Panax ginseng inhibits intestinal absorption of toxic Aconitum carmichaeli alkaloids in Vitro.
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OBJECTIVE
To evaluate the rationality and compatibility of Shenfu Formula (, SFF), a typical Chinese medicine (CM) comprised of Panax ginseng and Aconitum carmichaeli.
METHODS
Caco-2 cells were used to study the permeability of Aconitum carmichaeli marker compounds when the CM preparation was combined with Panax ginseng. P-glycoprotein (P-gp) activity and protein as well as multidrug resistance 1 (MDR1) mRNA were analyzed with rhodamine123 efflflux, western blot and real time quantitative polymerase chain reaction.
RESULTS
Aconitine (AC), mesaconitine (MA), hypaconitine (HA) and fifive other active alkaloids in Aconitum carmichaeli were selected as marker compounds. Panax ginseng inhibited intestinal absorption of highly toxic AC, MA and HA from Aconitum carmichaeli in Caco-2 cells. P-gp and breast cancer resistance protein (BCRP) were observed to be involved in AC, MA and HA efflflux. Panax ginseng induced P-gp activity in Caco-2 cells via increased MDR1/P-gp expression. Thus, Panax ginseng facilitated P-gp-mediated efflflux of toxic Aconitum carmichaeli alkaloids and restricted their intestinal absorption without inflfluencing other active components.
CONCLUSIONS
Future studies to elucidate mechanism of reduced toxicity of Aconitum carmichaeli when combined with Panax ginseng will guide future formula optimization.
