Systemic pharmacological verification of Baixianfeng decoction regulating TNF-PI3K-Akt-NF-κB pathway in treating rheumatoid arthritis.
Systemic pharmacological verification of Baixianfeng decoction regulating TNF-PI3K-Akt-NF-κB pathway in treating rheumatoid arthritis.
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百先锋汤调节TNF-PI3K-Akt-NF-κB通路治疗类风湿关节炎的全身药理学验证
DOI：
10.1016/j.bioorg.2021.105519
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发表时间：
2021-11
影响因子：
5.1
通讯作者：
Hu Wei
中科院分区：
文献类型：
--
作者：
Wei Xin;Zhou Renpeng;Chen Yong;Ma Ganggang;Yang Yang;Lu Chao;Xu Weiping;Hu Wei
中医治疗复杂疾病的历史悠久，尤其是对全身性疾病的调理。已有文献报道白仙风口服液治疗类风湿关节炎（RA）可能与其全身调节作用有关，但其具体作用机制尚不清楚。本研究运用系统药理学的研究理念和方法，探讨补肾活血方治疗类风湿关节炎的作用机制。利用TCMSP数据库检索BXF制剂成分，筛选ADME参数。参数指标设定为OB ≥ 30%，DL ≥ 0.18，HL ≥ 4 h。利用TCMSP和Target-Prediction平台对筛选出的化合物进行靶标搜索和预测。通过DisGeNET、OMIM和PharmGkb数据库获得RA的疾病靶标。利用Cytoscape 3.2.1软件进行了一系列的网络构建和分析，并利用大卫数据库进行了途径富集。采用佐剂性关节炎大鼠模型进行动物实验验证，从病理表型、炎症因子、通路蛋白表达等方面验证预测的通路结果。结果显示，药物中81个活性成分的相关靶点与RA的56个靶点交叉，这些共同靶点富集在83个显著通路中，其中TNF信号通路具有研究意义。动物实验证明，补肾活血方对佐剂性关节炎大鼠有明显的治疗作用。药物能减轻大鼠的病理表型，并呈剂量依赖性。降低血清TNF-α、IL-1β含量，降低脾组织TNF-α、IL-6基因表达。在大鼠软骨组织蛋白中，抑制Ⅱ型胶原蛋白的降解。BXF抑制软骨组织中p-PI 3 K、p-Akt和p-P65蛋白的活化，并减少凋亡蛋白如cleaved-caspase 8和cleaved-caspase 3的过度表达。同时抑制MMP 9、TNF-α、IL-6、IL-1β的蛋白表达。综上所述，本研究成功实践了全身药理学与实验验证相结合，阐明了补肾活血方通过TNF-PI 3 K-Akt-NF-κB信号轴抑制佐剂性关节炎大鼠的进展。为进一步研究补肾活血方治疗类风湿关节炎的作用机制提供了新的证据。
Traditional Chinese medicine has a long history of treating complex diseases, especially for the conditioning of systemic diseases. It has been reported thatBaixianfeng (BXF) decoctionused to treat rheumatoid arthritis (RA) may be due to its systemic regulatory effect, but the specific mechanism still remains to be elucidated. The research philosophy and methods of systemic pharmacology were used to explore the mechanism ofBXF decoctionin treating RA in this study. TCMSP database was used to search the ingredients ofBXF decoctionand screen the ADME parameters. The parameter index was set as OB ≥ 30%, DL ≥ 0.18, HL ≥ 4 h. The targets of the screened compounds were searched and predicted by TCMSP and Target-Prediction platforms. The disease targets of RA were obtained through the DisGeNET, OMIM, and PharmGkb databases. A series of network construction and analysis relied on Cytoscape 3.2.1 software, and the DAVID database was used for pathway enrichment. The adjuvant arthritis rat model was used for the verification of animal experiments to verify the predicted pathway results in terms of pathological phenotype, inflammatory factors, and pathway protein expression. The results showed that the related targets of 81 active ingredients in the drug crossed 56 targets of RA, and these common targets were enriched in 83 significant pathways, among which the TNF signaling pathway had research significance. Animal experiments have proved thatBXF decoctionwas effective in treating adjuvant arthritis rats. The drug relieved the pathological phenotype of rats in dose-dependent. It reduced the serum content of TNF-α and IL-1β, and reduced the gene expression of TNF-α and IL-6 in spleen tissue. In the cartilage tissue protein of rats, it inhibited the degradation of collagen Ⅱ protein. Further,BXF decoctionreduced the activation of p-PI3K, p-Akt, and p-P65 protein, and decreased the overexpression of apoptotic proteins such as cleaved-caspase8 and cleaved-caspase3 in cartilage tissue. Meanwhile, it inhibited the protein expression of MMP9, TNF-α, IL-6, and IL-1β. In conclusion, this study successfully practiced the combination of systemic pharmacology and experimental verification, and clarified thatBXF decoctioninhibited the progression of adjuvant arthritis rats through the TNF-PI3K-Akt-NF-κB signal axis. It provides new evidence for the study of the mechanism ofBXF decoctionin treating RA.
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DOI：
10.1007/s10495-018-1474-7
发表时间：
2018-12
期刊：
Apoptosis : an international journal on programmed cell death
影响因子：
--
作者：
Gao J;Kong R;Zhou X;Ji L;Zhang J;Zhao D
通讯作者：
Zhao D
影响因子：
5.1
作者：
Yuan Yin;Chengjuan Chen;Ru-Nan Yu;Lei Shu;Zhi-jian Wang;Tian-tai Zhang;Da-yong Zhang
通讯作者：
Yuan Yin;Chengjuan Chen;Ru-Nan Yu;Lei Shu;Zhi-jian Wang;Tian-tai Zhang;Da-yong Zhang
影响因子：
--
作者：
di Meglio, Paola;Ianaro, Angela;Ghosh, Sankar
通讯作者：
Ghosh, Sankar
影响因子：
27.4
作者：
Tolboom, TCA;Pieterman, E;Huizinga, TWJ
通讯作者：
Huizinga, TWJ
影响因子：
7.5
作者：
Guazelli, Carla F. S.;Staurengo-Ferrari, Larissa;Verri, Waldiceu A., Jr.
通讯作者：
Verri, Waldiceu A., Jr.