Lycorine attenuates lipopolysaccharide-induced acute lung injury through the HMGB1/TLRs/NF-κB pathway

Abstract

Lung injury associated with systemic inflammatory response is a common problem affecting human health. Previous studies have shown that lycorine exerts a anti-inflammatory effect. However, whether lycorine alleviates lung injury remains unclear. To explore this issue, BALB/c mice and MLE-12 cells were treated with lipopolysaccharide (LPS) to establish lung injury mouse model and cell model, respectively. Glycyrrhizic acid, known as an inhibitor of ALI, was also used to study the effects of lycorine in vitro. Our results showed that after LPS treatment, the lung injury score, lung wet-to-dry weight ratio, and malondialdehyde (MDA) production in the lung tissues and the expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in bronchoalveolar lavage fluid were significantly increased, whereas their levels were decreased by lycorine. Additionally, LPS injection activated the high-mobility group box 1 (HMGB1)/Toll-like receptors (TLRs)/NF-κB pathway. However, lycorine treatment attenuated the activity of the HMGB1/TLRs/NF-κB pathway in the lung tissues. In vitro studies showed that lycorine administration significantly decreased the levels of inflammatory cytokines and MDA and attenuated the activity of the HMGB1/TLRs/NF-κB pathway in LPS-treated cells. Moreover, the inhibitory effects of lycorine on the inflammatory response and oxidative stress in LPS-treated lung cells were similar with that of glycyrrhizic acid, and this inhibition was intensified by both lycorine and glycyrrhizic acid treatment. We suggest that lycorine could alleviate LPS-induced lung injury of inflammation and oxidative stress by blocking the HMGB1/TLRs/NF-κB pathway, which gives a new perspective for ALI therapy to treat lycorine as a potential treatment clinically.

Lycorine ameliorates isoproterenol-induced cardiac dysfunction mainly via inhibiting inflammation, fibrosis, oxidative stress and apoptosis

“…As an alkaloid, LYC has been reported by several studies to have some significant anti-inflammatory, anti-fibrosis, antiviral, anti-aging, and anti-tumor activities [8][9][10][11][12]. LYC protects against acute lung injury induced by lipopolysaccharide mainly through inhibiting the production of pro-inflammatory mediators [25]. LYC also inhibits bleomycininduced pulmonary fibrosis, principally via suppressing the inflammatory response, which displays a similar effect of danshensu in bleomycin-induced pulmonary fibrosis [26,30].…”

“…Moreover, studies reported that LYC can attenuate lipopolysaccharide-induced acute lung injury and bleomycin-induced pulmonary fibrosis by suppressing inflammation. This implies that LYC might serve as a new potential therapeutic agent to alleviate inflammation and fibrosis in pulmonary diseases [ 25 , 26 ]. Due to these beneficial biological activities of LYC, we conducted a study to explore its effect on isoproterenol (ISO)-induced cardiac dysfunction.…”

Systematic identification of the interventional mechanism of Qingfei Xiaoyan Wan (QFXYW) in treatment of the cytokine storm in acute lung injury using transcriptomics-based system pharmacological analyses

“…Additionally, TLRs have special functions in lung-related diseases; for example, the activation of TLRs leads to the secretion of key inflammatory cytokines (IL-6 and TNF-α) (Ge et al. 2020 ), which have been reported to play a key role in early-stage ALI. Previous studies have shown that the JAK-STAT signalling pathway is regulated by a variety of cytokines, exerting a critical role in lung injury and immune mediation (Zheng and Li 2018 ).…”

Herbal Active Ingredients: Potential for the Prevention and Treatment of Acute Lung Injury

“…The anti-ALI mechanisms of herbal active ingredients are summarized in Figure 7. TLR2 or TLR4 activation can ease immune and inflammatory responses [93]. Studies have shown that hydroxysafflor yellow A and ginsenoside Rb1 can alleviate ALI by inhibiting the expression of TLR4 or TLR2 [37,94].…”

“…After invading the lung, LPS binds to the TLR2 or TLR4 receptor, which activates the NF- κ B pathway and induces inflammation. Therefore, inhibition of TLR2 or TLR4 activation can ease immune and inflammatory responses [ 93 ]. Studies have shown that hydroxysafflor yellow A and ginsenoside Rb1 can alleviate ALI by inhibiting the expression of TLR4 or TLR2 [ 37 , 94 ].…”