Decoding Ginsenosides: The Structural and Therapeutic Core of Ginseng

Ginseng (Panax ginseng C.A. Meyer), a highly valued traditional herb in traditional medicine, exerts its major health benefits through ginsenosides — its core bioactive triterpenoid saponins. With a characteristic steroidal structure, ginsenosides interact with cell membranes, receptors, and signaling cascades to produce diverse pharmacological effects. This review summarizes the pharmacological properties, molecular mechanisms, structure-activity relationships, and advanced delivery strategies of key ginsenosides, including Rb1, Rg1, Rg3, Rh2, compound K (CK), and Rd. These compounds exhibit potent anti-oxidant, anti-inflammatory, cardioprotective, neuroprotective, antidiabetic, anti-obesity, anticancer, and anti-aging activities, acting through well-characterized pathways such as PI3K/Akt, Nrf2/ARE, AMPK, MAPK, and NF-[Formula: see text]B. Notably, their bioactivity is strongly governed by the number and position of sugar moieties: ginsenosides with fewer glycosyl groups (e.g., Rg3, Rh2, and CK) generally display higher potency in vitro and in vivo, whereas multi-glycosylated forms like Rb1 and Rc show milder effects. Despite their promising efficacy, poor oral bioavailability, rapid metabolism, and nonspecific tissue distribution remain major hurdles for clinical translation. To overcome these limitations, recent nanotechnology-based delivery systems have been developed, including liposomes, polymeric nanoparticles, inorganic nanocarriers, self-assembled micelles, and exosome-based platforms, to enhance solubility, prolong circulation, enable targeted delivery, and improve therapeutic outcomes. By integrating current knowledge on ginsenoside pharmacology and formulation engineering, this work supports their translational research and clinical application as multi-target agents for treating inflammatory, metabolic, cardiovascular, neurodegenerative, and malignant disorders.