Hidrosmin Attenuates Inflammatory Response Induced by IL1β by Suppressing the Activation of NF-κB Involving Nrf2/HO1 Pathway in Human Osteoarthritis Chondrocytes

Osteoarthritis (OA) is a disorder of joints involving degeneration and destruction of cartilages. Inflammation has been found to play an important role in the development of OA. Hidrosmin (HDS) is a flavone useful in venous insufficiency disorders and cancer. However, its role in OA remains unexplored. Here we reported the anti-inflammatory effect of Hidrosmin in OA utilizing both in vivo and in vitro studies.The primary chondrocytes were used for in vitro studies. Chondrocytes were submitted to immunofluorescence and toluidine blue staining. C57BL/6 male mice were used for In vivo experiment for creating an osteoarthritis model by surgical destabilization of the medial meniscus. CCK-8 assay was done for cell viability studies, Levels of nitric oxide were studied by Griess reaction, western blot analysis and qRT-PCR analysis was done for analyzing the levels of PGE-2, TNF-α, IL-6, collagen II, COX-2, iNOS, MMP-13, ADAMTS, Nrf2, HO-1, p65 and IκBα. Immunohistochemical assay and histopathological analysis were done for tissue studies. In silico analysis was done by performing molecular docking studies with MGL tools.The in vitro results suggested HDS inhibited the levels of cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), nitric oxide (NO) and IL-1β mediated levels of iNOS. Hidrosmin also suppressed the levels of ADAMTS-5 and IL-1β-induced MMP-13, whereas the levels of aggrecan and collagen II were up-regulated. Mechanistic study suggested HDS suppressed the nuclear factor kappa B (NF-κB) via targeting the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in chondrocytes. The outcomes of molecular docking studies confirmed that Nrf2 had a potential binding affinity with Hidrosmin as seen by lower binding energies.The findings of the study suggested HDS could be a potential molecule for halting the progression and development of osteoarthritis.