Introduction: To investigate the neuroprotective mechanisms of Glycyrrhiza glabra and its active components against Cerebral Ischemia-Reperfusion Injury (CI/RI). Method: In databases such as PubMed, Web of Science, CNKI, Wanfang, etc., keywords related to CIRI, medicinal plant Glycyrrhiza glabra, glycyrrhizic acid, glycyrrhetinic acid, glycyrrhetin, Isoliquiritigenin, Liquiritin, and molecular mechanism were searched. By systematically reviewing the existing research evidence, the mechanisms underlying the neuroprotective effects of Glycyrrhiza glabra and its active components in CI/RI were summarized. Results: Glycyrrhiza glabra active components exert neuroprotective effects through multiple pathways: (1) activating Nrf2/ARE and other antioxidant pathways to alleviate oxidative stress; (2) inhibiting HMGB1/TLR4/NF-κB and other inflammatory signaling pathways to reduce neuroinflammation; (3) antagonizing NMDA receptors to alleviate excitotoxicity and related mitochondrial fragmentation; (4) regulating the Bcl-2/Bax ratio to inhibit mitochondrial apoptosis pathways and promoting cell survival through the PI3K/Akt signaling; (5) regulating JAK2/STAT3, AMPK/mTOR, and PINK1/Parkin pathways to affect autophagy processes; (6) protecting tight junction proteins to maintain the integrity of the blood-brain barrier. Discussion: This review correlates the traditional therapeutic effects of Glycyrrhiza glabra with its modern multi-target neuroprotective mechanisms, thereby laying a crucial foundation for the clinical management of ischemic brain injury and the development of relevant innovative pharmaceuticals. Nevertheless, given that the current evidence is predominantly derived from preclinical investigations, its clinical translation remains encumbered by bottlenecks. Further verification is required regarding its direct molecular targets, pharmacokinetic profiles, and long-term safety profiles. Conclusion: Glycyrrhiza glabra and its active components exert neuroprotection in CI/RI through multi-target mechanisms.
Huang et al. (Fri,) studied this question.