Osteoarthritis (OA) is an age-related degenerative disease. Oxidative stress (OS) modulates OA pathogenesis by enhancing chondrocyte apoptosis and extracellular matrix (ECM) degeneration via activation of the endoplasmic reticulum (ER) stress. Prior studies revealed that safranal plays a critical role in multiple diseases treatments, but there are no reports on its effect on OA. Therefore, investigating the effect of safranal on OA is needed. As a compound that can lead to excessive reactive oxygen species (ROS) accumulation, tert-butyl hydroperoxide (TBHP) was used to induce OS and OS-mediated endoplasmic reticulum (ER) stress for imitating OA in vitro. Besides, the bilateral medial meniscus was removed to induce joint instability and excessive friction of the joint surface to establish destabilization of medial meniscus for imitating the initiation and progression of OA in vivo. We, next, conducted Western blot and RT-PCR analyses to identify biomarkers of the underlying signaling pathway. Our results demonstrated that 30 μM safranal strongly upregulated Sirt1 expression, suppressed TBHP-mediated ER stress, and, in turn, prevented chondrocyte apoptosis and ECM degeneration. Furthermore, compared with the other two classic signaling pathways of ER stress, safranal can inhibit the PERK-eIF2α-CHOP axis at the lower concentration (5 and 15 μM). In vivo, using Safranin O staining, X-ray, immunofluorescence (IF), and immunohistochemical (IHC) staining, we demonstrated that OA progression can be postponed with intraperitoneal injection of 90 and 180 mg/kg safranal in an OA mouse model. Taken together, our analyses revealed that safranal can potentially prevent OA development.
Citation: Zhang Z, Wu J, Teng C, Wang J, Wang L, Wu L, Chen W, Zhen Lin, and Zhongke Lin. Safranal Treatment Induces Sirt1 Expression and Inhibits Endoplasmic Reticulum Stress in Mouse Chondrocytes and Alleviates Osteoarthritis Progression in a Mouse Model. Journal of Agricultural and Food Chemistry Article ASAP. 2022. DOI: 10.1021/acs.jafc.2c01773