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Polygonatum sibiricum polysaccharides prevent LPS-induced acute lung injury by inhibiting inflammation via the TLR4/Myd88/NF-?B pathway.

ABSTRACT: Inflammation plays an important role in cases of acute lung injury (ALI), and the Toll-like receptor 4/nuclear factor-?B (TLR4/NF-?B) pathway, which can be regulated by Polygonatum sibiricum polysaccharides (PSPs), is closely related to the dynamics of lipopolysaccharide (LPS)-induced inflammation. Thus, we sought to evaluate whether or not PSPs prevent LPS-induced ALI by way of inhibiting inflammation via the TLR4/NF-?B pathway in rats. We established an ALI rat model by tracheal instillation of LPS, and by pre-injection of PSPs into rats to examine PSPs in the ALI rat model. We found that PSPs attenuated LPS-induced lung pathological changes in ALI rats, decreased LPS-induced myeloperoxidase (MOP) activity, and elevated malondialdehyde (MDA) levels in lung tissue. However, PSPs also decreased the LPS-induced increase in the neutrophil ratio, and decreased inflammatory factor levels in bronchoalveolar lavage fluid (BALF). Moreover, PSPs decreased LPS-induced increases in inflammatory factors measured by mRNA expression, and altered the levels of expression of TLR4, medullary differentiation protein 88 (Myd88), p-IKB-?/IKB-? and p-p65/p65 proteins in lung tissue. In vitro, PSPs also reduced apoptosis induced by LPS in BEAS-2B cells by suppressing inflammation through its effect of inhibiting the TLR4/NF-?B pathway. In conclusion, our results suggest that PSPs may be a potential drug for effective treatment of LPS-induced ALI, due to the ability to inhibit inflammation through effects exerted on the TLR4/Myd88/NF-?B pathway.

SUBMITTER: Liu TY

PROVIDER: S-EPMC7444378 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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<i>Polygonatum sibiricum</i> polysaccharides prevent LPS-induced acute lung injury by inhibiting inflammation via the TLR4/Myd88/NF-κB pathway.

Liu Tian-Yin TY Zhao Li-Li LL Chen Shi-Biao SB Hou Ben-Chao BC Huang Jian J Hong Xiu X Qing Lian L Fang Yu Y Tao Zhe Z

Experimental and therapeutic medicine 20200805 4

Inflammation plays an important role in cases of acute lung injury (ALI), and the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway, which can be regulated by <i>Polygonatum sibiricum</i> polysaccharides (PSPs), is closely related to the dynamics of lipopolysaccharide (LPS)-induced inflammation. Thus, we sought to evaluate whether or not PSPs prevent LPS-induced ALI by way of inhibiting inflammation via the TLR4/NF-κB pathway in rats. We established an ALI rat model by tracheal instill ...[more]

PMID: 32855724

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Project description:Background:It is widely accepted that inflammation may contribute to cognitive impairment in patients with vascular dementia (VD). Our prior clinical researches have reported that acupuncture can alleviate cognitive function in VD, but the underlying mechanisms are still unclear. The purpose of this research was to explore whether acupuncture alleviates cognitive impairment by suppressing the microRNA-93- (miR-93-) mediated Toll-like receptor (TLR) signaling pathway, which triggers inflammatory responses in the central nervous system. Methods:VD was established by permanent bilateral common carotid artery occlusion in male Wistar rats. Three days after operation, the rats began daily treatment with acupuncture for two weeks. The levels of miR-93, Toll-like receptors (TLR2 and TLR4), intracellular signaling molecules (myeloid differentiation factor 88 (MyD88) and nuclear factor-kappa B (NF-?B)), and inflammatory cytokines were subsequently detected. TLR4 colocalized with neurons, microglia, and astrocytes in the hippocampus was evaluated. Neuroinflammation and cognitive function were determined after intracerebroventricular injection of TLR4 antagonist TAK-242 or agonist lipopolysaccharide (LPS) with or without acupuncture. Results:We found that acupuncture notably repressed the expression of inflammatory cytokines in the hippocampus and plasma of VD rats. The expression of TLR4, but not TLR2, was markedly downregulated by acupuncture, accompanied by a decrease in miR-93 and MyD88/NF-?B signaling pathway activation. The overexpression of TLR4 in microglia, but not in astrocytes and neurons, was reversed by acupuncture. Furthermore, intracerebroventricular injection of TAK-242 had similar effects to acupuncture on inflammation and cognitive function, while LPS injection abolished the beneficial effects of acupuncture. Conclusions:Taken together, these findings provide evidence that acupuncture attenuates cognitive impairment associated with inflammation through inhibition of the miR-93-mediated TLR4/MyD88/NF-?B signaling pathway in experimental VD. Acupuncture serves as a promising alternative therapy and may be an underlying TLR4 inhibitor for the treatment of VD.

Dataset Information

Polygonatum sibiricum polysaccharides prevent LPS-induced acute lung injury by inhibiting inflammation via the TLR4/Myd88/NF-?B pathway.

Publications

<i>Polygonatum sibiricum</i> polysaccharides prevent LPS-induced acute lung injury by inhibiting inflammation via the TLR4/Myd88/NF-κB pathway.

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