No abstract

Three new flavonoid glycosides, together with 15 known flavonoids, have been isolated from the leaves of Eriobotrya japonica, and characterized as (2S)- and (2R)-naringenin 8-C-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosides, and cinchonain Id 7-O-beta-D-glucopyranoside, respectively, based on spectral analyses including two dimensional (2D) NMR techniques. Higher proanthocyanidin fraction in the water-soluble portion of the extract was characterized as a procyanidin oligomer mixture mainly composed of undecameric procyanidin. These polyphenols have also been assessed for cytotoxic activity against two human oral tumor (human squamous cell carcinoma and human salivary gland tumor) cell lines. Selective cytotoxicity of the procyanidin oligomer between tumor and normal gingival fibroblast cells, and its possible mechanism, were also described.

We investigated the effect of ␥-mangostin purified from the fruit hull of the medicinal plant Garcinia mangostana on spontaneous prostaglandin E 2 (PGE 2 ) release and inducible cyclooxygenase 2 (COX-2) gene expression in C6 rat glioma cells. An 18-h treatment with ␥-mangostin potently inhibited spontaneous PGE 2 release in a concentration-dependent manner with the IC 50 value of approximately 2 M, without affecting the cell viability even at 30 M. By immunoblotting and reverse-transcription polymerase chain reaction, we showed that ␥-mangostin concentration-dependently inhibited lipopolysaccharide (LPS)-induced expression of COX-2 protein and its mRNA, but not those of constitutive COX-1 cyclooxygenase. Because LPS is known to stimulate inhibitor B (IB) kinase (IKK)-mediated phosphorylation of IB followed by its degradation, which in turn induces nuclear factor (NF)-B nuclear translocation leading to transcriptional activation of COX-2 gene, the effect of ␥-mangostin on the IKK/IB cascade controlling the NF-B activation was examined. An in vitro IKK assay using IKK protein immunoprecipitated from C6 cell extract showed that this compound inhibited IKK activity in a concentration-dependent manner, with the IC 50 value of approximately 10 M. Consistently ␥-mangostin was also observed to decrease the LPSinduced IB degradation and phosphorylation in a concentration-dependent manner, as assayed by immunoblotting. Furthermore, luciferase reporter assays showed that ␥-mangostin reduced the LPS-inducible activation of NF-B-and human COX-2 gene promoter region-dependent transcription. ␥-Mangostin also inhibited rat carrageenan-induced paw edema. These results suggest that ␥-mangostin directly inhibits IKK activity and thereby prevents COX-2 gene transcription, an NF-B target gene, probably to decrease the inflammatory agent-stimulated PGE 2 production in vivo, and is a new useful lead compound for anti-inflammatory drug development.

The fruit hull of mangosteen, Garcinia mangostana L. has been used as a Thai indigenous medicine for many years. However, its mechanism of action as a medicine has not been elucidated. The present study was undertaken to examine the effects of mangosteen extracts (100% ethanol, 70% ethanol, 40% ethanol and water) on histamine release and prostaglandin E 2 synthesis. We found that the 40% ethanol extract of mangosteen inhibited IgE-mediated histamine release from RBL-2H3 cells with greater potency than the water extract of Rubus suavissimus that has been used as an anti-allergy crude drug in Japan. All extracts of mangosteen potently inhibited A23187-induced prostaglandin E 2 synthesis in C6 rat glioma cells, while the water extract of Rubus suavissimus had no effect. The 40% ethanol extract of mangosteen inhibited the prostaglandin E 2 synthesis in a concentration-dependent manner with relatively lower concentrations than the histamine release. In addition, passive cutaneous anaphylaxis (PCA) reactions in rats were significantly inhibited by this ethanol extract as well as by the water extract of Rubus suavissimus. These results suggest that the 40% ethanol extract of mangosteen has potent inhibitory activities of both histamine release and prostaglandin E 2 synthesis.

OBJECTIVE: To investigate the inhibitory effects of CT-II, extract of Nomame Herba, on lipase activity in vitro and on obesity in rats fed a high-fat diet in vivo. DESIGN: The assay for the inhibitory effect of CT-II on lipase activity was performed by measuring released free fatty acids after the incubation of the medium with CT-II, porcine pancreatic lipase and triolein (experiment 1). In vivo experiments, lean rats or obese rats (570 ± 718 g) were fed a high-fat diet containing 60% fat with or without CT-II for 8 weeks (experiment 2), for 14 days (experiment 3) or for 12 weeks (experiment 4), respectively. MEASUREMENT: The time course of body weight, food intake, organ weight (parametrial fat, liver, heart and kidney) and plasma parameters (triglyceride, total cholesterol, glucose, AST, ALT and insulin), fecal output of total fat and total cholesterol were measured. Hepatic histological examinations were also performed. RESULTS: CT-II inhibited the porcine lipase activity dose-dependently in vitro (experiment 1). Body and liver weight were reduced and hepatic histological examination showed an amelioration of fatty liver in CT II treated animals (experiment 2). CT-II signi®cantly inhibited body weight gain and plasma triglyceride elevation in a dose-dependent manner, without affecting food intake in lean rats fed the high-fat diet. Elevated plasma AST and ALT were also decreased (experiment 3). When obese rats fed the high-fat diet were treated with CT-II for up to 6 months, body weight was initially reduced and thereafter weight gain was signi®cantly suppressed. Total body fat was also signi®cantly reduced and signi®cant reduction of plasma AST and ALT was observed (experiment 4). CONCLUSIONS: These results demonstrated that the lipase inhibitor CT-II is effective in preventing and ameliorating obesity, fatty liver and hypertriglyceridemia in rats fed a high-fat diet.