Hesperidin ameliorates bleomycin-induced experimental pulmonary fibrosis via inhibition of TGF-β1/Smad3/AMPK and IκBα/NF-κB pathways

Authors

  • Zheng Zhou Department of Respiratory Medicine, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, 450014, China
  • Amit D. Kandhare Department of Pharmacology, Center for Advanced Research in Pharmaceutical Sciences, Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Pune-411 038, India
  • Anwesha A. Kandhare Department of Pharmacology, Center for Advanced Research in Pharmaceutical Sciences, Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Pune-411 038, India
  • Subhash L. Bodhankar Department of Pharmacology, Center for Advanced Research in Pharmaceutical Sciences, Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Pune-411 038, India. Phone: +91-20-25437237, Fax: +91-20-25439383; E-mail: drslbodh@gmail.com

DOI:

https://doi.org/10.17179/excli2019-1094

Keywords:

AMPK, Bleomycin, Hesperidin, IκBα, NF-kB, Nrf2, Pulmonary fibrosis, Smad3, TGF-β1

Abstract

Bleomycin (BLM) is a chemotherapeutic agent which is associated with Idiopathic pulmonary fibrosis (IPF) due to its chronic administration. Hesperidin, a bioflavonoid has been reported to possess antioxidant, anti-inflammatory, wound healing, and antiapoptotic potential. To evaluate the therapeutic potential of hesperidin against BLM-induced pulmonary fibrosis and decipher its possible mechanism of action. Intraperitoneal administration of BLM (6 IU/kg) caused induction of IPF in Sprague-Dawley rats. Rats were treated with hesperidin (25, 50, and 100 mg/kg, p.o.) for 28 days, followed by estimation of various parameters in bronchoalveolar lavage fluid (BALF) and lung. Hesperidin (50 and 100 mg/kg) administration significantly ameliorated (p < 0.05) alterations induced by BLM in lung index, percent oxygen saturation, serum ALP and LDH levels, BALF differential cell count, and lung function test. Elevated levels of oxido-nitrosative stress, hydroxyproline, and myeloperoxidase levels in BALF and lung were significantly decreased by hesperidin on day 14. Hesperidin significantly inhibited BLM-induced down-regulated lung Nrf2 and HO-1 as well as up-regulated TNF-α, IL-1β, IL-6, collagen-1, TGF-β, and Smad-3 mRNA expressions. Western blot analysis showed that alteration in lung NF-κB, IκBα, AMPK, and PP2C-α protein expressions were ameliorated by hesperidin on day 28. Furthermore, BLM induced histological and ultrastructural aberrations in the lung which were attenuated by hesperidin treatment. Hesperidin alleviates BLM-induced IPF via inhibition of TGF-β1/Smad3/AMPK and IκBα/NF-κB pathways which in turn ameliorate the modulation of oxido-inflammatory markers (Nrf2 and HO-1) and pro-inflammatory markers (TNF-α, IL-1β, and IL-6) to reduce collagen deposition during pulmonary fibrosis.

Downloads

Published

2019-08-29

How to Cite

Zhou, Z., Kandhare, A. D., Kandhare, A. A., & Bodhankar, S. L. (2019). Hesperidin ameliorates bleomycin-induced experimental pulmonary fibrosis via inhibition of TGF-β1/Smad3/AMPK and IκBα/NF-κB pathways. EXCLI Journal, 18, 723–745. https://doi.org/10.17179/excli2019-1094

Issue

Vol. 18 (2019)

Section

Original articles

License

Authors who publish in this journal agree to the following terms:

  • The authors keep the copyright and grant the journal the right of first publication under the terms of the Creative Commons Attribution license, CC BY 4.0. This licencse permits unrestricted use, distribution and reproduction in any medium, provided that the original work is properly cited.
  • The use of general descriptive names, trade names, trademarks, and so forth in this publication, even if not specifically identified, does not imply that these names are not protected by the relevant laws and regulations.
  • Because the advice and information in this journal are believed to be true and accurate at the time of publication, neither the authors, the editors, nor the publisher accept any legal responsibility for any errors or omissions presented in the publication. The publisher makes no guarantee, express or implied, with respect to the material contained herein.
  • The authors can enter into additional contracts for the non-exclusive distribution of the journal's published version by citing the initial publication in this journal (e.g. publishing in an institutional repository or in a book).