The rise of dehydrated ginsenosides: phytochemistry and pharmacology

Plants of the Panax genus, such as P. ginseng, P. notoginseng, and P. quinquefolius, have been utilized for culinary and medicinal purposes for millennia. Their pharmacological effects are largely attributed to ginsenosides-unique compounds derived from the glycosylation of dammaranediol and dammaranetriol. Rare ginsenosides are dammarane-type triterpenoids that occur naturally at low abundance (typically < 0.1 %) and often exhibit stronger bioactivity than macro ginsenosides. Dehydrated ginsenosides (DHGs, e.g., ginsenosides Rk1, Rg5, and Rk2), characterized by a C‑20/21 or C‑20/22 double bond on the dammarane side chain, constitute a subgroup of rare ginsenosides that are scarce or absent in native Panax species but enriched in processed products. Structure-activity relationship studies indicate that replacing the C‑20 hydroxyl with a double bond enhances bioactive properties relative to precursor ginsenosides. Despite this promise, an integrative and comprehensive review of DHGs has been lacking.

This review systematically summarizes the current knowledge on DHGs, covering their chemical structure characteristics, preparation strategies, pharmacological activities with underlying mechanisms, and structure-activity relationships, providing new insights into their therapeutic potential and future applications.

To date, a total of 92 DHGs with diverse skeletons have been identified, including Δ20-PPD type DHGs (e.g., Rk1, Rg5, Rk2, and Rh3), Δ20-PPT type DHGs (e.g., Rk3, Rh4, Rg6, and F4) and their side chain derivatives. Current preparation methods for DHGs encompass physical, chemical, and biological transformations, chemical synthesis, and batch-processing techniques. DHGs demonstrate a broad spectrum of pharmacological activities-such as anti-tumor, anti-diabetic, neuroprotective, cardiovascular protective, and antimicrobial effects-often surpassing their precursor ginsenosides. This review also explores the structure-activity relationships of DHGs to guide the development of more effective derivatives.