Ginseng is an herbal medicine used worldwide. It is reported to have a wide range of pharmacological activities because of a diversified group of steroidal saponins called ginsenosides. Compared to extensive pharmacological studies of ginseng, the pharmacokinetics, especially the metabolism of this herb, has received less attention. In this article we review the known pharmacokinetic data on ginseng. Understanding ginseng's pharmacokinetics may reduce the potential for interactions in patients who use both ginseng and prescription medications.
BACKGROUND: Western diets increase colon cancer risk. Epidemiological evidence and experimental studies suggest that ginseng can inhibit colon cancer development. In this study we asked if ginseng could inhibit Western diet (20% fat) promoted colonic tumorigenesis and if compound K, a microbial metabolite of ginseng could suppress colon cancer xenograft growth. METHODS: Mice were initiated with azoxymethane (AOM) and, two weeks later fed a Western diet (WD, 20% fat) alone, or WD supplemented with 250-ppm ginseng.
Intestinal microbiota contribute to diverse mammalian processes including the metabolic functions of drugs. It is a potential new territory for drug targeting, especially for dietary herbal products. Because most herbal medicines are orally administered, the chemical profile and corresponding bioactivities of herbal medicines may be altered by intestinal microbiota. Ginseng is one of the most commonly used herbs and it is an attractive natural product to study its effect in the body.
American ginseng is a commonly used herbal medicine in the United States. When ginseng is taken orally, its active components, ginsenosides, are reportedly biotransformed by intestinal microbiota. Previous pharmacokinetic evaluations of ginseng in humans have focused on its parent constituents. However, the metabolites, especially those transformed by intestinal microbiota, have not been carefully studied.
Ulcerative colitis is a chronic inflammatory condition associated with a high colon cancer risk. We have previously reported that American ginseng extract significantly reduced the inflammatory parameters of chemically induced colitis. The aim of this study was to further delineate the components of American ginseng that suppress colitis and prevent colon cancer. Among five different fractions of American ginseng (butanol, hexane, ethylacetate, dichloromethane, and water), a hexane fraction has particularly potent antioxidant and proapoptotic properties.
OBJECTIVES: Panaxadiol is a purified sapogenin of ginseng saponins that exhibits anticancer activity. Irinotecan is a second-line anticancer drug, but clinical treatment with irinotecan is limited due to its side effects. In this study, we have investigated the possible synergistic anticancer effects of panaxadiol and irinotecan on human colorectal cancer cells and explored the potential role of apoptosis in their synergistic activity. KEY FINDINGS: The combination of panaxadiol and irinotecan significantly enhanced antiproliferative effects in HCT-116 cells (P< 0.05).
Drug Metabolism and Disposition: The Biological Fate of Chemicals
Ginsenosides are hydrolyzed extensively by gut microflora after oral administration, and their metabolites are pharmacologically active against lung cancer cells. In this study, we measured the metabolism of various ginsenosides by gut microflora and determined the mechanisms responsible for the observed pharmacokinetic behaviors of its active metabolite, Compound K (C-K).
Ulcerative colitis (UC) is debilitating and carries a high colon cancer risk. Apoptosis of inflammatory cells is a key mechanism regulating UC. We have recently shown that American ginseng (AG), and to a greater extent, a Hexane fraction of AG (HAG) can cause apoptosis and suppress mouse colitis through a p53-mediated mechanism. Here, we tested the hypothesis that HAG suppresses colitis through a p53 mechanism. We found only a limited impact of p53 in the ability of HAG to induce inflammatory cell apoptosis and suppress mouse colitis in vitro and in vivo.
ETHNOPHARMCOLOGICAL RELEVANCE: Ginseng, a folk medicine which has been used for thousands of years in Asia, has been promoted for the treatment or prevention of health problems including cardiovascular disease. However, the molecular mechanism of ginseng-induced cardiovascular protection is unclear. Thus, we investigated signaling mechanism by which American ginseng inhibits vascular smooth muscle cell (VSMC) proliferation, a key feature of diverse vascular disease.
BACKGROUND: Protopanaxadiol (PPD) is a triterpenoid that can be prepared from steamed ginseng. PPD possesses anticancer potential via caspase-dependent apoptosis. Whether paraptosis, a type of the caspase-independent cell death, is also induced by PPD has not been evaluated. METHODS: Cell death, the cell cycle and intracellular reactive oxygen species (ROS) were analyzed by flow cytometry after staining with annexin V/PI, PI/RNase or H2DCFDA. We observed morphological changes by crystal violet staining assay. Mitochondrial swelling was measured by ultraviolet-visible spectrophotometry.