Absolute stereostructures of novel norcadinane- and trinoreudesmane-type sesquiterpenes with nitric oxide production inhibitory activity from Alpinia oxyphylla.

Novel 14-norcadinane-type sesquiterpenes, oxyphyllenodiols A and B, and 11,12,13-trinoreudesmane-type sesquiterpenes, oxyphyllenones A and B, were isolated from the methanolic extract of kernels of Alpinia oxyphylla. The absolute stereostructures of these norsesquiterpenes were determined on the basis of physicochemical and chemical evidence. In addition, oxyphyllenodiol A and oxyphyllenone A were found to inhibit the NO production in lipopolysaccharide-activated macrophages.

Inhibitors from rhubarb on lipopolysaccharide-induced nitric oxide production in macrophages: structural requirements of stilbenes for the activity.

By bioassay-guided separation, three stilbenes (rhapontigenin, piceatannol, and resveratrol), two stilbene glucoside gallates (rhaponticin 2"-O-gallate and rhaponticin 6"-O-gallate), and a naphthalene glucoside (torachrysone 8-O-beta-D-glucopyranoside) with inhibitory activity against nitric oxide (NO) production in lipopolysaccharide-activated macrophages were isolated (IC(50)=11--69 microM). The oxygen functions (-OH, -OCH(3)) of stilbenes at the benzene ring were essential for the activity. The glucoside moiety reduced the activity, while the alpha,beta-double bond had no effect. Furthermore, the active stilbenes (rhapontigenin, piceatannol, and resveratrol) did not inhibit inducible NO synthase activity, but they inhibited nuclear factor-kappa B activation following expression of inducible NO synthase.

Antioxidant constituents from rhubarb: structural requirements of stilbenes for the activity and structures of two new anthraquinone glucosides.

The methanolic extracts from five kinds of rhubarb were found to show scavenging activity for DPPH radical and .O2-. Two new anthraquinone glucosides were isolated from the rhizome of Rheum undulatum L. together with two anthraquinone glucosides, a naphthalene glucoside, and 10 stilbenes. In the screening test for radical scavenging activity of rhubarb constituents, stilbenes and a naphthalene glucoside showed activity, but anthraquinones and sennosides did not. In addition, most stilbenes inhibited lipid peroxidation of erythrocyte membrane by tert-butyl hydroperoxide. Detailed examination of the scavenging effect on various related compounds suggested the following structural requirements; 1) phenolic hydroxyl groups are essential to show the activity; 2) galloyl moiety enhances the activity; 3) glucoside moiety reduces the activity; 4) dihydrostilbene derivatives maintain the scavenging activity for the DPPH radical, but they show weak activity for .O2-. In addition, several stilbenes with both the 3-hydroxyl and 4'-methoxyl groups inhibited xanthine oxidase.

Medicinal foodstuffs. XXVIII. Inhibitors of nitric oxide production and new sesquiterpenes, zedoarofuran, 4-epicurcumenol, neocurcumenol, gajutsulactones A and B, and zedoarolides A and B, from Zedoariae Rhizoma.

A new eudesmane-type sesquiterpene, zedoarofuran, and six new guaiane- or seco-guaiane-type sesquiterpenes, 4-epicurcumenol, neocurcumenol, gajutsulactones A and B, and zedoarolides A and B, were isolated from aqueous acetone extract of Zedoariae Rhizoma together with 36 known sesquiterpenes and two diarylheptanoids. Their stereostructures were elucidated on the basis of chemical and physicochemical evidence. The effects of isolated components on nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages were examined and 16 sesquiterpenes including gajutsulactones A and B, and bis(4-hydroxycinnamoyl)methane were found to show inhibitory activity.

Inhibitory effects of sesquiterpenes from bay leaf on nitric oxide production in lipopolysaccharide-activated macrophages: structure requirement and role of heat shock protein induction.

