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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.

WOS: 000414231000054, PubMed ID: 29089569, Peroxisome proliferator-activated receptor gamma (PPAR gamma) has received significant attention as a key regulator of glucose and lipid homeostasis. In this study, we synthesized and tested a library of novel 5-benzylidene-thiazolidin-2,4-dione (BTZD) derivatives bearing a substituent on nitrogen of TZD nucleus (compounds 1a-1k, 2i-10i, 3a, 6a, and 8a-10a). Three compounds (1a, 1i, and 3a) exhibited selectivity towards PPAR. and were found to be weak to moderate partial agonists. Surface Plasmon Resonance (SPR) results demonstrated binding affinity of 1a, 1i and 3a towards PPAR gamma. Furthermore, docking experiments revealed that BTZDs interact with PPAR gamma through a distinct binding mode, forming primarily hydrophobic contacts with the ligand-binding pocket (LBD) without direct H-bonding interactions to key residues in H12 that are characteristic of full agonists. In addition, 1a, 1i and 3a significantly improved hyperglycemia and hyperlipidaemia in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats at a dose of 36 mg/kg/day administered orally for 15 days. Histopathological investigations revealed that microscopic architecture of pancreatic and hepatic cells improved in BTZDs-treated diabetic rats. These findings suggested that 1a, 1i and 3a are very promising pharmacological agents by selectively targeting PPAR. for further development in the clinical treatment of type 2 diabetes mellitus., UGC-MANF [MUS-JH-12-13-11472], First author acknowledge UGC-MANF (MUS-JH-12-13-11472) for award of JRF fellowship. We are also thankful to DST-FIST (SR/FST/CSI-242/2012) for NMR facility at Birla Institute of Technology, Mesra and Institute of Life Sciences, Hyderabad, AP, India for providing spectral data.

ObjectiveTo evaluate the wound healing and antimicrobial activity of root extracts of Ixora coccinea (I. coccinea).MethodsTo investigate the wound healing efficacy of root extract of I. coccinea Linn, five groups of animals were divided each containing six animals. Two wound models including incision and excision wound models were used in this study. The parameters studied were tensile strength on incision wound model and in terms of wound contraction for excision wound model were compared with standard Nitrofurazone (NFZ) ointment (0.2% w/w). Six extracts (ethanol, aqueous, petroleum ether, benzene, chloroform and ethyl acetate) of I. coccinea were screened for in vitro growth inhibiting activity against different bacterial strains viz, Staphylococcus aureus, Bacillus pumilius, Enterococcus faecalis, Escherichia coli, Salmonella typhi and Pseudomonas aeruginosa and fungi Candida albicans and Aspergillus niger were compared with the standard drugs ciprofloxacin and chloramphenicol for antibacterial and griseofulvin for antifungal screening. The serial dilution and cup (or) well plate methods were used for the antimicrobial study and MIC was determined.ResultsThe ethanolic extract showed significant (P

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.

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