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 O<sub>2</sub><sup>-</sup> 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.