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

Abstract

Although osteoarthritis (OA) significantly affects the quality of life of the elderly, there is still no effective treatment strategy. The standardized Ginkgo biloba L. extract preparation has been shown to have a wide range of therapeutic effects. Bilobalide, a unique ingredient of Ginkgo biloba, has anti-inflammatory and antioxidant pharmacological properties, but its mechanism of action on OA remains unknown. In this study, we investigated the effects of bilobalide on the development of OA through in vivo and in vitro experiments, as well as its potential anti-inflammatory mechanisms. The in vitro experiments demonstrated that bilobalide significantly inhibited the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and matrix metalloproteinase 13 (MMP13) in ATDC5 chondrocytes induced by Interleukin-1β (IL-1β). At the molecular level, bilobalide induced chondrocyte autophagy by activating the AMPK/SIRT1/mTOR signaling pathway, which increased the expression of autophagy-related Atg genes, up-regulated the expression of LC3 protein, and reduced the expression of the p62 protein. In vivo, bilobalide exerted significant anti-inflammatory and anti-extracellular matrix (ECM) degradation effects in a rat model of post-traumatic OA (PTOA) induced by anterior cruciate ligament transection (ACLT). Bilobalide could relieve joint pain in PTOA rats, inhibit the expression of iNOS and COX-2 protein in cartilage via the AMPK/SIRT1/mTOR pathway, and reduce the level of ECM degradation biomarkers in serum. In conclusion, bilobalide exhibits vigorous anti-inflammatory activity, presenting it as an interesting potential therapeutic agent for OA.

Osthole Suppresses Knee Osteoarthritis Development by Enhancing Autophagy Activated via the AMPK/ULK1 Pathway

“…In addition, autophagy inhibitor 3-MA was used to incubate IL-1β-treated chondrocytes to demonstrate the role of autophagy in osthole-mediated attenuation of OA-related degeneration. The expression of LC3 II protein and mRNA in chondrocytes treated with IL-1β for 24 h was decreased, whereas the expression of p62 was increased relative to controls, which was consistent with a previous report [ 17 ]. Similarly, immunofluorescence staining data showed that the level of LC3 II in IL-1β-treated chondrocytes was significantly reduced, as was the number of APs.…”

tRNA-Derived Fragment tRF-5009A Regulates Autophagy and Degeneration of Cartilage in Osteoarthritis via Targeting mTOR

“…Recent evidence has suggested that autophagy stabilizes the chondrocyte extracellular matrix, increases anabolism, but decreases catabolism, apoptosis, and ROS production [ 12 , 38 ]. Several studies have shown that mTOR signaling is involved in the activation of autophagy in chondrocytes in OA [ 36 , 39 , 40 ]. Inhibition of the activity of mTOR improves autophagy by directly phosphorylating the serine sites of ULK1, an important regulatory protein for autophagy induction [ 41 ].…”

Ginkgolide C slows the progression of osteoarthritis by activating Nrf2/HO-1 and blocking the NF-κB pathway

“…Ginkgo biloba L. has anti-inflammatory effects on human articular chondrocytes and OA rats ( Chen et al, 2013 ). The main components of Ginkgo biloba L. extract, bilobalide and ginkgolide B, have been reported to reverse OA ( Hu et al, 2018 ; Mao et al, 2019 ; Ma et al, 2022a ). However, the biological function of GC on cartilage has not been reported.…”

“…There are recent discoveries in the chemistry and mechanism of action of compounds in Ginkgo biloba L. extract ( Ma et al, 2022a ; Zhang R. et al, 2022 ; Samec et al, 2022 ). However, not many reports highlight the benefit of GC on degenerative cartilage diseases.…”