Abstract: Objective　To verify the effectiveness and scientific validity of sophoridine in anti anxiety treatment, and to explore its preliminary mechanism of action.Methods　Forty SPF grade male C57BL/ 6J mice were randomly divided into a normal group, a low-dose sophoridine group (10 mg/kg), a medium-dose group (20 mg/kg), and a high-dose group (40 mg/kg) according to their body weight. The mice were administered at a fixed time every day for 28 days. After the administration, behavioral tests were conducted to evaluate changes in mouse anxiety behavior. ELISA experiment was used to detect the levels of SOD, NGF, IL-6, TNF-α, and GSH in mouse serum. Western blot experiment detected the interaction between sophoridine and key subunits of GABAAR. Computer molecular docking analysis of the interaction sites between sophoridine and GABAAR ultimately demonstrated the anti-anxiety efficacy and anti anxiety targets of sophoridine. Results　After intervention with sophoridine, the time and frequency of entry into the central area of OFT, the time and frequency of entry into the open arm of EPM, and the time and frequency of entry into the bright area of LDB all significantly increased. The incubation period of NSFT feeding was significantly shortened. The levels of SOD and NGF in mouse serum significantly increased. The levels of serum IL-6, TNF-α, and GSH were significantly reduced. The expression levels of GABAAR α1, β1, and γ2 subunit protein molecules were significantly increased; sophoridine alkaloid directly binds to the beta1, alpha1, and gamma2 subunits of GABAAR. Conclusion　After intraperitoneal administration of sophoridine, a potential trend toward ameliorating anxiety-like behaviors was observed, and its effects may be related to the targeting of GABAAR subunits by sophoridine. 

Key words: sophoridine, anxiety, behavior, mechanism of action

摘要： 目的　验证槐定碱抗焦虑的有效性和科学性,并探讨其初步作用机制。方法　将40只SPF级雄性C57BL/6J 小鼠按照随机区组设计方法(根据体质量)分为正常组、槐定碱低剂量组(10 mg/kg)、中剂量组(20 mg/kg)、高剂量 组(40 mg/kg),每天固定时间给药,持续28 d,给药结束后,开展行为学测试,评估小鼠焦虑行为的变化;Elisa实验 检测小鼠血清中SOD、NGF、IL-6、TNF-α和GSH含量;Western blot实验检测槐定碱与γ-氨基丁酸A型受体 (GABAAR)关键亚基的作用关系;计算机分子对接分析槐定碱与GABAAR的关键亚基相互作用位点,最终证明槐 定碱抗焦虑的疗效和抗焦虑的作用靶点。结果　槐定碱干预后,OFT中央区的进入时间和次数、EPM开放臂进入 时间和次数、LDB明区进入时间和次数均显著增加;NSFT摄食潜伏期显著缩短;小鼠血清SOD和NGF含量显著增 加;血清IL-6、TNF-α和GSH含量显著降低;GABAAR的α1、β1和γ2 亚基蛋白分子表达量明显升高;槐定碱与 GABAAR的α1、β1和γ2亚基结合。结论　槐定碱腹腔注射给药干预后表现出改善焦虑样行为的潜在趋势,其作 用可能与槐定碱靶向GABAAR亚单位有关。

关键词: 槐定碱, 焦虑, 行为学, 作用机制