Glucagon-like peptide-1 (GLP-1) is an endogenous peptide secreted from the gut in response to the presence of food. GLP-1 and its longer acting analog exendin-4 have multiple synergistic effects on glucose dependent, insulin secretion pathways of the pancreatic β-cell and on plasticity in neuronal cells. Recently the development of these peptides as a novel therapeutic strategy for non-insulin-dependent (type 2) diabetes mellitus and associated neuropathy has been the focus of much interest. Here we describe the biological actions of GLP-1 and its related analogs.

Health complications associated with obesity include diabetes, hypertension, hyperlipidemia, cardiovascular disease, and associated co-morbidities including non-alcoholic steatohepatitis (NASH). Additionally, NASH has been associated with several drugs. Though steatohepatitis is a rare form of drug induced liver disease, it has generated great interest in the recent past. Oral hypoglycemic agents, lipid lowering agents, antihypertensives, and antiobesity medication underlie a significant proportion of well-recognized hepatotoxicity. While some medications have predictable toxicity, many more are associated with idiosyncratic reactions. The toxic mechanism appears to involve mitochondrial injury, impaired β -oxidation, generation of reactive oxygen species and ATP depletion. If a drug is suspected, it is probably prudent to stop this medication.

Increasing attention has been focused on the role of peroxisome proliferator-activated receptors (PPARs) in the past decade. Compelling data have begun to unite work from various arenas, such as epidemiology and vascular biology. Clinical trials with synthetic PPAR agonists have exhibited therapeutic benefits in treating various chronic diseases like atherosclerosis, diabetes mellitus and cardiovascular diseases. The PPARs, a family of nuclear receptors (NRs), are a set of three receptor sub-types encoded by distinct genes. They function as lipid sensors to regulate a broad range of genes in many metabolically active tissues. The discovery of PPAR-specific ligands has led to a significant advancement in our understanding of the structure of these receptor proteins and molecular mechanisms of their ligand dependent activation. Herein, we have tried to delineate the role of PPARs as molecular targets for the development of new drugs to treat human metabolic diseases.

Objective: The objective of the study was to investigate the anxiolytic activity of petroleum ether, alcohol and water extracts, obtained from the flowers of Sphaeranthus indicus Linn, in mice. Materials and Methods: Elevated plus maze (EPM), open field test (OFT) and foot-shock induced aggression (FSIA) were the screening tests used to assess the anxiolytic activity of the extracts on mice. Diazepam (1 mg/kg) served as the standard anxiolytic agent. Results: The animals receiving extracts or diazepam (1 mg/kg) showed an increase in the time spent, percent entries and total entries in the open arm of the EPM; increased ambulation, activity at centre and total locomotion in the OFT; and decreased fighting bouts in the FSIA, suggesting anxiolytic activity. Petroleum ether extract (10 mg/kg), alcoholic extract (10 mg/kg) and water extract (30 mg/kg) resulted in prominent activity in the mice. Petroleum ether extract (10 mg/kg) resulted in more prominent anxiolytic activity in the EPM and OFT than ethanolic or water extracts, but was less than that produced by diazepam (1 mg/kg). Conclusion: Petroleum ether extract of S. indicus flowers produces prominent anxiolytic activity in mice.

Objective : To evaluate the therapeutic activity of cyclophosphamide alone and in combination with ascorbic acid against murine ascites Dalton's lymphoma. Materials and Methods: Cyclophosphamide (CP) is an anticancer drug with immunosuppressive activity, while ascorbic acid (AA) is an antioxidant. Ascites Dalton's lymphoma (DL) was maintained by intraperitoneal (i.p.) transplantation of tumor cells in Swiss albino mice. Tumor transplanted mice were divided into four groups. Group-I mice received normal saline only and served as control. Group-II mice were given 1% ascorbic acid through drinking water from the 5th to the 10th day. Group-III mice were injected i.p. with a single dose of CP (200 mg/kg) on the 10th day of tumor transplantation. Group IV mice received 1% ascorbic acid from the 5th day onwards and, then, a single dose of CP, i.p., on the 10th day of tumor transplantation. In groups III and IV, after 24, 48, 72, and 96 h of CP treatment the liver, kidneys, spleen, and tumor tissue were collected for biochemical determinations. In group II, which received AA only from the 5th to the 10th day, the same tissues were collected on the 10th day of tumor transplantation. The changes in reduced glutathione (GSH) and carbohydrate in tumor cells as well as the liver, kidney, and spleen of tumor-bearing mice in relation to the antitumor activity of CP alone or in combination with AA were evaluated. The quantitative changes in sialic acid level of DL cells under these treatment conditions were also determined. Results: AA and CP combination in tumor-bearing mice was found to be more effective against DL as it caused a 257% increase in life span compared with control, while it was 106% with AA and 188% with CP alone (ANOVA, P < 0.001). The reduced glutathione (GSH) level increased in DL cells with tumor growth. Compared with CP alone, the combination treatment (AA + CP) resulted in a more pronounced effect causing decreases in non-protein thiol (NPSH) as well as sialic acid levels in DL cells (ANOVA, P < 0.001). Conclusion: The drug-mediated lowering of GSH levels in DL cells may be involved in the cytotoxicity due to CP (group-III) as well as AA + CP combination (group-IV). An overall decrease in the sialic acid content of DL cells after combination treatment may also play a role to bring about alterations in the tumor cells, cell-cell interaction and enhanced tumor regression.

