Luo Cheng, Ye Yuan-Hang, Jiang Cheng, Ning Bo, Ke Jia, Chen Gang
College of Traditional Chinese Medicine, Hubei University of Chinese Medicine Wuhan 430061, China.
Hubei Provincial Hospital of Traditional Chinese Medicine/Affiliated Hospital of Hubei University of Chinese Medicine/Hubei Academy of Traditional Chinese Medicine Wuhan 430074, China.
Zhongguo Zhong Yao Za Zhi. 2024 Aug;49(16):4329-4337. doi: 10.19540/j.cnki.cjcmm.20240513.702.
This study aims to investigate the mechanism of Xuanbai Chengqi Decoction in treating acute lung injury(ALI) based on network pharmacology and animal experiments. The potential targets and signaling pathways of Xuanbai Chengqi Decoction in regulating ALI were predicted by network pharmacology. The rat model of ALI was constructed and administrated with different doses of Xuanbai Chengqi Decoction. The pathological changes in the lung tissue of rats were observed by hematoxylin-eosin(HE) staining. The levels of interleukin-6(IL-6), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) in the peripheral blood were measured by enzyme-linked immunosorbent assay(ELISA). The mRNA and protein levels of factors in the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway were determined by quantitative real-time PCR(qPCR) and Western blot, respectively. A total of 52 compounds from Xuanbai Chengqi Decoction were predicted to be involved in the treatment of ALI, including β-sitosterol, emodin, stigmasterol, glabridin, and aloe-emodin, which corresponded to 112 targets,and 4 723 targets of ALI were predicted. The compounds and ALI shared 94 common targets. The key targets included TNF, IL-1β,prostaglandin-endoperoxide synthase 2(PTGS2), and tumor protein 53(TP53). Lipids and atherosclerosis, p53 signaling pathway,IL-17 signaling pathway, and PI3K/Akt signaling pathway were mainly involved in the treatment. Animal experiments showed that compared with the model group, Xuanbai Chengqi Decoction alleviated the pathological changes in the lung tissue, lowered the serum levels of IL-6, IL-1β, and TNF-α, down-regulated the mRNA and protein levels of PI3K, Akt, and mTOR, and reduced the p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR ratios in ALI rats. The results showed that Xuanbai Chengqi Decoction exerted its therapeutic effects on ALI via multiple components, targets, and pathways. Meanwhile, Xuanbai Chengqi Decoction may reduce the inflammation and attenuate the lung injuries of ALI rats by inhibiting the PI3K/Akt/mTOR signaling pathway.
本研究旨在基于网络药理学和动物实验探讨宣白承气汤治疗急性肺损伤(ALI)的机制。通过网络药理学预测宣白承气汤调控ALI的潜在靶点和信号通路。构建ALI大鼠模型并给予不同剂量的宣白承气汤。采用苏木精-伊红(HE)染色观察大鼠肺组织的病理变化。采用酶联免疫吸附测定(ELISA)法检测外周血中白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的水平。分别采用定量实时聚合酶链反应(qPCR)和蛋白质免疫印迹法检测磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/雷帕霉素靶蛋白(mTOR)信号通路中相关因子的mRNA和蛋白水平。预测宣白承气汤共有52种化合物参与ALI的治疗,包括β-谷甾醇、大黄素、豆甾醇、光甘草定和芦荟大黄素,这些化合物对应112个靶点,同时预测得到ALI的4723个靶点。化合物与ALI共有94个共同靶点。关键靶点包括TNF、IL-1β、前列腺素内过氧化物合酶2(PTGS2)和肿瘤蛋白53(TP53)。主要涉及的治疗通路有脂质与动脉粥样硬化、p53信号通路、IL-17信号通路和PI3K/Akt信号通路。动物实验表明,与模型组相比,宣白承气汤减轻了肺组织的病理变化,降低了血清中IL-6、IL-1β和TNF-α的水平,下调了ALI大鼠PI3K、Akt和mTOR的mRNA和蛋白水平,降低了p-PI3K/PI3K、p-Akt/Akt和p-mTOR/mTOR的比值。结果表明,宣白承气汤通过多种成分、靶点和通路发挥对ALI的治疗作用。同时,宣白承气汤可能通过抑制PI3K/Akt/mTOR信号通路减轻ALI大鼠的炎症反应并减轻肺损伤。