 1 group compared with the 2,4,6-trinitrobenzene sulfonic acid alone group. These results demonstrate that combined therapy with R. tanguticum polysaccharide 1 and low-dose 5-amino salicylic acid had more favorable effects on 2,4,6-trinitrobenzene sulfonic acid-induced colitis in rats, and its effects may be associated with inhibiting nuclear factor-kappa Bp65 protein expression and tumor necrosis factor-α production, resulting in a decrease of cyclooxygenase 2 and inducible nitric oxide synthase protein expressions. [ABSTRACT FROM AUTHOR]

A chronic, unhealed diabetic wound is one of the severe complications of diabetes mellitus. Azadir-achta indica has been reported to have antidia-betic and antiapoptotic properties. The present work incorporates the healing potential of 50% ethanol A. indica leaves extract against deep surgical wounds in streptozotocin-induced mild diabetic rats. A. indica leaves extract (500 mg/kg) was administered orally, once daily for ten days. Serum glucose, cholesterol, and triglycerides as well as body weight, food, and water intake, and tissue antioxidants (catalase, superoxide dismutase and reduced glutathione), free radicals (lipid peroxi-dation and nitric oxide), myeloperoxidase, total collagens (hydroxyproline, hexuronic acid and hexosamine), protein, vascular endothelial growth factor, and cytokines (tumor necrotic factor-α and interleukin-1β) were estimated. Histology was done for connective tissue formation and inflammatory and healing in deep granulation tissue after A. indica leaves extract treatment. Diabetic rats showed an increase in serum glucose, cholesterol, and triglycerides levels, food and water intake, and granular tissue free radicals, myeloperoxidase, and cytokines, but a decrease in body weight, total collagen, and vascular endothelial growth factor levels. A. indica leaves extract reversed the increased serum glucose, cholesterol, and triglycerides, food and water intake, and tissue free radicals, myeloperoxidase and, cytokines, but increased body weight, tissue antioxidants, total collagen, and vascular endothelial growth factor contents. The results thus indicated an improvement in wound healing by A. indica leaves extract in diabetic rats through enhanced angiogenesis mediated through the inhibition of hyperglycemia, oxidative stress, and down- and upregulation of inflammatory mediators and growth factor expression. [ABSTRACT FROM AUTHOR]

Praziquantel is the drug of choice for the treatment of schistosomiasis. However, several strains of Schistosoma mansoni are resistant to praziquantel, making it necessary to discover new drugs that might be used for its treatment. With this in mind, the properties of a schistosomicidal ethanolic extract of Garcinia brasiliensis Mart. ep-icarp, the fractions obtained by partitioning this extract, including the hexane fractions, ethyl acetate fraction, and the aqueous fraction, and the isolated compounds 7-epiclusianone, a major component from these fractions, and fukugetin were tested in vitro on adult worms of S. mansoni. Mortality, damage to membranes, and excretory system activity were observed at 100.0, 50.0, 75.0, and 14.0ug/mL for the ethanolic extract of G. brasiliensis Mart. epicarp, its hexane fractions, the ethyl acetate fraction, and 7-epiclusianone, respectively. For 7-epiclusianone, these data were confirmed by fluorescent probe Hoechst 33258 and resorufin. Additionally, the biocidal effect of 7-epiclusianone was even higher than the hexane fractions. Moreover, an inhibitory effect of 7-epiclusianone on the egg laying of female adult S. mansoni worms was observed in cercariae and schistossomula. Thus, 7-epiclusianone is a promising schistosomicidal compound; however, more studies are needed to elucidate its mechanism of toxicity and to evaluate the in vivo activity of this compound. [ABSTRACT FROM AUTHOR]

High-fat diets are associated with the development of cardiovascular diseases. The efficacy of the current strategies of treatment is still not entirely satisfactory, and new approaches are being considered. To analyze the beneficial effects of extra virgin olive oil as a major component of the Mediterranean diet, we studied systolic blood pressure and angiotensinase activities, since this enzyme is involved in the metabolism of angiotensins, in the kidney of hypertensive rats fed during 12 weeks with a diet enriched with extra virgin olive oil compared with a standard diet. As a reflex of oxidative stress, 8-isoprostanes and nitric oxide were quantified in urine. Results demonstrated a progressive increase in systolic blood pressure until the end of the feeding period in both groups. However, this increase was delayed in the extra virgin olive oil group until week six, with the systolic blood pressure being always lower in this group. Nitric oxide and 8-isoprostanes were lower in the extra virgin olive oil group. While we can deduce a higher formation of angiotensin 2-10 in the renal cortex, a higher availability of angiotensin II may be presumed in the renal medulla of animals fed an extra virgin olive oil diet than in animals fed a standard diet. Our results support the beneficial influence of extra virgin olive oil on cardiovascular function and suggest that the Mediterranean diet may be beneficial in itself but it may also be an effective tool in the treatment of hypertension. [ABSTRACT FROM AUTHOR]

