Pharmacological mechanisms and drug delivery systems of ginsenoside Rg3: A comprehensive review

Ginsenoside Rg3, as one of the major active components of Panax ginseng, exhibits significant anti-tumor, anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, wound healing and immunomodulatory pharmacological effects and has been developed as an adjuvant therapy in clinical practice. However, its poor water solubility and low permeability result in limited bioavailability, restricting its clinical application. This review systematically summarizes the pharmacological mechanisms of ginsenoside Rg3, including its anti-tumor effects through multiple signaling pathways that inhibit cancer cell proliferation, induce apoptosis, and suppress tumor angiogenesis; anti-inflammatory properties via the inhibition of NF-κB and related factors; antioxidant effects by increasing antioxidant enzyme levels and regulating the Nrf2 pathway; antidiabetic effects via the promotion of insulin secretion by inhibiting the MAPK pathway; hepatoprotective effects via the attenuation of hepatic inflammation through suppressing NF-κB phosphorylation; wound-healing-promoting effects via modulating the TGF-β/SMAD signaling pathway, and immunomodulatory activities through immune cell regulation and inhibition of PD-L1 glycosylation. Additionally, this review discusses the pharmacokinetic properties of Rg3, such as rapid oral absorption but low plasma concentration and bioavailability. Furthermore, this review highlights various drug delivery systems, including liposomes, solid dispersions, cyclodextrin inclusion complexes, microspheres, electrospun nanofiber membranes, hydrogels, nanoparticles, micelles, and microneedles, which have been developed to improve its physicochemical properties and enhance its therapeutic efficacy. By systematically summarizing the pharmacological mechanisms and formulation optimization strategies of Rg3, this review provides theoretical insights and technical support for future research and clinical translation.