The methanolic extract from the leaves of Laurus nobilis (bay leaf, laurel) was found to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-activated mouse peritoneal macrophages. Through bioassay-guided separation, fourteen known sesquiterpenes were isolated from the active fraction and were examined for ability to inhibit the NO production. Seven sesquiterpene lactones (costunolide, dehydrocostus lactone, eremanthine, zaluzanin C, magnolialide, santamarine and spirafolide) potently inhibited LPS-induced NO production (IC50 = 1.2 approximately 3.8 microM). Other sesquiterpene constituents also showed the inhibitory activity (IC50 > or = 21 microM), but their inhibitory activities were less than those of sesquiterpene lactones. Alpha-methylene-gamma-butyrolactone also showed inhibitory activity (IC50 = 9.6 microM), while mokko lactone and watsonol A etc., reductants of the alpha-methylene-gamma-butyrolactone moiety by NaBH4 or DIBAL, and a 2-mercaptoethanol adduct of dehydrocostus lactone showed little activity (IC50 > or = 18 microM). These results indicated that the alpha-methylene-gamma-butyrolactone moiety is important for the activity. Furthermore, costunolide and dehydrocostus lactone inhibited inducible nitric oxide synthase (iNOS) induction in accordance with induction of heat shock protein 72 (HSP 72). These results suggested that, as one of their mechanisms of action, sesquiterpene lactones induce HSP 72 thereby preventing nuclear factor-kappaB activation followed by iNOS induction.

Medicinal flowers. II. Inhibitors of nitric oxide production and absolute stereostructures of five new germacrane-type sesquiterpenes, kikkanols D, D monoacetate, E, F, and F monoacetate from the flowers of Chrysanthemum indicum L.

The methanolic extract and ethyl acetate-soluble portion from the flowers of Chrysanthemum indicum L., Chrysanthemi Indici Flos, were found to show inhibitory activity against nitric oxide (NO) production in lipopolysaccharide-activated macrophages. Five new germacrane-type sesquiterpenes, kikkanols D, D monoacetate, E, F, and F monoacetate, were isolated from the ethyl acetate-soluble portion. Their absolute stereostructures were elucidated on the basis of chemical and physicochemical evidence, which included application of the modified Mosher's method. The effects of fifteen principal components from the ethyl acetate-soluble portion of this medicinal flower against NO production were examined and, among them, acetylenic compounds and flavonoids were found to show potent inhibitory activity.

Effects of stilbene constituents from rhubarb on nitric oxide production in lipopolysaccharide-activated macrophages.

Two new anthraquinone glucosides [chrysophanol 8-O-beta-D-(6'-galloyl)-glucopyranoside, aloe-emodin 1-O-beta-D-glucopyranoside] together with various known stilbenes and their glucosides, anthraquinone glucosides, and a naphthalene glucoside were isolated from the rhizome of Rheum undulatum L. Three stilbenes (rhapontigenin, piceatannol, resveratrol), a naphthalene glucoside (torachrysone 8-O-beta-D-glucopyranoside), and two stilbene glucoside gallates (rhaponticin 2''-O-gallate, rhaponticin 6''-O-gallate) showed inhibitory activity of NO production in lipopolysaccharide-activated macrophages, (IC50 = 11-69 microM). The oxygen functions (-OH,-OCH3) at the benzene ring were found to be essential to show the activity. Whereas, the glucoside moiety reduced the activity, while the alpha,beta-double bond did not affect the activity. Furthermore, the active stilbenes (rhapontigenin, piceatannol, resveratrol) inhibited iNOS induction.

Effects of sesquiterpenes and triterpenes from the rhizome of Alisma orientale on nitric oxide production in lipopolysaccharide-activated macrophages: absolute stereostructures of alismaketones-B 23-acetate and -C 23-acetate.

