Radix Tetrastigma flavonoid ameliorates inflammation and prolongs the lifespan of Caenorhabditis elegans through JNK, p38 and Nrf2 pathways

The main flavonoid components of Radix Tetrastigma (RTF) were extracted and identified by UPLC-TOF/MS. In vitro, RTF prevented inflammation in RAW 264.7 cells by suppressing morphological (both cell and nucleus) changes, and decreasing nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) contents. Exposure to LPS also leads to oxidant damage, and RTF alleviated damage to mitochondria, decreased O₂⁻ accumulation, and restored the glutathione level. RTF intervention decreased the expression of c-Jun N-terminal kinase (JNK) and p38 phosphorylation, accompanied by downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and forkhead box protein O1 (FoxO1). In vivo, aging of Caenorhabditis elegans (C. elegans) by paraquat (PQ) was observed through lifespan, lipofuscin, and enzyme analysis. RTF protected against damage in N2 worms but not in daf-16 mutants. Gene expression was further assessed, and p38/PMK-1 and Nrf2/SKN-1 expression in worms was suppressed by PQ, which was reversed by RTF treatment. Together, these results suggested that RTF could help ameliorate inflammation-induced damage through JNK, p38 and Nrf2 pathways.