Ginsenoside Rb1 Alleviates Lipopolysaccharide-Induced Inflammatory Injury by Downregulating miR-222 in WI-38 Cells

Abstract

Pneumonia is a serious respiratory tract infection disease in children, which threatens to the health or life of children patients. Ginsenoside Rb1 (Rb1) is a principle active ingredient extracted from the root of Panax notoginseng (Burk.) F.H. Chen with anti-inflammatory effect. Our study aimed to determine the effects and molecular mechanisms of Rb1 on lipopolysaccharide (LPS)-induced inflammatory injury of lung fibroblasts WI-38 cells. Cell viability and apoptosis were evaluated by CCK-8 and flow cytometry, respectively. The production of inflammatory cytokines were measured by ELISA and RT-qPCR. miR-222 expression was examined by RT-qPCR. The expression levels of the nuclear factor-kappa B (NF-κB) p65 and phosphorylated p65 were detected by western blot. We found that LPS stimulation induced WI-38 cell inflammatory injury by inhibiting cell viability, and inducing apoptosis and inflammatory cytokine production, while treatment with Rb1 significantly attenuated LPS-induced inflammatory injury in WI-38 cells. Additionally, Rb1 decreased LPS-induced upregulation of miR-222 and activation of the NF-κB pathway in WI-38 cells. Overexpression of miR-222 abolished the inhibitory effects of Rb1 on LPS-induced viability reduction, apoptosis, inflammatory cytokine production and activation of the NF-κB pathway. In conclusion, Rb1 alleviated LPS-induced inflammatory injury in WI-38 cells via downregulating miR-222 and inactivation of the NF-kB pathway.

CITED2 alleviates lipopolysaccharide-induced inflammation and pyroptosis in - human lung fibroblast by inhibition of NF-κB pathway

“…25 Lipopolysaccharide induced the activation of NF-κB in lung fibroblasts, and facilitated the inflammatory injury in infantile pneumonia. 26 CITED2 has been shown to interact with p300, dissociat p65 from p300, and restrain p65 binding to the target promoters. 27 The overexpression of CITED2 weakened lipopolysaccharide-induced recruitment of NF-κB p65 to target promoters, thus inhibiting the transcriptional activity of NF-κB.…”

Ginsenosides from Panax ginseng as Key Modulators of NF-κB Signaling Are Powerful Anti-Inflammatory and Anticancer Agents

“…Rb1 reverses the immune cell population in lung tissue by inhibiting IκBα degradation, which leads to the inactivation of the NLRP3 inflammasome and IL-1β. Rb1 also downregulates inflammatory responses in an LPS-treated WI-38 human lung fibroblast cell line by targeting NF-κB signaling [ 120 ]. Specifically, Rb1 suppresses miR-222 activation, which is responsible for NF-κB activation [ 121 ].…”

Ginsenosides: a potential natural medicine to protect the lungs from lung cancer and inflammatory lung disease

“…156 Ginsenosides have been reported to reduce lung inflammation and lung injury caused by Staphylococcus aureus, lipopolysaccharides, intestinal ischemia-reperfusion, diabetes and so forth. [157][158][159][160][161] They mainly attenuate the inflammatory response by downregulating the NF-κB and MAPK pathways and inhibiting the expression of TLR4 receptors, COX-2 and NLRP3 inflammasomes, and attenuate oxidative stress and apoptosis by activating the Nrf2 signalling pathway and inhibiting endoplasmic reticulum stress, mitochondrial and death receptor- In vivo: g-PPT (10 mg/kg day −1 ) + gefitinib (50 mg/kg day −1 ), 4 weeks Induced the apoptosis of gefitinib-resistant cells "↑" means upregulation or increase, "↓" means downregulation or reduction, and "-" means not mentioned.…”