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Insulin resistance is a major pathophysiological feature in the development of type 2 diabetes (T2DM). Ferulic acid is known for attenuating the insulin resistance and reducing the blood glucose in T2DM rats. In this work, we designed and synthesized a library of new ferulic acid amides (FAA), which could be considered as ring opening derivatives of the antidiabetic PPARγ agonists Thiazolidinediones (TZDs). However, since these compounds displayed weak PPAR transactivation capacity, we employed a proteomics approach to unravel their molecular target(s) and identified the peroxiredoxin 1 (PRDX1) as a direct binding target of FAAs. Interestingly, PRDX1, a protein with antioxidant and chaperone activity, has been implied in the development of T2DM by inducing hepatic insulin resistance. SPR, mass spectrometry-based studies, docking experiments and in vitro inhibition assay confirmed that compounds VIe and VIf bound PRDX1 and induced a dose-dependent inhibition. Furthermore, VIe and VIf significantly improved hyperglycemia and hyperlipidemia in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats as confirmed by histopathological examinations. These results provide guidance for developing the current FAAs as new potential antidiabetic agents.

Background: Hepatocellular Carcinoma (HCC) being proclaimed as the world's fifth common cancer shows a high mortality rate due to delayed diagnosis. Regular day-to-day activities expose us to promotive factors that potentiate further to risk of liver damage, cirrhosis, and carcinogenesis. Matrix metalloproteinases (MMPs), a proteolytic enzyme, involved in cancer invasion are considered as a prognostic biomarker for HCC. Naringin (NAR), a flavanone glycoside, is recognized to have therapeutic efficacy in HCC. Objectives: The present research work focuses on evaluation of chemotherapeutic efficiency, NAR against HCC in Sprague–Dawley rats. Materials and Methods: In vitro studies were primarily carried out to estimate the cell viability of NAR in HepG2 cells followed by further justifications through in vivo studies in N-nitrosodiethylamine developed HCC. The efficacy of NAR at doses 30mg/kg/day and 60mg/kg/day was assessed through estimation of liver marker enzymes, antioxidant levels, glycoproteins, and level of MMP-2 and 9 to confirm the hypothesis. Results: While in vitro results revealed pronounced potency of NAR in inhibiting HepG2 cell viability, NAR concurrently stabilized the serum levels of liver marker enzymes, antioxidant levels, and serum glycoproteins. It also significantly reduced the levels of MMPs in treatment groups which was confirmed by zymography. Conclusion: With the support of these results, it can be concluded that NAR attenuates HCC by controlling the alterations in morphological, biochemical, and histopathological parameters that make it a suitable candidate as a potential chemotherapeutic agent against HCC.

A series of nine 3-(2-hydroxyphenyl)-5-aryl-N-phenyl-4,5-dihydropyrazole-1-carbothioamide derivative s (3a-3i) that were earlier reported as potent rMAO-A inhibitors were evaluated for their antidepressant activity in Porsolt's behavioral despair test (forced swim test) and Tail Suspension test activity, among them, compounds (3e and 3h) were found to have potent antidepressant activity. Reduction in duration of immobility was significant for all the compounds in Porsolts swim test compared with tail suspension test. 3h was further evaluated for anxiolytic activity in Elevated plus maze and was found to be devoid of it.

Aim of the study To systematically investigate the anticonvulsant activity of methanol extract of Benkara malabarica roots and to provide a biochemical basis elucidating its mode of action. Methods The median lethal dose (LD 50 ) of Benkara malabarica extract was determined. The anticonvulsant activity of the extract was assessed in strychnine-induced and isoniazide-induced convulsion models; phenytoin (20 mg/kg) and diazepam (1 mg/kg) were used as standards, respectively. Percentage protection provided by the drug was accounted as decrease in the number of convulsions within 8 h of observation. Mechanism of action was studied by performing GABA transaminase (GABA-T) assay, isolated from rat brain. Active constituent was isolated and characterized from the plant extract. Results The median lethal dose (LD50) of Benkara malabarica was found to be more than 500 mg/kg. It demonstrated 30% and 35% protection against strychnine-induced convulsions and 60% and 80% protection against isoniazide-induced convulsions, at doses of 25 mg/kg and 50 mg/kg, respectively. Enzyme assay results revealed that Benkara malabarica extract possesses GABA-T inhibitory activity (IC50 = 0.721 mg/ml). Scopoletin which was identified as the major constituent of the extract was found to be an inhibitor of GABA-T (IC50 = 10.57 μM). Conclusions The anticonvulsant activity of the plant extract is predominantly GABA mediated and may be due to the action of scopoletin alone or is a result of synergy of different compounds in the extract in which scopoletin is the major constituent.

