Phthalide extract from stems and leaves of Ligusticum chuanxiong attenuates cerebral I/R injury via CaSR-mediated NLRP3 inflammasome suppression

文献类型： 外文期刊

第一作者： Wu, Jing

作者： Wu, Jing;Li, Chunrong;Liao, Qing;Chu, Tianzhe;Zhang, Dandan;Peng, Cheng;Tan, Yuzhu;Wu, Jing;Li, Gang;Wang, Li;Han, Xiaoyu

作者机构：

关键词： Ligusticum chuanxiong; Phthalide; Ischemic stroke; Calcium-sensing receptor; NLRP3 inflammasome

期刊名称：JOURNAL OF ETHNOPHARMACOLOGY （ 影响因子：5.4； 五年影响因子：5.4 ）

ISSN： 0378-8741

年卷期： 2025 年 351 卷

页码：

收录情况： SCI

摘要： Ethnopharmacological relevance: The stems and leaves of Ligusticum chuanxiong ("Miwu") have been historically documented in ancient texts such as "Shennong Bencao Jing Jizhu" for alleviating conditions like stroke and dizziness. However, the therapeutic potential of phthalide extract from the stems and leaves of Ligusticum chuanxiong (SLECX) needs further investigate. Aim of the study: This study aimed to investigate the neuroprotective effects of SLECX against cerebral ischemiareperfusion (I/R) injury and elucidate its mechanism of action. Materials and methods: SLECX was prepared from stems and leaves of Ligusticum chuanxiongvia ethanol extraction and macroporous resin purification, with major phthalides quantified by HPLC and LC-MS/MS. Neuroprotective effects were evaluated in Middle cerebral artery occlusion (MCAO) rats and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced HT22 cells. Molecular docking, surface plasmon resonance (SPR), and calcium imaging were employed to identify key active compounds targeting CaSR and NLRP3. Results: SLECX pretreatment significantly reduced cerebral infarct volume (29.6 % -> 16.4 %), alleviated neurological deficits, and attenuated brain edema in MCAO rats. It suppressed pro-inflammatory cytokines and inhibited CaSR/NLRP3 inflammasome activation in both in vivo and in vitro models. Molecular docking and SPR identified chuanxiongnolide B as a primary active compound, exhibiting strong CaSR binding (KD = 1.36 x 10-4 M) and reducing OGD/R-induced Ca2+ overload and apoptosis in HT22 cells. SLECX also restored blood-brain barrier (BBB) integrity by upregulating zona occludens 1 (ZO-1) and Occludin. Conclusions: SLECX mitigates cerebral I/R injury by inhibiting CaSR-mediated NLRP3 inflammasome activation, with chuanxiongnolide B as a pivotal bioactive component.

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