Table_2_Yin-Chen-Hao Tang Attenuates Severe Acute Pancreatitis in Rat: An Experimental Verification of In silico Network Target Prediction.DOC

Yin-Chen-Hao Tang (YCHT) is a classical Chinese medicine compound that has a long history of clinical use in China for the treatment of inflammatory diseases. However, the efficacy and mechanisms of YCHT for the treatment of severe acute pancreatitis (SAP) are not known. The current study investigated the pharmacological properties of YCHT against SAP and its underlying mechanisms. A computational prediction of potential targets of YCHT was initially established based on a network pharmacology simulation. The model suggested that YCHT attenuated SAP progress by apoptosis inducement, anti-inflammation, anti-oxidation and blood lipid regulation. These effects were validated in SAP rats. YCHT administration produced the following results: (1) significantly inhibited the secretion of pancreatic enzymes and protected pancreatic tissue; (2) obviously increased the number of in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells and induced apoptosis; (3) markedly inhibited neutrophil infiltration to the impaired pancreas and reduced the inflammatory reaction; (4) notably enhanced the activities of antioxidant enzymes and decreased the nitric oxide synthase levels; (5) significantly reduced the levels of triglycerides, total cholesterol and low-density lipoprotein and increased high-density lipoprotein; and (6) significantly up-regulated peroxisome proliferator-activated receptor-γ (PPARγ) and down-regulated nuclear factor-kappa B (NF-κB). In summary, these results demonstrated that YCHT attenuated SAP progress by inducing apoptosis, repressing inflammation, alleviating oxidative stress and regulating lipid metabolism partially via regulation of the NF-κB/PPARγ signal pathway.

茵陈蒿汤（Yin-Chen-Hao Tang，简称YCHT）是一种经典中药复方，在我国拥有悠久的临床应用历史，主要用于炎症性疾病的治疗。然而，YCHT用于治疗重症急性胰腺炎（severe acute pancreatitis，SAP）的疗效及作用机制尚不明确。本研究旨在探讨YCHT抗SAP的药理活性及其潜在分子机制。本研究首先通过网络药理学模拟，构建了YCHT潜在靶点的计算预测模型。该模型预测，YCHT可通过诱导细胞凋亡、抗炎、抗氧化及调节血脂来延缓SAP的疾病进程。上述效应在SAP大鼠模型中得到了验证。给予YCHT干预后可观测到如下结果：(1) 显著抑制胰酶分泌，保护胰腺组织；(2) 明显增加原位末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（terminal deoxynucleotidyl transferase dUTP nick-end labeling，TUNEL）阳性细胞数量，诱导细胞凋亡；(3) 显著抑制中性粒细胞向受损胰腺组织浸润，减轻炎症反应；(4) 显著增强抗氧化酶活性，降低一氧化氮合酶水平；(5) 显著降低甘油三酯、总胆固醇及低密度脂蛋白水平，同时升高高密度脂蛋白水平；(6) 显著上调过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptor-γ，PPARγ）的表达，下调核因子κB（nuclear factor-kappa B，NF-κB）的表达。综上，本研究结果表明，YCHT可通过诱导细胞凋亡、抑制炎症反应、缓解氧化应激及调节脂质代谢来延缓SAP进程，其作用部分依赖于对NF-κB/PPARγ信号通路的调控。