Phytochemicals Mediate Autophagy Against Osteoarthritis by Maintaining Cartilage Homeostasis

Abstract

Osteoarthritis (OA) is a common degenerative joint disease and is a leading cause of disability and reduced quality of life worldwide. There are currently no clinical treatments that can stop or slow down OA. Drugs have pain-relieving effects, but they do not slow down the course of OA and their long-term use can lead to serious side effects. Therefore, safe and clinically appropriate long-term treatments for OA are urgently needed. Autophagy is an intracellular protective mechanism, and targeting autophagy-related pathways has been found to prevent and treat various diseases. Attenuation of the autophagic pathway has now been found to disrupt cartilage homeostasis and plays an important role in the development of OA. Therefore, modulation of autophagic signaling pathways mediating cartilage homeostasis has been considered as a potential therapeutic option for OA. Phytochemicals are active ingredients from plants that have recently been found to reduce inflammatory factor levels in cartilage as well as attenuate chondrocyte apoptosis by modulating autophagy-related signaling pathways, which are not only widely available but also have the potential to alleviate the symptoms of OA. We reviewed preclinical studies and clinical studies of phytochemicals mediating autophagy to regulate cartilage homeostasis for the treatment of OA. The results suggest that phytochemicals derived from plant extracts can target relevant autophagic pathways as complementary and alternative agents for the treatment of OA if subjected to rigorous clinical trials and pharmacological tests.

Bilobalide Exerts Anti-Inflammatory Effects on Chondrocytes Through the AMPK/SIRT1/mTOR Pathway to Attenuate ACLT-Induced Post-Traumatic Osteoarthritis in Rats

“…Recent studies believe that autophagy is a key regulator of OA and a potential therapeutic target ( Valenti et al, 2021 ; Tian et al, 2021 ). The production of LC3II is a common sign of autophagy maturation, and the scaffold protein p62 is the substrate protein of autophagy, which mainly accumulates substances that need to be degraded in the cell, reflecting the degree of autophagy degradation ( Tanida, 2011 ).…”

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

“…Under the stresses of aging, inflammation and mechanical stimulation, increased apoptosis, decreased ECM production and excessive activation of proteases in chondrocytes contribute to the degeneration of cartilage and the destruction of the joint microarchitecture, leading to the development of diseases such as OA and RA. Contrarily, increased autophagy in chondrocytes can reduce the progression of these disorders by influencing intracellular metabolic processes, demonstrating the benefits of autophagy on chondrocyte survival and prevention of cartilage deterioration (Tian et al, 2021) (Figure 2E).…”

Daurisoline attenuates H2O2-induced chondrocyte autophagy by activating the PI3K/Akt/mTOR signaling pathway

“…Therefore, finding safe and effective drugs to treat OA is imperative. In recent years, traditional Chinese medicine (TCM) has been recognized worldwide for its natural advantages [ 32 ]. Daurisoline is an isoquinoline alkaloid mainly extracted from the Chinese herbal medicine Rhizoma Menispermi, which exhibits a wide range of pharmacological effects in the treatment of cardiovascular and cerebrovascular diseases, including anti-inflammatory and antitumor effects [ 20 , 22 , 23 ].…”