Ginsenoside Rg5 as an anticancer drug: a comprehensive review on mechanisms, structure-activity relationship, and prospects for clinical advancement.

Cancer remains one of the leading causes of death in the world. Despite the considerable success of conventional treatment strategies, the incidence and mortality rates are still high, making developing new effective anticancer therapies an urgent priority. Ginsenoside Rg5 (Rg5) is a minor ginsenoside constituent obtained exclusively from ginseng species and is known for its broad spectrum of pharmacological activities. This article aimed to comprehensively review the anticancer properties of Rg5, focusing on action mechanisms, structure-activity relationship (SAR), and pharmacokinetics attributes. The in vitro and in vivo activities of Rg5 have been proven against several cancer types, such as breast, liver, lung, bone, and gastrointestinal (GI) cancers. The modulation of multiple signaling pathways critical for cancer growth and survival mediates these activities. Nevertheless, human clinical studies of Rg5 have not been addressed before, and there is still considerable ambiguity regarding its pharmacokinetics properties. In addition, a significant shortage in the structure-activity relationship (SAR) of Rg5 has been identified. Therefore, future efforts should focus on further optimization by performing extensive SAR studies to uncover the structural features essential for the potent anticancer activity of Rg5. Thus, this review highlights the value of Rg5 as a potential anticancer drug candidate and identifies the research areas requiring more investigation.