In Vitro Metabolic Stability and Permeability of Gymnemagenin and Its In Vivo Pharmacokinetic Correlation in Rats – A Pilot Study

Abstract

Gymnema sylvestre is traditionally used for diabetes mellitus. A literature survey revealed very few reports, particularly on rat liver microsomal stability, caco-2 permeability and efflux concerns and its correlation with the bioavailability of gymnemagenin, an important component of G. sylvestre. Therefore, the objective of our study was to investigate the in vitro rat liver microsomal stability and caco-2 permeability along with the efflux of gymnemagenin and establish a probable correlation of these in vitro findings with pharmacokinetic parameters after oral and intravenous administration in rats. Rat liver microsomal stability studies to estimate the in vitro intrinsic half-life, clearance, and Caco-2 permeability after 21 days of culture to determine the apparent permeability from apical to basal and from basal to apical, and efflux ratio of gymnemagenin were performed using liquid chromatography-tandem mass spectrometry. A sensitive, robust bioanalytical method was validated and successfully applied to determine the plasma exposure of gymnemagenin. In vitro rat liver microsomal stability demonstrated that gymnemagenin metabolizes rapidly with a short apparent and intrinsic half-life (~?7?min) and high intrinsic clearance, i.e., 190.08??L/min/mg of microsomes. The results of the Caco-2 study indicated a poor permeability (1.31???10??6?cm/sec) with a very high efflux ratio. The pharmacokinetic study revealed poor oral bioavailability (~?14?%) of gymnemagenin and it was found to have a short half-life and a high clearance in rats. Our in vitro findings indicated low metabolic stability and poor Caco-2 permeability with high efflux, which might have a role in the observed poor oral bioavailability in rats.

Untitled

“…Appropriate documentation and quality control of the presence of active constituent can be done by HPTLC fingerprint analysis. Different chromatographic record (like HPLC, HPTLC, LC-MS/MS) can offer several elementary pieces of information like chemical compounds for identification, isolation, purification, metabolic safety, permeability, and pharmacokinetic profile of a particular plant species in the animal model also [39,40].…”

Sweet taste receptor inhibitors: Potential treatment for equine insulin dysregulation

“…The efficacy of lactisole (Sigma Aldrich, NSW, Australia) and G sylvestre (Nature’s Sunshine, NSW, Australia) in reducing the insulin response to oral D-glucose was measured during two separate dose-response studies performed with a 2 week wash-out period between studies, which was deemed generous based on the short duration of effect of both compounds [ 20 , 34 ]. Using data from previous human trials as a guide [ 35 , 36 ], lactisole was administered in parts per million (ppm) at 0, 50, 150 and 500 ppm of the NSC content of the meal provided; whereas G sylvestre was administered at 0, 3, 10 and 20 mg/kg BW.…”

Metabolic differentiation and quantification of gymnemic acid in Gymnema sylvestre (Retz.) R.Br. ex Sm. leaf extract and its fermented products

“…Aglycone form of G. sylvestre is gymnemagenin which is an active, potent molecule and responsible for its pharmacological action. Bioavailability of gymnemic acid depends on its biotransformation within the intestine by gut microbiota, where the glycosidic form of gymnemic acid is transformed into active glycone moiety gymnemagenin which is further absorbed from the gut to the main bloodstream . Gut microbiota is subjected to variations as per the different physical and medical conditions because of that bioavailability of the formulation might get affected …”