Adipogenic effects of piperlonguminine in 3T3-L1 cells and plasma concentrations of several amide constituents from Piper chaba extracts after treatment of mice.

In our previous study, piperlonguminine from the fruit of Piper chaba was reported to promote adipogenesis in 3T3-L1 cells like the peroxisome proliferator-activated receptor-γ (PPARγ) agonist, troglitazone. In the present study, the mode of action of piperlonguminine in cells was examined. Piperlonguminine increased mRNA levels of adiponectin, glucose transporter 4, and fatty acid-binding protein (aP2). It also increased mRNA levels of PPARγ2 but, unlike troglitazone, piperlonguminine did not activate PPARγ directly in a nuclear receptor cofactor assay. Analyses of plasma from mice treated with piperlonguminine, piperine, and retrofractamide A, and an extract of the fruit, showed that concentrations of piperlonguminine were higher than those of piperine and retrofractamide A, and that the "area-under-the-curve" of piperine increased following in vivo administration of the extract.

Medicinal flowers. XXXIII. Anti-hyperlipidemic and anti-hyperglycemic effects of chakasaponins I-III and structure of chakasaponin IV from flower buds of Chinese tea plant (Camellia sinensis).

Effects of principal saponins, chakasaponins I-III, from the flower buds of Camellia sinensis cultivated in Fujian province, China on plasma triglyceride (TG) and glucose levels in olive oil or sucrose-loaded mice were examined. Chakasaponins I-III at 50 and 100 mg/kg significantly inhibited increases in plasma TG and glucose levels. Furthermore, they prevented gastric emptying, suggesting that the former inhibitory effect is partly dependent on the inhibition of gastric emptying. In addition, the chemical structure of a new acylated oleanane-type triterpene oligoglycoside, chakasaponin IV, was elucidated on the basis of chemical and physicochemical evidence.

Antidiabetogenic oligostilbenoids and 3-ethyl-4-phenyl-3,4-dihydroisocoumarins from the bark of Shorea roxburghii.

A methanol extract of the bark of Shorea roxburghii (Dipterocarpaceae) was found to inhibit plasma glucose elevation in sucrose-loaded mice. From the extract, three new 3-ethyl-4-phenyl-3,4-dihydroisocoumarins, 1'S-dihydrophayomphenol A(2) (1) and phayomphenols B(1) (2) and B(2) (3), were isolated together with 24 known compounds including 20 stilbenoids and oligostilbenoids. The structures of 1-3 were determined on the basis of their spectroscopic properties as well as of chemical evidences. Among the isolates, (-)-hopeaphenol (6), hemsleyanol D (8), (+)-α-viniferin (15), and (-)-balanocarpol (18) showed inhibitory activity against plasma glucose elevation in sucrose-loaded rats at doses of 100-200mg/kg, p.o. To clarify the mode of action of the antihyperglycemic property, effects of these oligostilbenoids on gastric emptying in mice, those on glucose uptake in isolated intestinal tissues as well as inhibitory activities against rat intestinal α-glucosidase and rat lens aldose reductase were examined.

Anti-hyperlipidemic constituents from the bark of Shorea roxburghii.

The methanol extract from the bark of Shorea roxburghii (Dipterocarpaceae, "Phayom" in Thai) was found to suppress plasma triglyceride elevation in olive oil-treated mice, and also to inhibit pancreatic lipase activity (IC(50) = 31.6 µg/ml). From the extract, two new 3-acetyl-4-phenyl-3,4-dihydroisocoumarins, phayomphenols A(1) (1) and A(2) (2) were isolated, together with 22 known compounds. The structures of 1 and 2 were elucidated on the basis of chemical and spectroscopic evidence, including X-ray crystallographic analysis. Among the isolates, several oligostilbenoids, including (-)-hopeaphenol (3) and (+)-isohopeaphenol (4), showed inhibitory effects on plasma triglyceride elevation at a dose of 200 mg/kg p.o. and pancreatic lipase inhibitory activity (IC(50) = 32.9 and 26.5 µM, respectively).

Mate tea (Ilex paraguariensis) promotes satiety and body weight lowering in mice: involvement of glucagon-like peptide-1.