The methanolic extract from a Chinese herbal medicine, the rhizome of Alisma orientale, was found to exhibit inhibitory activity of nitric oxide (NO) production in lipopolysaccharide (LPS)activated macrophages. Novel triterpenes, alismaketones-B 23-acetate and -C 23-acetate, were isolated from the active extract together with eight sesquiterpenes and eighteen protostane-type triterpenes. The absolute stereostructures of new triterpenes were characterized on the basis of chemical and physicochemical evidence, which included the chemical correlations with known triterpenes. The guaiane-type sesquiterpenes (alismol, orientalols A and C) and protostane- and seco-protostane-types triterpenes (alisols C monoacetate, E-23-acetate, F, H, I, L-23-acetate, and M-23-acetate, alismaketones-B 23-acetate and -C 23-acetate, alismalactone 23-acetate, and 3-methylalismalactone 23-acetate) inhibited LPS-induced NO production (IC50 = 8.4-68 microM). Other triterpenes (alisols A, A monoacetate, B, B monoacetate, E, G, K-23-acetate, and N-23-acetate and 11-deoxyalisol B) also showed the potent inhibitory activity, but they showed cytotoxic effects more than 30 microM (MTT assay). In addition, alismol and alisol F were found to suppress iNOS induction.

Medicinal flowers. I. Aldose reductase inhibitors and three new eudesmane-type sesquiterpenes, kikkanols A, B, and C, from the flowers of Chrysanthemum indicum L.

The methanolic extract from the flowers of Chrysanthemum indicum L., Chrysanthemi Indici Flos, was found to show inhibitory activity against rat lens aldose reductase. By bioassay-guided separation, the active components, such as flavone and flavone glycosides, were isolated from the extract together with three new eudesmane-type sesquiterpenes, kikkanols A, B, and C. The structures of kikkanols A, B, and C were elucidated on the basis of chemical and physicochemical evidence, which included application of the modified Mosher's method.

Antidiabetic principles of natural medicines. II. Aldose reductase and alpha-glucosidase inhibitors from Brazilian natural medicine, the leaves of Myrcia multiflora DC. (Myrtaceae): structures of myrciacitrins I and II and myrciaphenones A and B.

The methanolic extract and ethyl acetate-soluble portion from a Brazilian natural medicine, the leaves of Myrcia multiflora DC., which has been used as a specific medicine against diabetes, were found to show inhibitory activities on aldose reductase and alpha-glucosidase and on the increase of serum glucose level in sucrose-loaded rats and in alloxan-induced diabetic mice. From the ethyl acetate-soluble portion, new flavanone glucosides, myrciacitrins I and II, and new acetophenone glucosides, myrciaphenones A and B, were isolated together with several known compounds such as five flavonol glycosides, myricitrin, mearnsitrin, quercitrin, desmanthin-1, and guaijaverin. The structures of new compounds were determined on the basis of physicochemical and chemical evidence. The principal components of this natural medicine including new glucosides, myrciacitrin I and myrciaphenone B, were found to show potent inhibitory activities on aldose reductase and alpha-glucosidase.

Hepatoprotective and nitric oxide production inhibitory activities of coumarin and polyacetylene constituents from the roots of Angelica furcijuga.

The methanolic extract from the roots of Angelica furcijuga KITAGAWA was found to exhibit protective effects on liver injury induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS). From the methanolic extract, seventeen coumarins, two phenylpropanoids, and two polyacetylenes were isolated and examined their in vitro and in vivo hepatoprotective effects and inhibitory activity of NO production in macrophages. A acylated khellactone, isoepoxypteryxin, showed protective activity against D-GalN-induced cytotoxicity in primary cultured rat hepatocytes. On the other hand, six acylated khellactones (hyuganins A, B, C, and D, anomalin, isopteryxin) and two polyacetylenes [(-)-falcarinol and falcarindiol] strongly inhibited NO production induced by LPS in cultured mouse peritoneal macrophages, and also other acylated khellactones (isoepoxypteryxin, pteryxin, and suksdorfin) and a coumarin glycosides (praeroside II) were found to show the activity. By comparison of the inhibitory activities for acylated khellactones with those for other coumarins, acyl groups were found to be essential to exerting potent activity.