Angiotensin II and endothelin-1 are potent vasoconstrictive peptides that play a central role in blood pressure regulation. Both peptides exert their pleiotropic effects via binding to their respective G-protein-coupled receptors, i.e., angiotensin AT1 and endothelin type A and type B receptors. In the present study, we have selected six structurally different plant-derived compounds with known cardioprotective properties to evaluate their ability to modulate calcium signaling of the above-mentioned receptors. For this purpose, we used and validated a cellular luminescence-based read-out system in which we measured intracellular calcium signaling in Chinese hamster ovary cells that express the calcium sensitive apo-aequorin protein. Firstly, silibinin, a flavanolignan that occurs in milk thistle (Silybum marianum), was investigated and found to be an antagonist for the human angiotensin AT1 receptor with an affinity constant of about 9 µM, while it had no effect on endothelin type A or type B receptor activation. Quercetin and crocin partially impeded intracellular calcium signaling resulting in a non-receptor-related reduction of the responses recorded for the three investigated G-protein-coupled receptors. Two organosulfur compounds, diallyl disulfide and diallyl trisulfide, as well as the triterpene saponin ginsenoside Rb1 did not affect the activation of the angiotensin AT1 and endothelin type A and type B receptors. In conclusion, we were able, by using a nonradioactive cellular read-out system, to identify a novel pharmacological property of the flavanolignan silibinin. [ABSTRACT FROM AUTHOR]

The purpose of this study was to explore the effect of polydatin on ventricular remodeling after myocardial infarction in coronary artery ligation rats and to elucidate the underlying mechanisms. A rat model of ventricular remodeling after myocardial infarction was established by left coronary artery ligation. Rats with coronary artery ligation were randomly divided into five groups: control, plus 40 mg/kg captopril, plus 25 mg/kg polydatin, plus 50 mg/kg polydatin, and plus 100 mg/kg polydatin. The sham-operated group was used as a negative control. Rats were administered intragastrically with the corresponding drugs or drinking water for seven weeks. At the end of the treatment, the left ventricular weight index and heart weight index were assessed. The cross-sectional size of cardiomyocytes was measured by staining myocardium tissue with hematoxylin and eosin. Collagen content was counted by Sirius red in aqueous saturated picric acid. The concentrations of angiotensin I, angiotensin II, aldosterone, and endothelin 1 in myocardium or serum were determined by radioimmunoassay. Hydroxyproline and nitric oxide concentrations and glutathione peroxidase and catalase activities in serum were measured by ultraviolet spectrophotometry. Our results showed that seven weeks of polydatin treatment resulted in a significantly reduced left ventricular weight index, heart weight index, serum concentrations of hydroxyproline and aldosterone, an increased concentration of nitric oxide as well as enhanced activities of glutathione peroxidase and catalase. Myocardial angiotensin I, angiotensin II, and endothelin 1 levels were also reduced. The cardiomyocyte cross-sectional area and collagen deposition diminished. This study suggests that polydatin may attenuate ventricular remodeling after myocardial infarction in coronary artery ligation rats through restricting the excessive activation of the renin-angiotensin-aldosterone system and inhibiting peroxidation. [ABSTRACT FROM AUTHOR]

In silico techniques in drug discovery may rationalise and speed up the identification of lead molecules from nature. Drug discovery from medicinal plants has mostly been confined to indications in accordance with their ethnical use only. However, the availability of multiple phytoconstituents in medicinal plants suggests that these may be much more useful beyond their traditional uses and in the management of chronic diseases, along with their comorbidities. In this study, the computer programmes PASS and PharmaExpert were used to reveal the medicinal plants useful in the comprehensive management of epilepsy and associated psychiatric disorders based on the pleiotropic effects predicted for their phytoconstituents. In silico analysis revealed that seven of 50 medicinal plants from traditional Indian medicine possessed the desired pleiotropic effect, i.e., anti-convulsanto antidepressanto and nootropic activities. The majority of phytoconstituents from Passiflora incarnata were concurrently predicted to have the desired pleiotropic effects. Therefore, P. incarnata was pharmacologically validated using the pentylenetetrazole kindling mouse model. Behavioural and neurochemical evaluations confirmed the ameliorative role of P. incarnata in epilepsy and the associated depression and memory deficit. The pharmacological findings from this study propose that PASS and PharmaExpert may serve as good tools for the optimisation of the selection of plants based on their phytoconstituents for the treatment of different ailments, even beyond their traditional use. [ABSTRACT FROM AUTHOR]

