Pharmacodynamic interaction of Tinospora cordifolia Willd. With Ocimum sanctum Linn. in isoproterenol-induced cardiac toxicity.

BACKGROUND: Cardiovascular diseases are the leading causes of deaths despite several advancements in the current medical interventions. Among them, myocardial infarction (MI) is the most alarming disease as about 17.1 million peoples die every year due to MI. AIM: The present study was designed to investigate the potential cardioprotective effect of combination of standardized extracts of Tinospora cordifolia (SETC) (250 mg/kg and 500 mg/kg) and Ocimum sanctum (SEOS) (50 mg/kg) in isoproterenol (ISO)-induced MI. MATERIALS AND METHODS: MI was induced in rats by subcutaneous injection of ISO for 2 consecutive days at an interval of 24 h. Rats were pretreated with test drugs for the period of 21 days, and ISO was administered on the 20th and 21st days. At the end of experiment, i.e., on 22nd-day electrocardiograph, a hemodynamic, biochemical, and histopathological study of heart tissues was evaluated from control and experimental groups and statistically analyzed by one-way analysis of variance followed by Tukey's test. RESULTS: ISO-administered rats showed significant changes in electrocardiograph, mean arterial blood pressure, heart rate, biochemical markers, antioxidant parameters, and histopathology of heart. The activities of cardiac biomarkers were reduced in serum, and there was an increase in antioxidants in heart tissue of test drug-treated animals. Similarly, electrocardiograph, mean arterial blood pressure, and heart rate were restored to normalcy in all test and standard drug-treated animals. CONCLUSION: The SETC 500 mg/kg in combination with SEOS 50 mg/kg was found to be effective in prevention of myocardial injury induced by ISO.

Pharmacophore mapping, molecular docking, chemical synthesis of some novel pyrrolyl benzamide derivatives and evaluation of their inhibitory activity against enoyl-ACP reductase (InhA) and Mycobacterium tuberculosis.

In an effort to produce new lead antimycobacterial compounds, herein we have reported the synthesis of a sequence of new pyrrolyl benzamide derivatives. The new chemical entities were screened to target enoyl-ACP reductase enzyme, which is one of the key enzymes of M. tuberculosis that are involved in type II fatty acid biosynthetic pathway. Compound 3q exhibited H-bonding interactions with Tyr158, Thr196 and co-factor NAD+ that binds the active site of InhA. All the pyrrolyl benzamide compounds were evaluated as inhibitors of M. tuberculosis H37Rv as well as inhibitors of InhA. Among them, few representative compounds were tested for mammalian cell toxicity on the human lung cancer cell-line (A549) and MV cell line that presented no cytotoxicity. Five of these compounds exhibited a good activity against InhA.

Polyphenolic enriched extract of Cassia glauca Lamk, improves streptozotocin-induced type-1 diabetes linked with partial insulin resistance in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally Cassia glauca (CG) has been used to treat diabetes. AIM OF THE STUDY: The study was undertaken to evaluate anti-diabetic and antioxidant activity of polyphenolic enriched extract of CG in standardized streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: The effect of ethanol (CGE) and water (CGW) extracts of CG (200 and 400mg/kg) treatment were evaluated in STZ (50mg/kg, iv) induced diabetic rats. On 10th day, oral glucose tolerance test and degree of insulin resistance was calculated. On 13th day, insulin tolerance test was performed to know the peripheral utilization of glucose. On 15th day, blood glucose, lipid profiles and endogenous antioxidant levels were estimated. In addition, the effects on oral glucose/sucrose tolerance test in normal rats. Further, HPLC fingerprinting profile of CGE and simultaneous quantification of biomarkers were carried out. RESULTS: Supplementation with CGE and CGW significantly reduced STZ-induced deleterious effects and improved glucose tolerance, and insulin tolerance. In addition, supplementation also decreased oxidative stress by improving endogenous antioxidant levels. Furthermore, administration significantly improves sucrose tolerance suggesting that extract possess inhibition of α-glucosidase enzyme. Further, HPLC studies revealed that CGE contains three bioactive polyphenolic compounds viz., rutin (0.10±0.01mg/g), luteolin-7-glucoside (0.06±0.01mg/g) and isorhoifolin (0.7±0.05mg/g). CONCLUSION: Observed beneficial outcome of CG might be attributed to the presence of polyphenolic compounds and mediated by interacting with multiple targets of diabetes and oxidative stress. Taken together, this study provided the scientific evidence for the traditional use of CG.

Synthesis, Antimicrobial and cytotoxic activity of New Heterocyclic Hybrids Based on 2,5-Dimethylpyrrole and Pyrrole Scaffolds.

A series of 4-(2,5-dimethylpyrrol-1-yl)/4-pyrrol-1-yl benzoic acid hydrazide analogs, some derived triazoles, azetidinones, thiazolidinones, and pyrroles have been synthesized in good yields and structures of these compounds were established by IR, (1)H NMR, (13)C NMR, mass spectral, and elemental analysis. These compounds were evaluated for their preliminary in vitro antibacterial, antifungal, and antitubercular activity against Mycobacterium tuberculosis H37 Rv strain by the broth dilution assay method. Twenty one of these compounds displayed good antimicrobial activity, with a MIC value of 1-4 µg/ml. Several compounds 4c, 8-10, 15b-15h, and 16b-16d exhibited good in vitro antitubercular activity with MIC value 1-2 µg/ml. Further, some title compounds were also assessed for their cytotoxic activity (IC50) against mammalian Vero cell lines and A549 (lung adenocarcinoma) cell lines using the MTT assay method. The results revealed that these compounds exhibit antitubercular activity at non-cytotoxic concentrations.