title: Evaluation of the bioavailability of major withanolides of Withania somnifera using an in vitro absorption model system.
abstract: Withania somnifera (L.) Dunal, shows several pharmacological properties which are attributed mainly to the withanolides present in the root. The efficacy of medicinally active withanolides constituents depends on the absorption and transportation through the intestinal epithelium. We examined these characteristics by employing the Sino-Veda Madin-Darby canine kidney cells culture system, which under in vitro condition shows the absorption characteristics similar to the human intestinal epithelium. Thus, the aim of the present investigation was to assess the bioavailability of individual withanolides. Withanolides were diluted in Hank's buffered saline at a concentration of 2 μg/ml were tested for permeability studies carried out for 1 h duration. Permeability was measured in terms of efflux pump (P eff) in cm/s. P eff values of withanolide A (WN A), withanone (WNN), 1,2-deoxywithastramonolide (1,2 DWM), withanolide B (WN B), withanoside IV-V (WS IV-V), and withaferin A were 4.05 × 10(-5), 2.06 × 10(-5), 1.97 × 10(-5), 1.80 × 10(-5), 3.19 × 10(-6), 3.03 × 10(-6) and 3.30 × 10(-7) respectively. In conclusion, the nonpolar and low molecular weight compounds (WN A, WNN, 1,2 DWM, and WN B) were highly permeable. As against this, the glycosylated and polar WS IV and WS V showed low permeability. Surprisingly and paradoxically, the highly biologically active withaferin A was completely impermeable, suggesting that further studies possibly using human epithelial colorectal adenocarcinoma (Caco-2) cells may be needed to delineate the absorption characteristics of withanolides, especially withaferin A.
authors.affiliation: Centre for Innovation Nutrition Health Disease - Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Medical College Campus, Pune, Maharashtra, India.
authors.forename: Santosh T
authors.initials: ST
authors.lastname: Devkar
authors.affiliation: Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, Maharashtra, India.
authors.forename: Amit D
authors.initials: AD
authors.lastname: Kandhare
authors.affiliation: SinoVeda Canada Inc. Suite 100, BBDC 2011-94 Street Edmonton, AB T6N 1H1 Canada.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Sloley
authors.affiliation: Interactive Research School for Health Affairs, Herbal Biotechnology Research Laboratory, Bharati Vidyapeeth University, Medical College Campus, Pune, Maharashtra, India.
authors.forename: Suresh D
authors.initials: SD
authors.lastname: Jagtap
authors.affiliation: SinoVeda Canada Inc. Suite 100, BBDC 2011-94 Street Edmonton, AB T6N 1H1 Canada.
authors.forename: James
authors.initials: J
authors.lastname: Lin
authors.affiliation: SinoVeda Canada Inc. Suite 100, BBDC 2011-94 Street Edmonton, AB T6N 1H1 Canada.
authors.forename: Yun K
authors.initials: YK
authors.lastname: Tam
authors.affiliation: Centre for Innovation Nutrition Health Disease - Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Medical College Campus, Pune, Maharashtra, India.
authors.forename: Surendra S
authors.initials: SS
authors.lastname: Katyare
authors.affiliation: Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, Maharashtra, India.
authors.forename: Subhash L
authors.initials: SL
authors.lastname: Bodhankar
authors.affiliation: Centre for Innovation Nutrition Health Disease - Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Medical College Campus, Pune, Maharashtra, India.
authors.forename: Mahabaleshwar V
authors.initials: MV
authors.lastname: Hegde
keywords: Absorption model; Caco-2 cells; Madin-Darby canine kidney cells; ashwagandha; bioavailability; withanolides