Preliminary Evaluation of the Interactions of Panax ginseng and Salvia miltiorrhiza Bunge with 5-Fluorouracil on Pharmacokinetics in Rats and Pharmacodynamics in Human Cells

Abstract

An increasing number of cancer patients are using herbs in combination with conventional chemotherapeutic treatment. It is therefore important to study the potential consequences of the interactions between herbs and anticancer drugs. The effects of extracts from Panax ginseng (PGS) and Salvia miltiorrhiza Bunge (SMB) on the pharmacokinetics of 5-fluorouracil (5-FU) were performed in vivo and detected by high performance liquid chromatography (HPLC), while, an ATP assay was used to study the pharmacodynamic interactions in vitro. The results of the pharmacokinetic experiments showed a significant increase in the elimination half-life (t1/2(k e )) of 5-FU in the PGS-pretreated group and in the area under the curve (AUC) in the SMB-pretreated group compared with the control group. However, after SMB pretreatment, weight loss was observed in rats. The results of pharmacodynamic experiments showed that neither PGS nor SMB, when used alone, directly inhibited cancer cell growth at 0.1-100 μg/ml. Moreover, PGS had a synergistic cytotoxic effect with 5-FU on human gastric cancer cells but not on normal gastric cells. The results imply that when combined with 5-FU, PGS may be a better candidate for further study. This study might provide insights for the selection of herbal-chemotherapy agent interactions.

Ginseng and Anticancer Drug Combination to Improve Cancer Chemotherapy: A Critical Review

“…Furthermore, the synergistic inhibitory effect of Panax ginseng when combined with 5-FU has been observed in human gastric cancer cell line BGC823 [16]. This appears to involve NO which has been found to directly suppress the growth of BGC823 cells by inducing G0/G1 phase arrest through the regulation of Akt signaling pathway.…”

“…This appears to involve NO which has been found to directly suppress the growth of BGC823 cells by inducing G0/G1 phase arrest through the regulation of Akt signaling pathway. Ginsenosides may increase NO production by inducing endothelial nitric oxide synthase (eNOS) phosphorylation via the ER-mediated PI3-kinase/Akt pathway [16]. …”

“…After pretreatment with 3.0 mg/kg Panax ginseng extract orally twice daily for ten consecutive days, the elimination half-life of 5-FU has been shown to significantly increase by approximately 58.8% (79.17 versus 125.72). The increase in t 1/2 caused by Panax ginseng extract can result in a higher drug exposure of 5-FU, which may lead to a longer drug effect [16]. The specific mechanism however is not known.…”

“…Ginseng extract may decrease the side effect of weight loss from anticancer drugs by increasing the protein and RNA contents of muscles and liver in rats [11, 16, 31, 36, 62]. In addition, Ge and coworkers have found the effect of Shengmai (Chinese herbal preparation consisting of red ginseng, lilyturf root, and magnolia vine fruit) to be capable of protecting diaphragm muscles from doxorubicin induced toxicity which appears to be correlated with a decrease in expression of iNOS and lipid peroxidation [39].…”

Microcrystalline Preparation of Akebia Saponin D for its Bioavailability Enhancement in Rats

“…The area under the ASD plasma concentration-time curve from 0 to 20 h (AUC 0À20h ) and mean residence time (MRT) were calculated using noncompartmental analysis (BAPP, Version 2.0, Centre of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Republic of China). The maximal plasma concentration of drug (C max ) and the time to reach maximum plasma concentration ðT max Þ were directly obtained from plasma data (Gu et al, 2013;Su et al, 2013). In order to compare the absorption of different polymorphs in vivo, the rats were administered with capsules, but other experimental procedures were consistent with the literature .…”