Tanshinone IIA inhibits osteoclastogenesis in rheumatoid arthritis via LDHC-regulated ROS generation

Abstract

Rheumatoid arthritis (RA) is characterized by bone destruction in the afflicted joints, and during the process of bone destruction, osteoclasts play a crucial role. Tanshinone IIA (Tan IIA) has shown anti-inflammatory effects in RA. However, the exact molecular mechanisms by which it delays bone destruction remain largely unexplained. Here, we found that Tan IIA decreased the severity of and ameliorated bone loss in an AIA rat model. In vitro, Tan IIA inhibited RANKL-induced osteoclast differentiation. By activity-based protein analysis (ABPP) combined with LC‒MS/MS, we discovered that Tan IIA covalently binds to the lactate dehydrogenase subunit LDHC and inhibits its enzymatic activity. Moreover, we found that Tan IIA inhibits the generation of osteoclast-specific markers by reducing the accumulation of reactive oxygen species (ROS), thus reducing osteoclast differentiation. Finally, our results reveal that Tan IIA suppresses osteoclast differentiation via LDHC-mediated ROS generation in osteoclasts. Tan IIA can thus be regarded as an effective drug for the treatment of bone damage in RA.

The combination of Tanshinone IIA and Astragaloside IV attenuates myocardial ischemia–reperfusion injury by inhibiting the STING pathway

“…The mice were randomly divided into different groups for the experiment, including the sham group (sham), ischemia/reperfusion (IR) group, IR + As-IV group, IR + Ta-IIA group, and IR + Co group, with each group consisting of six mice. The dosages of As-IV and Ta-IIA were determined based on previous studies [ 24 , 26 ], The sham and IR groups were given PBS. In the drug treatment groups, intraperitoneal injections of As-IV (15 mg/kg/day), Ta-IIA (10 mg/kg/day) and the combination therapy were initiated 7 days prior to the IR surgery and continued until 7 days after the surgery.…”

“…Tanshinone IIA (Ta-IIA), the main active ingredient in Salvia miltiorrhiza Bunge [ 19 , 22 , 23 ], and Astragaloside IV (As-IV), the main active ingredient in Astragalus membranaceus (Fisch.) Bunge [ 24 , 25 ], have antioxidant, anti-inflammatory properties, and are widely used in the treatment of cardiovascular diseases in clinic in China [ 26 , 27 ]. In addition, Ta-IIA can inhibit platelet aggregation and prevent blood clots formation [ 19 ], As-IV is capable of regulating immune function by modulating the polarization of macrophages [ 28 ].…”

A Review of Advances in Molecular Imaging of Rheumatoid Arthritis: From In Vitro to Clinic Applications Using Radiolabeled Targeting Vectors with Technetium-99m

“…Fibroblast-like synoviocytes (FLSs) produce IL-6, leukotrienes and prostaglandins and migrate from joint to joint for disease propagation [ 12 , 14 , 24 , 25 ]. Synovial cell proliferation reduces capillary flow, increasing fluid volume in the synovium and resulting in hypoxia at the inflamed site [ 12 , 26 , 27 , 28 , 29 , 30 , 31 ]. Due to the increased volume in the synovium, angiogenesis occurs, induced by various factors, such as vascular endothelial growth factor (VEGF) [ 32 , 33 , 34 , 35 ].…”