Submitted to: Planta Medica
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/11/2009
Publication Date: 1/25/2010
Citation: Madgula, V.L., Avula, B., Pawar, R.S., Shukla, Y.J., Khan, I.A., Walker, L.A., Khan, S.I. 2010. Characterization of in Vitro Pharmacokinetic Properties of Hoodigogenin A from Hoodia gordonii. Planta Medica. 76:62-69. Interpretive Summary: The manuscript describes about the pharmacological properties of hoodigogenin A isolated from Hoodia gordonii . Hoodia gordonii extract is an dietary supplement which is used extensively as a weight loss product.
Technical Abstract: This study was aimed to determine ADME properties of Hoodigogenin A, which is aglycone of oxypregnane steroidal glycoside P57AS3 (P57) isolated from Hoodia gordonii. A series of in vitro assays were used to predict its gastric, intestinal and metabolic stability, intestinal and blood brain barrier (BBB) transport, protein binding and interaction with major drug metabolising enzymes. In the simulated gastric fluid (SGF), hoodigogenin A was found to be stable (2% degradation in 60 minutes) where as P57 glycoside was highly unstable in SGF (45% degradation in 30 minutes). P57 was degraded to an extent of 8% in presence of simulated intestinal fluid (SIF) over a period of 180 minutes, while the corresponding aglycone (1%) was highly stable. Hoodigogenin A was efficiently transported by a simple passive diffusion across Caco-2 and MDR-MDCK monolayers with Papp values in the range of 32-33 x 10-6 cm/sec and 22 x 10-6 cm/sec respectively. The compound was metabolically unstable in HLM and S9 fractions with a T1/2 of less than 15 and 30 minutes and CL’int of 70.7 ± 8.1 mL.min-1.kg-1 and 120.4 ± 7.9 mL.min-1.kg-1 respectively. Aglycone was bound to the plasma proteins to an extent of 92%. The compound strongly inhibited CYP3A4 activity (IC50 3 µM) whereas activity of CYP 1A2, 2C9 and 2D6 were moderately affected. Inhibition of CYP3A4 by hoodigogenin A indicates possibility of drug-herb/botanical drug interactions when products containing H. gordonii are used simultaneously with other botanicals/herbs or drugs.