Chong-Zhi Wang

Ginsenosides from American ginseng: Chemical and pharmacological diversity

Ginseng occupies a prominent position in the list of best-selling natural products in the world. Compared to the long history of use and widespread research on Asian ginseng, the study of American ginseng is relatively limited. In the past decade, some promising advances have been achieved in understanding the chemistry, pharmacology and structure-function relationship of American ginseng. To date, there is no systematic review of American ginseng. In this review, the different structures of the ginsenosides in American ginseng are described, including naturally occurring compounds and those resulting from steaming or biotransformation. Preclinical and clinical studies published in the past decade are also discussed. Highlighted are the chemical and pharmacological diversity and potential structural-activity relationship of ginsenosides. The goal is that this article is a useful reference to chemists and biologists researching American ginseng, and will open the door to agents in drug discovery.

Isolation and analysis of ginseng: advances and challenges

Ginseng occupies a prominent position in the list of best-selling natural products in the world. Because of its complex constituents, multidisciplinary techniques are needed to validate the analytical methods that support ginsengs use worldwide. In the past decade, rapid development of technology has advanced many aspects of ginseng research. The aim of this review is to illustrate the recent advances in the isolation and analysis of ginseng, and to highlight new applications and challenges. Emphasis is placed on recent trends and emerging techniques.

American ginseng: potential structure-function relationship in cancer chemoprevention.

Ginseng has a prominent position on the list of best-selling herbal products in the world, and its main active constituents are thought to be ginsenosides. Compared with the long history of use and widespread research on Asian ginseng, studies of American ginseng are relatively limited, especially regarding cancer chemoprevention. In recent studies of American ginseng, steaming or heating altered the ginsenoside profile and thereby increased anticancer effects. Yet the ginsenoside structures and their activities have not been systematically elucidated. In this commentary, we introduce the different ginsenosides in American ginseng, both the naturally occurring compounds and those resulting from steaming or biotransformation. We briefly review American ginsengs reported anticancer effects and their mechanisms of action, and explore the possible structural-function relationship with a focus on sugar molecules, hydroxyl groups and stereoselectivity in ginsenosides. Understanding these relationships may produce insights into chemical and pharmacological approaches for enhancing the chemopreventive effects of ginsenoside and for developing novel anticancer agents.

Epigallocatechin Gallate (EGCG) Is the Most Effective Cancer Chemopreventive Polyphenol in Green Tea

Green tea is a popular drink consumed daily by millions of people around the world. Previous studies have shown that some polyphenol compounds from green tea possess anticancer activities. However, systemic evaluation was limited. In this study, we determined the cancer chemopreventive potentials of 10 representative polyphenols (caffeic acid, CA; gallic acid, GA; catechin, C; epicatechin, EC; gallocatechin, GC; catechin gallate, CG; gallocatechin gallate, GCG; epicatechin gallate, ECG; epigallocatechin, EGC; and epigallocatechin gallate, EGCG), and explored their structure-activity relationship. The effect of the 10 polyphenol compounds on the proliferation of HCT-116 and SW-480 human colorectal cancer cells was evaluated using an MTS assay. Cell cycle distribution and apoptotic effects were analyzed by flow cytometry after staining with propidium iodide (PI)/RNase or annexin V/PI. Among the 10 polyphenols, EGCG showed the most potent antiproliferative effects, and significantly induced cell cycle arrest in the G1 phase and cell apoptosis. When the relationship between chemical structure and anticancer activity was examined, C and EC did not show antiproliferative effects, and GA showed some antiproliferative effects. When C and EC esterified with GA to produce CG and ECG, the antiproliferative effects were increased significantly. A similar relationship was found between EGC and EGCG. The gallic acid group significantly enhanced catechin’s anticancer potential. This property could be utilized in future semi-synthesis of flavonoid derivatives to develop novel anticancer agents.

Ginsenoside Rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53

Ginsenosides are the main bioactive components in American ginseng, a commonly used herb. In this study, we showed that the ginsenoside Rh2 exhibited significantly more potent cell death activity than the ginsenoside Rg3 in HCT116 and SW480 colorectal cancer cells. Cell death induced by Rh2 is mediated in part by the caspase-dependent apoptosis and in part by the caspase-independent paraptosis, a type of cell death that is characterized by the accumulation of cytoplasmic vacuoles. Treatment of cells with Rh2 activated the p53 pathway and significantly increased the levels of the pro-apoptotic regulator, Bax, while decreasing the levels of anti-apoptosis regulator Bcl-2. Removal of p53 significantly blocked Rh2-induced cell death as well as vacuole formation, suggesting that both types of cell death induced by Rh2 are mediated by p53 activity. Furthermore, we show that Rh2 increased ROS levels and activated the NF-κB survival pathway. Blockage of ROS by NAC or catalase inhibited the activation of NF-κB signaling and enhanced Rh2-induced cell death, suggesting that the anti-cancer effect of Rh2 can be enhanced by antioxidants.

Phytochemical and analytical studies of Panax notoginseng (Burk.) F.H. Chen

Panax notoginseng (Burk.) F.H. Chen is distributed throughout the southwest of China, Burma and Nepal. The root of this plant, called notoginseng or sanchi, has a long history of use as a remedy in Oriental traditional medicine. Modern studies have found that extracts and compounds from notoginseng exert various physiological effects. The active constituents are mainly recognized as saponins. In this review, we summarized the discovery and analysis of chemical constituents in notoginseng. Fifty-six saponins from notoginseng were isolated and elucidated. All of them are dammarane saponins, 35 of which can be classified as belonging to the protopanaxadiols group, and 21 as belonging to the protopanaxatriols group. Evidence from phytochemical studies on notoginseng demonstrated that no oleanane-type saponin, which exists in Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius), was found. Other types of compounds such as non-protein amino acids, polyacetylenes, phytosterols, flavonoids, and polysaccharides, many of which have pharmacological activities, were also isolated from notoginseng. Analytical studies on notoginseng were carried out based on botanical and phytochemical advances. In the qualitative studies, identification of the herbal materials and extracts was the main objective. The utilization of high-performance liquid chromatography (HPLC) fingerprint and molecular biological methods made the identification accurate and efficient. Spectral, chromatographic and immunoassay methods were used for the quantitative analysis. HPLC methods are the main authority regarding the determination of saponins and other types of constituents. The chromatographic conditions and detectors employed in the HPLC are discussed.

