ABSTRACT
Korean red ginseng extract (RGE) is one of the most popular natural herbs modulating the immune system. Although the effects of RGE on immunity have been reported, its effects on inflammasomes, multi-protein complexes that activate caspase-1 to induce maturation of interleukin (IL)-1ß, have not been studied yet. In this study, we elucidated the effect of RGE on inflammasome activation using mouse and human macrophages. In our results, RGE inhibited IL-1ß maturation resulting from NLRP3 inflammasome activation in both in vitro and in vivo models. In addition, RGE strongly attenuated IL-1ß secretion as well as pathogen clearance via pyroptotic cell death by macrophages through inhibition of AIM2 inflammasome activation. Ginsenosides Rg1 and Rh3 were suggested as inhibitors of the inflammasome activation. Thus, we demonstrated that RGE inhibits both NLRP3 and AIM2 inflammasome activation, with predominant involvement of the AIM2 inflammasome.
Subject(s)
Carrier Proteins/antagonists & inhibitors , DNA-Binding Proteins/antagonists & inhibitors , Inflammasomes/drug effects , Macrophages/drug effects , Panax , Animals , Cell Line , Ginsenosides/pharmacology , Humans , Inflammasomes/immunology , Interleukin-1beta/immunology , Interleukin-1beta/metabolism , Listeria monocytogenes/immunology , Macrophages/immunology , Macrophages/microbiology , Male , Mice , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein , Plant Extracts/pharmacology , Salmonella typhimurium/immunologyABSTRACT
This work aimed to assess some pharmacological activities of P. leptostachya var. asiatica Hara. The dried roots of P. leptostachya var. asiatica Hara were extracted with 70% ethanol to generate the powdered extract, named PLE. Anti-angiogenic activity was detected using chick chorioallantoic membrane (CAM) assay. In vitro anti-inflammatory activity was evaluated via analyzing nitric oxide (NO) content, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Antioxidant activity was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and reactive oxygen species (ROS) level in the stimulated macrophage cells. Matrix metalloproteinase-9 (MMP-9) and -2 (MMP-2) activities in the culture media were detected using zymography. PLE exhibits an anti-angiogenic activity in the CAM assay, and displays an inhibitory action on the generation of NO in the LPS-stimulated macrophage cells. In the stimulated macrophage cells, it is able to diminish the enhanced ROS level. It can potently scavenge the stable DPPH free radical. It suppresses the induction of iNOS and COX-2 and the enhanced MMP-9 activity in the stimulated macrophage cells. Both monooxygenase and oxidase activities of tyrosinase were strongly inhibited by PLE. Taken together, the dried roots of P. leptostachya var. asiatica Hara possess anti-angiogenic, anti-inflammatory, antioxidant and skin whitening activities, which might partly provide its therapeutic efficacy in traditional medicine.
ABSTRACT
OBJECTIVES: This work aimed to determine some pharmacological properties of non-fermented (WG) and fermented (FWG) extracts of cultured wild ginseng root. METHODS: WG was treated with Bifidobacterium longum to generate FWG. Ginsenoside patterns were analysed using thin-layer chromatography and high-performance liquid chromatography. The effect of WG and FWG on reactive oxygen species (ROS) was examined in lipopolysaccharide-stimulated RAW264.7 macrophage cells. Intracellular ROS were detected by flow cytometry. Nitrite in culture supernatant fractions was determined using the Griess reaction. 1,1-Diphenyl-2-picrylhydrazyl was used to determine anti-radical activity. Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. KEY FINDINGS: FWG was rich in ginsenosides Rg3 and Rh2, compared with WG. FWG diminished the enhanced ROS level more strongly than WG in lipopolysaccharide-stimulated RAW264.7 macrophage cells. Both WG and FWG decreased the nitrite levels in stimulated macrophage cells with half-maximal inhibitory concentration (IC50) values of 2.7 and 1.5 mg/ml, respectively, implying that FWG had an enhanced anti-inflammatory activity. Neither WG nor FWG exhibited cytotoxicity on the macrophage cells. In the radical scavenging assay, the IC50 values of WG and FWG were 32.6 and 0.78 mg/ml, respectively, suggesting that FWG had an increased scavenging activity. CONCLUSIONS: FWG possesses enhanced antioxidative and anti-inflammatory activity, indicating that fermentation of cultured wild ginseng root extract with a probiotic bacterium can strengthen some of its desirable effects.