Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Aqueous extract of Aconitum carmichaelii Debeaux attenuates sepsis-induced acute lung injury via regulation of TLR4/NF-κB pathway

Qinghai You¹ , Jinmei Wang², Lijuan Jiang³, Yuanmin Chang¹, Wenmei Li¹

¹Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province 230022; ²Department of Respiratory Medicine, Jining City, Shandong Province 272029; ³Department of Respiratory Medicine, The Chest Hospital of Anhui Province, Hefei City, Anhui Province 230000, China.

For correspondence:- Qinghai You Email: QinghaiYoudhj@163.com Tel:+8655162922913

Accepted: 28 February 2020 Published: 31 March 2020

Citation: You Q, Wang J, Jiang L, Chang Y, Li W. Aqueous extract of Aconitum carmichaelii Debeaux attenuates sepsis-induced acute lung injury via regulation of TLR4/NF-κB pathway. Trop J Pharm Res 2020; 19(3):533-539 doi: 10.4314/tjpr.v19i3.11

© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the therapeutic effect of aqueous extract of Aconitum carmichaelii Debeaux (AEACD) on sepsis-induced acute lung injury (ALI), as well as explore the underlying mechanism of action.

Methods: C57BL/6 mice were treated with AEACD by gavage (4.0 g/kg/day) for 5 days before cecal ligation and puncture (CLP) challenge. After 24 h, the pathological morphology of lung tissue and the biochemical parameters in bronchoalveolar lavage fluid (BALF) were determined by H&E staining and enzyme-linked immunosorbent assay (ELISA). Furthermore, the total protein content and lactate dehydrogenase (LDH) level of BALF, as well as the oxidative biomarkers (malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD)) were evaluated in the lung homogenates by ELISA assay. The levels of pro-inflammatory cytokines, TNFα, IL-1β, and IL-6, in lung tissue were measured by qRT-PCR or ELISA. Finally, key proteins in Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in lung tissue were evaluated by western blot.

Results: CLP challenge induced abnormal changes in the histological structures of lung tissue, lung wet-to-dry weight (W/D) ratio, protein content and LDH levels of BALF, which were remarkably reversed by AEACD. In addition, AEACD decreased MDA levels, and increased GSH levels and SOD activity in the lung tissue of CLP–treated mice (p < 0.05). Furthermore, AEACD attenuated the CLP challenge-induced upregulation of TNFα, IL-1β, and IL-6. Finally, AEACD inactivated TLR4/NF-κB pathway by upregulating IκBα and downregulating TLR4 and phosphorylated-p65 levels.

Conclusion: AEACD administration protects mice against sepsis-induced ALI through the regulation of oxidative stress and inflammatory responses in lung tissues. The underlying mechanism occurs by inhibiting TLR4/NF-κB signaling pathway.

Keywords: Aconitum carmichaelii Debeaux, Acute lung injury, Sepsis, TLR4, NF-κB