Background. Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality and poor prognosis. The prognostic signatures related to conventional therapy response remain limited. The Wenfei Buqi Tongluo (WBT) formula, a traditional Chinese medicine (TCM) formula, has been widely utilized to treat respiratory diseases in China, which is particularly effective in promoting inflammatory absorption. In this study, we aim to explore the mechanism of the WBT formula in the inhibition of inflammatory response during IPF, based on network pharmacology and in vivo experiments. Methods. Network pharmacology was applied to predict the changes of biological processes and potential pathways for the WBT formula against IPF. Histopathological changes, inflammatory factors (IL-6, IL-1β, and TNF-α), and the proteins of the TLR4/MyD88/NF-κB pathway in bleomycin- (BLM-) induced mice model were examined by hematoxylin-eosin (H&E), Masson or immunohistochemistry staining, Western blot, and enzyme-linked immunosorbent assay analysis. Results. A total of 163 possible components and 167 potential targets between the WBT formula and IPF were obtained. The enrichments of network pharmacology showed that inflammation response, TNF, and NF-κB pathways were involved in the treatment of WBT against IPF. The in vivo experiments indicated that the WBT formula could ameliorate inflammatory exudation and collagen deposition at a histopathology level in the BLM-induced mice model. The levels of IL-6, IL-1β, and TNF-α were reduced after the WBT formula treatment. Moreover, the expressions of phosphorylated-NF-κB p65, TLR4, and MyD88 were significantly downregulated by the WBT formula, compared with the BLM-induced group. Conclusion. These results indicated that the WBT formula can suppress BLM-induced IPF in a mouse model by inhibiting the inflammation via the TLR4/MyD88/NF-κB pathway. This study provides a new insight into the molecular mechanisms of the WBT formula in the application at the clinic.

Objective: To investigate the effects of hematoxylin extract on serum interleukin, hypersensitive C-reactive protein, aortic TLR4 mRNA and NF-xB p65 mRNA in atherosclerosis model rats. Methods: Vitamin D3 combined with high-fat feed was used to prepare an atherosclerosis rat model. According to the random number method, 60 rats were divided into normal control group, model group, hematoxylin extract low dose group (containing hematoxylin ethyl acetate extract 1.15g), hematoxylin extract medium dose group (hematoxylin ethyl acetate Ester extract 2.30g), hematoxylin extract high dose group (hematoxylin ethyl acetate extract 3.45g), simvastatin group. The levels of interleukin-1 (11.-6) and hypersensitive C-reactive protein (hs-CRP) were measured by enzyme-linked immunosorbent assay; the expression cif TOLL-like receptor 4 (aortic TLR4 mRNA) was measured by real-time fluorescent quantitative PCR; Real-time fluorescent quantitative PCR method was used to detect the mRNA level of nuclear factor xB (NF-xB) p65. Results: Compared with the normal control group, the levels of IL-6, hs-CRP, TLR4 mRNA and NF-xB p65 mRNA in the model group were significantly increased (P<0.05). Compared with the model group, the levels cif IL-6, hs-CRP, TLR4 mRNA, and NE-x.8 p65 mRNA of hematoxylin extracts in the low, medium and high dose groups and simvastatin group were significantly reduced (P<0.05). Compared with the simvastatin group, there was no significant difference in the levels of IL-6, hs CRP, TLR4 mRNA and NF- xB p65 mRNA between the low, medium, and high dose groups of hematoxylin extract. Conclusion: Hematoxylin extract can inhibit the body's inflammatory response, protect the vascular endothelium and resist the formation of atherosclerosis, and can be used as a candidate drug for AS treatment.

To explore the inhibitory effects of Astragalus polysaccharide on myocardial apoptosis induced by hypoxia/ reoxygenation in rats based on the high mobility group box 1/toll-like receptor 4/nuclear factor kappa B signaling pathway. The hypoxia/reoxygenation injury model of H9C2 myocardial cells was established and divided into control group, hypoxia/reoxygenation group, Astragalus polysaccharide group and high mobility group box 1 inhibitor group. Cell proliferation and apoptosis were detected by cell counting kit-8 assay and Annexin V-fluorescein isothiocyanate/propidium iodide double staining. The messenger RNA expressions of high mobility group box 1, toll-like receptor 4 and nuclear factor kappa B were detected by quantitative reverse transcription polymerase chain reaction and the contents of tumor necrosis factor alpha, interleukin-1β and interleukin-6 were determined using enzyme-linked immunosorbent assay. Compared with control group, cell proliferation was significantly weakened, apoptosis was significantly enhanced and the messenger RNA expressions of high mobility group box 1, toll-like receptor 4 and nuclear factor kappa B and the contents of tumor necrosis factor alpha, interleukin-1β and interleukin-6 significantly increased in hypoxia/reoxygenation group (p<0.05). Compared with hypoxia/reoxygenation group, Astragalus polysaccharide group and high mobility group box 1 inhibitor group had significantly enhanced cell proliferation, weakened apoptosis and decreased messenger RNA expressions of high mobility group box 1, toll-like receptor 4 and nuclear factor kappa B and contents of tumor necrosis factor alpha, interleukin-1β and interleukin-6 (p<0.05). Astragalus polysaccharide can repair the hypoxia/ reoxygenation injury of H9C2 myocardial cells, which may suppress apoptosis through inhibiting the high mobility group box 1/toll-like receptor 4/nuclear factor kappa B signaling pathway.