The identification of natural products that can modulate blood glucose levels is of great interest as it can possibly facilitate the utilization of mild interventions such as herbal medicine or functional foods in the treatment of chronic diseases like diabetes. One of the established drug targets for antihyperglycemic therapy is glycogen phosphorylase. To evaluate the glycogen phosphorylase inhibitory properties of an in-house compound collection consisting to a large extent of natural products, a stepwise virtual and experimental screening protocol was devised and implemented. The fact that the active site of glycogen phosphorylase is highly hydrated emphasized that a methodological aspect needed to be efficiently addressed prior to an in silico evaluation of the compound collection. The effect of water molecules on docking calculations was regarded as a key parameter in terms of virtual screening protocol optimization. Statistical analysis of 125 structures of glycogen phosphorylase and solvent mapping focusing on the active site hydration motif in combination with a retrospective screening revealed the importance of a set of 29 crystallographic water molecules for achieving high enrichment as to the discrimination between active compounds and inactive decoys. The scaling of Van der Waals radii of system atoms had an additional effect on screening performance. Having optimized the in silico protocol, a prospective evaluation of the in-house compound collection derived a set of 18 top-ranked natural products that were subsequently evaluated in vitro for their activity as glycogen phosphorylase inhibitors. Two phenolic glucosides with glycogen phosphorylase-modulating activity were identified, whereas the most potent compound affording mid-micromolar inhibition was a glucosidic derivative of resveratrol, a stilbene well-known for its wide range of biological activities. Results show the possible phytotherapeutic and nutraceutical potential of products common in the Mediterranean countries, such as red wine and Vitis products in general or green raw salads and herbal preparations, where such compounds are abundant. [ABSTRACT FROM AUTHOR]

The aim of this study was to use the pharmacokinetic information of avicularin in rats to project a dose for humans using allometric scaling. A highly sensitive and specific bioanalytical assay to determine avicularin concentrations in the plasma was developed and validated for UPLC-MS/MS. The plasma protein binding of avicularin in rat plasma determined by the ultrafiltration method was 64%. The pharmacokinetics of avicularin in nine rats was studied following an intravenous bolus administration of 1mg/kg and was found to be best described by a two-compartment model using a nonlinear mixed effects modeling approach. The pharmacokinetic parameters were allometrically scaled by body weight and centered to the median rat weight of 0.23 kg, with the power coefficient fixed at 0.75 for clearance and 1 for volume parameters. Avicularin was rapidly eliminated from the systemic circulation within 1 h post-dose, and the avicularin pharmacokinetic was linear up to 5mg/kg based on exposure comparison to literature data for a 5-mg/kg single dose in rats. Using allometric scaling and Monte Carlo simulation approaches, the rat doses of 1 and 5 mg/kg correspond to the human equivalent doses of 30 and 150 mg, respectively, to achieve comparable plasma avicularin concentrations in humans. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the anti-inflammatory activity of the ethanolic extract of the aerial parts of Trichosanthes dioica and its successive fractions. The effect on oxidative stress involved in the pathogenesis of inflammation was evaluated. The ethanolic extract and its successive fractions were administered at a dose of 150 and 300 mg/kg b.w. for testing their anti-inflammatory activity by a carrageenan-induced edema model. The results showed that the ethyl acetate fraction exhibited significant potency against inflammation. Pertaining to mechanistic insight, the anti-inflammatory effect might be attributed to the attenuation in tumor necrosis factor-α level (ELISA assay) and reduced expression of cyclooxygenase-2 and nuclear transcription factor-κB (immunohistochemistry). The alleviation in oxidative stress has been pertinent to the elevation in the activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione) by active fractions. Furthermore, the ulcerogenic effect was insignificant even at a three times higher dose. Finally, it was concluded that the ethyl acetate fraction which showed significant biological potential against inflammation and oxidative stress could be viewed as a source of effective treatment. [ABSTRACT FROM AUTHOR]

