Activation of autophagy contributes to the protective effects of lycopene against oxidative stress‐induced apoptosis in rat chondrocytes

Abstract

Oxidative stress is commonly associated with osteoarthritis (OA). Lycopene (LYC), a natural carotenoid compound, is an effective antioxidant with potential cartilageprotecting actions. However, how it affects hydrogen peroxide (H 2 O 2 )-induced damage to the cartilage is unclear. In this study, an in vitro oxidative stress model was developed via treating primary chondrocytes with H 2 O 2 . Western blot, immunohistochemistry, and quantitative RT-PCR (qRT-PCR) were used to assess the levels of related factors. Reactive oxygen species (ROS) and apoptosis levels were analyzed by the use of appropriate probes and flow cytometry. The expression and activity of stress-specific enzymes (malondialdehyde, superoxide dismutase, and catalase) were also assessed. The role of autophagy was explored by using the inhibitor, 3-methyladenine (3-MA), as well as monodansylcadaverine staining, western blotting, and red fluorescent protein-green fluorescent protein-light chain 3 lentivirus infection. The result showed LYC exerted significant chondrocyte-protective effects, including reduced inflammation and chondrocyte degradation, increased chondrocyte proliferation, apoptosis inhibition, and reduced ROS production. LYC could effectively induce autophagy in the H 2 O 2 treatment group, and this effect could be attenuated by 3-MA. In terms of mechanism, LYC played a role in inhibiting MAPK and PI3K/Akt/NF-κB axis, which down-regulates levels of mTOR and had a potential therapeutic significance for cartilage degeneration.

Flavokawain A alleviates the progression of mouse osteoarthritis: An in vitro and in vivo study

“…Also, bioinformatic analysis suggested that the PI3K/AKT pathway and MAPK pathway could be two potential mechanisms of FKA involved in the occurrence and progression of OA. These mechanisms are directly linked to the onset and progression of OA (Wu et al, 2021), as well as closely Frontiers in Bioengineering and Biotechnology frontiersin.org related to autophagy. It has been demonstrated in previous studies that the PI3K/AKT/mTOR and MAPK pathways inhibition can reduce the inflammatory response in OA (Zhou et al, 2019).…”

Effects of Lycopene Attenuating Injuries in Ischemia and Reperfusion

“…As a highly effective antioxidant, lycopene can decrease the risk of disease by neutralizing reactive oxy-gen species (ROS) and reducing oxidative damage of some biomolecules (DNA, proteins, and lipids) [44,45]. In addition, lycopene has also acted through other mechanisms, including anti-inflammation [40], autophagy [46,47], apoptosis [48,49], proliferation [50,51], and pyroptosis [52].…”

Autophagy: An important target for natural products in the treatment of bone metabolic diseases

“…Currently, most studies based on natural products for the treatment of OA have been conducted by inducing autophagy in cartilage, and these products include the saponin Astragaloside IV from Astragalus membranaceus (Liu et al, 2017), polyphenol curcumin from Curcuma longa (Li X. et al, 2017;Chen T. et al, 2021;Yao et al, 2021;Jin et al, 2022), coumarins isopsoralen from Psoralea corylifolia seeds (Chen Z. et al, 2020), Icariin (Mi et al, 2018;Tang et al, 2021a), furocoumarin Columbianetin from the root of Radix Angelicae Pubescentis (Chen W. et al, 2022), glucoxilxanthone mangiferin from in various parts of Mangifera indica , flavonoid baicalin from the root of Scutellaria baicalensis (Li Z. et al, 2020), polyphenolic compound chlorogenic acid from coffee and plants such as Lonicera japonica (Zada et al, 2021), polyphenol anthocyanidin delphinidin from various brightly colored fruits and vegetables (Lee et al, 2020), polyphenol tannin punicalagin from the peel of Punica granatum (Kong (Wu et al, 2021), polymethoxylated flavonoid Sinensetin from citrus fruits (Zhou et al, 2021), isoflavonoid glabridin from the root of Glycyrrhiza glabra (Dai et al, 2021), triterpenoid saponin compound saikosaponin D from Bupleurum falcatum (Jiang et al, 2020), polyphenols (-)-Epigallocatechin 3-gallate from green tea (Huang et al, 2020), flavonoid rhoifolin from Rhus succedanea (Yan et al, 2021), quercetin (Lv et al, 2022), and naphthoquinone compound Shikonin from the root of Lithospermum erythrorhizon (Wang A. et al, 2022). Because of the large number, we have summarized in the table the specific mechanisms involved in these studies.…”