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Protective Effect of Astragaloside IV Against Paraquat-Induced Lung Injury in Mice by Suppressing Rho Signaling

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Abstract

The purpose of the present study was to evaluate the protective effects of astragaloside IV (AS IV) against paraquat (PQ)-induced pulmonary injury in vivo. Fifty BALB/C mice were randomized into five groups: (1) control, (2) PQ, (3) PQ + dexamethasone (Dex, 5 mg/kg), (4) PQ + AS IV (50 mg/kg), and (5) PQ + AS IV (100 mg/kg). A single dose of PQ (50 mg/kg, i.p.) was intraperitoneally given to induced acute lung injury. Then, mice were treated with AS IV (50 and 100 mg/kg/day, orally) for 5 days. At the end of the experiment, animals were euthanized; then, the bronchoalveolar lavage fluid (BALF) and lung tissues were collected for histological observation, biochemical assay, and Western blot analysis. Malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in lung tissues, and interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α) levels in BALF were determined. Histological examination indicated that AS IV attenuated lung damage caused by PQ. Biochemical results showed that AS IV treatment significantly reduced the levels of MDA, MPO, and inflammatory cytokines while increased the levels of SOD, CAT, and GSH-Px compared with those in PQ group. Western blot results revealed that AS IV attenuated the Txnip/Trx expressions and inhibited Rho/ROCK/nuclear factor kappaB (NF-κB) signaling pathway in PQ-challenged mice. These findings suggested the protective effect of AS IV as a natural product on PQ-induced pulmonary injury.

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Acknowledgments

This study was supported by grants of the Natural Science Foundation of Jiangsu Province of China (BK20150707) and the Fundamental Research Funds for the Central Universities JKZD2013009 and ZJ15030). This Project also funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Research Innovation Program Project for Graduate Students in Jiangsu Province (CXZZ13_03), National Undergraduate Training Programs for Innovation and Entrepreneurship (G13034) and the Representational Achievement Cultivating Project of State Key Laboratory of Natural Medicines (SKLNMBZ201402).

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Authors and Affiliations

  1. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China

    Tong Chen, Ruoning Wang, Wenjiao Jiang, Ang Xu, Guo Lu, Yi Ren, Yangmei Xu, Yangyang Song, Hui Ji & Zhanqiang Ma

  2. School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China

    Huimin Wang & Shoulei Yong

  3. Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 210009, China

    Zhanqiang Ma

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  1. Tong Chen
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Chen, T., Wang, R., Jiang, W. et al. Protective Effect of Astragaloside IV Against Paraquat-Induced Lung Injury in Mice by Suppressing Rho Signaling. Inflammation 39, 483–492 (2016). https://doi.org/10.1007/s10753-015-0272-4

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