Preclinical Herb–Drug Pharmacokinetic Interaction of Panax ginseng Extract and Selegiline in Freely Moving Rats

Abstract

Selegiline, an inhibitor of monoamine oxidase B, is prescribed during the early stages of Parkinson's disease. The nutritional herbal medicine Panax ginseng C.A. Meyer has been reported to show potential neuroprotective activity; however, the herb−drug pharmacokinetic interaction between selegiline and P. ginseng extract has not been characterized. Our hypothesis is that the ginseng extract and selegiline produce pharmacokinetic interactions at certain doses. To investigate this hypothesis, a validated ultraperformance liquid chromatography−tandem mass spectrometry (UPLC−MS/MS) method was developed to monitor selegiline in rat plasma. Experimental rats were divided into groups treated with selegiline alone (10 mg/kg, i.v.; 30 mg/kg, p.o.), with the low-dose ginseng extract (1 g/kg, p.o., for 5 consecutive days) or with the high-dose ginseng extract (3 g/kg, p.o., for 5 consecutive days). The pharmacokinetic results demonstrated that the oral bioavailability of selegiline alone was approximately 18%; however, when rats were pretreated with low and high doses of the ginseng extract, the bioavailability of selegiline was 7.2 and 29%, respectively. These results suggested that the ginseng extract may produce a biphasic pharmacokinetic phenomenon. In summary, ginseng alters the oral bioavailability of selegiline, and these observations might provide preclinical information concerning the pharmacokinetic interactions between selegiline and herbal supplements.

Herb‐drug interactions: A short review on central and peripheral nervous system drugs

“…Nowadays, it is experimentally validated that some ginsenosides (Figure 5) display an anti‐depressant like action by activating complex cellular signalling pathways leading to the regulation of monoamine neurotransmitters, hypothalamic–pituitary–adrenal axis, neurotrophic factors and neurogenesis (Jin et al, 2019). Preliminary data, obtained while studying the potential herb–drug pharmacokinetic interaction of P. ginseng extract with selegiline in freely moving rats, demonstrated that ginseng extract may produce a biphasic pharmacokinetic phenomenon suggested to be mediated by a significantly enhancement of CYP1A2 activity and reduced CYP3A activity, both isoforms participate in the metabolism of selegiline (Yang et al, 2020).…”

Precision and Advanced Nano-Phytopharmaceuticals for Therapeutic Applications

“…Nonetheless, the dosage of ginseng extract, when co-administered with a synthetic drug (e.g. selegiline), determines the pharmacokinetics in the body: lower doses result in poorer bioavailability due to CYP1A2 induction, while higher concentrations cause inhibition of CYP3A4 and thus enhanced systemic exposure [63].…”

Metabolism-involved drug interactions with traditional Chinese medicines in cardiovascular diseases

“…In addition, it is worth noting that the inconsistencies in Ginseng-drug interactions between in vitro and in vivo results or between laboratory studies may be caused by many uncontrolled variables, such as dosing regimens, TCM cultivation conditions, and matrix differences. The dose-dependent biphasic effects of Ginseng may also be one of the reasons for the contradictory results [ 112 ].…”