Ginsenoside Rh2: A shining and potential natural product in the treatment of human nonmalignant and malignant diseases in the near future

Ginseng is well-known as one of the most valuable and commonly used Chinese medicines not only in ancient China but also worldwide including East, Russia, Southeast Asia, North America and some Western European countries. Ginsenosides, as one of the main high active components of Ginseng, have various pharmacological activities, such as anti-inflammatory, antianaphylaxis, anti-depression, and anticancer activities. Ginsenoside Rh2 (Rh2), one of the major bioactive ginsenosides in Panax ginseng, also exhibits versatile pharmacological activities, such as increasing non-specific resistance and specific immune response, improving cardiac function and fibrosis, anti-inflammatory effects and antitumor effects, which may serve as an excellent medicinal potential.As one of hundreds of ginsenosides being identified from ginseng, Rh2 exerts a markedly pharmacological effect on various diseases without severe toxicity, it has attracted many researchers 'attention. Although Rh2 plays important roles in some animal models and cell lines to simulate human diseases, its underlying molecular mechanisms have yet to be determined. During the past ten years, nearly 450 studies on Rh2 in the treatment of complex disease have been reported, however, up to now, no comprehensive reviews about the roles of Rh2 in animal models and cellular lines of human nonmalignant and malignant diseases have been conducted.We searched articles on ginsenoside-related diseases from December 2010 to February 2023 in peer-reviewed and nonclinical databases, which include Web of Science, Scopus, PubMed, China national knowledge internet and Medline, and using the following keywords: Ginsenoside Rh2, Human diseases, Cancer, Mechanisms, Chinese herbal medicine, Natural products and Signaling pathway.Therefore, in this review, we make a comprehensive summary on the roles of Rh2 and support the potential mechanisms of Rh2 according to the disease classification, including nonmalignant disease such as ulcerative colitis, neuropathic pain, Asthma, myocardial injury, depression and malignant disease such as breast cancer, colorectal cancer, hepatocellular carcinoma and gastric cancer. Finally, the combination therapy of Rh2 and other medications in human diseases are summarized, apart from that, there are other problems such as the bioavailability of oral administration Rh2 to be overcome in following research.These findings provide strong evidence that Ginsenoside Rh2 plays important roles in the treatment of nonmalignant and malignant diseases.