Antidiarrhoeal activity of eriosematin E isolated from the roots of Eriosema chinense Vogel.

BACKGROUND: Roots of the plant Eriosema chinense Vogel (Fabaceae) is distributed mainly over the Eastern Himalayan region of India and China. The roots of the plant are used as a vegetable by the people of Northern Australia, China and North East India and are used traditionally by the tribal people of Meghalaya (India) for the treatment of diarrhoea. It has been reported to have significant antidiarrhoeal, cytotoxic and antimycobacterial activity. PURPOSE/OBJECTIVE: The present investigation was undertaken to isolate a lead molecule responsible for the observed antidiarrhoeal activity. METHODS: Eriosematin E, a prenylated flavanone, was isolated using column chromatography and was characterized by comparing its melting point and spectroscopic data (UV, IR, 1H NMR, 13C NMR, Mass Spectra) from literature. Eriosematin E (2.5, 5 and 10mg/kg p.o.) was then screened for normal faecal excretion rate and castor oil-induced diarrhoea models in rats. Further, it was examined for small intestinal transit, intestinal fluid accumulation and PGE2 induced enteropooling models in rats. Biochemical estimations and Na+ and K+ concentration in intestinal fluid were also determined along with colonic histopathological studies. RESULTS: The results illustrated a significant (P< 0.05) reduction in normal faecal output at 10mg/kg p.o. after 5th and 7thh of treatment and also showed maximum protection of 69.43% from diarrhoea in the castor oil-induced diarrhoea model. Significant results were also observed at the maximum effective dose of eriosematin E (10mg/kg p.o.) in inhibiting peristaltic index (small intestinal transit) and reducing intestinal fluid volume of castor oil induced and PGE2 induced enteropooling models. Further, eriosematin E restored all the alterations in biochemical parameters such as nitric oxide, protein, DNA, superoxide dismutase, catalase and lipid peroxidation. It also significantly recovered Na+ and K+ loss from body and confirmed its protective nature through the histopathological studies. CONCLUSION: The study corroborates the antidiarrhoeal potential of eriosematin E which may be attributed to its antisecretory and antioxidant potential.

Design, Synthesis and Molecular Docking Studies of New Potential Piperazine Derivatives as Cognition Enhancers.

BACKGROUND: In 2016, the statistical reports stated that Alzheimer is not just memory loss but it kills and has become the 6th leading cause of death. The number of dementia patients is increasing rapidly and expected to rise to 131.5 million by 2050. Still there is not a drug candidate that can cure the cognitive deficits completely. OBJECTIVE: Series of novel piperazine derivatives have been designed, synthesized and evaluated for cognition enhancing activity. METHODS: The synthesized compounds were screened for their in vitro AChE inhibition and reversal of scopolamine induced memory deficit in a passive avoidance stepdown animal model in mice. Enzyme kinetics and molecular docking studies were carried out to elucidate the mechanism of AChE inhibition. RESULTS: All the compounds exhibited excellent IC50 values with potential dual binding site inhibition activity. The IC50 values and inhibition constants of the most promising compounds 1d and 3c were found to be 2.23 µM, 1.05 µM, 14.38 µM and 6.93 µM respectively. They potentially reversed the scopolamine induced memory deficit at a dose of 1.0 mg/kg i.p. in mice. Furthermore, 1d and 3c showed high CNS penetration and brain AChE inhibition in ex vivo experiments. Additionally, significant free radical scavenging activity was determined taking trolox as the standard. CONCLUSION: Compounds 1d and 3c were emerged as promising of the series and further can be investigated for the future pursuit as drug candidates.