Identification of anti-inflammatory effects of Protaetia brevitarsis seulensis larvae in IL-1β-induced chondrosarcoma cells based on systematic transcriptome analysis

Osteoarthritis (OA) is a complex degenerative joint and multi-factorial disease. Developing new targeting strategies that can be used to understand its molecular mechanisms is critical owing to the difficulty in treating OA. Protaetia brevitarsis seulensis larvae present high therapeutic value; however, the presence of various active compounds and the multi-factorial risk factors for OA renders the precise mechanisms of action unclear. We screened the key mechanisms of action of P. brevitarsis seulensis larvae aqueous extract (PBSL) and its compounds using systematic transcriptome analysis. Major mechanisms and transcription factors of PBSL were analyzed by profiling gene expression changes in interleukin (IL)-1β-induced human chondrosarcoma cell (SW1353) treated with PBSL. Furthermore, an in vitro assay was perfomed to validate the efficacy of the novel mechanism and targets of PBSL. PBSL exerted anti-inflammatory effects on SW1353 cells by regulating many molecular pathways. The IL-6/JAK/STAT3 pathway was significantly downregulated by PBSL, and STAT3 was identified as a major transcription factor regulating PBSL-induced target gene expression. Furthermore, we found that among the six PBSL compounds, the major compound was regulated by the IL-6/JAK/STAT3 pathway. Our findings reinforce the idea that inhibiting the IL-6/JAK/STAT3 pathway is a therapeutic target for treating OA, providing potential novel mechanisms and transcription factors for PBSL and its active compounds against OA. To investigate the transcriptomic signatures of PBSL, we performed RNA-sequencing data on the untreated cells (NC; n=3), IL-1β-induced SW1353 cells (IL1b; n=3), and IL-1β-induced and PBSL-treated cells (PBSL; n=3).