Effects of Devil's Claw (Harpagophytum procumbens) on the multidrug transporter ABCB1/P-glycoprotein.
Devil's Claw (Harpagophytum procumbens) a plant native to Southern Africa, has historically been used in traditional medicine to treat a wide range of diseases and currently is widely employed as anti-inflammatory and pain-relieving natural remedy in Europe and other parts of the world.


OBJECTIVE
Little is known about possible herb-drug interactions arising from effects of Devil's Claw on the major drug metabolizing enzymes or transporters. This study evaluated in vitro the effects of Devil's Claw on the multidrug transporter ABCB1/P-glycoprotein.


METHODS
The effects of three commercially available Devil's Claw preparations and that of pure harpagoside were studied in the human kidney (HK-2) proximal tubule cell line, constitutively expressing ABCB1/P-glycoprotein (P-gp). Pgp activity and expression were tested by the calcein-AM test and by Western blotting, respectively.


RESULTS
Commercial preparations inhibited P-gp activity, even if to a different extent, while pure harpagoside was almost ineffective. In cells cultured for three days in the presence of Devil's Claw preparations or pure harpagoside, a dose-dependent P-gp upregulation was found.


CONCLUSIONS
Our results demonstrate for the first time that Devil's Claw may interact with the multidrug transporter ABCB1/P-gp, the effect not appearing strictly related to the harpagoside relative content. Modulation of both P-gp activity and P-gp expression by Devil's Claw raise the possibility of herb-drug interactions, to be further explored in depth.
Romiti
Nadia
N
Dipartimento di Patologia Sperimentale, Sezione di Patologia Generale e Clinica, Università degli Studi di Pisa, Pisa, Italy.
Tramonti
Gianfranco
G
Corti
Alessandro
A
Chieli
Elisabetta
E
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006027:Glycosides / Q000494:pharmacology*; D031684:Harpagophytum / Q000737:chemistry*; D041743:Herb-Drug Interactions; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D011714:Pyrans / Q000494:pharmacology*; D015854:Up-Regulation
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006027:Glycosides; D010936:Plant Extracts; D011714:Pyrans; C033249:harpagoside