Dachengqi decoction dispensing granule ameliorates LPS-induced acute lung injury by inhibiting PANoptosis in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) is a serious health-threatening syndrome of intense inflammatory response in the lungs, with progression leading to acute respiratory distress syndrome (ARDS). Dachengqi decoction dispensing granule (DDG) has a pulmonary protective role, but its potential modulatory mechanism to alleviate ALI needs further excavation. AIM OF THE STUDY: This study aims to investigate the effect and potential mechanism of DDG on lipopolysaccharide (LPS)-induced ALI models in vivo and in vitro. MATERIALS AND METHODS: LPS-treated Balb/c mice and BEAS-2B cells were used to construct in vivo and in vitro ALI models, respectively. Hematoxylin-eosin (HE), Wet weight/Dry weight (W/D) calculation of lung tissue, and total protein and Lactic dehydrogenase (LDH) assays in BALF were performed to assess the extent of lung tissue injury and pulmonary edema. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-18 (IL-18) in BALF, serum, and cell supernatant. The qRT-PCR was used to detect inflammatory factors, Z-DNA binding protein 1 (ZBP1), and receptor-interacting protein kinase 1 (RIPK1) expression in lung tissues and BEAS-2B cells. Double immunofluorescence staining and co-immunoprecipitation were used to detect the relative expression and co-localization of ZBP1 and RIPK1. The effects of LPS and DDG on BEAS-2B cell activity were detected by Cell Counting Kit-8 (CCK-8). Western blot (WB) was performed to analyze the expression of PANoptosis-related proteins in lung tissues and BEAS-2B cells. RESULTS: In vivo, DDG pretreatment could dose-dependently improve the pathological changes of lung tissue in ALI mice, and reduce the W/D ratio of lung, total protein concentration, and LDH content in BALF. In vitro, DDG reversed the inhibitory effect of LPS on BEAS-2B cell viability. Meanwhile, DDG significantly reduced the levels of inflammatory factors in vitro and in vivo. In addition, DDG could inhibit the expression levels of PANoptosis-related proteins, especially the upstream key regulatory molecules ZBP1 and RIPK1. CONCLUSION: DDG could inhibit excessive inflammation and PANoptosis to alleviate LPS-induced ALI, thus possessing good anti-inflammatory and lung-protective effects. This study establishes a theoretical basis for the further development of DDG and provides a new prospect for ALI treatment by targeting PANoptosis.

Herba Patriniae and its component Isovitexin show anti-colorectal cancer effects by inducing apoptosis and cell-cycle arrest via p53 activation.

Colorectal cancer (CRC) is the most prevalent cancer of the digestive tract. Herba Patriniae (also known as Bai Jiang Cao, HP) have been widely used to manage diarrhea, ulcerative colitis, and several cancers, including CRC. Nonetheless, the molecular mechanisms underlying the pharmacological action of HP on CRC remain unclear. This study investigated the underlying mechanisms of HP against CRC using network pharmacology analysis and in vitro and in vivo experiments. The results revealed nine bioactive compounds of HP. Furthermore, 3460 CRC-related targets of the identified active compounds were predicted from the Gene Expression Omnibus (GEO) database. Furthermore, 65 common targets were identified through the intersection of two related targets. Moreover, ten hub genes, including CDK4, CDK2, CDK1, CCND1, CCNB1, CCNA2, MYC, E2F1, CHEK1, and CDKN1A were identified through the topological analysis. Meanwhile, the GO and KEGG pathway analysis revealed that the core target genes were majorly enriched in the p53 and HIF-1 signaling pathways. Moreover, HP promoted apoptosis and suppressed cell proliferation by activating the p53 signaling pathway in a dose-dependent manner, while a similar effect was observed for Isovitexin (the primary component of HP). Overall, this study provides valuable insights into the underlying mechanisms of HP and its component Isovitexin against CRC, providing a theoretical foundation for additional experimental verification of its clinical application.