Int. J. Mol. Sci. 2013, 14(12), 23581-23596; doi:10.3390/ijms141223581
Article

Protective Role of Andrographolide in Bleomycin-Induced Pulmonary Fibrosis in Mice

1,†email, 2,†email, 1email, 3email and 1,* email
1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, and State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China 2 Respiratory Medicine, First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan, China 3 Laboratory of Cellular and Molecular Biology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 9 October 2013; in revised form: 1 November 2013 / Accepted: 22 November 2013 / Published: 3 December 2013
(This article belongs to the Section Molecular Pathology)
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Abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic devastating disease with poor prognosis. Multiple pathological processes, including inflammation, epithelial mesenchymal transition (EMT), apoptosis, and oxidative stress, are involved in the pathogenesis of IPF. Recent findings suggested that nuclear factor-κB (NF-κB) is constitutively activated in IPF and acts as a central regulator in the pathogenesis of IPF. The aim of our study was to reveal the value of andrographolide on bleomycin-induced inflammation and fibrosis in mice. The indicated dosages of andrographolide were administered in mice with bleomycin-induced pulmonary fibrosis. On day 21, cell counts of total cells, macrophages, neutrophils and lymphocytes, alone with TNF-α in bronchoalveolar lavage fluid (BALF) were measured. HE staining and Masson’s trichrome (MT) staining were used to observe the histological alterations of lungs. The Ashcroft score and hydroxyproline content of lungs were also measured. TGF-β1 and α-SMA mRNA and protein were analyzed. Activation of NF-κB was determined by western blotting and electrophoretic mobility shift assay (EMSA). On day 21 after bleomycin stimulation, andrographolide dose-dependently inhibited the inflammatory cells and TNF-α in BALF. Meanwhile, our data demonstrated that the Ashcroft score and hydroxyproline content of the bleomycin-stimulated lung were reduced by andrographolide administration. Furthermore, andrographloide suppressed TGF-β1 and α-SMA mRNA and protein expression in bleomycin-induced pulmonary fibrosis. Meanwhile, andrographolide significantly dose-dependently inhibited the ratio of phospho-NF-κB p65/total NF-κB p65 and NF-κB p65 DNA binding activities. Our findings indicate that andrographolide compromised bleomycin-induced pulmonary inflammation and fibrosis possibly through inactivation of NF-κB. Andrographolide holds promise as a novel drug to treat the devastating disease of pulmonary fibrosis.
Keywords: andrographolide; bleomycin (BLM); pulmonary fibrosis; transforming growth factor-β1 (TGF-β1); alpha-smooth muscle actin (α-SMA); nuclear factor-κB (NF-κB)

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MDPI and ACS Style

Zhu, T.; Zhang, W.; Xiao, M.; Chen, H.; Jin, H. Protective Role of Andrographolide in Bleomycin-Induced Pulmonary Fibrosis in Mice. Int. J. Mol. Sci. 2013, 14, 23581-23596.

AMA Style

Zhu T, Zhang W, Xiao M, Chen H, Jin H. Protective Role of Andrographolide in Bleomycin-Induced Pulmonary Fibrosis in Mice. International Journal of Molecular Sciences. 2013; 14(12):23581-23596.

Chicago/Turabian Style

Zhu, Tao; Zhang, Wei; Xiao, Min; Chen, Hongying; Jin, Hong. 2013. "Protective Role of Andrographolide in Bleomycin-Induced Pulmonary Fibrosis in Mice." Int. J. Mol. Sci. 14, no. 12: 23581-23596.

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