From medicinal herb to neuroprotective candidate: A review of curculigoside's potential in central nervous system...

Central nervous system disorders represent a major global cause of mortality and disability, with limited effective treatments available. Traditional Chinese Medicine theory posits a close link between kidney and brain function. Curculigoside, the primary bioactive phenolic glycoside and chemical marker of the kidney-tonifying herb Curculigo orchioides Gaertn, can cross the blood-brain barrier and demonstrates neuroprotective potential. However, to date, no comprehensive review has summarized its effects on central nervous system disorders. To our knowledge, this is the first comprehensive review to summarize and critically evaluate the therapeutic potential and mechanisms of curculigoside across a wide spectrum of central nervous system disorders.

This study aimed to summarize the therapeutic effects and underlying mechanisms of curculigoside against various central nervous system disorders, evaluate its clinical translational potential, and provide new insights and strategies for clinical treatment.

This study comprehensively searched PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure, and Wanfang Database for studies published before 31 May 2025.

Studies demonstrate curculigoside's efficacy in models of Alzheimer's disease, post-traumatic stress disorder, major depressive disorder, cerebral ischemic stroke, post-stroke depression, perioperative neurocognitive disorders, vascular dementia, and spinal cord injury. Its multifaceted mechanisms include enhancing neurotransmitter systems, reducing neurotoxic proteins, improving synaptic plasticity, and exerting anti-apoptotic, anti-inflammatory, antioxidant, and anti-ferroptotic effects, alongside promoting mitophagy, angiogenesis, oxidative phosphorylation, and neurogenesis/neural regeneration. Collectively, this evidence positions curculigoside as a multi-target neuroprotective agent with promising development prospects; however, its translational potential depends on future breakthroughs in addressing key challenges, including the conduct of large-scale clinical studies to verify its efficacy and safety, a deeper elucidation of its pharmacological mechanisms and toxicological profile, and the development of innovative strategies to improve its bioavailability, blood-brain barrier penetration, and retention in the brain.