Gut-liver axis modulation of Panax notoginseng saponins in nonalcoholic fatty liver disease

Yu Xu, Ning Wang, Hor Yue Tan, Sha Li, Cheng Zhang, Yibin Feng*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

33 Citations (Scopus)

Abstract

Background and aims: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related comorbidity, and it is characterized as a spectrum of liver abnormalities, including inflammation, steatosis, and fibrosis. The gut-liver axis is implicated in the pathogenesis and development of NAFLD. A promising drug agent targeting the gut-liver axis is expected to reverse NAFLD.

Methods: We utilized high-fat diet (HFD)-induced obese mice and obesity-prone Lepob mice to examine the gut-liver regulation of the natural medicine Panax Notoginseng Saponins (PNS) on NAFLD.

Results: PNS exhibited potent anti-lipogenesis and anti-fibrotic effects in NAFLD mice, that was associated with the TLR4-induced inflammatory signalling pathway in liver. More strikingly, PNS treatment caused a deceleration of gut-to-liver translocation of microbiota-derived short chain fatty acids (SCFAs) products. PNS-induced TLR4 inhibition and restoration of Claudin-1 and ZO-1 proteins in the gut-liver axis contributed to the reverse of leaky gut, which in turn abolished by the addition of lipopolysaccharide (LPS), an agonist of TLR4. Specifically, hepatic steatosis in HFD-treated mice was attenuated by PNS through regulating AMPKα, but restored by the replenishment of LPS. Meanwhile, the anti-fibrotic effect of PNS was abolished by LPS stimulation via the overproduction of collagen I/IV and α-SMA.

Conclusion: PNS exerted hepatoprotection against NAFLD in both ob/ob and HFD-induced obese mice, primarily by mediating the gut-liver axis in a TLR4-dependent manner.

Original languageEnglish
Pages (from-to)350-365
Number of pages16
JournalHepatology International
Volume15
Issue number2
DOIs
Publication statusPublished - Apr 2021

Scopus Subject Areas

  • Hepatology

User-Defined Keywords

  • Ampkα
  • Fibrosis
  • Gut translocation
  • Gut-liver axis
  • Leaky gut
  • NAFLD
  • PNS
  • Scfas
  • Steatosis
  • TLR4

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