Exploring the Anti-Inflammatory Activity of the Heat-Processed Gynostemma pentaphyllum Extract (Actiponin®) in RAW264.7 Cells and Carrageenan-Induced Rat Models

<i>Gynostemma pentaphyllum</i> (GP) is a medicinal plant that has long been used as drug for the treatment of rheumatism, liver disease, and diabetes. In this study, GP was extracted with 50% ethanol extract, and then the extract was heat-processed under high pressure to analyze the anti-inflammatory potential of these extract (named actiponin (AP)) and its derived components, damulin A and damulin B, in RAW264.7 cells and carrageenan-induced rat models. Ap had no effect on RAW264.7 cells up to 180 μg/mL, but DA and DB showed cytotoxicity from 18 μM. Pretreatment with AP significantly suppressed the LPS-induced increase in nitric oxide (NO) and inducible nitric oxide synthase (iNOS) protein expression via griess reagent and Western blot analysis, and these effects were similar to those of DA and DB. AP, DA, and DB also significantly suppressed the expression of prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2) protein, which were increased by LPS, in a concentration-dependent manner. In addition, AP, DA, and DB inhibited the LPS-induced increase in pro-inflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in RAW264.7 cells. The anti-inflammatory activities of AP, DA, and DB are mediated by the suppression of the nuclear factor (NF)-κB and phosphorylation of mitogen-activated protein kinases (MAPKs) signaling pathways. Oral administration of 30, 50, 100, or 200 mg/kg (AP) suppressed carrageenan-induced edema in a concentration-dependent manner. Collectively, these results suggest that AP exerts potential anti-inflammatory activity by suppressing the inflammatory-mediators and pro-inflammatory cytokines via the NF-κB and MAPK pathways in vitro and by reducing the thickness of carrageenan-induced paw edema in vivo.