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Influenza viral pneumonia is a common complication after influenza virus infection. Xijiao Dihuang Decoction combined with Yinqiao Powder (XDY) is effective on improving influenza viral pneumonia. This study further explores the anti-inflammatory mechanism of XDY in the treatment of influenza viral pneumonia. The effects of XDY on inflammation, autophagy, NACHT-LRR-PYD-containing protein 3 (NLRP3) inflammasome and pyroptosis were assessed in the mice with influenza viral pneumonia. In addition, the mouse macrophage cell line (J774A.1) infected with influenza virus was adopted to decode the in vitro effects of XDY on autophagy, reactive oxygen species (ROS), NLRP3 inflammasome and pyroptosis. We analyzed the XDY-induced autophagy, especially the mitophagy-related ROS clearance, and the subsequent inhibition of ROS/NLRP3 inflammasome/pyroptosis signaling in the infected macrophages by different assays based on quantitative polymerase chain reaction, western blot, flow cytometry, immunofluorescence and enzyme-linked immunosorbent assay. In vivo , XDY could effectively improve the lung inflammatory response in the mice with influenza virus pneumonia, due to an intact autophagy flux-promoting effect and the inhibiting roles on NLRP3 inflammasome and pyroptosis. Notably, in vitro , compared with the infected macrophages treated by the NLRP3 inflammasome agonist (Monosodium urate) or the mitochondrial-targeted antioxidant agent, the XDY-dependent treating could inhibit pyroptosis by negatively regulating the signaling axis of ROS/NLRP3 inflammasome/pyroptosis in the influenza virus-infected macrophages. More interestingly, XDY could promote an intact autophagy flux, inducing mitophagy eliminating the damaged mitochondria to reduce the intracellular ROS accumulation, and thus decrease the oxidative stress in the infected macrophages. Especially, the inhibitor of autophagy inition, 3-Methyladenine, could reverse the inhibitory effect of XDY on ROS-NLRP3 inflammasome-mediated pyroptosis, indicating an XDY-promoted mitophagy-dependent ROS scavenging. XDY can promote an intact autophagy flux to eliminate damaged mitochondria, namely mitophagy, which reduces the intracellular ROS accumulation contributing to NLRP3 inflammasome activation, restricting pyroptosis and eventually alleviating the influenza virus-induced inflammatory lesions. The obtained results provide new insights into the mechanism of action of XDY in alleviating influenza virus pneumonia, especially the roles of XDY in anti-oxidation, anti-inflammation and anti-pyroptosis, with potential therapeutic targets for future application in integrative medicine. [ABSTRACT FROM AUTHOR]

Gastric carcinoma (GC) treatment needs to be developed rapidly. Compound Kushen Injection (CKI), a formula from traditional Chinese medicine, has been used clinically in combination with chemotherapy to treat GC with satisfactory results. However, the molecular mechanism by which CKI acts to cure GC is still unclear. In the present study, in vivo and in vitro experiments were used to assess the efficacy of CKI. Using ceRNA microarray and TMT technologies, the molecular mechanism of CKI was further investigated at the transcriptional and protein levels, and a bioinformatics approach was employed to investigate and functionally validate key CKI targets in GC. When combined with cisplatin (DDP), CKI significantly increased its efficacy in preventing the proliferation and metastasis of GC cells and malignant-looking tumors in mice. High-throughput sequencing data and bioinformatics analysis showed that CKI regulated the TNF signaling pathway, epithelial-mesenchymal transition (EMT), with VCAM1 as a key target. The transcription factors CEBPB, JUN, RELA, NFKB1, the EMT mesenchymal-like cell markers N-cadherin and vimentin, as well as the expression of VCAM1 and its upstream signaling driver TNF, were all downregulated by CKI. In contrast, the expression of the EMT epithelial-like cell marker E-cadherin was upregulated. CKI can effectively inhibit GC growth and metastasis, improve body's immunity, and protect normal tissues from damage. The molecular mechanism by which CKI inhibits metastasis of GC is by regulating VCAM1 induced by the TNF signaling pathway to inhibit EMT of GC. Our results provide an important clue to clarify precisely the multi-scale molecular mechanism of CKI in the treatment of GC. [Display omitted] [ABSTRACT FROM AUTHOR]