Tetrahydrocoptisine Protects Rats from LPS-Induced Acute Lung Injury

Abstract

Recent studies show that nuclear factor-kappa B (NF-κB) signaling pathway plays a key role in contributing to the development of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Tetrahydrocoptisine is one of the main active components of Chelidonium majus L. and has been described to be effective in suppressing inflammation. The aim of the present study is to evaluate the protective effect of tetrahydrocoptisine on LPS-induced ALI in rats and clarify its underlying mechanisms of action. We found that in vivo pretreatment with tetrahydrocoptisine to rats 30 min before inducing ALI by LPS markedly decreased the mortality rate, lung wet weight to dry weight ratio, and ameliorated lung pathological changes. Meanwhile, tetrahydrocoptisine significantly inhibited the increase of the amounts of inflammatory cells, total protein content, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) secretion in the bronchoalveolar lavage fluids (BALFs). Furthermore, tetrahydrocoptisine inhibited myeloperoxidase (MPO) accumulation in lung tissue and alleviated TNF-α and IL-6 production in serum. Additionally, immunohistochemistry showed that tetrahydrocoptisine efficiently reduced nuclear factor-kappa B (NF-κB) activation by inhibiting the translocation of NF-κBp65. In conclusion, our results demonstrate that tetrahydrocoptisine possesses a protective effect on LPS-induced ALI through inhibiting of NF-κB signaling pathways, which may involve the inhibition of pulmonary inflammatory process.

Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms

“… Compounds Structure In vitro/in vivo Model (effective dose) Cells (effective concentration) Related pharmacological indicators Related molecular mechanisms Refs. Berberine 40 LPS/Cigarette smoke (10 mg/kg) 16HBE (10 μM) MPO↓ TNF-α↓ IL-6↓ IL8↓ KC↓ MIP-2↓ cPLA-2↓ MCP-1↓ Regulation of PERK‐mediated Nrf2/HO‐1 signaling pathway Inhibition of NF-κB signaling pathway [ [191] , [192] , [193] ] Tetrahydroberberrubine 41 LPS (10 mg/kg) THP-1 (10 μM) TNF-α↓ NO↓ Inactivation of MAPK, AKT and NF-κB signaling pathways [ 194 ] Cavidine 42 LPS (3 mg/kg) A549 (10 μg/mL) TNF-α↓ IL-6↓ Inhibition of NF-κB signaling pathway [ 195 ] Corynoline 43 LPS (15 mg/kg) MPO↓ TNF-α↓ IL-1β↓ IL-6↓ Up-regulation of Nrf2 signaling pathway Inactivation of NF-κB signaling pathway [ 196 ] Ukrain 44 I/R (70 mg/kg) TAS↓ TOS↓ OSI↓ None [ 197 ] Tetrahydhydrocoptisine 45 LPS (10 mg/kg) MPO↓ TNF-α↓ IL-6↓ Inhibition of NF-κB signaling pathway [ 198 ] Protostemonine 46 LPS (10 mg/kg) RAW264.7/BMDMs (30 μM) MPO↓ TNF-α↓ IL1-β↓ IL-6↓ iNOS↓ NO↓ Inactivation of MAPK and AKT signaling pathway [ 199 , ...…”

“…However, these protective effects of 20 mg/kg tetrahydhydrocoptisine were slightly weaker than of 5 mg/kg DEX. Additionally, the effects of tetrahydhydrocoptisine were due to its inhibition of the NF-κB signaling pathway [ 198 ].…”

Febuxostat protects rats against lipopolysaccharide-induced lung inflammation in a dose-dependent manner

“…Febuxostat-mediated anti-inflammatory effects are potentially related to its ability to limit oxidative stress. ROS are known to induce the expression of inflammation-related cytokines, which in turn promote the infiltration of inflammatory cells and subsequent further ROS generation by infiltrated neutrophils (Bhatia and Moochhala 2004;Guo and Ward 2007;Li et al 2014). Fig.…”

Platycodin D attenuates acute lung injury by suppressing apoptosis and inflammation in vivo and in vitro

“…NF-κB is required for maximal transcription of many cytokines, including pro-inflammatory mediator tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. These cytokines are activated by bacterial endotoxin via NF-κB signaling and released in the early stage of ALI [5][6][7]. Besides, the dysregulation of apoptotic pathways is thought to play an important role in the pathogenesis of ALI for the loss of normal functional cells in the lung.…”