Published online Dec 6, 2021. doi: 10.12998/wjcc.v9.i34.10451
Peer-review started: July 20, 2021
First decision: August 9, 2021
Revised: August 24, 2021
Accepted: October 18, 2021
Article in press: October 18, 2021
Published online: December 6, 2021
Sepsis is a major medical challenge. Magnolol is an active constituent of Houpu that improves tissue function and exerts strong anti-endotoxin and anti-inflammatory effects, but the mechanism by which it reduces intestinal inflammation in sepsis is yet unclear.
To assess the protective effect of magnolol on intestinal mucosal epithelial cells in sepsis and elucidate the underlying mechanisms.
Enzyme-linked immunosorbent assay was used to measure tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and regulated on activation, normal T-cell expressed and secreted (RANTES) levels in serum and ileal tissue in animal studies. The histopathological changes of the ileal mucosa in different groups were observed under a microscope. Cell Counting Kit-8 and cell permeability assays were used to determine the concentration of drug-containing serum that did not affect the activity of Caco2 cells but inhibited lipopolysaccharide (LPS)-induced decrease in permeability. Immunofluorescence and Western blot assays were used to detect the levels of RANTES, inhibitor of nuclear factor kappa-B kinase β (IKKβ), phosphorylated IKKβ (p-IKKβ), inhibitor of nuclear factor kappa-B kinase α (IκBα), p65, and p-p65 proteins in different groups in vitro.
In rats treated with LPS by intravenous tail injection in the presence or absence of magnolol, magnolol inhibited the expression of proinflammatory cytokines, IL-1β, IL-6, and TNF-α in a dose-dependent manner. In addition, magnolol suppressed the production of RANTES in LPS-stimulated sepsis rats. Moreover, in vitro studies suggested that magnolol inhibited the increase of p65 nucleation, thereby markedly downregulating the production of the phosphorylated form of IKKβ in LPS-treated Caco2 cells. Specifically, magnolol inhibited the translocation of the transcription factor nuclear factor-kappa B (NF-κB) from the cytosol into the nucleus and down-regulated the expression level of the chemokine RANTES in LPS-stimulated Caco2 cells.
Magnolol down-regulates RANTES levels by inhibiting the LPS/NF-κB signaling pathways, thereby suppressing IL-1β, IL-6, and TNF-α expression to alleviate the mucosal barrier dysfunction in sepsis.
Core Tip: In this study, it was found that magnolol inhibited the lipopolysaccharide-induced nuclear factor-kappa B signaling pathway in the intestinal mucosal epithelium to regulate the secretion of regulated on activation, normal T-cell expressed and secreted (RANTES) and thus reduce intestinal inflammation in sepsis. Various biological constituents, isolated from traditional Chinese medicine, show multifunctional activities. Magnolol, isolated from Magnolia, has been documented to possess a range of biological activities. The current results for the first time proved that magnolol plays a role in the treatment of sepsis by down-regulating RANTES. Thus, additional studies on its anti-inflammatory mechanism might provide novel ideas and methods for the clinical prevention and treatment of sepsis.