2. Academic Validation
  3. Capsaicin Attenuates LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Autophagy Through Regulation of the TRPV1/AKT Pathway

Capsaicin Attenuates LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Autophagy Through Regulation of the TRPV1/AKT Pathway

  • J Inflamm Res. 2024 Jan 9:17:153-170. doi: 10.2147/JIR.S441141.
Qin Hu 1 2,  Haoran Liu 1 2,  Ruiyu Wang 3,  Li Yao 3,  Shikun Chen 4,  Yang Wang 3,  Chuanzhu Lv 2 3 5
Affiliations

Affiliations

  • 1 Emergency and Trauma College, Hainan Medical University, Haikou, People's Republic of China.
  • 2 Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Medical University, Haikou, People's Republic of China.
  • 3 Emergency Medicine Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
  • 4 Department of Anesthesiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
  • 5 Research Unit of Island Emergency Medicine, Chinese Academy of Medical Sciences (No. 2019RU013), Hainan Medical University, Haikou, People's Republic of China.
PMID: 38223422 DOI: 10.2147/JIR.S441141
Abstract

Purpose: Acute lung injury (ALI) is a severe pulmonary disease characterized by damage to the alveoli and pulmonary blood vessels, leading to severe impairment of lung function. Studies on the effect of capsaicin (8-methyl-N-geranyl-6-nonamide, CAP) on lipopolysaccharide (LPS)-induced ALI in bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B) are still limited. This study aimed to investigate the effect and specific mechanism by which CAP improves LPS-induced ALI.

Methods: The present study investigated the effect of CAP and the potential underlying mechanisms in LPS-induced ALI in vitro and vivo via RNA Sequencing, Western blotting (WB), quantitative real-time Reverse transcription PCR (qRT‒PCR), enzyme-linked immunosorbent assay (ELISA), and transmission electron microscopy (TEM). The TRPV1 inhibitor AMG9810 and the Akt Agonist SC79 were used to confirm the protective effect of the TRPV1/Akt axis against ALI. The Autophagy agonist rapamycin (Rapa) and the Autophagy inhibitors 3-methyladenine (3-MA) and bafilomycin A1 (Baf-A1) were used to clarify the characteristics of LPS-induced Autophagy.

Results: Our findings demonstrated that CAP effectively suppressed inflammation and Autophagy in LPS-induced ALI, both in vivo and in vitro. This mechanism involves regulation by the TRPV1/Akt signaling pathway. By activating TRPV1, CAP reduces the expression of P-AKT, thereby exerting its anti-inflammatory and inhibitory effects on pro-death Autophagy. Furthermore, prior administration of CAP provided substantial protection to mice against ALI induced by LPS, reduced the lung wet/dry ratio, decreased proinflammatory cytokine expression, and downregulated LC3 expression.

Conclusion: Taken together, our results indicate that CAP protects against LPS-induced ALI by inhibiting inflammatory responses and autophagic death through the TRPV1/Akt signaling pathway, presenting a novel strategy for ALI therapy.

Keywords

AKT; Inflammation; TRPV1; acute lung injury; autophagy; capsaicin.

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