2. Academic Validation
  3. A polysaccharide from Codonopsis pilosula roots attenuates carbon tetrachloride-induced liver fibrosis via modulation of TLR4/NF-κB and TGF-β1/Smad3 signaling pathway

A polysaccharide from Codonopsis pilosula roots attenuates carbon tetrachloride-induced liver fibrosis via modulation of TLR4/NF-κB and TGF-β1/Smad3 signaling pathway

  • Int Immunopharmacol. 2023 Apr 15;119:110180. doi: 10.1016/j.intimp.2023.110180.
Xianqun Meng 1,  Haixue Kuang 2,  Qiuhong Wang 3,  Hui Zhang 1,  Dan Wang 4,  Tingguo Kang 5
Affiliations

Affiliations

  • 1 Department of Traditional Chinese Medicine Identification, Liaoning University Of Traditional Chinese Medicine, Dalian 116600, China.
  • 2 Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China.
  • 3 Key Laboratory of Chinese Medicinal Herbs Preparation, Guangdong Pharmaceutical University, Guangdong 510000, China.
  • 4 Department of Traditional Chinese Medicine Identification, Liaoning University Of Traditional Chinese Medicine, Dalian 116600, China. Electronic address: [email protected].
  • 5 Department of Traditional Chinese Medicine Identification, Liaoning University Of Traditional Chinese Medicine, Dalian 116600, China. Electronic address: [email protected].
PMID: 37068337 DOI: 10.1016/j.intimp.2023.110180
Abstract

The present work reported the extraction, purification, characterization of a polysaccharide from roots of Codonopsis pilosula (CPP-A-1) and its effect on liver fibrosis. The findings exhibited that the molecular weight of CPP-A-1 was 9424 Da, and monosaccharide composition were glucose and fructose and minor contents of arabinose. Structural characterization of CPP-A-1 has a backbone consisting of→(2-β-D-Fruf-1)n→ (n ≈ 46-47). Treatment with CPP-A-1 inhibited the proliferation of transforming growth factor-beta 1 (TGF-β)-activated human hepatic stellate cell line (LX-2), and induced cell Apoptosis. We used carbon tetrachloride (CCl4) to construct mice model of liver fibrosis and subsequently administered CPP-A-1 treatment. The results showed that CPP-A-1 alleviated CCl4-induced liver fibrosis as demonstrated by reversing liver histological changes, decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) contents, collagen deposition, and downregulated fibrosis-related collagen I and α-smooth muscle actin (α-SMA), and inhibited the generation of excessive extracellular matrix (ECM) components by restoring the balance between Matrix Metalloproteinases (MMPs) and its inhibitor (TIMPs). Moreover, CPP-A-1 improved anti-oxidation effects detected by promoting liver superoxide dismutase (SOD), glutathione (GSH) and Mn-SOD levels, and inhibition of liver malondialdehyde (MDA) and iNOS levels. CPP-A-1 also ameliorated the inflammatory factor (tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6), and expression of inflammatory factor genes (TNF-α, IL-11 mRNA). In addition, our results showed that CPP-A-1 inhibited Toll-like Receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) and transforming growth factor-β1 (TGF-β1)/drosophila mothers against decapentaplegic 3 (SMAD3) signaling pathways. Furthermore, In vitro tests of LX-2 cells demonstrated that CPP-A-1 not only inhibited α-SMA expression with lipopolysaccharide (LPS) or TGF-β1 stimulation, but also inhibited TLR4/NF-κB and TGF-β1/SMAD3 signaling, similar to corresponding small-molecule inhibitors. Therefore, CPP-A-1 might exert suppressive effects against liver fibrosis by regulating TLR4/NF-κB and TGF-β1/SMAD3 signaling, our findings support a possible application of CPP-A-1 for the treatment of liver fibrosis.

Keywords

Liver fibrosis; NF-κB and TGF-β1; Polysaccharides from Codonopsis pilosula roots; Smad3 signaling pathway; TLR4.

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