Structurally diverse sesquiterpenoids from Curcuma longa and their anti-inflammatory activities

Inflammation is a key pathogenic mediator in the development of a multitude of diseases, such as metabolic disorders, cardiovascular events, and neurodegenerative diseases. Inspired by the excellent beneficial effects of Curcuma longa in anti-inflammatory, the EtOH extract of C. longa was phytochemically investigated, which led to the isolation of nineteen sesquiterpenoids (1-19) including eight previously unreported compounds (1-8). Their structures including absolute configurations were established by comprehensive spectroscopic analyses, ECD calculation, and NMR calculation. Furthermore, the anti-inflammatory activities of all the isolates were evaluated in LPS-induced RAW 264.7 cells, and compound 14 exhibited the best anti-inflammatory effect at 50 μM. Mechanistically, RNA sequencing indicated that the anti-inflammatory effect of compound 14 is mediated by the toll-like receptor signaling pathway. Western-blot, CETSA, and DARTS assays exhibited that compound 14 directly targeted TLR4, thereby influencing the TLR4/MyD88/NF-κB signaling pathway to alleviate inflammation. These findings suggested that the sesquiterpenoids from C. longa are a class of potential anti-inflammatory agents.