未经批准:黄淮(HH),由黄芩的干根(中国黄琴)和槐花的干花和芽(中国怀化)制成,是一种传统的中国配方,用于治疗功能失调性子宫出血(DUB)(Benglou中文),并在我们先前的研究中被证明可有效治疗止血。通过网络药理学和分子对接研究黄淮(HH)的潜在机制,并进行药效学实验验证其疗效。
未经批准:TCMSP,UniProt,GeneCards,STRING,DAVID数据库,和Cytoscape3.7.2用于构建复合靶途径网络。将潜在的有效成分与潜在的目标对接。进行潜在有效成分的HPLC分析。在体内,热板试验模型用于研究镇痛活性,蛋清用于研究小鼠鞋底的肿胀反应,并通过毛细管法研究了止血效果,断尾法和流产子宫试验。
UNASSIGNED:结果表明,六种化合物(acacetitin,β-谷甾醇,Wogonin,黄芩素,山奈酚和槲皮素)和化合物-靶标途径网络中的四个潜在靶标(PTGS2,AKT1,TP53和TNF)是HH治疗DUB的潜在物质基础。可以看出,acacetin的结合能,Wogonin,黄芩素,β-谷甾醇,山奈酚和槲皮素在HH中与受体蛋白PTGS2,AKT1,TP53和TNF对接远低于-5.0kJ/mol,这意味着分子具有低构象能,结构稳定,结合活性高。HPLC分析结果表明,Wogonin,黄芩素,山奈酚、槲皮素是HH止血机制的潜在有效成分,β-谷甾醇由于含量低而被去除。体内检测潜在的有效成分,这表明,通过HPLC鉴定的潜在有效成分组可增加疼痛阈值,抑制蛋白诱导的小鼠后爪肿胀,减少出血时间和凝血时间,减少子宫出血,减少子宫重量,增加子宫匀浆组织中Ca和ET-1的含量,降低NO的含量,流产大鼠子宫血清中E2和P含量降低,其疗效等于HH。
UNASSIGNED:结果表明,从网络药理学获得的HH和潜在活性成分组可以治疗DUB并发挥止血作用。网络药理学研究结果具有一定的可靠性。本研究为进一步研究HH对DUB的作用机制以及开发HH或其成分作为DUB患者的替代疗法提供了新的指征。同时,网络药理学策略的应用可为探索中药作用机制和发现新的生物活性成分提供有力工具。
UNASSIGNED: The Huanghuai (HH), which is made from the dried roots of Scutellaria baicalensis (Huangqin in Chinese) and the dried flowers and buds of Sophora japonica (Huaihua in Chinese), is a traditional Chinese formula used to treat dysfunctional uterine bleeding (DUB) (Benglou in Chinese) and proven to treat hemostasis effectively in our previous study. Network pharmacology and molecule docking were performed to study the underlying mechanism of Huanghuai (HH), and pharmacodynamic experiments were conducted to verify its curative effect.
UNASSIGNED: TCMSP, UniProt, GeneCards, STRING, DAVID databases, and Cytoscape 3.7.2 were utilized for the construction of a compound-target-pathway network. Docking the potential effective components with potential targets. The HPLC analysis of the potential effective components was performed. In vivo, the hot plate test model was used to study the analgesic activity, the egg white was used to study the swollen reaction in the sole in mice, and the hemostasis effect was studied by the capillary method, tail-breaking method and abortion uterus test.
UNASSIGNED: The results showed that six compounds (acacetin, beta-sitosterol, wogonin, baicalein, kaempferol and quercetin) and four potential targets (PTGS2, AKT1, TP53 and TNF) in the compound-target-pathway network were the potential material basis for HH to treat DUB. It can be seen that the binding energy of the acacetin, wogonin, baicalein, beta-sitosterol, kaempferol and quercetin in HH docked with the receptor proteins PTGS2, AKT1, TP53, and TNF were far less than -5.0 kJ/mol, which means the molecules have low conformational energy, stable structure and high binding activity. And the result of HPLC analysis showed that acacetin, wogonin, baicalein, kaempferol and quercetin were the potential effective components of the hemostasis mechanism of HH, beta-sitosterol was removed due to low content. In vivo testing of the potential effective components, it revealed that the group of potential effective components identified by HPLC could increase the pain threshold, inhibit the swelling hind paws of mice induced by egg white, reduce the bleeding time and clotting time, reduce uterine bleeding, decrease the uterine weight, increase the content of Ca and ET-1, and reduce the content of NO in uterine homogenate tissue, and decrease of E2 and P content in uterine serum in aborted rats, whose efficacy was equal to HH.
UNASSIGNED: The results indicated that HH and potential active ingredient groups obtained from network pharmacology can treat DUB and play a hemostatic effect. The results obtained by network pharmacology have certain reliability. This study provides new indications for further mechanism research of HH on DUB and the development of HH or its components as an alternative therapy for patients with DUB. At the same time, the application of network pharmacology strategy may provide a powerful tool for exploring the mechanism of traditional Chinese medicine and discovering new biologically active ingredients.