Spikenard, the dried roots of Nardostachys chinensis, contains sesquiterpenoids and is widely used as an herbal tranquilizer. We previously demonstrated that spikenard vapor showed a sedative effect when administered by inhalation, and we identified hydrocarbon sesquiterpenoids as active components. Here we investigated the other components that contribute to the effects of spikenard. Six oxygenated sesquiterpenoids, including aristolane- and guaiane-types, were isolated from an acetone extract of spikenard. We evaluated the sedative activities of these oxygenated compounds using an inhalation administration method in a caffeine-treated excitatory mouse model. We identified aristolen-1(10)-en-9-ol and patchouli alcohol as highly effective sedative components. These compounds inhibited locomotion in mice by approximately 60% at a dose of 300 μg/cage. In addition, aristolen-1(10)-en-9-ol prolonged pentobarbital-induced sleep to the same extent as 1 mg/kg diazepam. This effect completely disappeared with the administration of the GABAA-benzodiazepine receptor antagonist flumazenil (3 mg/kg), suggesting that the sedative effect of aristolen-1(10)-en-9-ol is expressed via the GABAergic system. Furthermore, differently from diazepam, inhalation of aristolen-1(10)-en-9-ol for 1 h did not affect the motor coordination in the rota-rod test. In the present study, we identified active components and provided evidence supporting the traditional sedative use of spikenard. Our research suggests that aristolen-1(10)-en-9-ol may be an effective aromatherapy, providing mild sedation. [ABSTRACT FROM AUTHOR]

The adverse effects of anticancer drugs can prompt patients to end their treatment despite the efficacy. Cisplatin is a platinum-based molecule widely used to treat various forms of cancer, but frequent and long-term use of cisplatin is limited due to severe nephrotoxicity. In the present study, we investigated the protective effect and mechanism of tetrahydrocurcumin on cisplatin-induced kidney damage, oxidative stress, and inflammation to evaluate its possible use in renal damage. Cisplatin-induced LLC-PK1 renal cell damage was significantly reduced by tetrahydrocurcumin treatment. Additionally, the protective effect of tetrahydrocurcumin on cisplatin-induced oxidative renal damage was investigated in rats. Tetrahydrocurcumin was orally administered every day at a dose of 80 mg/kg bodyweight for ten days, and a single dose of cisplatin was administered intraperitoneally (7.5 mg/kg body weight) in 0.9% saline on day four. The creatinine clearance levels, which were markers of renal dysfunction, in cisplatin-treated rats were recovered nearly back to normal levels after administration of tetrahydrocurcumin. Moreover, tetrahydrocurcumin exhibited protective effects against cisplatin-induced oxidative renal damage in rats by inhibiting cyclooxygenase-2 and caspase-3 activation. These results collectively provide therapeutic evidence that tetrahydrocurcumin ameliorates renal damage by regulating inflammation and apoptosis. [ABSTRACT FROM AUTHOR]

Hyperuricemia has been considered to be a key risk factor for kidney disease. The formation of uric acid crystals in the kidney further stimulates an intensive inflammatory response. Rhein possesses various pharmacological activities, including anti-inflammatory, antioxidative, antitumor, purgative effects, and so on. To our knowledge, no previous work has been reported about the therapeutic effect of rhein on urate nephropathy. In this study, a model of hyperuricemia and nephropathy induced by adenine and ethambutol inmicewas established.Meanwhile, the potential beneficial effects and mechanisms of rhein on hyperuricemia and nephropathy were also investigated. The results demonstrated that rhein significantly decreased the serum uric acid level by inhibiting the xanthine oxidase activity and increasing the excretion of urinary uric acid. In addition, rhein also markedly improved kidney damage related to hyperuricemia. Further investigation indicated that rhein improved the symptoms of nephropathy through decreasing the production of proinflammatory cytokines, including interleukin 1β, prostaglandin E2, and tumor necrosis factor-α and inhibiting the expression of transforming growth factor-β1. The present study suggests that rhein may have a considerable potential for development as an anti-hyperuricemic and nephroprotective agent for clinical application. [ABSTRACT FROM AUTHOR]

