Taohong Siwu decoction ameliorates atherosclerosis in rats possibly through toll-like receptor 4/myeloid differentiation primary response protein 88/nuclear factor-κB signal pathway

J Tradit Chin Med. 2024 Feb;44(1):103-112. doi: 10.19852/j.cnki.jtcm.20231215.003.

Abstract

Objective: To investigate the effect of Taohong Siwu decoction (, TSD) on atherosclerosis in rats as well as investigate the underlying mechanism based on molecular docking.

Methods: Sixty healthy male Sprague-Dawley rats were randomly divided into 6 groups with 10 rats in each group: control group, model group, atorvastatin group (AT, 2.0 mg/kg), and TSD groups (20, 10, 5 g/kg) after 7 d of acclimation. The model of atherosclerosis was successfully established except the control group by high fat diet (HFD) and vitamin D2. Biochemical analyzers were used to detect the levels of triglyceride (TG), total cholestero (TC), low density lipoprotein-cholesterol (LDL-C) and high density lipid-cholesterol (HDL-C) in blood lipid. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were determined by enzyme-linked immunosorbent assay. Sudan IV staining and Hematoxylin and eosin staining (HE staining) were performed to observe the pathological changes in aortic tissue. Molecular docking technology was used to predict the best matching between the main components of TSD and the target proteins. The expression of target proteins was further detected by quantitative real time polymerase chain reaction (qRT-PCR) and Western blot analysis.

Results: The results showed that TSD restricted atherosclerosis development and decreased the inflammatory cytokines in plasma. Molecular docking results predicted that the main components of TSD showed a strong binding ability with toll-like receptor (TLR4), myeloid differentiation primary response protein 88 (MyD88), and nuclear factor kappa-B (NF-κB). The results of qRT-PCR and Western blot analysis showed that the mRNA and protein expressions of TLR4, MyD88 and NF-κB p65 in the aorta were reduced in atorvastatin group and TSD group.

Conclusions: TSD can ameliorate atherosclerosis in rats, and the underlying mechanism is supposed be related to the suppression of inflammatory response by regulating TLR4/MyD88/NF-κB signal pathway.

Keywords: NF-kappa B; Taohong Siwu decoction; atherosclerosis; molecular docking simulation; myeloid differentiation factor 88; signal transduction; toll-like receptor 4.

MeSH terms

  • Animals
  • Atherosclerosis* / drug therapy
  • Atherosclerosis* / genetics
  • Atorvastatin / therapeutic use
  • Cholesterol
  • Drugs, Chinese Herbal*
  • Lipids
  • Male
  • Molecular Docking Simulation
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • NF-kappa B* / genetics
  • NF-kappa B* / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • NF-kappa B
  • Toll-Like Receptor 4
  • Taohong Siwu decoction II
  • Myeloid Differentiation Factor 88
  • Atorvastatin
  • Tumor Necrosis Factor-alpha
  • Lipids
  • Cholesterol
  • Drugs, Chinese Herbal