Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Loureirin B attenuates amiodarone-induced pulmonary fibrosis by suppression of TGFβ1/Smad2/3 pathway

Weixiu Ma¹, Haixia Shi², Guangming Wei³, Mao Hua¹, Jinhua Ma⁴, Jinxia Cui¹, Honggang Yu⁵

¹Department of Medicine; ²Department of Emergency Medical; ³Department of Nuclear Medicine, The Second Affiliated Hospital of Air Force Military Medical University, Xi'an City, Shaanxi Province 710038; ⁴Department of Oncology, Affiliated Hospital of Qinghai, Xining City, Qinghai Province 810000; ⁵Department of Pulmonary Disease, Xi'an Hospital of Traditional Chinese Medicine, Xi'an City, Shaanxi Province 710000, China.

For correspondence:- Honggang Yu Email: GHY76Ykju@163.com Tel:+862989626831

Accepted: 22 June 2020 Published: 31 July 2020

Citation: Ma W, Shi H, Wei G, Hua M, Ma J, Cui J, et al. Loureirin B attenuates amiodarone-induced pulmonary fibrosis by suppression of TGFβ1/Smad2/3 pathway. Trop J Pharm Res 2020; 19(7):1371-1376 doi: 10.4314/tjpr.v19i7.5

© 2020 The authors.
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Abstract

Purpose: To investigate the therapeutic effect of loureirin B (LB) on amiodarone (AD)-induced pulmonary fibrosis (PF).

Methods: Forty-eight male C57BL/6 mice, 8–10 weeks of age, were divided into four groups (n=12). Oral administration of amiodarone hydrochloride (AD) was performed for 4 weeks to induce pulmonary fibrosis. The degree of fibrosis was assessed by Masson staining, while collagen I and α-smooth muscle actin (α-SMA) levels were evaluated by Western blot analysis. ELISA was used to measure the levels of cytokines TNF-α, IL-1β, and IL-6 in bronchoalveolar lavage fluid (BALF) and lung tissue. Levels of p-Smad2, Smad2, p-Smad3 and Smad3 were determined by western blotting.

Results: AD treatment increased the collagen levels and expression levels of collagen I and α-smooth muscle actin (α-SMA) in lung tissue and of inflammatory cytokines TNF-α, IL-1β, and IL-6, in both bronchoalveolar lavage fluid (BALF) and lung tissue in a dose-dependent manner (p < 0.01). Furthermore, AD increased the levels of p-Smad2/3. AD-induced increases in collagen I and α-SMA levels were reversed by loureirin B (LB). In addition, LB reduced AD-induced increased levels of the inflammatory cytokines TNF-α, IL-1β, and IL-6 in both bronchoalveolar lavage fluid (BALF) and lung tissue (p < 0.01).

Conclusion: These results demonstrate that LB downregulates expression of fibrosis-related proteins and suppresses AD-induced PF. The mechanism responsible for the protective effect of LB on AD-induced PF might involve inhibition of the Smad2/3 pathway. Thus, LB is a potential therapeutic agent for the management of PF.

Keywords: Amiodarone, Loureirin B, Pulmonary fibrosis, Smad, Inflammation