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The Inhibitory Effects of Cyclodepsipeptides from the Entomopathogenic Fungus Beauveria bassiana on Myofibroblast Differentiation in A549 Alveolar Epithelial Cells

1
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea
2
Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knöll-Institute, Beutenbergstraße 11a, 07745 Jena, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equality to this work.
Molecules 2018, 23(10), 2568; https://doi.org/10.3390/molecules23102568
Received: 6 September 2018 / Revised: 1 October 2018 / Accepted: 6 October 2018 / Published: 8 October 2018
(This article belongs to the Section Natural Products Chemistry)
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Abstract

Pulmonary fibrosis (PF) is a chronic and fatal lung disease with few treatment options. Although the pathogenesis of PF is not clear, a chronic inflammatory response to continuous damage is considered the cause of pulmonary fibrosis. PF is characterized by excessive accumulation of extracellular matrix (ECM), therefore, inhibition of myofibroblast differentiation is a good therapeutic target for PF. As part of our continuing endeavor to explore biologically active metabolites from insect-associated microbes, we found that the MeOH extract of the culture broth from the entomopathogenic fungus Beauveria bassiana inhibited collagen induction and E-cadherin down-regulation. In order to identify active compounds, we carried out chemical analysis of the MeOH extract with the assistance of LC/MS-guided isolation approach, which led to the successful identification of four cyclodepsipeptides 14. Among the isolates, compound 2 showed inhibitory effects on myofibroblast differentiation induced by TGF-β1. Compound 2 inhibited induction of α-SMA and N-cadherin, which are myofibroblast markers, and blocked the accumulation of ECM proteins such as collagen and fibronectin. Overall these findings demonstrate that compound 2 can be used to attenuate pulmonary fibrosis by targeting myo- fibroblast differentiation. View Full-Text
Keywords: pulmonary fibrosis; Beauveria bassiana; cyclodepsipeptides; myofibroblast differentiation; extracellular matrix (ECM) pulmonary fibrosis; Beauveria bassiana; cyclodepsipeptides; myofibroblast differentiation; extracellular matrix (ECM)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Park, Y.J.; Lee, S.R.; Kim, D.M.; Yu, J.S.; Beemelmanns, C.; Chung, K.H.; Kim, K.H. The Inhibitory Effects of Cyclodepsipeptides from the Entomopathogenic Fungus Beauveria bassiana on Myofibroblast Differentiation in A549 Alveolar Epithelial Cells. Molecules 2018, 23, 2568.

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