Prenylflavonoids isolated from Epimedii Herba show inhibition activity against advanced glycation end-products.

Introduction: As inhibitors of advanced glycation end products (AGEs), such as pyridoxamine, significantly inhibit the development of retinopathy and neuropathy in rats with streptozotocin-induced diabetes, treatment with AGE inhibitors is believed to be a potential strategy for the prevention of aging, age-related diseases, and lifestyle-related diseases, including diabetic complications. In the present study, the MeOH extract of Epimedii Herba (EH; aerial parts of Epimedium spp.) was found to inhibit the formation of N ε -(carboxymethyl)lysine (CML) and N ω -(carboxymethyl) arginine (CMA) during the incubation of collagen-derived gelatin with ribose. Materials and methods: EH was purchased from Uchida Wakan-yaku Co., and a MeOH extract was prepared. Several steps of column chromatography purified the extract. Each fraction was tested for inhibitory activity by ELISA using monoclonal antibodies for CML and CMA. Results: After activity-guided fractionation and purification by column chromatography, three new prenylflavonoids [named Koreanoside L (1), Koreanoside E1 (2), and Koreanoside E2 (3)] and 40 known compounds (4-43) were isolated from EH, and their inhibitory effects against CML and CMA formation were tested. Among these, epimedokoreanin B (8), epimedonin E (21), epicornunin B (22), and epicornunin F (24) inhibited the formation of both CML and CMA, with epimedokoreanin B (8) having the most potent inhibitory effect among the isolated compounds. To obtain the structure-activity relationships of 8, the phenolic hydroxy groups of 8 were methylated by trimethylsilyl-diazomethane to afford the partially and completely methylated compounds of 8. Prenyl derivatives of propolis (artepillin C, baccharin, and drupanin) were used in the assay. Discussion: As only 8 showed significant activity among these compounds, the catechol group of the B ring and the two prenyl groups attached to the flavanone skeleton were essential for activity. These data suggest that 8 could prevent the clinical complications of diabetes and age-related diseases by inhibiting AGEs.

Identification and characterization of organic and glycosidic acids in the crude resin glycoside fraction of Ipomoea alba seeds.

Resin glycosides act as laxatives in crude drugs derived from plants of the Convolvulaceae family. These compounds have exhibited antibacterial, ionophoric, anti-inflammatory, antiviral, and multidrug resistance-modulating properties, as well as cytotoxicity against cancer cells. This study investigated the organic acid, hydroxyl fatty acid, monosaccharide, and glycosidic acid components of the crude resin glycoside fraction obtained from the methanol extract of Ipomoea alba L. (Convolvulaceae) seeds, which was subjected to alkaline and acidic hydrolysis. The alkaline hydrolysis yielded acetic, isobutyric, (E)-2-methylbut-2-enoic, and 2S-methyl-3S-hydroxybutyric acids as organic acid components, along with a glycosidic acid fraction. The acidic hydrolysis of the glycosidic acid fraction resulted in the isolation of 11S-hydroxytetradecanoic and 11S-hydroxyhexadecanoic acids as hydroxyl fatty acid components, as well as d-glucose, d-quinovose, d-fucose, d-xylose, and l-rhamnose as monosaccharide components. In addition, 10 new glycosidic acid methyl esters were isolated from the glycosidic acid fraction treated with trimethylsilyldiazomethane-hexane, along with one known glycosidic acid methyl ester. Of these, eight compounds contained new glycans. Four of these compounds were unusual natural glycosides with four glycosidic linkages to one monosaccharide. Their structures were determined using MS and NMR spectral analyses, which provided valuable insights into the unique glycosidic composition of I. alba seeds.

Four new resin glycosides from Ipomoea muricata seeds: muricatins XIV-XVII.

