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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

The findings of the study suggested HDS could be a potential molecule for halting the progression and development of osteoarthritis.

• Authors: Yu Mingchuan, Chen Xiang, Xiao Yuhong, Ye Jing, Liu Yu, Wang Di, Xiao Haili, Luo Jun
• Journal: Current cancer drug targets (Curr Cancer Drug Targets) (Feb 09 2023) ISSN: 1873-5576 [Electronic] Netherlands
• PMID: 36757036 (Publication Type: Journal Article)
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