Title:Mairin from Huangqi Decoction Mitigates Liver Cirrhosis through
Suppression of Pro-inflammatory Signaling Pathways: A Network
Pharmacology and Experimental Study
Volume: 14
Issue: 5
Author(s): Di Meng*Shuang Ren*
Affiliation:
- Department of Traditional Chinese Medicine, The First Hospital of China Medical University, Shenyang, China
- Department of Traditional Chinese Medicine, The First Hospital of China Medical University, Shenyang, China
Keywords:
Liver cirrhosis, inflammation, huangqi decoction, mairin, HSC, treatments.
Abstract:
Background: Liver cirrhosis is a consequence of various chronic liver conditions and may
lead to liver failure and cancer. Huangqi Decoction (HQD) is a Traditional Chinese Medicine (TCM)
effective for treating liver conditions, including cirrhosis. Therefore, both the active ingredients and
the pharmacological actions of HQD deserve further exploration. The active components and pharmacological
actions of HQD in preventing and treating liver cirrhosis were investigated using network
pharmacology. The actions of the principal active ingredient, Mairin, were investigated empirically.
Methods: Using network pharmacology, the critical components of HQD were identified from multiple
databases, and UPLC screening and targets were investigated using Swiss Target Prediction.
Targets associated with liver cirrhosis were identified using the GeneCards database. GO and KEGG
enrichment analysis of targets that overlapped between HQD and cirrhosis were analyzed in DAVID,
and a “component-target-pathway” network for HQD was created in Cytoscape 3.7.2. The biological
functions of the key active component, Mairin, were investigated using in silico docking, cell experiments,
and evaluation in a carbon-tetrachloride (CCl4)-induced mouse model of liver cirrhosis.
CCK-8 and F-actin assays were used to measure cell viability and hepatic stellate cell (HSC) activation,
respectively; fibrosis was measured by histological and immunohistochemical evaluations, and
the levels of the cirrhosis-related protein α-SMA and predicted essential target proteins in the PI3KAKT,
NFκB-IκBα, and NLRP3-IL18 pathways were determined by western blotting.
Results: Fourteen active HQD components, 72 targets, and 10 pathways common to HQD and cirrhosis
were identified. Network analysis indicated the association of Mairin with most targets and
with inflammation through the PI3K/Akt, NF-κB, and NLRP3 pathways. Dose-dependent reductions
in the activation and proliferation of LX-2 cells after Mairin treatment were observed. Mairin reversed
the histopathological changes in the livers of cirrhosis model mice. Mairin also significantly
reduced the α-SMA, NF-κB, IκBα, NLRP3, and IL-18 protein levels while increasing those of p-
PI3K and p-Akt, suggesting that Mairin mitigates liver cirrhosis through modulation of the PI3KAKT,
NFκB-IκBα, and NLRP3-IL18 pathways.
Conclusion: Using a comprehensive investigative process involving network pharmacology, bioinformatics,
and experimental verification, it was found that Mairin, an active component of HQD,
may be useful for developing specific treatments for preventing and treating liver cirrhosis.
