apigenin-7-o-glucuronide and Inflammation

Apigenin-7-O-β-D-glucuronide (AG), an active flavonoid derivative isolated from the agricultural residue of Juglans sigillata fruit husks, possesses multiple pharmacological activities, including anti-oxidant, anti-complement, and aldose reductase inhibitory activities. To date, no report has identified the anti-inflammatory mechanisms of AG. This study was therefore designed to characterize the molecular mechanisms of AG on lipopolysaccharide (LPS)-induced inflammatory cytokines in RAW 264.7 cells and on endotoxin-induced shock in mice. AG suppressed the release of nitric oxide (NO), prostaglandin E2 (PGE2), and tumour necrosis factor-α (TNF-α) in LPS-stimulated RAW 264.7 macrophages in a dose-dependent manner without affecting cell viability. Additionally, AG suppressed LPS-induced mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α. AG treatment decreased the translocation of c-Jun into the nucleus, and decreased activator protein-1 (AP-1)-mediated luciferase activity through the inhibition of both p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) phosphorylation. Consistent with the in vitro observations, AG protected mice from LPS-induced endotoxin shock by inhibiting proinflammatory cytokine production. Taken together, these results suggest that AG may be used as a source of anti-inflammatory agents as well as a dietary complement for health promotion.

Topics: Animals; Anti-Inflammatory Agents; Apigenin; Cell Survival; Cyclooxygenase 2; Dinoprostone; Dose-Response Relationship, Drug; Inflammation; Juglans; Lipopolysaccharides; Macrophages; MAP Kinase Signaling System; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; p38 Mitogen-Activated Protein Kinases; Plant Extracts; RAW 264.7 Cells; RNA, Messenger; Transcription Factor AP-1; Tumor Necrosis Factor-alpha

Erigeron multiradiatus (Lindl.) Benth., an herb that grows in the alpine and subalpine meadow of Qinghai-Tibet plateau, has been widely used as a folk remedy by the native people for treatment of various inflammatory ailments.. In order to isolate and identify the active components of Erigeron multiradiatus for anti-inflammatory activity, a preliminary phytochemical study and a bioassay-guided fractionation and purification process was performed.. The dry whole plant Erigeron multiradiatus was extracted with 50% ethanol and then separated into CHCl(3), n-BuOH, and aqueous fractions. The anti-inflammatory activities of each fraction were investigated using two in vivo inflammation models.. These results exhibited varying degrees of anti-inflammatory activities and the n-BuOH fraction showed the strongest anti-inflammatory activities. The n-BuOH fraction was then subjected to separation and purification using macroporous resins column chromatography and Sephadex LH-20 leading to two flavonoids glucuronides identified as scutellarein-7-O-beta-glucuronide and apigenin-7-O-beta-glucuronide. Furthermore, LC-MS/MS identification and quantification of isolated compounds were also performed.. Scutellarein-7-O-beta-glucuronide and apigenin-7-O-beta-glucuronide were considered as major components and principally responsible for the anti-inflammatory activity of Erigeron multiradiatus. Thus the results of our study provide a scientific basis for the utilization of Erigeron multiradiatus in traditional Tibetan medicine.

Topics: Animals; Anti-Inflammatory Agents; Apigenin; Biological Assay; Disease Models, Animal; Edema; Erigeron; Female; Flavonoids; Glucuronates; Inflammation; Male; Medicine, Tibetan Traditional; Mice; Plant Extracts; Rats; Rats, Sprague-Dawley; Tibet