Objective: To evaluate the antiulcer activity of the most active sub-fraction of Buchanania lanzan Spreng. leaves methanolic extract (BLE).Methods: The antioxidant activity of BLE fractions and sub-fractions has been assayed to determine the most active sub-fraction by using in vitro antioxidant methods like hydrogen peroxide free radical scavenging assay, hydroxyl radical scavenging assay, DPPH (1, 1-diphenyl-2-picryl hydrazyl) radical scavenging activity, total flavonoid and total phenolic content estimation. Then, the antiulcerogenic activity of most active sub-fraction of BLE (50 and 100 mg/kg, b.w., orally) was evaluated employing aspirin+pylorus ligation-induced (APL) and HCl/ethanol-induced (HE) gastric ulcer models in rats, and histopathological examination of stomach tissues of rats.Results: The most active sub-fraction of BLE exerted a significant (P<0.01) dose-dependent decrease in the ulcerative lesion index produced by APL and HE ulcer models in rats as compared to the standard drugs omeprazole (30 mg/kg, b.w. orally) and ranitidine (32 mg/kg, b.w. orally) respectively. The reduction in gastric fluid volume, total acidity and an increase in the pH of the gastric fluid in APL treated rats proved the antisecretory activity of most active subfraction of BLE. From histopathological examination, it was found that in tissues of both the models that received pretreatment with most activesub-fraction showed better protection of the gastric mucosa in a dose-dependent manner as indicated by reduction or absence of mucosal erosion and infiltration of leucocytes.Conclusion: These results suggest that leaves of Buchanania lanzan Spreng. possess potential antiulcer activity, which may be attributed to its antioxidant mechanism of action.

Objective: The current study investigated the anti-cancer potential of methanolic and ethyl acetate fraction of Lawsonia alba L. (Lythraceae) leaves extract on Hep-G2 and RAW 264.7 cells along with in vitro anti-oxidant property of the ethyl acetate fraction.Methods: The cytotoxic activity of methanolic extract and its fractions had been studied by MTT assay on Hep-G2 and RAW 264.7 cells. Morphological study of Hep-G2 cells was performed by light, fluorescence and confocal microscope. 1% agarose gel electrophoresis, detection of apoptosis and cell cycle arrest by flow cytometric analysis had been performed to determine the proportion and stages of cellular apoptosis of Hep-G2 cells. In vitro anti-oxidant study of various fractions of MLA were performed by DPPH and Hydroxyl radical scavenging assay.Results: Cytotoxicity study of MLA and ELA had been confirmed by MTT assay and the IC50 value were calculated to be 75.85μg/ml and 32.81μg/ml on Hep-G2 cell line respectively. Morphological study showed the arrays of nuclear changes including chromatin condensation and apoptotic body formation indicating that treatment with ELA, causes apoptotic changes in the hepatoma cells compared to the untreated control. Agarose gel electrophoresis study showed fragmented DNA in the form of a ladder. Flow cytometric analysis showed an appreciable number of cells in early apoptosis stage. The cells were arrested, mostly in G0/G1 phase of the cell cycle. Antioxidant property of ELA fraction was confirmed by free radical scavenging activity.Conclusion: Ethyl acetate fraction of Lawsonia alba L. leaves possess potent apoptotic activity against Hep-G2 cell line along with notable anti-oxidant activity.

Background: Silibinin is a semi-purified fraction of silymarin contained in milk thistle (Silybum marianum Asteraceae). Primarily known for its hepatoprotective actions, silymarin may also stimulate epithelialization and reduce inflammation in excision wound. Previous studies show antioxidant, anti-inflammatory, and antimicrobial actions of silibinin. However, wound healing property of silibinin is not well studied. Objective: This study investigates wound healing activity of silibinin topical formulation. Materials and Methods: Wound healing activity of 0.2% silibinin gel was assessed by incision and excision wound models in mice. Animals were divided into gel base, silibinin gel, and Mega Heal gel® treated groups with six animals in each group. Wound contraction, wound tissue tensile strength, and hydroxyproline content were measured, and histopathological evaluation of wound tissue of all the above treatment groups was carried out. Results: Application of 0.2% silibinin hydrogel for 8 days led to 56.3% wound contraction compared to 64.6% using standard Mega Heal gel with a subsequent increase in hydroxyproline content, which was significantly higher (P < 0.001) over control animals showing 33.2% contraction. After 14 days, percentage of contraction reached 96.1%, 97.6%, and 86.7%, respectively. Wound tissue tensile strength with silibinin (223.55 ± 3.82 g) and standard (241.38 ± 2.49 g) was significantly higher (P < 0.001) than control (174.06 ± 5.75 g). Histopathology of silibinin and standard gel treated wound tissue showed more fibroblasts, fewer macrophage infiltration, and well-formed collagen fibers. Conclusion: Here, we show potent wound healing activity of silibinin hydrogel formulation. SUMMARY 0.2% silibinin hydrogel showed potent wound healing activity in incision and excision wound models in mice. Abbreviations Used: ROS: Reactive oxygen species

A study was undertaken to evaluate the in vitro and in vivo antidiarrhoeal potential of chloroform extract of the root of Aegle marmelos (Correa) Linn. The in vitro activity was determined by agar dilution and disc diffusion techniques. The extract was studied in vivo in rats. Of the 35 tested pathogenic diarrhoea causing strains, the extract was found to be mostly active against the strains of Vibrio cholerae, followed by Escherichia coli and Shigella spp. The in vitro activity was found to be comparable to that of ciprofloxacin. Further, Aegle marmelos root extract (AMRE) treated animals showed significant inhibitory activity against castor oil-induced diarrhoea. The results so obtained thus established the efficacy of AMRE as an effective antidiarrhoeal agent.