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.

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

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Section

Original articles