Ipomoea muricata (L.) Jacq. seeds (Convolvulaceae) are used as a traditional laxative and carminative medicine. Muricatins XIV (1), XV (2), XVI (3), and XVII (4), were isolated from I. muricata seeds as four new resin glycosides, along with seven known compounds, three of which were isolated for the first time as natural products; their structures were determined using MS and NMR spectroscopy. Compounds 1-4 are macrolactones (jalapins); the sugar moieties of 1, 2, and 4 are partially acylated with 2S-methylbutyric acid, while that of 3 is esterified with 2S-methylbutyric and 2S-methyl-3S-hydroxybutyric acids. In addition, the antiviral activities of the seven compounds obtained in this study, together with five known compounds obtained in our previous study into resin glycosides from I. muricata seeds, were evaluated against herpes simplex virus type 1 (HSV-1); their cytotoxicities against HL-60 human promyelocytic leukemia cells were also investigated. All examined jalapins exhibited similar or slightly weaker anti-HSV-1 activities than acyclovir, the positive control; however, the glycosidic acid of 4 was inactive, while its methyl ester was weakly active. On the other hand, cytotoxicity testing against HL-60 cells showed similar results to those observed during anti-HSV-1 activity testing, with the exception that one jalapin was less active.

Identification and characterization of organic and glycosidic acids in the crude resin glycoside fraction of Ipomoea lacunosa seeds.

Resin glycosides are commonly found in plants belonging to the Convolvulaceae family. Ipomoea lacunosa L. (Convolvulaceae) is an herbaceous vine native to the United States. The resin glycosides of this plant have not been studied in detail. In this study, the components of the crude resin glycoside fraction extracted from the seeds of I. lacunosa are characterized. Alkaline hydrolysis of the crude resin glycoside fraction obtained from methanolic extract of the seeds yielded three organic acids, namely, 2S-methylbutyric, (E)-2-methylbut-2-enoic, and 2R-methyl-3R-hydroxybutyric acids, and a glycosidic acid fraction. Acidic hydrolysis of the glycosidic acid fraction yielded hydroxyl fatty acid components, including 7S-hydroxydecanoic, 11S-hydroxytetradecanoic, 11S-hydroxyhexadecanoic, 3S,11S-dihydroxytetradecanoic, 3S,11S-dihydroxyhexadecanoic, and 3S,12S-dihydroxyhexadecanoic acids, as well as monosaccharide components, including d-glucose, d-quinovose, d-fucose, and l-rhamnose. Trimethylsilyldiazomethane-hexane treatment of the glycosidic acid fraction further yielded eleven previously undescribed glycosidic acid methyl esters and two known glycosidic acid methyl esters. The structures of the obtained compounds were characterized using various spectral techniques. Four of the undescribed compounds were hexaglycosides, five were heptaglycosides, and two were octaglycosides. The aglycone of these compounds was either methyl 11S-hydroxytetradecanoate, methyl 3S,11S-dihydroxytetradecanoate, or methyl 3S,11S-dihydroxyhexadecanoate. Among the undescribed compounds identified, eight contained novel glycans, and three were rare bisdesmosides with sugar linkages at the C-3 and C-11 positions of methyl 3S,11S-dihydroxytetradecanoate.

Isolation and structural characterization of eight new resin glycosides, calyhedins XVI-XXIII, from the rhizomes of Calystegia hederacea.

Biological effects attributed to resin glycosides, including cytotoxicity against cancer cells and antibacterial, multidrug resistance-modulating, and antiviral activities have been documented. Penta-glycosides composed of calysolic acid A or calyhedic acid A, which are glycosidic acid components of the crude resin glycoside fraction of Calystegia hederacea, have not yet been isolated from this plant. In this study, eight new resin glycosides, termed calyhedins XVI (1)-XXIII (8), were isolated from the rhizomes of C. hederacea. Compounds 1-8 are penta- or hexa-glycosides with macrolactone structures, and their sugar moieties are partially acylated by five organic acids, including 2S-methylbutyric, (E)-2-methylbut-2-enoic, and 2R-methyl-3R-hydroxybutyric acids. Compounds 1-5 are the first identified macrocyclic resin glycosides with five monosaccharides obtained from this plant, and 2 and 4 are the first to be characterized as containing calyhedic acid A as the glycosidic acid component. Compounds 1-8 were of the four following macrolactone types: one with a 22-membered ring (5), another with a 23-membered ring (6-8), the third with a 27-membered ring (1, 3), and the fourth with a 28-membered ring (2, 4). Compounds 2-8 exhibited cytotoxic activity against HL-60 human promyelocytic leukemia cells comparable to that of the positive control, cisplatin.

Five new resin glycosides, calyhedins XI-XV, from Calystegia hederacea.

Calystegia hederacea Wall. (Convolvulaceae) is a perennial herbaceous vine that grows widely in India and East Asia. All parts of this plant are used to treat various disorders such as menoxenia and gonorrhea. Four new resin glycosides, calyhedins XI (1)-XIV (4), were isolated from the rhizomes of C. hederacea. A new glycoside, calyhedin XV (5), was isolated from its leaves and stems. Alkaline hydrolysis of 1 and 2 furnished a new glycosidic acid, calyhedic acid G (1a), from 1 and a new acid, calyhedic acid H (2a), from 2 along with 2S-methylbutyric acid and 2R-methyl-3R-hydroxybutyric (2R,3R-nilic) acid. The structures of 1-5, 1a, and 2a were determined using MS and NMR spectral analyses. Compounds 1a and 2a had the same sugar moiety, ß-D-glucopyranosyl-(1 → 6)-O-ß-D-glucopyranosyl-(1 → 6)-O-ß-D-glucopyranosyl-(1 → 3)-[O-ß-D-glucopyranosyl-(1 → 3)-O-α-L-rhamnopyranosyl-(1 → 2)]-O-ß-D-glucopyranosyl-(1 → 2)-ß-D-fucopyranose, while their aglycones were 11S-dihydroxyhexadecanoic acid and 12S-dihydroxyhexadecanoic acid, respectively. These compounds are the first glycosidic acids, with fucose as the monosaccharide component obtained from the resin glycosides of C. hederacea. Compounds 1-5, comprising either 1a or 2a, were heptaglycosides with macrolactone structures, and their sugar moieties were partially acylated with 5 mol of organic acids comprising 2S-methylbutyric, (E)-2-methylbut-2-enoic, and 2R,3R-nilic acids. Compounds 1 and 5 had 22-membered rings, while 2-4 had 28-membered rings. In addition, 1 and 5 exhibited cytotoxic activity against HL-60 human promyelocytic leukemia cells, comparable to that of the positive control cisplatin.

Four new resin glycosides, calyhedins VII-X, from the rhizomes of Calystegia hederacea.

Four new resin glycosides with macrolactone structures (jalapins), namely, calyhedins VII (1)-X (4), were isolated from the rhizomes of Calystegia hederacea Wall. (Convolvulaceae). The structures of 1-4 were determined based on spectroscopic data. They were classified into three ring types: a 27-membered ring (1), a 22-membered ring (2, 3), and a 23-membered ring (4). Their sugar moieties were partially acylated using five organic acids, including (E)-2-methylbut-2-enoic acid, 2S-methylbutyric acid, and 2 R-methyl-3R-hydroxybutyric acid. Compound 4 was the first genuine resin glycoside with calyhedic acid F as the glycosidic acid component. Additionally, the cytotoxic activities of 1, 2, and 4 towards HL-60 human promyelocytic leukaemia cells were evaluated. All compounds demonstrated almost the same activity as the positive control, cisplatin.

Identification and characterization of organic and glycosidic acids in the crude resin glycoside fraction from the leaves and stems of Calystegia japonica.

The alkaline hydrolysis of the crude resin glycoside fraction from the leaves and stems of the plant Calystegia japonica Choisy (Convolvulaceae) yielded organic acid and glycosidic acid fractions. The organic acid fraction was esterified with p-bromophenacyl bromide to obtain p-bromophenacyl 2R-methyl-3R-hydroxybutyrate (1) and p-bromophenacyl (E)-2-methylbut-2-enoate (2). By treating the glycosidic acid fraction with trimethylsilyldiazomethane-hexane, seven new methyl esters of glycosidic acids, namely calyjaponic acid A methyl ester (3) calyjaponic acid B methyl ester (5), calyjaponic acid C methyl ester (6), calyjaponic acid D methyl ester (7), calyjaponic acid E methyl ester (8), calyjaponic acid F methyl ester (9), and calyjaponic acid G methyl ester (10), were isolated along with one known ester (4). Their structures were characterized based on spectroscopic and chemical analyses. Compounds 3-8 had the same sugar moiety, α-L-rhamnopyranosyl-(1 → 2)-O-ß-D-glucopyranosyl-(1 → 2)-[O-α-L-rhamnopyranosyl-(1 → 6)]-O-ß-D-glucopyranose, and the aglycones of 3-8 were methyl 3S,11S-dihydroxyhexadecanoate, methyl 3S,12S-dihydroxyhexadecanoate, methyl 11S-hydroxyhexadecanoate, methyl 11S-hydroxypentadecanoate, methyl 3S,11S-dihydroxypentadecanoate, and methyl 3S,12S-dihydroxypentadecanoate, respectively. Compounds 9 and 10 were derivatives of 3 and 4, respectively, in which the C-6 of the second glucosyl residue was methylated. Compounds 6-8 contained methyl esters of unusual odd-carbon fatty acids as aglycones. The cytotoxicity of the crude resin glycoside fraction and 3 against HL-60 human promyelocytic leukemia cells was evaluated further; both were either weakly active or inactive compared to the positive control, cisplatin.

Two new resin glycosides, muricatins XII and XIII, from the seeds of Ipomoea muricata.

Two new resin glycosides, muricatins XII (1) and XIII (2), were isolated from the crude resin glycoside fraction of the seeds of Ipomoea muricata (L.) Jacq. (Convolvulaceae), along with three known ones, muricatins V (3), VI (4), and IX (5). Compounds 1 and 2 contained new glycosidic acids, muricatic acids E (1a) and F (2a), respectively. The structures of these compounds were determined using data obtained from spectroscopy measurements and chemical evidence. The results suggested that 1 and 2 have macrolactone structures (jalapins). Furthermore, the cytotoxic activity of the crude resin glycoside fraction and 3-5 against HL-60 human promyelocytic leukaemia cells was evaluated. All tested samples demonstrated cytotoxic activities.

Two new glycosidic acids, calyhedic acids E and F, in crude resin glycoside fraction from Calystegia hederacea.

Two new glycosidic acids, calyhedic acids E (1a) and F (2a), were isolated from the glycosidic acid fraction afforded by alkaline hydrolysis of the crude resin glycoside fraction obtained from whole plants of Calystegia hederacea Wall. Compounds 1a and 2a were characterised as 11S-hydroxyhexadecanoic acid 11-O-ß-D-glucopyranosyl-(1→6)-O-ß-D-glucopyranosyl-(1→6)-O-ß-D-glucopyranosyl-(1→3)-[O-α-L-rhamnopyranosyl-(1→2)]-O-ß-D-glucopyranosyl-(1→2)-ß-D-quinovopyranoside and an isomer of 1a, in which the 11S-hydroxyhexadecanoyl residue of 1a was replaced by a 12S-hydroxyhexadecanoyl residue, respectively, on the basis of spectroscopic data.

A new steroidal glycoside from the fruits of Solanum myriacanthum.

A new cholestane-type steroidal glycoside, solamyriaside A (1), was isolated from the fruits of Solanum myriacanthum Dunal (Solanaceae), along with two known steroidal glycosides, namely, solaviaside A (2) and aculeatiside A (3), and three known steroidal alkaloid glycosides, namely, solamargine (4), khasianine (5) and solasonine (6), which were isolated for the first time from this plant. Based on spectroscopic data as well as chemical evidence, 1 was determined to be 3-O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl-(1→4)]-ß-D-glucopyranosyl-22R,25R-cholest-5-ene-3ß,16α,22,26-tetraol 26-O-ß-D-glucopyranoside. The cytotoxic activity of 1-6 against HL-60 human promyelocytic leukaemia cells was examined. Compounds 4-6 showed cytotoxic activity. Among them, 4 exhibited the strongest activity with an IC50 value of 4.64 ± 0.17 µM, similar to the activity of cisplatin, a positive control.

Glutaminase inhibitory activity of umbelliferone isolated from kabosu (Citrus sphaerocarpa Hort. ex Tanaka).

Kabosu (Citrus sphaerocarpa Hort. ex Tanaka) fruits have pleasant and fresh odors and have been used as raw materials for vinegar, seasonings, jams, marmalades and juices in Japan. The n-butanol extracts from kabosu fruits were prepared and a component in the extract was purified by column chromatography and HPLC to afford compounds 1-3. Three compounds, 5-(hydroxymethyl)-2-furaldehyde (1), umbelliferone (2) and oxypeucedanin hydrate (3), have been isolated from kabosu, and the structures of compounds 1-3 were elucidated by 1 D and 2 D NMR as well as EI-MS. Compound 2 exhibited potent glutaminase inhibitory activity with an IC50 value of 1.33 mM. This is the first report on glutaminase inhibitory activity of 2 and the isolation of three compounds 1-3 from kabosu fruits.

Calyhedins I-VI: Resin glycosides from the rhizomes of Calystegia hederacea.

Six previously undescribed resin glycosides, calyhedins I-VI, were isolated from the rhizomes of Calystegia hederacea Wall., which are the first genuine resin glycosides isolated from C. hederacea. The structures of calyhedins I-VI were determined based on spectroscopic data and chemical evidence. All the compounds have macrolactone structures (jalapins), and their sugar moieties were partially acylated by five organic acids. Calyhedins I, II-V, and VI have 27-, 28-, and 23-membered rings, respectively, and calyhedins IV-VI are the first jalapins with a sugar chain consisting of seven monosaccharides. Additionally, the cytotoxic activity of calyhedins II and III toward HL-60 human promyelocytic leukemia cells was evaluated. Both compounds demonstrated almost the same activity as the positive control, cisplatin.

A New Glycosidic Acid, Muricatic Acid D, and Resin Glycosides, Muricatins X and XI, from the Crude Resin Glycoside Fraction of the Seeds of Ipomoea muricata.

Alkaline hydrolysis of crude resin glycoside fraction of the seeds of Ipomoea muricata (L.) Jacq. (Convolvulaceae) yielded a new glycosidic acid, muricatic acid D; three known glycosidic acids, namely, muricatic acids A, B, and C; and three known organic acids, namely, isobutyric, 2S-methylbutyric, and 2S-methyl-3S-hydroxybutyric acid. Two new genuine resin glycosides with macrolactone structures (jalapins), muricatins X and XI, were also isolated from the fraction. Their structures were determined using spectroscopic data and chemical evidence.

Two new triterpenoids from the leaves and stems of Lantana camara.

Two new oleanane-type triterpenoids with an epoxy bridge between C-3 and C-25, named lantacamaric acids A and B, were isolated from the leaves and stems of Lantana camara L. (Verbenaceae). In addition, seven known triterpenoids, two known iridoid glycosides, four known phenylethanoid glycosides, one known flavonoid glycoside, and one known cyanogenic glycoside were isolated. Their structures were determined based on the spectroscopic data. Furthermore, the cytotoxic activities of the isolated triterpenoids toward HL-60 cells were examined. The IC50 values of all compounds were obtained and ranged from 1.16 to 68.4 µM, with three compounds exhibiting stronger activities than the positive control, cisplatin. In addition, the structure-activity relationship was investigated.

Comparative studies of the biological activities of selected herbal extracts and phenolic compounds isolated from Rosa gallica.

This study aimed to compare the biological activities of 35 herbal hydroethanolic extracts and select high potential extract, which showed antioxidative activity and inhibitory activities of α-glucosidase, lipase, and hyaluronidase, and to investigate the isolation, structural elucidation, and biological activities of five phenolic compounds from the selected extracts of Rosa gallica. On the basis of one-dimensional nuclear magnetic resonance together with the comparison with the literature values, the phenolic compounds were identified as methyl gallate (1), kaempferol-3-O-arabinofuranoside (2), multinoside A acetate (3), kaempferol (4), and quercetin (5), respectively. The results suggest that the extracts from R. gallica show the strongest biological activities in 35 herbal extracts and that 1, 4, and 5 among the five isolated compounds from rose extracts are effective in promoting antioxidative and enzymatic inhibitory activities.

Identification and characterization of organic and glycosidic acids in crude resin glycoside fraction from Calystegia hederacea.

Resin glycosides are well known as the purgative ingredients, which are characteristic of convolvulaceous plants. Calystegia hederacea Wall. is a perennial herbaceous vine that is widespread throughout India and East Asia. All parts of this plant are used for the treatment of menoxenia, gonorrhea, etc. Alkaline hydrolysis of the crude resin glycoside fraction of the whole plants of C. hederacea yielded four new glycosidic acids, calyhedic acids A, B, C, and D, along with two known glycosidic acids, calysolic acids A and C, and three known organic acids, 2S-methylbutyric, tiglic, and 2R,3R-nilic acids. Their structures were characterized on the basis of spectroscopic data and chemical evidence. Calyhedic acids A, B, and D were penta-, hexa-, and hepta-glycosides of 12S-hydroxyhexadecanoic acid, respectively, and cayhedic acid C was an isomer of calyhedic acid D, in which the 12S-hydroxyhexadecanoyl residue of calyhedic acid D was replaced by a 11S-hydroxyhexadecanoyl residue. Additionally, cytotoxic activity toward HL-60 human promyelocytic leukemia cells of the crude resin glycoside fraction, the glycosidic acid fraction, calyhedic acid A, and calysolic acid A from C. hederacea was evaluated. Furthermore, to clarify the structure-activity relationship of resin glycosides, the activities of six genuine resin glycosides with calysolic acid A or calysolic acid C as the glycosidic acid, which were isolated from C. soldanella, were examined. Among them, the crude resin glycoside fraction and five genuine resin glycosides with macrolactone structures demonstrated clear cytotoxic activities, while the glycosidic acid fraction, calyhedric acid A, calysolic acid A, and a genuine non-macrolactone-type resin glycoside were either inactive or exhibited weaker activity than the tested macrolactone-type resin glycosides.

Seven new resin glycosides from the seeds of Quamoclit × multifida.

Seven new resin glycosides, multifidins III (1)-IX (7), were isolated from the seeds of Quamoclit × multifida (syn. Q. sloteri House) (Convolvulaceae), along with five known glycosides, quamoclinic acid B methyl ester (8), operculin XIII (9), quamoclin I (10), QM-10 (11), and QM-12 (12). Their structures were determined on the basis of spectroscopic data and chemical evidence. These compounds were of two different types, i.e., those with macrolactone structures and those with non-macrolactone structures. Additionally, cytotoxic activity towards HL-60 human leukemia cells of 1, 2, 5, 8, 9, 11, and 12 was evaluated. Among them, macrolactone-type resin glycosides (jalapins), 1, 2, and 9, specifically demonstrated clear cytotoxic activity with IC50 values of 3.46, 14.7, and 10.9 µM, respectively.

Four new resin glycosides, murasakimasarins I-IV, from the tuber of Ipomoea batatas.

Four new resin glycosides having macrolactone structures (jalapins), murasakimasarins I-IV, were isolated from the tubers of Ipomoea batatas (L.) Lam. ('Murasakimasari', Convolvulaceae), along with three known glycosides. Their structures were determined on the basis of spectroscopic data as well as chemical evidence. Murasakimasarin III is the first representative of a resin glycoside with 10-methylundecanoic acid as the component organic acid.

A new resin glycoside from Calystegia soldanella and its antiviral activity towards herpes.

A new resin glycoside, named calysolin XVIII (1), was isolated from the leaves, stems and roots of Calystegia soldanella Roem. et Schult. (Convolvulaceae). The structure of 1 was defined as 11S-jalapinolic acid 11-O-ß-d-glucopyranosyl-(1 → 3)-O-(2-O-2S-methylbutyryl,4-O-3-hydroxy-2-methylenebutyryl)-α-l-rhamnopyranosyl-(1 → 2)-[O-ß-d-glucopyranosyl-(1 → 6)-O-(34-di-O-2S-methylbutyryl)-ß-d-glucopyranosyl-(1 → 3)]-O-ß-d-glucopyranosyl-(1 → 2)-ß-d-quinovopyranoside, intramolecular 1,2″'″'-ester on the basis of spectroscopic data. Compound 1 is the first known resin glycoside to feature 3-hydroxy-2-methylenebutyric acid as a component organic acid. In addition, 1 demonstrated an antiviral activity against herpes simplex virus type 1, with an IC50 value 2.3 µM.