Extraction, preparation, pharmacological activities, and potential applications of ginsenosides Rk1 and Rg5

Panax species (Panax ginseng, Panax quinquefolius L., and Panax notoginseng) are globally recognized as valuable medicinal and dietary resources with a long history of use in traditional medicine. Ginsenosides are their primary active constituents, among which rare ginsenosides, particularly Rk1 and Rg5, exhibit superior physiological activities-including antitumour, anti-inflammatory, and immunomodulatory effects-compared to common ginsenosides. However, their industrial application is hindered by low natural abundance, structural complexity, and challenges in sustainable production.

This review systematically summarizes recent advances in rare ginsenosides Rk1 and Rg5, covering their natural sources, extraction and processing techniques, structural characteristics, pharmacological mechanisms, and potential applications in functional foods and nutraceuticals. By consolidating existing evidence, this work aims to bridge the gap between preclinical research and clinical translation, facilitating their broader utilization in healthcare and nutrition.

A comprehensive literature search was conducted using PubMed, Web of Science, and other databases for English publications from March 2005 to March 2025. Keywords included "rare ginsenosides," "Rk1," "Rg5," "pharmacological effects," and "biosynthesis." Additionally, network pharmacology and molecular docking techniques were employed to predict the potential anticancer and reproductive protective effects of Rk1 and Rg5.

As representative rare ginsenosides, Rk1 and Rg5 exhibit significantly superior biological activities compared to common saponin components such as Rb1 and Rg1. This advantage primarily stems from their unique structural characteristics: a reduction in the number of glycosyl groups and decreased polarity during thermal processing, which markedly enhance cell membrane permeability and oral bioavailability, thereby improving in vivo absorption and tissue distribution. In various pharmacological models, Rk1 and Rg5 demonstrate stronger anti-tumor, antibacterial, anti-inflammatory, and neuroprotective effects. Currently, the production of Rk1 and Rg5 mainly relies on chemical and physical transformation methods, while emerging technologies-such as artificial intelligence-assisted biotransformation and synthetic biology strategies-offer new avenues for large-scale, high-efficiency preparation. These compounds show broad therapeutic potential in oncology, metabolic diseases, neuroprotection, and cardiovascular health. Through network pharmacology and molecular docking analyses, key target proteins have been identified, providing a theoretical basis for subsequent mechanistic studies and application development.

Rare ginsenosides Rk1 and Rg5 represent promising candidates for next-generation nutraceuticals and therapeutics. Future research should prioritize optimizing extraction protocols, clarifying pharmacokinetic profiles, and conducting rigorous clinical trials to validate their efficacy. Addressing these challenges will unlock their full potential in meeting global health demands.