We previously investigated the effects of an aqueous extract of maté (mate) tea, made from the leaves of Ilex paraguariensis, on the diabesity and metabolic syndrome features in a mouse model. Mate induced significant decreases in body weight (BW), body mass index, and food intake (FI). In this study, to verify the mode of action of mate on FI and consequently on BW, we examined the anorexic effects of mate on the appetite and satiety markers glucagon-like peptide 1 (GLP-1) and leptin in high-fat diet-fed ddY mice. GLP-1 is a peptide signal generated by the gastrointestinal tract, which regulates appetite and influences BW, whereas leptin is an afferent signal from the periphery to the brain in a homeostatic feedback loop that regulates adipose tissue mass, thus leading to decreased appetite and FI and increased energy expenditure. Chronic administration of mate (50, 100 mg/kg) for 3 weeks significantly reduced FI, BW, and ameliorated blood fats, liver fats, and adipose tissue. Mate induced significant increases in GLP-1 levels and leptin levels compared with the control. Acute administration of major constituents of mate showed significant increases in GLP-1 levels by dicaffeoyl quinic acids and matesaponins, and significant induction of satiety by caffeoyl quinic acids and caffeine in ddY mice. These findings suggest that mate may induce anorexic effects by direct induction of satiety and by stimulation of GLP-1 secretion and modulation of serum leptin levels.

Anti-obesity effects of the methanolic extract and chakasaponins from the flower buds of Camellia sinensis in mice.

The methanolic extract from the flower buds of Camellia sinensis cultivated in Fujian Province showed inhibitory effects on body weight gain and the weight of visceral fats in high-fat diet-fed mice and/or Tsumura Suzuki Obese Diabetic (TSOD) mice. A suppressive effect of the extract on food intake was suggested to contribute to the anti-obesity effect. The n-butanol (BuOH)-soluble fraction also reduced food intake in normal diet-fed mice. A principal constituent, chakasaponin II, inhibited gastric emptying (GE) as well as food intake. These inhibitory effects were partly reduced by pretreatment with a high dose of capsaicin. The n-BuOH-soluble fraction and chakasaponin II suppressed mRNA levels of neuropeptide Y (NPY), an important regulator of body weight through its effects on food intake and energy expenditure, in the hypothalamus. Furthermore, chakasaponin II enhanced the release of serotonin (5-HT) from the isolated ilea of mice in vitro. These findings suggested that the active saponins suppressed the appetite signals in the hypothalamus through stimulation of the capsaicin-sensitive sensory nerves, probably vagal afferent nerves, or enhancement of 5-HT release from the ilea, leading to reduced food intake and body weight gain.

Medicinal Flowers. XXXII. Structures of oleanane-type triterpene saponins, perennisosides VIII, IX, X, XI, and XII, from the flowers of Bellis perennis.

Five new triterpene saponins perennisosides VIII (1), IX (2), X (3), XI (4), and XII (5) were isolated from the MeOH-eluated fraction of the methanolic extract from the flowers of Bellis perennis. The MeOH-eluted fraction of the methanolic extract from the flowers of B. perennis was found to inhibit gastric emptying in olive oil-loaded mice at a dose of 200 mg/kg, per os (p.o.). The stereostructures of 1-5 were elucidated on the basis of chemical and spectroscopic evidence.

Antidiabetogenic constituents from the Thai traditional medicine Cotylelobium melanoxylon.

The methanolic extracts from the wood and bark of Cotylelobium melanoxylon were found to inhibit plasma glucose elevation after sucrose loading in rats and triglyceride elevation after olive oil loading in mice. A new stilbene dimer, melanoxylin A, together with the known stilbene dimers [(+)-ampelopsin F, (+)-isoampelopsin F, and (+)-epsilon-viniferin] and a trimer (vaticanol G) and a lignan [(+)-lyoniresinol] were isolated from the wood extract, and a new stilbene trimer, melanoxylin B, together with the known stilbene dimers [(+)-epsilon-viniferin and cis-(+)-epsilon-viniferin] and trimers (vaticanols A, E, and G) were isolated from the bark extract of C. melanoxylon. The principal constituents, vaticanols A, E, and/or G, inhibited plasma glucose and triglyceride elevation after sucrose loading in rats and olive oil loading in mice, respectively. In addition, vaticanols A, E, and/or G inhibited the enzyme activities of rat intestinal alpha-glucosidase, porcine pancreatic lipase, and rat lens aldose reductase.

Structures of acetylated oleanane-type triterpene saponins, rarasaponins IV, V, and VI, and anti-hyperlipidemic constituents from the pericarps of Sapindus rarak.

The methanolic extract and its saponin fraction (methanol-eluted fraction) of the pericarps of Sapindus rarak DC. were found to suppress plasma triglyceride elevation in olive oil-treated mice. From the active fraction, three new acylated oleanane-type triterpene saponins, rarasaponins IV (1), V (2), and VI (3), were isolated. The structures of 1-3 were elucidated on the basis of chemical and spectroscopic evidence. The principle saponin constituents, hederagenin 3-O-alpha-L-arabinopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside (4) and hederagenin 3-O-(3,4-di-O-acetyl-alpha-L-arabinopyranosyl)-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside (5), showed inhibitory effects on plasma triglyceride elevation at a dose of 200 mg/kg, per os.