<p>Punicalagin Inhibits Tert-Butyl Hydroperoxide-Induced Apoptosis and Extracellular Matrix Degradation in Chondrocytes by Activating Autophagy and Ameliorates Murine Osteoarthritis</p>

Abstract

Background Osteoarthritis (OA) is a prevalent articular disorder and has no entirely satisfactory treatment. Punicalagin (PUG) is a polyphenol which has shown multiple pharmacological effects on various diseases. However, the role of PUG in the treatment of OA has not been well defined. Methods The effects of PUG on anti-oxidative stress, anti-apoptosis, extracellular matrix (ECM) degradation and autophagy were evaluated in chondrocytes through Western blot and immunofluorescence (IF) staining. Meanwhile, the effects of PUG on destabilization of the medial meniscus (DMM) model were also assessed in vivo by performing histopathologic analysis and IF staining. Results In vitro, PUG treatment not only increased the level of HO-1 and SOD1 against oxidative stress but also suppressed the expression of apoptotic proteins and inhibited ECM degradation. Meanwhile, PUG treatment activated autophagy and restores autophagic flux in chondrocytes after tert-butyl hydroperoxide (TBHP) insult, inhibition of autophagy by 3-methyladenine (3-MA) partly abrogated the protective effects of PUG on chondrocytes. In vivo, degeneration of the articular cartilage following DMM was also ameliorated by PUG treatment. Conclusion PUG prevents the progression of OA through inhibition of apoptosis, oxidative stress and ECM degradation in chondrocytes, which mediated by the activation of autophagy.

Systematic review of the effects of pomegranate (Punica granatum) on osteoarthritis

“…In five articles, both animal and in vitro designs were detected. 24 , 25 , 27 , 28 , 47 Tables 2 - 4 demonstrated details of investigations.…”

“…Furthermore, animal and in vitro studies showed benefits of pomegranate in improving clinical features and reducing inflammatory and oxidative markers in OA. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]47 Discrepancy in findings on the clinical status and inflammatory markers between studies can be due to using different dosages, administration types, and preparation procedures.…”

“…14 Also, animal 19,20 and human 21,22 researches did not indicate any undesirable outcomes after pomegranate intake. Experimental studies [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] and clinical trials [40][41][42][43][44] investigated the beneficial properties of pomegranate in OA prevention and treatment. Nevertheless, no systematic review exists regarding pomegranate and OA; therefore, in present article, we systematically studied accessible researches regarding pomegranate and OA in human, animal, and in vitro models and likely mechanistic pathways.…”

Phytochemicals Mediate Autophagy Against Osteoarthritis by Maintaining Cartilage Homeostasis

“…Liu et al found that PUG promotes autophagy through the forkhead box O1/proteoglycan 4 (FOXO1/Prg4)/HIF3 α axis, inhibits inflammation and extracellular matrix degradation, and attenuates inflammatory damage caused by lipopolysaccharide (LPS) in rat chondrocytes ( Liu et al, 2021 ). In addition, Kong injected PUG in a mouse DMM model and showed that PUG increased antioxidant enzymes and reduced the degradation of apoptotic proteins and ECM by mediating autophagy, thus effectively stopping the progression ( Kong et al, 2020 ). Although preclinical studies have shown that PUG can reduces chondrocyte apoptosis and ECM degradation through mediating autophagy, its solubility is low and insufficient for effective use after oral administration, which greatly limits its clinical application ( Cerdá et al, 2005 ).…”

Rock2 Regulates Proliferation and Differentiation of Chondrocytes in Osteoarthritis through β-catenin Signaling

“…Previous studies aver that osteoarthritis (OA) is the most common degenerative joint disease [1], which is characterized by degradation of extracellular matrix (ECM) or progressive loss of cartilage [2,3]. With rising number of elderly population, number of patients with osteoarthritis is increasing, which adversely affect quality of life of elderly patients.…”