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, and finding specific targets and effective drugs is a scientific concern. Currently, various biological constituents are isolated from traditional Chinese medicine and have been confirmed to possess multifunctional activities.
Magnolol is an active constituent of Houpu, which improves tissue function and exerts strong anti-endotoxin and anti-inflammatory effects. Thus, we aimed to identify the role of magnolol in the treatment of sepsis.
To assess the protective effect of magnolol on intestinal mucosal epithelial cells in sepsis and elucidate the underlying mechanisms.
We carried out animal studies and cell studies in vitro, respectively. In animal studies, enzyme-linked immunosorbent assay was used to measure the differentially expressed inflammatory factors and regulated on activation, normal T-cell expressed and secreted (RANTES) levels in serum and ileal tissue. In the in vitro experiments, Cell Counting Kit-8 and cell permeability assays were employed to determine the concentration of drug-containing serum that did not affect the activity of Caco2 cells but inhibited lipopolysaccharide (LPS)-induced permeability reduction. Immunofluorescence and Western blot assays were used to detect the protein 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 in different groups.
In animal studies, magnolol inhibited the expression of proinflammatory cytokines tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6 in a dose-dependent manner and suppressed the production of RANTES in sepsis rats. In the in vitro studies, magnolol inhibited the increase of p65 nucleation and down-regulated the production of the phosphorylated form of IKKβ in LPS-treated Caco2 cells. Moreover, magnolol inhibited the translocation of the transcription factor nuclear factor-kappa B (NF-κB) from the cytosol into the nucleus and downregulated the expression level of the chemokine RANTES in LPS-stimulated Caco2 cells.
Magnolol downregulates RANTES levels by inhibiting the LPS/NF-κB signaling pathway, resulting in the suppression of IL-1β, IL-6, and TNF-α expression that in turn, alleviates the mucosal barrier dysfunction in sepsis.
This study, for the first time, proved that magnolol plays a role in the treatment of sepsis by down-regulating RANTES, and further studies on the anti-inflammatory mechanism might provide an in-depth insight into novel methods for the clinical prevention and treatment of sepsis.