目的 通过网络药理学预测生地黄-牡丹皮药对（SM）治疗银屑病的作用机制，并采用体内和体外实验进行验证。方法 通过网络药理学获取SM的活性成分与银屑病的交集靶点，并进行富集分析。采用咪喹莫特（IMQ）构建银屑病小鼠模型，设对照组，模型组，生地黄组，牡丹皮组、SM低、中、高剂量（4.095、8.190、16.380 g·kg^-1）组及甲氨蝶呤（MTX）组，通过银屑病严重程度指数（PASI）、皮肤病理学变化及组织中增殖细胞标志物（Ki67）的表达情况对药物效果进行评估。采用CCK-8法筛选药物的安全浓度，Western blotting检测磷脂酰肌醇3-激酶/丝氨酸和苏氨酸激酶（PI3K/Akt）通路蛋白表达，并采用PI3K抑制剂LY294002进行验证。结果 通过网络药理学发现SM共有169个银屑病相关靶点，显著富集于PI3K/Akt等信号通路。体内实验结果表明，SM能明显减轻IMQ诱导的红斑、鳞屑及皮肤增厚，降低PASI评分，减少炎症浸润与Ki67的表达。体外实验证实，SM浓度≤8 mg·mL^-1时无细胞毒性，能剂量相关性地降低p-PI3K/PI3K和p-Akt/Akt的表达。加入LY294002后，SM能进一步降低p-PI3K和p-Akt的表达。结论 SM对银屑病小鼠具有显著保护作用，其机制可能是通过抑制PI3K/Akt信号通路，从而发挥抗银屑病作用。

Objective To predict the potential mechanisms underlying the therapeutic effects of the Rehmanniae Radix-Moutan Cortex herb pair (SM) against psoriasis using network pharmacology, and to validate the predicted mechanisms through in vivo and in vitro experiments. Methods Network pharmacology was used to identify the active constituents of SM, obtain the intersection targets between SM and psoriasis, and perform enrichment analyses. An imiquimod (IMQ)-induced mouse model of psoriasis was established. Mice were divided into the control, model, Rehmanniae Radix, Moutan Cortex, low-, medium-, and high-dose (4.095, 8.190, and 16.380 g·kg^-1) SM, and methotrexate (MTX, positive control) groups. The therapeutic effects were evaluated based on the Psoriasis Area and Severity Index (PASI), histopathological changes in skin lesions, and Ki67 expression in skin tissues. The non-cytotoxic concentration range of SM was determined using the CCK-8 assay. The expression levels of PI3K/Akt pathway-related proteins were detected by Western blotting. The PI3K inhibitor LY294002 was further used for mechanistic verification. Results Network pharmacology analysis identified 169 psoriasis-related targets of SM, which were significantly enriched in several signaling pathways, including the PI3K/Akt signaling pathway. In vivo experiments showed that SM markedly alleviated IMQ-induced erythema, scaling, and skin thickening, reduced PASI scores, and decreased inflammatory infiltration and Ki67 expression. In vitro experiments demonstrated that SM showed no obvious cytotoxicity at concentrations ≤ 8 mg·mL^-1 and dose-dependently reduced the phosphorylation levels of PI3K and Akt, as indicated by decreased p-PI3K/PI3K and p-Akt/Akt ratios. After treatment with LY294002, SM further decreased the expression of p-PI3K and p-Akt. Conclusion SM exerts a significant protective effect against psoriasis in mice. The underlying mechanism may be associated with inhibition of the PI3K/Akt signaling pathway, and exert an anti-psoriatic effect.

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