Trigonelline inhibits intestinal microbial metabolism of choline and its associated cardiovascular risk.

Gut microbiota based metabolism of choline produces trimethylamine (TMA) which is further converted to a pro-atherosclerotic metabolite, trimethylamine-N-oxide (TMAO) by flavin monooxygenase (FMO3). Trigonelline from the plant Trigonella foenum-graecum has been reported for the treatment of CVD. Aim of the present study was to check the effect of trigonelline on the gut microbiota based conversion of TMA to TMAO. Trigonelline was isolated from hydroalcoholic extract of seeds of Trigonella foenum-graecum. The isolated trigonelline was characterized through TLC and UPLC-MS. Anaerobic microbe responsible for the metabolism of choline to TMA was isolated by culturing the human gut microbiota in choline enriched medium. The isolated bacteria was identified at molecular level based on PCR amplification of 1500bp of 16S rRNA gene sequence. Isolated FMO3 was used for ex vivo conversion of TMA to TMAO. Further, we investigated the effect of trigonelline in isolated gut microbe based metabolism of choline, lipid profile and TMAO levels in mice with or without suppression of gut microbiota with antibiotics. Liquid-liquid purification and chromatographic analysis confirmed the trigonelline purity (87.26%) and which was also confirmed by mass spectroscopy with m/z 137.4 in positive ionization mode. A total of 30 anaerobic microbes responsible for TMA production were isolated and Citrobacter freundii was the superior among others for the production of TMA. In vitro culture of C. freundii in choline enriched medium supplemented with trigonelline resulted in significantly reduction TMA and followed by TMAO production. In ex vivo, a maximum of 85.3% TMAO production was reduced by trigonelline at concentration of about 300 µg/mL. Serum level of lipids and TMAO were significantly altered in choline fed animals with or without suppression of gut microbiota and this phenomenon was reversed upon the oral administration of trigonelline in a dose-dependent manner. This study demonstrates the effect of trigonelline on gut microbiota responsible for choline metabolism and this can be used as a model for evaluation of herbal drugs and its effect in gut microbiota prompted cardiovascular disorders.

Effect of aloe vera (Aloe barbadensis Miller) gel on doxorubicin-induced myocardial oxidative stress and calcium overload in albino rats.

Administration of a single dose of doxorubicin (DOX) (7.5 mg/kg, i.v.) produces cardiotoxicity, manifested biochemically by significant decrease in blood glutathione (GSH) and tissue GSH along with elevated levels of serum lactate dehydrogenase (LDH) and serum creatine phosphokinase (CPK). In addition, cardiotoxicity was further confirmed by significant increase in lipid peroxides expressed as malondialdehyde (MDA, secondary indicator of lipid peroxidation), tissue catalase and tissue superoxide dismutase (SOD). Administration ofA. vera gel (100 and 200 mg/kg) orally for 10 days produced a significant protection against cardiotoxicity induced by DOX evidenced by significant reductions in serum LDH, serum CPK, cardiac lipid peroxides, tissue catalase and tissue SOD along with increased levels of blood and tissue GSH. The results revealed that A. vera gel produced a dose dependent protection against DOX induced cardiotoxiaty.

Transdermal drug delivery systems of a beta blocker: design, in vitro, and in vivo characterization.

The matrix type transdermal drug delivery systems (TDDS) of metoprolol were prepared by film casting technique using a fabricated stainless steel film casting apparatus and characterized in vitro by drug release, skin permeation, skin irritation, and in vivo pharmacodynamic and stability studies. Four formulations were prepared that differed in the ratio of matrix forming polymers. Formulations M-1, M-2, M-3, and M-4 were composed of Eudragit RL-100 and polyvinyl acetate with the following ratios: 2:8, 4:6, 6:4, and 8:2, respectively. All the four formulations carried 10% (w/w) of metoprolol tartrate, 5% (w/w) of dibutylphthalate, and 5% (w/w) of (+/-) menthol in dichloromethane:isopropyl alcohol (80:20 v/v). Cumulative amount of drug released in 48 hr from the four formulations was 79.16%, 81.17%, 85.98%, and 95.04%. The corresponding values for cumulative amount of drug permeated for the said formulations were 59.72%, 66.52%, 77.36%, and 90.38%. On the basis of in vitro drug release and skin permeation performance, formulation M-4 was found to be better than the other three formulations and it was selected as the optimized formulation. The formulation appeared to be stable when stored at 40 degrees C and 75% RH with negligible degradation of the drug. The TDDS was found to be free of any skin irritation as suggested by skin irritation score of 1.16 (<2.00) under Draize score test. Statistically significant reduction in mean blood pressure (p < .01) was achieved in methyl prednisolone-induced hypertensive rats on treatment with the TDDS.