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

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. See also Figure 1(Fig. 1).