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Background: Yinzhihuang granules (YZHG) is a commonly used Chinese patent medicine for the treatment of liver disease. However, the mechanism of YZHG in alcoholic liver disease (ALD) is still unclear. Methods: This study combined liquid chromatography-mass spectrometry technology, pharmacodynamics, network pharmacology and molecular docking methods to evaluate the potential mechanism of YZHG in the treatment of ALD. Results: A total of 25 compounds including 4-hydroxyacetophenone, scoparone, geniposide, quercetin, baicalin, baicalein, chlorogenic acid and caffeic acid in YZHG were identified by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The pharmacodynamic investigations indicated that YZHG could improve liver function and the degree of liver tissue lesions, and reduce liver inflammation and oxidative stress in ALD mice. Network pharmacology analysis showed that YZHG treated ALD mainly by regulating inflammation-related signaling pathways such as the PI3K-Akt signaling pathway. The results of the PPI network and molecular docking showed that the targets of SRC, HSP90AA1, STAT3, EGFR and AKT1 could be the key targets of YZHG in the treatment of ALD. Conclusion: This study explored the potential compounds, potential targets and signaling pathways of YZHG in the treatment of ALD, which is helpful to clarify the efficacy and mechanism of YZHG and provide new insights for the clinical application of YZHG. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is one of the most lethal cancers worldwide. Aidi injection (ADI) is a representative antitumor medication based on Chinese herbal injection, but its antitumor mechanisms are still poorly understood. Materials and methods: In this work, the subcutaneous xenograft model of human pancreatic cancer cell line Panc-1 was established in nude mice to investigate the anticancer effect of ADI in vivo. We then determined the components of ADI using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) and explored the possible molecular mechanisms against pancreatic cancer using network pharmacology. Results: In vivo experiments, the volume, weight, and degree of histological abnormalities of implanted tumors were significantly lower in the medium and high concentration ADI injection groups than in the control group. Network pharmacology analysis identified four active components of ADI and seven key targets, TNF, VEGFA, HSP90AA1, MAPK14, CASP3, P53 and JUN. Molecular docking also revealed high affinity between the active components and the target proteins, including Astragaloside IV to P53 and VEGFA, Ginsenoside Rb1 to CASP3 and Formononetin to JUN. Conclusion: ADI could reduce the growth rate of tumor tissue and alleviate the structural abnormalities in tumor tissue. ADI is predicted to act on VEGFA, P53, CASP3, and JUN in ADI-mediated treatment of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Aidi injection (ADI) is a popular anti-tumor Chinese patent medicine, widely used in clinics for the treatment of hepatocellular carcinoma (HCC) with remarkable therapeutic effects through multiple targets and pathways. However, the scientific evidence of the synergistic role of the complex chemical component system and the potential mechanism for treating diseases are ignored and remain to be elucidated. This study aimed to elucidate and verify the cooperative association between the potential active ingredient of ADI, which is of significance to enlarge our understanding of its anti-HCC molecular mechanisms. Firstly, the anti-HCC effect of ADI was evaluated in various HCC cells and the zebrafish xenograft model. Subsequently, a variety of bioinformatic technologies, including network pharmacology, weighted gene co-expression network analysis (WGCNA), meta-analysis of gene expression profiles, and pathway enrichment analysis were performed to construct the competitive endogenous RNA (ceRNA) network of ADI intervention in HCC and to establish the relationship between the critical targets/pathways and the key corresponding components, which were involved in ADI against HCC in a synergistic way and were validated by molecular biology experiments. ADI exerted remarkable anti-HCC in vitro cells and in vivo zebrafish model, especially that the Hep 3B2.1-7 cell showed substantial sensibility to ADI. The ceRNA network revealed that the EGFR/PI3K/AKT signaling pathway was identified as the promising pathway. Furthermore, the meta-analysis also demonstrated the critical role of BIRC5 and FEN1 as key targets. Finally, the synergistic effect of ADI was revealed by discovering the inhibitory effect of cantharidin on BIRC5, formononetin on FEN1 and EGFR, as well as isofraxidin on EGFR. Our study unveiled that the incredible protective effect of ADI on HCC resulted from the synergistic inhibition effect of cantharidin, formononetin, and isofraxidin on multiple targets/pathways, including BIRC5, FEN1, and EGFR/PI3K/AKT, respectively, providing a scientific interpretation of ADI against HCC and a typical example of pharmacodynamic evaluation of other proprietary Chinese patent medicine. [Display omitted] • Systematically elucidated the role of ADI in the regulation of ncRNA in HCC. • Proved the synergistic effect of multiple components and pathways of ADI against HCC. • Established and confirmed the correspondence between components and targets in ADI. [ABSTRACT FROM AUTHOR]

Yinzhihuang granule (YZHG) has liver protective effect and can be used for clinical treatment of non-alcoholic fatty liver disease (NAFLD), but its material basis and mechanism need to be further clarified. This study aims to reveal the material basis and mechanism of YZHG treating NAFLD. Serum pharmacochemistry were employed to identify the components from YZHG. The potential targets of YZHG against NAFLD were predicted by system biology and then preliminarily verified by molecular docking. Furthermore, the functional mechanism of YZHG in NAFLD mice was elucidated by 16S rRNA sequencing and untargeted metabolomics. From YZHG, 52 compounds were identified, of which 42 were absorbed into the blood. Network pharmacology and molecular docking showed that YZHG treats NAFLD with multi-components and multi-targets. YZHG can improve the levels of blood lipids, liver enzymes, lipopolysaccharide (LPS), and inflammatory factors in NAFLD mice. YZHG can also significantly improve the diversity and richness of intestinal flora and regulate glycerophospholipid and sphingolipid metabolism. Moreover, Western Blot experiment showed that YZHG can regulate liver lipid metabolism and enhance intestinal barrier function. YZHG may treat NAFLD by improving the disruption of intestinal flora and enhancing the intestinal barrier. This will reduce the invasion of LPS into the liver subsequently regulate liver lipid metabolism and reduce liver inflammation. [Display omitted] • Identification of potential active components of YZHG. • Revealing the effect of YZHG on intestinal flora of NAFLD mice. • Revealing the effect of YZHG on liver metabolism in NAFLD mice. [ABSTRACT FROM AUTHOR]