Therapeutic effects of Nimbolide, an autophagy regulator, in ameliorating pulmonary fibrosis through attenuation of TGF-β1 driven epithelial-to-mesenchymal transition

International Immunopharmacology
M Prashanth GoudChandraiah Godugu

Abstract

Pulmonary fibrosis is an irreversible lung disorder with predictable decline in lung function leading to respiratory insufficiency. Incidence of pulmonary fibrosis has been apparently increasing worldwide. Though aetiology of this disease remains unclear, potential roles of infection, disordered cell biology, genetic influence etc. have been proposed. Pirfenidone and nintedanib are the only two US FDA approved drugs to treat pulmonary fibrosis. Autophagy is a catabolic intracellular pathway that plays a crucial role in maintaining cellular homeostasis, which is involved in many disorders including fibrotic diseases. The present study investigated the role of Nimbolide, an important active constituent of Neem in TGF-β1 induced in vitro and bleomycin induced in vivo model of pulmonary fibrosis, with a slight emphasis on regulation of fibrosis related autophagy. Protein expression studies showed significant reduction in mesenchymal, fibrotic markers and a substantial up regulation of epithelial markers upon treatment with Nimbolide. Nimbolide regulated autophagy signaling by dampening LC-3 and p-62 expression and increasing Beclin 1 expression as evidenced by immunohistochemistry and confocal microscopy. Our study demonstrates Nim...Continue Reading

Citations

Feb 7, 2020·Bioscience, Biotechnology, and Biochemistry·Wenjing MaYan He
Nov 28, 2019·Therapeutic Advances in Respiratory Disease·Shi-Xia LiaoYao Ou-Yang
Sep 4, 2020·Phytotherapy Research : PTR·Sai Manohar ThotaVenketesh Sivaramakrishnan
Feb 7, 2021·BioFactors·Seyede Atefe HosseiniAmirhossein Sahebkar
Mar 20, 2021·Journal of Medicinal Chemistry·Siddavaram NaginiRajakishore Mishra
Oct 8, 2021·Biomolecules & Therapeutics·Chawon YunChoong Jae Lee

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