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

Shen,San-Ying; Ren,Li-Quan; Chen,Hui-Dong; Zhu,Hong-Fei; Zhou,Deng-Feng; Zhang,Bo; Tan,Xiao-Qin; Xie,Yong-Hua

doi:10.3892/etm.2021.10668

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

Authors:
- San-Ying Shen
- Li-Quan Ren
- Hui-Dong Chen
- Hong-Fei Zhu
- Deng-Feng Zhou
- Bo Zhang
- Xiao-Qin Tan
- Yong-Hua Xie
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Affiliations: Department of Respiratory Medicine, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430033, P.R. China, Department of Medical Services, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430033, P.R. China, Department of Respiratory Medicine, Wuhan Jinyintan Hospital, Wuhan, Hubei 430023, P.R. China, Hubei Research Institute of Traditional Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430072, P.R. China, Department of Traditional Chinese Medicine, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430033, P.R. China
Published online on: August 31, 2021 https://doi.org/10.3892/etm.2021.10668
Article Number: 1234
Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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