Ginseng Metabolites on Cancer Chemoprevention: An Angiogenesis Link?

Chong-Zhi Wang,Yi Cai,Chun-Su Yuan,Samantha Anderson

doi:10.3390/diseases3030193

Abstract

Cancer is a leading cause of death in the United States. Angiogenesis inhibitors have been introduced for the treatment of cancer. Based on the fact that many anticancer agents have been developed from botanical sources, there is a significant untapped resource to be found in natural products. American ginseng is a commonly used herbal medicine in the U.S., which possesses antioxidant properties. After oral ingestion, natural ginseng saponins are biotransformed to their metabolites by the enteric microbiome before being absorbed. The major metabolites, ginsenoside Rg3 and compound K, showed significant potent anticancer activity compared to that of their parent ginsenosides Rb1, Rc, and Rd. In this review, the molecular mechanisms of ginseng metabolites on cancer chemoprevention, especially apoptosis and angiogenic inhibition, are discussed. Ginseng gut microbiome metabolites showed significant anti-angiogenic effects on pulmonary, gastric and ovarian cancers. This review suggests that in addition to the chemopreventive effects of ginseng compounds, as angiogenic inhibitors, ginsenoside metabolites could be used in combination with other cancer chemotherapeutic agents in cancer management.

Highlights

Cancer is a leading cause of human death in the United States [1]
American ginseng as an example, we have summarized recent research progress on the anticancer activities of ginseng parent compounds and their intestinal microbiome metabolites, focusing on their angiogenesis inhibitory potentials
It is generally believed that the active compounds in Asian ginseng, notoginseng and American ginseng are triterpene glycosides or dammarane saponins, commonly referred to as ginseng saponins

Summary

Introduction

Cancer is a leading cause of human death in the United States [1]. The clinical management of cancer invariably involves diverse conventional modalities, including surgery, radiation, and chemotherapy [1,2]. Previous reports revealed that compound biotransformation resulted from reactions carried out by the enteric microbiome [17]. These studies involved monitoring compound metabolism during the ex vivo fecal incubation with a given compound [18], showing that orally ingested natural products can be biotransformed to their metabolites by microbiota in the gut. Information regarding the role of the enteric microbiome in botanical bioactivity is still limited and this situation obstructs the evaluation of natural products with anticancer potential. American ginseng as an example, we have summarized recent research progress on the anticancer activities of ginseng parent compounds and their intestinal microbiome metabolites, focusing on their angiogenesis inhibitory potentials. Molecular mechanisms involved in the ginseng metabolites’ actions, including those targeted on angiogenesis are discussed

American Ginseng is a Commonly Used Antioxidant Botanical

Biotransformation of American Ginseng Saponins

Effects of Ginsenoside Metabolites on Cancer Cell Death Induction

The Role of Ginsenoside Metabolites in Angiogenesis for Cancer Treatment

Findings

Conclusions