Geniposide protects pulmonary arterial smooth muscle cells from lipopolysaccharide‑induced injury via α7nAchR‑mediated TLR‑4/MyD88 signaling

Abstract

Geniposide is a bioactive iridoid glucoside derived from Gardenia jasminoides that has proven anti-inflammatory effects against acute lung injury. The aim of this study was to determine whether geniposide could protect pulmonary arterial smooth muscle cells (PASMCs) from lipopolysaccharide (LPS)-induced injury and to explore the participation of α7 nicotinic acetylcholine receptor (α7nAChR), which was previously reported to suppress pro-inflammatory cytokine production in LPS-stimulated macrophages. In the present study, rat PASMCs were isolated and stimulated using LPS. The effect of geniposide on LPS-induced PASMC injury was then explored. Geniposide exerted anti-apoptotic and anti-inflammatory effects on LPS-treated PASMCs, as demonstrated by the downregulation of pro-apoptotic proteins and pro-inflammatory cytokines, respectively. Furthermore, the α7nAChR agonist PNU282987 accentuated the protective effect of geniposide against LPS-induced injury in PASMCs by inhibiting toll-like receptor-4/myeloid differentiation primary response 88 (TLR-4/MyD88) signaling and downregulating nuclear factor (NF)-κB expression. Conversely, methyllycaconitine, an inhibitor of α7nAChR, attenuated the effects of geniposide. These findings collectively suggested that in conjunction with geniposide, the activation of α7nAChR may contribute to further mitigating LPS-induced PASMC apoptosis and inflammation. In addition, the underlying mechanisms critically involve the NF-κB/MyD88 signaling axis. These results may provide novel insights into the treatment and management of lung diseases via geniposide administration.

Efficacy and Safety of Re Du Ning Injection for Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

“…Geniposide (the main iridoid in Gardenia) and chlorogenic acid in honeysuckle can inhibit acute and chronic inflammatory disease-related macrophage responses, reduce the release of inflammatory factors, lower C-reactive protein, and suppress infection at the same time [ 41 ]. Pharmacological experiments also showed that geniposide can protect pulmonary artery smooth muscle from lipopolysaccharide damage by affecting the tlr-4/myd88 signalling pathway, improve pulmonary function, and avoid the formation of pulmonary hypertension [ 42 ]. These mechanisms confirm the authenticity of the results of this study on FEV1 and FEV 1 /FVC, suggesting that Re Du Ning may be a new approach for improving exercise tolerance and delaying pulmonary function decline in patients with COPD.…”

Screening of new Paenibacillus polymyxa S3 and its disease resistance of grass carp (Ctenopharyngodon idellus)

“…MyD‐88 is an important linker signalling molecule in the pathway. They cooperate with other immune factors to remove the antigens in organisms (Shen et al, 2021). Based on the above analysis, strain S3 could upregulate the expression of immune‐related genes in grass carp tissues, thereby improving the immunity of grass carp.…”