Anti-sepsis effect of Xiaochaihu decoction based on the TLR4/MyD88/NF-κB signalling pathway

Qingxin Yang1, Yulong Wang2, Gefei Cao2

  • 1Department of Pharmacy, MianYang Orthopaedic Hospital, Mianyang, 621000, PR China.

Heliyon
|March 4, 2024
PubMed

Insights

Xiaochaihu decoction demonstrates significant anti-inflammatory and anti-septic effects in mice by modulating the TLR4-MyD88-NF-κB pathway. High and medium doses effectively reduced inflammatory mediators, supporting its clinical use.

Area of Science:

  • Pharmacology
  • Immunology
  • Traditional Chinese Medicine

Background:

  • Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection.
  • The Toll-like receptor 4 (TLR4)-MyD88-NF-κB signaling pathway plays a crucial role in the inflammatory response during sepsis.

Purpose of the Study:

  • To investigate the protective effects of Xiaochaihu decoction against sepsis in mice.
  • To elucidate the anti-inflammatory mechanisms of Xiaochaihu decoction involving the TLR4-MyD88-NF-κB pathway.
  • To identify the key active components responsible for the decoction's anti-inflammatory properties.

Main Methods:

  • Sepsis was induced in mice via intraperitoneal injection.
  • Effects were assessed by measuring white blood cells (WBC), platelets (PLT), serum nitric oxide (NO), IL-6, IL-1β, and TNF-α.
  • Gene and protein expression of key pathway components were analyzed using RT-PCR and Western blotting; tissue pathology was examined via HE staining.

Main Results:

  • Xiaochaihu decoction significantly reduced inflammatory mediators (IL-6, IL-1β, TNF-α, NO) in septic mice.
  • The decoction downregulated the expression of TLR4, MYD88, TRAF6, IKK, IKBα, and p65 at both gene and protein levels.
  • Significant protective effects were observed with high and medium doses, but not the low dose.

Conclusions:

  • Xiaochaihu decoction exhibits potent in vivo anti-inflammatory and anti-septic effects in a mouse model of sepsis.
  • These effects are mediated through the inhibition of the TLR4-MyD88-NF-κB signaling pathway.
  • The findings provide a scientific basis for the clinical application of Xiaochaihu decoction in managing sepsis.