Commonly Used Antioxidant Botanicals: Active Constituents and their Potential Role in Cardiovascular Illness

Cardiovascular disease continues to be the leading cause of death in the US. Recent studies found that reactive oxygen species (ROS) have been incriminated in the pathogenesis of both acute and chronic heart disease. Many botanicals possess antioxidant properties, and these herbal antioxidants may protect against cardiovascular diseases by contributing to the total antioxidant defense system of the human body. In this article, we reviewed the antioxidant components and properties of four putative antioxidant botanicals (i.e., grape seeds, green tea, Scutellaria baicalensis, and American ginseng), and their potential role in treating cardiovascular illness. The antioxidant activities of the herbal active constituents, and the relationship between their chemical structures and biological functions were also discussed. Further investigations are needed on the mechanisms of action of these botanicals as they affect salient cellular and molecular pathways involved in major diseases. Data obtained from future studies will have the potential for translation into practical benefits for human health.

Potential Role of Ginseng in the Treatment of Colorectal Cancer

Colorectal cancer remains one of the most prevalent cancer and a leading cause of cancer related death in the US. Many currently used chemotherapeutic agents are derived from botanicals. Identifying herbal sources, including those from ginseng family, to develop better anti-cancer therapies remains an essential step in advancing the treatment of the cancer. In this article, potential roles of ginseng herbs, especially American ginseng and notoginseng, in colorectal cancer therapeutics are presented. The major pharmacologically active constituents of ginsengs are ginsenosides, which can be mainly classified as protopanaxadiol and protopanaxatriol groups. Structure-activity relationship between their chemical structures and pharmacological activities are discussed. In addition, various steaming temperature and time treatment of the ginseng herbs can change ginsenoside profiles, and enhance their anti-cancer activities. This heat treatment process may increase the role of ginseng in treating colorectal cancer.

Biotransformation and metabolic profile of American ginseng saponins with human intestinal microflora by liquid chromatography quadrupole time-of-flight mass spectrometry.

American ginseng is a widely used natural product. Ginseng products are usually taken orally, and human intestinal microflora may metabolize ginsenosides. Existing publications report the metabolite fates of ginsenosides. However, investigations on the comprehensive metabolic profile of American ginseng extract are absent because of the chemical complexity and limitation of analytical methods. In this work, we studied the biotransformation and metabolic profile of American ginseng extract by human intestinal microflora. Human fecal microflora was prepared from a healthy Chinese man and then anaerobically incubated with American ginseng sample at 37 °C for 24 h. A rapid and simple liquid-liquid extraction method was used for sample pretreatment. A highly sensitive and selective liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) method was used to characterize ginsenosides and related metabolites in the reaction samples. The LC-Q-TOF-MS provides superior data quality and advanced analytical capabilities for profiling, identifying, and characterizing complex metabolites in matrix-based biological samples. A total of 25 metabolites were detected, 13 of which were undoubtedly assigned by comparison with reference compounds, and 12 others were tentatively identified. The three most abundant metabolites are 20S-ginsenoside Rg3, ginsenoside F2 and compound K. The main metabolic pathways of ginseng saponins are deglycosylation reactions by intestinal microflora through stepwise cleavage of sugar moieties. Subsequent dehydration reactions also occur. Protopanaxadiol- and oleanane-type triterpenoids are easy to metabolize. The intestinal microbiota may play an important role in mediating the metabolism bioactivity of American ginseng.

Ginsenoside Rg3 inhibits colorectal tumor growth through the down-regulation of Wnt/ß-catenin signaling

Colorectal cancer (CRC) is one of the most common and deadly malignancies in the world. Most CRCs are initiated by aberrant activation of the Wnt/ß-catenin signaling pathway. Despite the advances in its early diagnosis, optimized surgical approaches, and chemotherapies, the clinical management of advanced CRC requires effective adjuvant agents. Ginsenoside Rg3 is a single compound isolated from American ginseng (Panax quinquefolius L., Araliaceae) and Asian ginseng (Panax ginseng C. A. Meyer). We investigated the anticancer activity of Rg3 on colon cancer cells and its potential molecular mechanism behind Rg3s anticancer activity. We found that Rg3 inhibits cell proliferation and viability of cancer cells in vitro. This inhibitory effect of Rg3 is, at least in part, mediated by blocking nuclear translocation of the ß-catenin protein and hence inhibiting ß-catenin/Tcf transcriptional activity. Allelic deletion of the oncogenic ß-catenin in HCT116 cells renders the cells more sensitive to Rg3-induced growth inhibition. Using the xenograft tumor model of human colon cancer, we have demonstrated that Rg3 effectively inhibits the growth of tumors derived from the human colon cancer cell line HCT116. Histologic examination revealed that Rg3 inhibits cancer cell proliferation, decreases PNCA expression and diminishes nuclear staining intensity of ß-catenin. Taken together, our results strongly suggest that the anticancer activity of Rg3 may be in part caused by blocking the nuclear translocation of ß-catenin in colon cancer cells. This line of investigation may lead to the development of novel therapies in which Rg3 can be used as an effective adjuvant agent for the clinical management of colorectal cancers.