Panax notoginseng saponins against ischemic stroke: From molecule to clinic

Ischemic stroke is a global public health problem with limited effective therapeutic options. Panax notoginseng saponins (PNS), the active extract derived from the well-known medicinal material called San-Qi in Chinese, has been widely used in the intervention of ischemic stroke.

This systematic literature review aims to integrate the evidence for PNS against ischemic stroke and proposes future research directions.

With "Panax notoginseng saponins" and "ischemic stroke" as keywords, we conducted systemic literature search across eight databases update to May 2025, including Scopus, PubMed, Embase, Web of Science, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Database, the WanFang Database, and the Chinese Science and Technology Journals Database. Eligible studies focused on the phytochemical profiles, pharmacokinetic characteristics, pharmacological mechanisms, and clinical applications were integrated in this review.

More than 200 saponins have been identified from PNS, with ginsenoside Rg₁, Rb₁, Rd, Re and notoginsenoside R₁ accounts for 90 % of the saponins content. Extensive degradation in digestive tract and poor intestinal absorption are the primary reasons for low bioavailability of PNS. Pharmacological evidences suggest that PNS can regulate the oxidative stress, inflammatory responses, apoptosis, ferroptosis, pyroptosis, angiogenesis, and neurogenesis in ischemic stroke. It can support the treatment of ischemic stroke by lowering the neurological deficit score, inhibiting the inflammatory level, improving cerebral hemorheology, and promoting neurological function recovery. However, there are still some flaws in the research and application of PNS, including incomprehensive quality control, low bioavailability and the lack of high-quality clinical evidence (e.g. relatively small sample size and non-standardized drug combination).

Existing experimental studies and clinical applications have indicated the therapeutic potential of PNS against ischemic stroke, but high-quality clinical trails are required for validation. Future studies should focus on the overall quality control involved rare ginsenosides, improvement of bioavailability, and high-quality clinical evidence.