Abstract
Scabiosa comosa and S. tschilliensis (SCST) are traditionally used for liver diseases in Mongolian medicine. However, their active ingredients and molecular mechanisms are unknown. The present study employed network pharmacology and experimental verification approaches to decipher the common pharmacological mechanisms of SCST on liver fibrosis, which is the key step in liver diseases. We predicted the targets of all available SCST ingredients with the SWISS and SuperPred servers and clustered the targets related to liver fibrosis from DrugBank, the OMIM database and the literature. We further evaluated the links between the herbal ingredients and pharmacological actions to explore the potential mechanism of action of SCST. We found that the PPARG signalling pathway could be regulated by SCST for liver fibrosis through enrichment analysis. The key targets included 8 co-targets, including HSP90AA1, PPARG, HSP90AB1, STAT1, etc., which play pivotal roles in the pathogenesis of liver fibrosis. Additionally, the top 15 key compounds included flavonoids and phenylpropanoids. Central to the pathogenesis of liver fibrosis is trans-differentiation or activation of hepatic stellate cells (HSCs). Therefore, LX2 cells, an immortalized human HSC line, were studied. Here, a total 37 components were isolated and identified from the inflorescences of SCST, including the new compound tschilliensisin, and the first separated components, β-sitosterol and luteolin, and these compounds were assessed against anti-hepatic fibrosis. An MTT assay and quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses demonstrated that the flavonoids of SCST revealed anti-hepatic fibrosis effects via anti-proliferation and increases in the Stat1, Pparg, Hsp90aa1 genes and STAT1 and PPARG proteins in LX-2 cells. In conclusion, these results indicate that SCST has multi-targeted and multi-component synergistic anti-hepatic fibrosis effects.
Highlights
Hepatic fibrosis is a pathological consequence of chronic liver diseases, which can lead to cirrhosis and hepatocellular c arcinoma1,2
By mapping the candidate targets to the 66 known genes associated with hepatic fibrosis obtained from OMIM and DrugBank, 10 co-targets were found, including HSP90AA1, peroxisome proliferator-activated receptor gamma (PPARG), MAPT, HSP90AB1, signal transduction and transcriptional activator 1 (STAT1), and PPARA
Scabiosa comosa and S. tschilliensis (SCST) has been used in Mongolian medicine to treat liver diseases, and the ingredients of SCST mainly consist of flavonoids, phenylpropanoids and iridoids
Summary
Hepatic fibrosis is a pathological consequence of chronic liver diseases, which can lead to cirrhosis and hepatocellular c arcinoma. Quiescent HSCs (qHSCs) are lipid-containing cells that store retinoids and express higher levels of lipid-related genes, such as peroxisome proliferator-activated receptor gamma (PPARG). QHSCs are transformed into activated hepatic stellate cells (aHSCs) and gradually lose their fatstoring phenotype. It is clinically used to treat diseases such as pulmonary heat, liver heat, throat heat, headache, fever, cough, and jaundice. It is clinically used to treat diseases such as pulmonary heat, liver heat, throat heat, headache, fever, cough, and jaundice7 It was reviewed in the literature that SCST showed some pharmacological actions, such as fever relief, anti-inflammatory, antioxidative, renal ischaemia reperfusion injury protection, platelet aggregation inhibition, conscious sedation, and immune function enhancement. TCM network pharmacology can be used to understand the scientific basis of TCM herbal formulae at the molecular level and from a systemic perspective
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