Objective: Hypericum perforatum extract (HPE), known for its antidepressant effect, has been explored in the present study for its protective role against MPTP induced neurotoxicity. Materials and Methods: Mice were treated with 20 mg/kg of MPTP, four injections i.p., at 2 h intervals within 24 h. HPE was administered at different doses of 100, 200 and 300 mg/kg (p.o) in different groups once a day for seven days and the dose on the first day was given 30 min prior to first MPTP injection. Striatal dopamine (DA) and its metabolites, antioxidant status were analysed. The behavioural changes were studied using the rotarod test, hang test and narrow beam test. Results: HPE significantly ( P <0.05) improved the behavioural activities, striatal neurotransmitter levels and striatal antioxidant status in a dose dependent manner and significantly ( P <0.05) reduced TBARS levels. Conclusion: HPE possesses significant antioxidant activity and renders neuroprotection which was more pronounced at the dose of 300 mg/kg against MPTP induced neurotoxicity.

Objective: To evaluate the immunomodulatory activity of the aerial roots of Ficus benghalensis (Family Moraceae). Materials and Methods: Various extracts of the aerial roots of Ficus benghalensis were evaluated for potential immunomodulatory activity, using the in vitro polymorphonuclear leucocyte (human neutrophils) function test. The methanol extract was evaluated for immunomodulatory activity in in vivo studies, using rats as the animal model. The extracts were tested for hypersensitivity and hemagglutination reactions, using sheep red blood cells (SRBC) as the antigen. Distilled water served as a control in all the tests. Results: The successive methanol and water extracts exhibited a significant increase in the percentage phagocytosis versus the control. In the in vivo studies, the successive methanol extract was found to exhibit a dose related increase in the hypersensitivity reaction, to the SRBC antigen, at concentrations of 100 and 200 mg/kg. It also resulted in a significant increase in the antibody titer value, to SRBC, at doses of 100 and 200 mg/kg in animal studies. Conclusion: The successive methanol extract was found to stimulate cell mediated and antibody mediated immune responses in rats. It also enhanced the phagocytic function of the human neutrophils, in vitro.

Objective: To investigate the in vitro antioxidant activity of the hydromethanolic extract of the aerial parts (leaves and stems) of Salvia verbenaca L. towards fatty acids (linoleic and linolenic acids) and human, low density lipoproteins (LDL) peroxidation. Materials and Methods: Lipid peroxidation was carried out in the presence of the S. verbenaca L. hydromethanolic extract (10 and 100 µg of extract/ml). CuSO4 (10 µM) was used as the oxidation initiator. Conjugated dienes (CD) formation, oxygen consumption and thiobarbituric acid reactive substances (TBARS) formation were assessed to monitor the antioxidant properties of the plant extract. Butylated hydroxytoluene (BHT) at 50 µg/ml was used as a standard antioxidant. The quantification of total polyphenolic compounds was carried out, according to the Folin-Ciocalteu method. Results: The hydromethanolic extract of S. verbenaca showed a significant antioxidant effect at 100 µg/mL. A strong inhibition of oxygen consumption (92%, P <0.001) and CD formation of LDL peroxidation (92%, P <0.001) as well as TBARS formation of linolenic acid oxidation (93%, P <0.001) were observed. The quantitative analysis revealed that the extract used contained a high amount of phenolic compounds, suggesting a possible role of these products in the observed antioxidant properties. Conclusion: S. verbenaca could be considered as a potential source of natural antioxidants.