Beyond Traditional Use: The Scientific Evidence for the Role of Astragali radix in Organ Protection via Modulating Oxidative Stress, Cell Death, and Immune Responses

Astragali radix (AR) is a traditional Chinese herbal medicine derived from the roots of Astragalus membranaceus and A. mongholicus. AR exhibits a wide range of pharmacological activities, such as cardioprotective, hypoglycemic, antitumor, antiviral, and multi-organ restorative effects. Nearly 400 bioactive compounds have been identified in AR by phytochemical investigations, with astragalus polysaccharides (APS), astragalosides (I–IV), formononetin (FMN), and calycosin (CA) established as principal bioactive constituents. These components exhibit multifunctional mechanisms encompassing antioxidative stress, apoptotic suppression, autophagy regulation, anti-inflammation, and immune regulation, thereby exerting significant protective effects on critical organ systems such as the cardiovascular, renal, neural, hepatic, gastrointestinal, and immune systems. This review synthesized research over the past three decades, elucidating the organ protective mechanisms of AR through phytochemical profiling. Key findings demonstrated that FMN-mediated Nrf2 pathway activation could attenuate reactive oxygen species (ROS) generation, while astragaloside IV (AS-IV) could suppress endoplasmic reticulum stress by inactivating the PERK/ATF6/CHOP axis to ameliorate apoptosis. Additionally, comprehensive safety assessment and pharmacokinetic analysis also substantiated favorable bioavailability and toxicological profiles. To sum up, these findings provide a comprehensive theoretical basis and offer innovative strategies for preventing and treating complex diseases associated with multi-organ dysfunction, thereby facilitating future clinical applications.