Ginsenoside Rh₂ Enhances Antitumour Activity and Decreases Genotoxic Effect of Cyclophosphamide

Abstract

Ginsenoside Rh 2 , a panoxadiol saponins, possesses various antitumour properties. Cyclophosphamide, an alkylating agent, has been shown to possess various genotoxic and carcinogenic effects, however, it is still used extensively as an antitumour agent and immunosuppressant in the clinic. Previous reports reveal that cyclophosphamide is involved in some secondary neoplasmas. In this study, the antitumour activity and genotoxic effect of oral intake of ginsenoside Rh 2 combined with intraperitoneal injection of cyclophosphamide was investigated. Meanwhile, C57BL/6 mice bearing B16 melanoma and Lewis lung carcinoma cells were respectively used to estimate the antitumour activity in vivo. The clastogenic activity in bone marrow polychromatic erythrocytes was assayed by frequency of micronucleus. The DNA damage in peripheral white blood cells was assayed by single cell gel electrophoresis as well. The results indicated that oral administration of Rh 2 (5, 10 and 20 mg/kg body weight) alone has no obvious antitumour activity and genotoxic effect in mice, while Rh 2 synergistically enhanced the antitumour activity of cyclophosphamide (40 mg/kg body weight) in a dose-dependent manner. Rh 2 decreased the micronucleus formation in polychromatic erythrocytes and DNA strand breaks in white blood cells in a dose-dependent way. Our results suggest that ginsenoside Rh 2 is able to enhance the antitumour activity and decrease the genotoxic effect of cyclophosphamide.

20(S)-Ginsenoside Rh2 Noncompetitively Inhibits P-Glycoprotein In Vitro and In Vivo: A Case for Herb-Drug Interactions

“…On the other hand, a DDI sometimes might benefit the patients by producing an enhanced effect from increased systemic levels of the target drug. The synergistic effect of Rh2 on anticancer therapies has already been reported (Jia et al, 2004;Wang et al, 2006;Xie et al, 2006). In the present study, the pharmacokinetic basis for this synergism was elucidated.…”

Protection by Panax ginseng C.A. Meyer against the genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster

“…Ginsan, which itself is not mutagenic, decreases the frequency of micronucleated polychromatic erythrocytes induced by gamma radiation in bone marrow cells of C57BL/6 male mice (Ivanova et al, 2006). Similarly, the ginsenoside Rh 2 enhances the antitumor activity and decreases the genotoxicity of cyclophosphamide in mice (Wang et al, 2006). Ginseng has powerful antioxidant (Cho et al, 2008) and antimutagenic (Geetha et al, 2006;Ivanova et al, 2006) properties, although the mechanisms of these protective effects remain to be elucidated.…”

Enhancement of Oral Bioavailability of 20(S)-Ginsenoside Rh2 through Improved Understanding of Its Absorption and Efflux Mechanisms

“…Ginsenoside Rh2s is one of the most studied ginsenosides because it displays potent anticancer activity, especially in lung cancer cell lines (Cheng et al, 2005;Wang et al, 2006). A 9-week animal study also showed that Rh2s had a tendency to decrease lung tumor incidence in mice after its oral consumption (Yun, 2003).…”