Quercetin attenuates oxidative stress‐induced apoptosis via SIRT1/AMPK‐mediated inhibition of ER stress in rat chondrocytes and prevents the progression of osteoarthritis in a rat model

Abstract

Apoptosis of chondrocytes are the main initiator of osteoarthritis (OA) and can be explained by oxidative stress and endoplasmic reticulum (ER) stress, thus the pharmacological interventions aimed at inhibiting of these pathways may be a promising approach for the management of OA. Quercetin is a member of the flavonoid family and has antioxidant and anti‐inflammatory properties in degenerative diseases. However, its effects and potential mechanisms on the pathological process of OA are not very clear. The present study aimed to investigate the protective effects of quercetin on OA and the underlying mechanisms. The tert‐butyl hydroperoxide (TBHP)‐stimulated rat chondrocytes and destabilization of the medial meniscus OA rat model was used to explore the protective effects of quercetin. Our results showed that quercetin treatment can attenuate oxidative stress, ER stress, and associated apoptosis. Moreover, quercetin inhibited ER stress through activating the sirtuin1/adenosine monophosphate‐activated protein kinase (SIRT1/AMPK) signaling pathway. The protective effects of quercetin were also observed in OA rat model which is evidenced by abolished cartilage degeneration and decreased chondrocytes apoptosis in the knee joints. Our results suggested that quercetin is a promising treatment for OA.

Silver Fir (Abies alba L.) Polyphenolic Extract Shows Beneficial Influence on Chondrogenesis In Vitro under Normal and Inflammatory Conditions

“…Pycnogenol at concentrations of up to 200 µg/mL has been shown to suppress pro-inflammatory responses in human chondrocytes and synovial fibroblasts in vitro [ 28 ]. Quercetin at 25 μM (7.6 µg/mL) has shown protective effects on tert -butyl hydroperoxide-stimulated rat chondrocytes, via the attenuation of oxidative stress and apoptosis [ 19 ]. In addition, 10 μM quercetin was shown to channel the differentiation of human bone-marrow-derived MSCs into adipocytes, rather than osteoblast bone cells [ 29 ].…”

“…Moreover, in patients with osteoarthritis, clinical studies with Pycnogenol as an adjunct supplement have provided pain relief, the improvement of stiffness, and enhanced mobility [ 17 ]. Quercetin is one of the most abundant polyphenols in the ‘Mediterranean diet’, and it has also been shown to promote reduced inflammation and pain relief in animal models of osteoarthritis [ 18 , 19 ]. Belinal is also a commercially available polyphenolic extract that is isolated from the branches of silver fir ( Abies alba L.).…”

Pathogenesis of Osteoarthritis: Risk Factors, Regulatory Pathways in Chondrocytes, and Experimental Models

“…These homocysteine-induced changes, along with proapoptosis effect, can be reversed by activating SIRT1/AMPK/PGC-1α signaling [123]. Animal studies show that quercetin attenuates oxidative stress-induced apoptosis and mitochondrial dysfunction via upregulated AMPK/SIRT1 signaling pathway in chondrocytes, thus preventing OA progression in murine models [124,125]. In a human study, transcription factor A mitochondrial (TFAM)-mediated activation of the AMPK/SIRT-1/PGC-1α pathway could reverse the deficiency of mitochondrial biogenesis in human OA chondrocytes, suggesting the potential of pharmacologic AMPK activators in mitigating OA progression [126].…”

The Citrus Flavonoid Naringenin Protects the Myocardium from Ageing-Dependent Dysfunction: Potential Role of SIRT1

“…In particular, in H9c2 cardiomyoblasts submitted to oxidative stress by H 2 O 2 treatment, NAR contained the βgalactosidase activity, as well as the expression of p21 and p16, well-known markers of ageing [15]; furthermore, bergamot juice, containing a high amount of NAR, increased the genic expression of the antiageing markers SIRT1, Nrf2, and FOXO1 in cardiac tissues [16]. Noteworthly, NAR exhibits close structural analogies with well-known SIRT1 activators, such as such as resveratrol (RES) and quercetin [17][18][19][20]. Therefore, we hypothesize that NAR can possess an interesting antisenescence SIRT1-mediated profile, useful as nutraceutical tool in humans.…”