目的 应用正交试验设计，结合层次分析法（analytic hierarchy process，AHP）-熵权法，优化经典名方黄连解毒汤（Huanglian Jiedu Decoction，HJD）的提取工艺，并通过细胞实验验证其抗炎效果，为HJD的合理化提取提供参考依据。方法 以HJD中代表成分小檗碱、黄芩苷、栀子苷和绿原酸的含量以及上清液和自沉淀干膏率为考察指标；以加水量、提取时间和提取次数为关键工艺参数；采用正交试验结合AHP-熵权法确定各指标的权重系数，计算综合评分。通过脂多糖（lipopolysaccharide，LPS）诱导的小鼠小胶质BV2细胞炎症模型，探讨HJD提取工艺综合评分与其抗炎活性的相关性，并验证优选的提取工艺的抗炎稳定性。结果HJD优化提取工艺为10倍水量、提取30 min、提取3次。取综合评分为7.67、9.82和12.05的提取工艺制备HJD，分别命名为H1、H2、H3，进行药效学验证。结果显示，与对照组相比，LPS诱导BV2细胞分泌NO、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）和白细胞介素-6（interleukin-6，IL-6）；与LPS组相比，H1、H2、H3均能降低各组的炎症因子水平，且相关性分析表明，评分较高的提取工艺制备的HJD可能具有更好的抗炎潜力。进一步对H3进行抗炎活性验证，结果显示H3在100、200、400 μg/mL剂量下均能降低LPS诱导的炎症因子水平，并呈现良好的剂量效应关系。结论 正交试验结合AHP-熵权法筛选的HJD提取工艺准确可靠，且稳定可行，研究结果可为HJD后续开发和应用提供科学依据。

Objective To optimize the extraction process of the classical herbal formula Huanglian Jiedu Decoction (HJD, 黄连解毒汤) by orthogonal experimental design combined with analytic hierarchy process (AHP) and entropy weight method (EWM), and validate its anti-inflammatory effects through cellular assays, so as to provide a reference for the rational extraction of HJD. Methods The contents of representative components in HJD, including berberine, baicalin, geniposide, and chlorogenic acid, as well as the mass of the supernatant and precipitated dry extract rate, were used as indicators. Key extraction parameters, such as the amount of water added, extraction time, and number of extractions, were selected. An orthogonal experiment combined with AHP-EWM was used to determine the comprehensive weight coefficients for each indicator, and a total score was calculated. The correlation between the comprehensive score of the extraction process of HJD and its anti-inflammatory activity was explored using the LPS-induced BV2 microglial cell inflammation model, and the anti-inflammatory stability of the optimized extraction process was verified. Results The optimized extraction process for HJD was determined to be 10 times the amount of water, with an extraction time of 30 min and three extractions. Extraction processes with comprehensive scores of 7.67, 9.82, and 12.05 were used to prepare HJD, named H1, H2, and H3, respectively, for pharmacological validation. The results showed that, compared to the blank control group, LPS-induced BV2 cells secreted NO, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Compared to the LPS group, H1, H2, and H3 all reduced the levels of inflammatory cytokines. Furthermore, correlation analysis revealed that HJD with higher extraction process scores exhibited stronger anti-inflammatory effects. Anti-inflammatory activity was further validated for H3, and the results demonstrated that H3, at three doses (100, 200, 400 μg/mL), significantly reduced LPS-induced inflammatory cytokine levels, demonstrating a good dose-response relationship. Conclusion The extraction process of HJD optimized by the orthogonal experiment combined with AHP-EWM is accurate, reliable, stable, and feasible. The research results can provide reference for subsequent studies on development and application of HJD.

R283.6

国家自然科学基金资助项目（82174358）；四川省中医药管理局资助项目（2023MS481）