[Effect of modified Danggui Shaoyao Powder on SOCS3/TLR4 signaling pathway in rats with chronic atrophic gastritis]

Zhongguo Zhong Yao Za Zhi. 2022 Aug;47(15):4128-4135. doi: 10.19540/j.cnki.cjcmm.20220325.701.
[Article in Chinese]

Abstract

This study aims to investigate the effect of modified Danggui Shaoyao Powder on the suppressor of cytokine signaling 3(SOCS3)/Toll-like receptor 4(TLR4) signaling pathway in gastric tissue of rats with chronic atrophic gastritis(CAG).Sixty SPF-grade SD rats were randomly assigned into the normal group, model group, Moluo Pills group, and high-, medium-, and low-dose groups of modified Danggui Shaoyao Powder.The rats in other groups except the normal group were treated with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) to establish the CAG model.After 12 weeks of modeling, the rats in each group were administrated with corresponding drugs by gavage for 8 weeks.After the last administration, the histopathological changes of rat gastric mucosa were observed via hematoxylin-eosin(HE) staining.The serum levels of IL-6, TNF-α, and CRP were determined by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of SOCS3 and TLR4 were determined by real-time PCR.The protein levels of SOCS3, TLR4, JAK2, p-JAK2, STAT3, and p-STAT3 in rat gastric tissue were measured by Western blot.Immunohistochemical method was employed to determine the protein levels of NF-κB, MyD88, NLRP3, Bcl-2, Bax, and Bad in rat gastric tissue.The results showed that modified Danggui Shaoyao Powder alleviated gastric mucosal atrophy of rats, significantly lowered the levels of IL-6, TNF-α, and CRP in rat serum, up-regulated the mRNA level of SOCS3, and down-regulated the mRNA level of TLR4 in rat gastric tissue.Furthermore, modified Danggui Shaoyao Powder up-regulated the protein level of SOCS3, down-regulated the protein levels of TLR4, p-JAK2, p-STAT3, NF-κB, MyD88, NLRP3, Bax, and Bad, and promoted the expression of Bcl-2 protein.Therefore, modified Danggui Shaoyao Powder may mitigate the gastric mucosal atrophy of rats by regulating the SOCS3/TLR4 signaling pathway.

Keywords: chronic atrophic gastritis; modified Danggui Shaoyao Powder; suppressor of cytokine signaling 3/Toll-like receptor 4 signaling pathway.

MeSH terms

  • Animals
  • Atrophy
  • Gastritis, Atrophic* / drug therapy
  • Gastritis, Atrophic* / genetics
  • Interleukin-6 / metabolism
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Powders
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Suppressor of Cytokine Signaling 3 Protein / genetics
  • Suppressor of Cytokine Signaling 3 Protein / metabolism
  • Toll-Like Receptor 4* / genetics
  • Toll-Like Receptor 4* / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Interleukin-6
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Powders
  • RNA, Messenger
  • Socs3 protein, rat
  • Suppressor of Cytokine Signaling 3 Protein
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein