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.     

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.     

Medicinal flowers. XXIII. New taraxastane-type triterpene, punicanolic acid, with tumor necrosis factor-alpha inhibitory activity from the flowers of Punica granatum

The methanolic extract from the flowers of Punica granatum L. (Punicaceae) was found to show inhibitory effect on tumor necrosis factor-alpha (TNF-alpha, 1 ng/ml)-induced cytotoxicity in L929 cells. By bioassay-guided separation, a new taraxastane-type triterpene, punicanolic acid (1), was isolated from the active fraction (ethyl acetate-soluble fraction) together with four triterpenes (2--5), two galloyl glucoses (6, 7), two flavones (8, 9), and beta-sitosterol. Among the constituents, 1, oleanolic acid (2), maslinic acid (4), 1,2,6-tri-O-galloyl beta-D-glucopyranoside (6), 1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl beta-D-glucopyranoside (7), and luteolin (8) significantly inhibited TNF-alpha-induced cytotoxicity in L929 cells at 30 microM.     

Bioactive constituents from Chinese natural medicines. XX. Inhibitors of antigen-induced degranulation in RBL-2H3 cells from the seeds of Psoralea corylifolia

The ethyl acetate-soluble fraction of the methanolic extract from the seeds of Psoralea corylifolia was found to inhibit the release of beta-hexosaminidase, as a marker of antigen-IgE-induced degranulation in RBL-2H3 cells. Sixteen constituents were isolated from the ethyl acetate-soluble fraction and several constituents, Delta(1),3-hydroxybakuchiol (IC(50) = 49 microM), Delta(3),2-hydroxybakuchiol (69 microM, bavachin (58 microM), and psoralidin (ca. 100 microM), showed inhibitory activities against the antigen-induced degranulation.     

Bioactive constituents of Chinese natural medicines. V. Radical scavenging effect of Moutan Cortex. (1): Absolute stereostructures of two monoterpenes, paeonisuffrone and paeonisuffral

The methanolic extract and the ethyl acetate-soluble and methanol-eluted fractions from Chinese Moutan Cortex, the roots of Paeonia suffruticosa ANDREWS, were found to exhibit scavenging effect on 1,1-diphenyl-2-picrylhydrazyl radical and superoxide anion radical generated by the xanthine-xanthine oxidase system. Two monoterpenes called paeonisuffrone and paeonisuffral were isolated from the ethyl acetate-soluble fraction. Their absolute stereostructures were elucidated on the basis of chemical and physiochemical evidence, which included the application of a modified Mosher's method and lipase catalyzed debenzoylation reaction.     

Bioactive constituents from Chinese natural medicines. XV. Inhibitory effect on aldose reductase and structures of Saussureosides A and B from Saussurea medusa

The 80% aqueous acetone extract from the whole plant of Saussurea medusa MAXIM. was found to inhibit rat lens aldose reductase (IC50=1.4 microg/ml). From this extract, flavonoids, lignans, and quinic acid derivatives were isolated together with two new ionone glycosides, saussureosides A and B. Their absolute stereostructures were elucidated on the basis of chemical and physicochemical evidence including the application of modified Mosher's method. In addition, some isolates were found to show an inhibitory effect on aldose reductase.     

Bioactive saponins and glycosides. XXVII. Structures of new cucurbitane-type triterpene glycosides and antiallergic constituents from Citrullus colocynthis

The methanolic extract from the fruit of Citrullus colocynthis showed an inhibitory effect on ear passive cutaneous anaphylaxis reactions as a type I allergic model in mice. From the methanolic extract, two new cucurbitane-type triterpene glycosides, colocynthosides A and B, were isolated together with 17 known constituents. The structures of colocynthosides A and B were elucidated on the basis of chemical and physicochemical evidence. In addition, the principal cucurbitane-type triterpene glycoside, cucurbitacin E 2-O-beta-D-glucopyranoside, and its aglycon, cucurbitacin E, exhibited the antiallergic activity at a dose of 100 and 1.25 mg/kg, p.o., respectively.     

Medicinal flowers. XV. The structures of noroleanane- and oleanane-type triterpene oligoglycosides with gastroprotective and platelet aggregation activities from flower buds of Camellia japonica

The methanolic extract from the flowers buds of Camellia japonica L. (Theaceae) were found to exhibit potent inhibitory activities on ethanol- or indomethacin-induced gastric mucosal lesions in rats. Through bioassay-guided separation, 28-noroleanane-type triterpene oligoglycosides, camelliosides A, B, and C, and an oleanane-type triterpene oligoglycoside, camellioside D, were isolated from the methanolic extract together with five known compounds. The absolute stereostructures of camelliosides were determined on the basis of chemical and physicochemical evidence, which included the structure revision of the nortriterpene aglycons (camellenodiol and camelledionol). The principal oligoglycosides, camelliosides A and B, showed platelet aggregation activity in addition to the gastroprotective effects on ethanol- or indomethacin-induced gastric mucosal lesions in rats.     

Structural requirements of flavonoids and related compounds for aldose reductase inhibitory activity

The methanolic extracts of several natural medicines and medicinal foodstuffs were found to show an inhibitory effect on rat lens aldose reductase. In most cases, flavonoids were isolated as the active constituents by bioassay-guided separation, and among them, quercitrin (IC(50)=0.15 microM), guaijaverin (0.18 microM), and desmanthin-1 (0.082 microM) exhibited potent inhibitory activity. Desmanthin-1 showed the most potent activity, which was equivalent to that of a commercial synthetic aldose reductase inhibitor, epalrestat (0.072 microM). In order to clarify the structural requirements of flavonoids for aldose reductase inhibitory activity, various flavonoids and related compounds were examined. The results suggested the following structural requirements of flavonoid: 1) the flavones and flavonols having the 7-hydroxyl and/or catechol moiety at the B ring (the 3',4'-dihydroxyl moiety) exhibit the strong activity; 2) the 5-hydroxyl moiety does not affect the activity; 3) the 3-hydroxyl and 7-O-glucosyl moieties reduce the activity; 4) the 2-3 double bond enhances the activity; 5) the flavones and flavonols having the catechol moiety at the B ring exhibit stronger activity than those having the pyrogallol moiety (the 3',4',5'-trihydroxyl moiety).     

Medicinal flowers. XIV. New acylated oleanane-type triterpene oligoglycosides with antiallergic activity from flower buds of chinese tea plant (Camellia sinensis)

The methanolic extract from the flower buds of Chinese tea plant (Camellia sinensis (L.) O. KUNTZE) was found to inhibit release of beta-hexosaminidase from RBL-2H3 cells. From the methanolic extract, six new acylated oleanane-type triterpene oligoglycosides, floratheasaponins D-I, were isolated together with 21 known compounds including floratheasaponins A-C. The chemical structures of floratheasaponins D-I were elucidated on the basis of chemical and physicochemical evidence. The principal constituents, floratheasaponins A-F, were found to show the inhibitory activity on the release of beta-hexosaminidase from RBL-2H3 cells.     

Water-soluble constituents of amomum seed

From the water-soluble portion of the methanolic extract of the amomum seed (seed of Amomum xanthioides WALL.), which has been used as a medicine for stomachic and digestive disorders, ten compounds, including two new and three newly isolated monoterpenoid glucosides and a newly isolated octane-tetrol, were isolated. Their structures were determined by spectral investigation.     

Medicinal Flowers. XXXV. Nor-oleanane-type and acylated oleanane-type triterpene saponins from the flower buds of Chinese Camellia japonica and their inhibitory effects on melanogenesis(1))

The methanolic extract and its 1-butanol-soluble fraction from the flower buds of Camellia japonica, cultivated in Yunnan Province, China, showed inhibitory effects on melanogenesis in theophylline-stimulated B16 melanoma 4A5 cells. From the 1-butanol-soluble fraction, a new 28-nor-oleanane-type and three new oleanane-type triterpene saponins, sanchakasaponins A-D, were isolated together with four known triterpene saponins. Their chemical structures were elucidated on the basis of chemical and physicochemical evidence. The inhibitory effects on melanogenesis in theophylline-stimulated B16 melanoma 4A5 cells and structure-activity relationships of the saponins were investigated.     

Bioactive constituents from Chinese natural medicines. XXXII. aminopeptidase N and aldose reductase inhibitors from Sinocrassula indica: structures of sinocrassosides B(4), B(5), C(1), and D(1)-D(3)

From the methanolic extract of the whole plant of Sinocrassula indica (Crassulaceae), six new flavonol glycosides, sinocrassosides B(4) (1), B(5) (2), C(1) (3), D(1) (4), D(2) (5), and D(3) (6), were isolated together with 30 compounds. The structures of 1-6 were elucidated on the basis of chemical and physicochemical evidence. In addition, several constituents were found to show inhibitory effects on aminopeptidase N and aldose reductase.     

Studies on lens-aldose-reductase inhibitor in medicinal plants. II. Active constituents of Monochasma savatierii Franch. et Maxim

The 70% acetone extract of Monochasma savatierii FRANCH. et MAXIM. showed very strong inhibition of rabbit lens aldose reductase (AR). From the active fraction, five iridoid glucosides along with the two phenolic glycosides, acteoside and dehydroacteoside, have been isolated. Among them, acteoside showed the highest activity, being about 2.5 times more potent than baicalein, a known natural inhibitor of AR (IC50 = 9.8 x 10(-7) M). Demethylmussaenoside and 7-O-acetyl-8-epi-loganic acid, which are iridoid glucosides, had weak inhibitory activity.     

Bioactivity-guided study of antiproliferative activities of Salvia extracts

The cytotoxic activities of the n-hexane, chloroform and aqueous methanolic fractions prepared from the methanolic extract of the leaves of 23 Salvia taxa were studied for their cell growth-inhibitory activity against human cervix adenocarcinoma (HeLa), skin carcinoma (A431) and breast adenocarcinoma (MCF7) cells using the MTT assay. The n-hexane fractions of six Salvia taxa (S. hispanica, S. nemorosa, S. nemorosa 1. albiflora, S. pratensis, S. recognita and S. ringens) and the chloroform fraction ofS. officinalis 1. albiflora produced over 50% growth inhibition of the skin carcinoma cell line. None of the tested extracts showed substantial (above 50%) antiproliferative effects against HeLa and MCF7 cells. S. ringens was the most powerful among the studied Salvia species with a 61.8% cell growth inhibitory activity on A431 cells. In the case of S. ringens, other plant parts were also tested for antiproliferative effect, and the highest activities were recorded for the root extract. This was subjected to bioactivity-guided fractionation, which yielded four abietane diterpenes (royleanone, horminone, 7-O-methyl-horminone and 7-acetyl-horminone), one triterpene (erythrodiol-3-acetate) and beta-sitosterol. Horminone, 7-acetyl-horminone and erythrodiol-3-acetate displayed marked concentration-dependent antiproliferative effects, while royleanone and 7-O-methyl-horminone produced weaker activities.     

Phenolics Profiling of Carpobrotus edulis (L.) N.E.Br. and Insights into Molecular Dynamics of Their Significance in Type 2 Diabetes Therapy and Its Retinopathy Complication

Adverse effects associated with synthetic drugs in diabetes therapy has prompted the search for novel natural lead compounds with little or no side effects. Effects of phenolic compounds from Carpobrotus edulis on carbohydrate-metabolizing enzymes through in vitro and in silico methods were assessed. Based on the half-maximal inhibitory concentrations (IC₅₀), the phenolic extract of the plant had significant (p < 0.05) in vitro inhibitory effect on the specific activity of alpha-amylase (0.51 mg/mL), alpha-glucosidase (0.062 mg/mL) and aldose reductase (0.75 mg/mL), compared with the reference standards (0.55, 0.72 and 7.05 mg/mL, respectively). Molecular interactions established between the 11 phenolic compounds identifiable from the HPLC chromatogram of the extract and active site residues of the enzymes revealed higher binding affinity and more structural compactness with procyanidin (−69.834 ± 6.574 kcal/mol) and 1,3-dicaffeoxyl quinic acid (−42.630 ± 4.076 kcal/mol) as potential inhibitors of alpha-amylase and alpha-glucosidase, respectively, while isorhamnetin-3-O-rutinoside (−45.398 ± 4.568 kcal/mol) and luteolin-7-O-beta-d-glucoside (−45.102 ± 4.024 kcal/mol) for aldose reductase relative to respective reference standards. Put together, the findings are suggestive of the compounds as potential constituents of C. edulis phenolic extract responsible for the significant hypoglycemic effect in vitro; hence, they could be exploited in the development of novel therapeutic agents for type-2 diabetes and its retinopathy complication.     

In Vitro Alpha-Glucosidase Inhibitory Activity and the Isolation of Luteolin from the Flower of Gymnanthemum amygdalinum (Delile) Sch. Bip ex Walp.

Diabetes mellitus is a major health issue that has posed a significant challenge over the years. Gymnanthemum amygdalinum is a well-known plant that can be potentially used to treat this disease. Therefore, this study aimed to evaluate the inhibitory effect of its root, stem bark, leaves, and flower extracts on alpha-glucosidase using an in vitro inhibition assay to isolate the bioactive compounds and determine their levels in the samples. The air-dried plant parts were extracted by maceration using methanol. The results showed that the flower extract had the greatest inhibitory effect (IC50 47.29 ± 1.12 µg/mL), followed by the leaves, roots, and stem bark. The methanolic flower extract was further fractionated with different solvents, and the ethyl acetate fraction showed the strongest activity (IC50 19.24 ± 0.12 µg/mL). Meanwhile, acarbose was used as a positive control (IC50 73.36 ± 3.05 µg/mL). Characterization based on UV, 1H-, and 13C-NMR established that the ethyl acetate fraction yielded two flavonoid compounds, namely, luteolin and 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-methoxy-4H-chromen-4-on, which had IC50 values of 6.53 ± 0.16 µg/mL and 39.95 ± 1.59 µg/mL, respectively. The luteolin levels in the crude drug, methanolic extract, and ethyl acetate fraction were 3.4 ± 0.2 mg (0.3%), 32.4 ± 0.8 mg (3.2%), and 68.9 ± 3.4 mg (6.9%) per 1 g samples, respectively. These results indicated that the G. amygdalinum flower extract exerted potent inhibitory alpha-glucosidase activity.     

Medicinal flowers. VIII. Radical scavenging constituents from the flowers of Prunus mume: structure of prunose III

The methanolic extract and its fractions from the fresh flowers of Prunus mume SIEB. et ZUCC. were found to show scavenging effects on 1,1-diphenylpicryl-2-hydrazyl (DPPH) radical and superoxide. The fragrance constituents of P. mume were analyzed by GC-MS and a new polyacylated sucrose, prunose III, was isolated from the ethyl acetate-soluble fraction. The structure of prunose III was determined on the basis of chemical and physicochemical evidence as 4,3',4',6'-tetra-O-acetyl-6-O-p-coumaroylsucrose. In addition, the scavenging effects of the principal constituents on DPPH radical and superoxide were examined.     

Studies on aldose reductase inhibitors from natural products. II. Active components of a Paraguayan crude drug "Para-parai mí," Phyllanthus niruri

Aldose reductase (AR) inhibitory activity-directed fractionation of the 70% ethanolic extract of Para-parai mí, Phyllanthus niruri, has led to the isolation of three active components, ellagic acid (1), brevifolin carboxylic acid (4) and ethyl brevifolin carboxylate (5). Among them, 1 showed the highest inhibitory activity, being about 6 times more potent than quercitrin, which is a known natural inhibitor of AR.     

Chemical composition and biological activities of Indigofera hirsuta aerial parts’ methanol fractions

Abstract

Methanol extract of Indigofera hirsuta, was evaluated for its antiradical potential and capacity in inhibiting lipoxygenase and aldose/aldehyde reductase enzymes. The ethyl acetate fraction derived from the methanol extract partition, showed the greatest antioxidant capacity, while the butanol was the strongest inhibitor of lipoxygenase enzyme. All fractions (diethyl ether, ethyl acetate, butanol and the aqueous residue) exhibited strong inhibition capacity of both aldose/aldehyde reductase enzymes, which comes in agreement with the ethnomedicinal plant utilization as an antidiabetic agent. LC-DAD-MS(ESI+) fraction analysis verified the findings above, leading to a conclusion regarding the biological activities attributed to the main compounds. Phytochemical analysis led to the identification of an indolic dimer, cinnamic acids, phenolics, flavonoid glycosides, a cyclic polyol, the rare sugar 1-methyl-β-D-glucopyranoside and glycerol. Many of these compounds were isolated for the first time in Indigofera species while the indolic dimer was isolated for the first time in the Fabaceae family.