Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China; Graduate School of China Academy of Chinese Medical Sciences, Beijing, China.
Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China.
J Ethnopharmacol. 2022 Aug 10;294:115386. doi: 10.1016/j.jep.2022.115386. Epub 2022 May 14.
Chronic prostatitis (CP) is a complex, intractable and prevalent urological disorder in men with no effective treatment. Guihuang formula (GHF) is a traditional Chinese medicine compound that is advantageous as a CP treatment, but its aetiology is poorly understood. Research and exploration of the mechanism of GHF will help the development of a potentially valuable drug for CP and provide deeper insight into CP.
To examine and further clarify the multi-target therapeutic mechanism of GHF on CP.
The chemical components in GHF were identified using UPLC-Q/TOF-MS. The active components and potential targets of GHF for the treatment of CP were screened and analyzed using network pharmacology and molecular docking. We constructed a CP rat model to investigate the therapeutic effect of GHF on CP and verify the influence of key targets and core pathways based on the results of network pharmacology.
A total of 143 ingredients were identified in GHF using UPLC-Q/TOF-MS, and 111 potential targets for GHF of CP were predicted. The "drug-ingredient-target-pathway" network was constructed and in compliance with the "Jun-Chen-Zuo-Shi" principle. GHF significantly reduced the prostate index, alleviated histological damage in the prostate, decreased CD3 T cells and CD45 leukocyte infiltration in the prostate, downregulated the expression of the proinflammatory cytokines IL-1β, IL-6, IL-18, COX-2, MCP-1 and TNF-α, decreased ROS levels and alleviated the production of MDA accompanied by an increase of SOD and GSH-PX levels. Meanwhile, GHF suppressed apoptosis in macrophages, downregulated the mRNA levels of PI3K, AKT and P65 NF-κB and inhibited the phosphorylation of the PI3K, AKT and P65 NF-κB.
A network pharmacology and experimental validation-based strategy was used to elucidate the underlying "multicomponent, multitarget, and multipathway" mode of action of GHF against CP. We verified that GHF inhibited oxidative stress and inflammatory response, suppressed apoptosis in macrophages, inhibited the activation of the inflammation-related PI3K/AKT/NF-κB pathway in CP rat. These findings extend the conventional views of "one drug hits one target", and offer novel insights and indication paradigm for the future discovery on the multi-target therapeutic mechanism of traditional Chinese medicine compound.
慢性前列腺炎（CP）是一种复杂、难治且普遍存在的男性泌尿系统疾病，目前尚无有效的治疗方法。龟黄方（GHF）是一种中药复方，在 CP 治疗方面具有优势，但病因尚不清楚。研究和探索 GHF 的作用机制将有助于开发一种有潜力的 CP 治疗药物，并为 CP 提供更深入的认识。
探讨和进一步阐明 GHF 治疗 CP 的多靶点治疗机制。
采用 UPLC-Q/TOF-MS 鉴定 GHF 中的化学成分。利用网络药理学和分子对接筛选和分析 GHF 治疗 CP 的活性成分和潜在靶点。构建 CP 大鼠模型，研究 GHF 对 CP 的治疗作用，并基于网络药理学的结果验证关键靶点和核心途径的影响。
采用 UPLC-Q/TOF-MS 鉴定出 GHF 中的 143 种成分，预测出 GHF 治疗 CP 的 111 个潜在靶点。构建了“药物-成分-靶标-通路”网络，并符合“君臣佐使”原则。GHF 显著降低前列腺指数，减轻前列腺组织学损伤，减少前列腺内 CD3 T 细胞和 CD45 白细胞浸润，下调促炎细胞因子 IL-1β、IL-6、IL-18、COX-2、MCP-1 和 TNF-α的表达，降低 ROS 水平，减轻 MDA 的产生，同时增加 SOD 和 GSH-PX 水平。此外，GHF 抑制巨噬细胞凋亡，下调 PI3K、AKT 和 P65 NF-κB 的 mRNA 水平，并抑制 PI3K、AKT 和 P65 NF-κB 的磷酸化。
采用网络药理学和实验验证相结合的策略，阐明了 GHF 治疗 CP 的潜在“多成分、多靶点、多途径”作用模式。我们验证了 GHF 抑制氧化应激和炎症反应，抑制 CP 大鼠巨噬细胞凋亡，抑制炎症相关 PI3K/AKT/NF-κB 通路的激活。这些发现扩展了“一种药物针对一个靶点”的传统观点，为传统中药复方多靶点治疗机制的未来发现提供了新的见解和指示范例。
