Abstract
P57AS3 (P57), an oxypregnane steroidal glycoside, is known to be responsible for the appetite suppressing activity of Hoodia gordonii, a dietary supplement used for weight loss. In this study, bioavailability, pharmacokinetics, and tissue distribution of P57 were determined in CD1 female mice after administration of a single dose of enriched methanolic extract of Hoodia gordonii (equivalent to a dose of 25 mg of P57/kg) by oral gavage or a single dose of purified P57 (25 mg/kg) intravenously. The level of P57 in plasma and tissues (brain, liver, kidney, and intestine) was determined by UPLC‐MS. After oral administration of Hoodia extract, the peak plasma level of P57 was achieved in 0.6 h. Upon intravenous administration, the plasma clearance rate of P57 was 1.09 L/h/kg. P57 was rapidly distributed and eliminated from the tissues within 4 hours. The level of tissue distribution was highest in the kidney followed by liver and brain. Upon oral administration, P57 was not detected in the brain and a very low concentration was seen in the intestine, kidney, and liver. Tissue/plasma ratio was 0.33 for brain, 0.57 for liver, and 0.75 for kidney with IV route and 0.11 for intestine, 0.02 for liver, and 0.04 for kidney with oral route. The half-life of the elimination phase was similar with both routes. The oral bioavailability was 47.5 % and the half-life of the absorption phase was 0.13 h. In conclusion, P57 showed moderate bioavailability and was eliminated rapidly.
Key words
Hoodia gordonii
- Asclepiadaceae - P57AS3 - bioavailability - tissue distribution - UPLC/MS
References
-
1 South African National Biodiversity Institute .Plants of Southern Africa. Available at. http://www.plantzafrica.com Accessed April 4, 2009
-
2 Rubin D I, Cawthorne M A, Bindra J S. Extracts, compounds and pharmaceutical compositions having anti-diabetic activity and their uses. US Patent 7416744B2. 2008
-
3 Rubin D I, Cawthorne M A, Bindra J S. Extracts, compounds and pharmaceutical compositions having anti-diabetic activity and their use. Euro Patent 1166792. 2002
-
4
Bray G A.
Medical consequences of obesity.
J Clin Endocrinol Metab.
2004;
89
2583-2589
-
5
van Heerden F R.
Hoodia gordonii: a natural appetite suppressant.
J Ethnopharmacol.
2008;
119
434-437
-
6
Pawar R S, Shukla Y J, Khan S I, Avula B, Khan I A.
New oxypregnane glycosides from appetite suppressant herbal supplement Hoodia gordonii.
Steroids.
2007;
72
524-534
-
7
van Heerden F R, Marthinus Horak R, Maharaj V J, Vleggaar R, Senabe J V, Gunning P J.
An appetite suppressant from Hoodia species.
Phytochemistry.
2007;
68
2545-2553
-
8
MacLean D B, Luo L G.
Increased ATP content/production in the hypothalamus may be a signal for energy-sensing of satiety: studies of the anorectic mechanism of a plant steroidal glycoside.
Brain Res.
2004;
1020
1-11
-
9
Davies B, Morris T.
Physiological parameters in laboratory animals and humans.
Pharm Res.
1993;
10
1093-1095
-
10
Madgula V L, Avula B, Pawar R S, Shukla Y J, Khan I A, Walker L A, Khan S I.
Characterization of in vitro pharmacokinetic properties of Hoodigogenin A from Hoodia gordonii.
Planta Med.
2009;
75
1-8
-
11
Madgula V L, Avula B, Pawar R S, Shukla Y J, Khan I A, Walker L A, Khan S I.
In vitro metabolic stability and intestinal transport of P57AS3 (P57) from Hoodia gordonii and its interaction with drug metabolizing enzymes.
Planta Med.
2008;
74
1269-1275
Shabana I. Khan
National Center for Natural Products Research
School of Pharmacy
University of Mississippi
University, MS 38677
USA
Phone: + 01 66 29 15 10 41
Fax: + 01 66 29 15 70 62
Email: skhan@olemiss.edu
