Hibiscus sabdariffa L. (Roselle flower) extract exerts protective effects against lipopolysaccharide-induced inflammation by ameliorating TLR4/NF-κB and NLRP3 inflammasome activation.

The phytochemical constituents of various plant extracts have shown potential in mitigating oxidative stress and inflammation. Hibiscus sabdariffa L. (HS), known as the roselle flower, has demonstrated antioxidant and anti-inflammatory effects in several models. Our study aimed to evaluate the effects of aqueous HS extract on modulating the TLR4/MyD88/NF-κB and Caspase-11/NLRP3 inflammasome signaling pathways during lipopolysaccharide (LPS)-induced mitochondrial stress and inflammation in macrophages by several in vitro assays. The results demonstrated that compared with LPS alone, HS extract significantly reduced the production of ROS, nitric oxide and proinflammatory cytokines (IL-6, TNF-α, PG-E2, IL-1β, and IFN-γ) by lowering the gene expression of p^22phox and iNOS and suppressed IκBα-dependent NF-κB signaling. Furthermore, HS treatment induced the polarization of macrophages from the M1 phenotype to the M2 phenotype, as demonstrated by qPCR and flow cytometry. The proteomic data revealed that HS extract can downregulate the expression of several mitochondria-associated proteins and reduce mitochondrial DNA leakage during LPS activation, suppressing Caspase-11/Gasdermin-D /NLRP3 inflammasome activation. In summary, the protective effects of HS extract against LPS-induced inflammation, which is mediated through the TLR4/NF-κB/NLRP3 signaling pathway, may significantly promote anti-inflammatory responses and alleviate related diseases.