Journal Article

Picroside II suppresses chondrocyte pyroptosis through MAPK/NF-κB/NLRP3 signaling pathway alleviates osteoarthritis

Wang, Haibin, Pan, Zhaofeng, Zhou, Chi, He, Qi, Xiao, Jiacong, Li, Shaocong, Wang, Fanchen, Wang, Xintian, Li, Miao

2024

Overview

Picroside II (P-II) is the main bioactive constituent of Picrorhiza Kurroa, a traditional Chinese herb of interest for its proven anti-inflammatory properties. Its beneficial effects have been noted across several physiological systems, including the nervous, circulatory, and digestive, capable of treating a wide range of diseases. Nevertheless, the potential of Picroside II to treat osteoarthritis (OA) and the mechanisms behind its efficacy remain largely unexplored. This study aims to evaluate the efficacy of Picroside II in the treatment of osteoarthritis and its potential molecular mechanisms. In vitro, we induced cellular inflammation in chondrocytes with lipopolysaccharide (LPS) and subsequently treated with Picroside II to assess protective effect on chondrocyte. We employed the Cell Counting Kit-8 (CCK-8) assay to assess the impact of Picroside II on cell viability and select the optimal Picroside II concentration for subsequent experiments. We explored the effect of Picroside II on chondrocyte pyroptosis and its underlying molecular mechanisms by qRT-PCR, Western blot (WB) and immunofluorescence. In vivo, we established the destabilization of the medial meniscus surgery to create an OA mouse model. The therapeutic effects of Picroside II were then assessed through Micro-CT scanning, Hematoxylin-eosin (H&E) staining, Safranin O-Fast Green (S&F) staining, immunohistochemistry and immunofluorescence. In in vitro studies, toluidine blue and CCK-8 results showed that a certain concentration of Picroside II had a restorative effect on the viability of chondrocytes inhibited by LPS. Picroside II notably suppressed the expression levels of caspase-1, IL-18, and IL-1β, which consequently led to the reduction of pyroptosis. Moreover, Picroside II was shown to decrease NLRP3 inflammasome activation, via the MAPK/NF-κB signaling pathway. In vivo studies have shown that Picroside II can effectively reduce subchondral bone destruction and osteophyte formation in the knee joint of mice after DMM surgery. Our research suggests that Picroside II can inhibit chondrocyte pyroptosis and ameliorate osteoarthritis progression by modulating the MAPK/NF-κB signaling pathway.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Anti-inflammatory agents / Antibodies / Arthritis / Biology and Life Sciences / Bone growth / Bone surgery / Cartilage / Caspase-1 / Cell culture / Cell viability / Cholecystokinin / Chondrocytes / Chondrocytes - drug effects / Chondrocytes - metabolism / Chondrocytes - pathology / Cinnamates - pharmacology / Cinnamates - therapeutic use / Computed tomography / Destabilization / Effectiveness / Herbal medicine / Immunofluorescence / Immunohistochemistry / In vitro methods and tests / In vivo methods and tests / Inflammasomes / Iridoid Glucosides - pharmacology / Lipopolysaccharides / Lipopolysaccharides - pharmacology / Male / MAP kinase / MAP Kinase Signaling System - drug effects / Medical research / Medicine and Health Sciences / Meniscus / Mice / Mice, Inbred C57BL / Molecular modelling / NF-kappa B - metabolism / NF-κB protein / NLR Family, Pyrin Domain-Containing 3 Protein - metabolism / Osteoarthritis / Osteoarthritis - drug therapy / Osteoarthritis - metabolism / Osteoarthritis - pathology / Phosphorylation / Physiological effects / Proteins / Pyroptosis / Pyroptosis - drug effects / Research and Analysis Methods / Signal transduction / Signal Transduction - drug effects / Staining / Subchondral bone / Surgery / Toluidine / Toluidine blue