Tetrastigma hemsleyanum Diels et Gilg ameliorates lipopolysaccharide induced sepsis via repairing the intestinal mucosal barrier

Biomed Pharmacother. 2022 Apr:148:112741. doi: 10.1016/j.biopha.2022.112741. Epub 2022 Feb 24.

Abstract

Objective: Sepsis causes excessive systemic inflammation and leads to multiple organ dysfunction syndrome (MODS). The intestine plays a key role in the occurrence and development of sepsis. Tetrastigma hemsleyanum Diels et Gilg (San ye qing, SYQ), a precious Chinese medicine, has been widely used for centuries due to its high traditional value, such as a remarkable anti-inflammatory effect. However, the role of SYQ in intestinal permeability during the development of sepsis needs to be discovered.

Methods: Mice were intraperitoneally injected with lipopolysaccharide (LPS) to simulate intestinal mucosal barrier function damage in sepsis. Pathological section, inflammatory cytokines, tight junctions, cell apoptosis, and intestinal flora were detected to evaluate the protective effect of SYQ on intestinal mucosal barrier injury in LPS-induced septic mice.

Results: The results showed that SYQ treatment obviously attenuated LPS-induced intestinal injury and reduced the production of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6). Besides, SYQ also up-regulated the expressions of tight junctions, including Zonula occludens 1 (ZO-1), Claudin-5, and Occludin along with a decreased in the levels of myosin light chain kinase (MLCK) and myosin light chain (MLC). In addition, SYQ down-regulated the expression of Bax/Bcl2 as well as that of cleaved caspase-3 to prevent the cells from undergoing apoptosis. Further, SYQ restored the diversity of the intestinal flora, increased the abundance of Firmicutes, and decreased the abundance of Bacteroidota.

Conclusions: The study indicated that SYQ exerted its protective effect on intestinal mucosal barrier injury in LPS-induced septic mice by reducing inflammatory response, improving the tight junction protein expression, inhibiting cell apoptosis, and adjusting the intestinal flora structure.

Keywords: Intestinal mucosal barrier damage; Lipopolysaccharide; Sepsis; Tetrastigma hemsleyanum Diels et Gilg (San ye qing).

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cytokines / metabolism
  • Drugs, Chinese Herbal / pharmacology*
  • Gastrointestinal Microbiome / drug effects
  • Interleukin-6 / metabolism
  • Intestinal Mucosa / drug effects*
  • Intestines / pathology
  • Lipopolysaccharides / adverse effects
  • Male
  • Mice
  • Mice, Inbred ICR
  • Myosin Light Chains / metabolism
  • Myosin-Light-Chain Kinase / metabolism
  • Occludin / metabolism
  • Sepsis / drug therapy*
  • Sepsis / metabolism
  • Tight Junction Proteins / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Vitaceae / chemistry*

Substances

  • Cytokines
  • Drugs, Chinese Herbal
  • Interleukin-6
  • Lipopolysaccharides
  • Myosin Light Chains
  • Occludin
  • Tight Junction Proteins
  • Tumor Necrosis Factor-alpha
  • Myosin-Light-Chain Kinase