Chronic inflammation has been implicated in the pathogenesis of various neurodegenerative diseases. During the neuroinflammatory process, microglial cells release neurotoxic and proinflammatory mediators. In the present study, using activity-guided fractionation, we have purified an anti-inflammatory compound determined by spectroscopic methods to be a sesquiterpene lactone named achillolide A from Achillea fragrantissima (Forsk.) Sch. Bip. In primary cultures of lipopolysaccharide-activated microglial cells, achillolide A inhibited the lipopolysaccharide-induced levels of proinflammatory and toxic mediators including glutamate, nitric oxide, matrix metalloproteinase- 9, cyclooxygenase-2, induced nitric oxide synthase, interleukin-1β, and tumor necrosis factor-α. Achillolide A also exhibited an antioxidant capacity, as was shown in a cell free system as well as by its ability to reduce intracellular reactive oxygen species levels in microglial cells. Thus, achillolide A might have therapeutic potential for treatment of neurodegenerative diseases and deserves further studies. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the effects of catalpol administration on atherosclerosis. Atherogenesis was induced by a high-cholesterol chow in male New Zealand White rabbits that were randomly assigned to receive atorvastatin (5mg/kg/day), catalpol (5 mg/kg/day), or vehicle by oral gavage for 12 weeks. The rabbits were sacrificed after 12 weeks, and the thoracic aorta and serum were collected for further pathological and molecular biological analysis. Catalpol administration resulted in significantly attenuated atherosclerotic lesions. Total cholesterol, triglycerides, and low-density lipoprotein cholesterol were remarkably reduced, and high-density lipid cholesterol was elevated in the catalpoltreated group. Catalpol reduced the levels of tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, soluble vascular cell adhesion molecule-1, and soluble intercellular adhesion molecule-1 in the serum, as well as vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, tumor necrosis factor-α protein, inducible nitric oxide synthase, matrix metalloproteinases-9, and nuclear factor-κB protein65 in the aortic arch. In addition, catalpol treatment reduced the lipid peroxidation levels, while elevating antioxidant capacity. Catolpol pretreatment inhibited the nuclear translocation and DNA binding activity of nuclear factor-κB protein in oxygenized low-density lipoprotein-stimulated EA.hy926 cells. Furthermore, catolpol pretreatment activated nuclear factor erythroid 2-related factor 2 and upregulated the expression of its downstream antioxidant enzyme heme oxygenase. In summary, catalpol attenuated atherosclerotic lesions by the inhibition of inflammatory cytokines and oxidative stress status in a rabbit atherosclerotic model and enhanced the antioxidant capacity in oxygenized low-density lipoprotein- stimulated EA.hy926 cells. These results suggest that catalpol may be used to prevent and attenuate atherosclerosis. [ABSTRACT FROM AUTHOR]

The present work was undertaken to investigate the effects and the molecular mechanism of the standardized ethanolic extract of Allium cepa (onion) on the glucose transport for controlling diabetes mellitus. A. cepa stimulates glucose uptake by the rat skeletal muscle cells (L6 myotubes) in both time- and dose-dependent manners. This effect was shown to be mediated by the increased translocation of glucose transporter typ 4 protein from the cytoplasm to the plasma membrane as well as the synthesis of glucose transporter typ 4 protein. The effect of A. cepa extract on glucose transport was stymied by wortmannin, genistein, and AI½. In vitro phosphorylation analysis revealed that, like insulin, A. cepa extract also enhances the tyrosine phosphorylation of the insulin receptor-β, insulin receptor substrate-1, and the serine phosphorylation of Akt under both basal and insulin-stimulated conditions without affecting the total amount of these proteins. Furthermore, it is also shown that the activation of Akt is indispensable for the A. cepa-induced glucose uptake in L6myotubes. Taken together, these findings provide ample evidence that the ethanolic extract of A. cepa stimulates glucose transporter typ 4 translocation-mediated glucose uptake by the activation of the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt dependent pathway. [ABSTRACT FROM AUTHOR]

Syzygium aromaticum has been widely used in traditional medicine. Our study investigated the safety and antidepressant-like effects of the essential oil of S. aromaticum after acute or longterm treatment. Using GC-MS, a total of eight volatile constituents were identified in the essential oil of S. aromaticum. The single LD50 was approximately 4500 mg/kg based on a 24-h acute oral toxicity study. In a long-term repeated toxicity study of this essential oil (100, 200, and 400mg/ kg, p. o.), only 400 mg/kg induced a significant decrease in body weight. In addition, no significant changes in relative organweights and histopathological analysis were observed in all doses of essential oil-treated mice compared with the control group. Furthermore, acute S. aromaticum essential oil administration by gavage exerted antidepressant- like effects in the forced swimming test (200 mg/kg, p < 0.05) and tail suspension test (100 and 200 mg/kg, p < 0.05). Long-term S. aromaticum essential oil treatment via gavage significantly increased sucrose preference (50mg/kg, p < 0.05; 100 and 200 mg/kg, p < 0.01) as well as elevated the protein levels of hippocampal p- ERK, p-CREB, and brain-derived neurotrophic factor inmice exposed to chronic unpredictable mild stress. These results confirmed the safety of the essential oil of S. aromaticum and suggested that its potent antidepressant-like property might be attributed to the improvement in the hippocampal pERK1/2-pCREB-BDNF pathway in rats exposed to chronic unpredictable mild stress. [ABSTRACT FROM AUTHOR]