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.

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.

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.

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.

Thiolane-type sulfides from garlic, onion, and Welsh onion.

In this paper, we review our work in the last 10 years wherein we examined the sulfides in the acetone extracts of garlic (Allium sativum), onion (A. cepa), and Welsh onion (A. fistulosum), obtained and characterized the structures of new sulfides, three 3,4-dimethylthiolane-type sulfides from onion and Welsh onion, respectively, and four acyclic-type, nine 3,4-dimethyl- thiolane-type, four 2-methylthiolane (and thiane)-type, two 1,2-dithiolane-type, and two 2-oxothiolane-type sulfides, together with (E)-ajoene and one kujounin-type sulfide from garlic. During this process, structural corrections were made in onionin A group, garlicnin A, and garlicnin B group in some 3,4-dimethylthiolane-type sulfides. Next, hypothetical pathways for the production of the aforementioned sulfides were proposed. Furthermore, it was revealed that a typical 3,4-dimethylthiolane-type sulfide, onionin A1 obtained from onion, having the isomeric structure of garlicnin B1 obtained from garlic, decreased tumor proliferation and controlled tumor metastasis. These results showed that onionin A1 is an effective agent for controlling tumors, and that the antitumor effects observed in vivo are likely caused by reversing the antitumor immune system. Activation of the antitumor immune system by onionin A1 might be an effective adjuvant therapy for patients with osteosarcoma, ovarian cancer and other malignant tumors.

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.

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.

Increased phenolic content and antioxidant capacity of the heated leaves of yacon (Smallanthus sonchifolius).

We investigated the content of phenolic compounds and antioxidant capacity of two batches of non-heated and heated leaves of the yacon cultivar "Andes no yuki", grown in Japan. Lyophilized yacon leaves heated at 160°C for 20 min and 100°C for 60 min had a 1.96 to 9.69-times higher total phenolic content than that of the non-heated leaves. Heated leaves exhibited a 1.98 to 4.07-times higher antioxidant capacity than that of the non-heated leaves in three different free radical scavenging assays. Heated leaves were more efficient at attenuating the superoxide anion radical production in human granulocytic cells than the non-heated leaves. High-performance liquid chromatography analysis revealed that, in the heated leaves, the caffeic acid content was 2.13 to 3.64-times higher and the chlorogenic acid content was slightly lower than those in the non-heated leaves. Hence, heat processing may affect the active constituent contents in yacon leaves, potentiating its antioxidant capacity.Abbreviations: ABTS+: 2,2'-azinobis(2-ethylbenzothiazoline-6-sulfonic acid) cation; DPPH: 1,1-diphenyl-2-picrylhydrazyl, HPLC: high-performance liquid chromatography; NBT: nitroblue tetrazolium; O2-: superoxide anion; PMA: phorbol 12-myristate 13-acetate; PMS: phenazine methosulfate; TEAC: Trolox equivalent antioxidant capacity.

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.

Unique antioxidant effects of herbal leaf tea and stem tea from Moringa oleifera L. especially on superoxide anion radical generation systems.

This study aimed to investigate the unique antioxidative effects of Japanese moringa products, herbal leaf tea and stem tea, using established free radical assays, focusing on superoxide anion (O2-) radical generation systems. Hot-water extracts from moringa teas resulted in different but lower scavenging activities than Trolox in four synthetic free radical models. Interestingly, these extracts further showed higher O2- radical scavenging effects than Trolox in the phenazine methosulfate-NADH-nitroblue tetrazolium and xanthine oxidase assay systems. Incubating human neutrophils in the presence of these tea extracts rather than Trolox effectively suppressed cellular O2- radical generation. Among the eight known phenolic constituents of moringa leaves, caffeic acid and chlorogenic acid may be responsible for the O2-specific radical scavenging capacity stronger than that of Trolox. These results suggest that moringa herbal teas are a good source of natural antioxidants for preventing O2- radical-mediated disorders. Abbreviations: O2-: superoxide anion; ROS: reactive oxygen species; H2O2: hydrogen peroxide; XOD: xanthine oxidase; DPPH: 1,1-diphenyl-2-picrylhydrazyl; ABTS+: 2,2'-azinobis(2-ethylbenzothiazoline-6-sulfonic acid) cation; CPZ+: chlorpromazine cation; PMS: phenazine methosulfate; NBT: nitroblue tetrazolium; PMA: phorbol 12-myristate 13-acetate.

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.

New cyclic sulfides, garlicnins I2, M, N, and O, from Allium sativum.

One atypical thiolane-type sulfide, garlicnin I2 (1), two 3,4-dimethylthiolane-type sulfides, garlicnins M (2) and N (3), and one thiabicyclic-type sulfide, garlicnin O (4), were isolated from the acetone extracts of Chinese garlic bulbs, Allium sativum and their structures were characterized. Hypothetical pathways for the production of the respective sulfides were discussed.

New cyclic sulfides extracted from Allium sativum: garlicnins P, J2, and Q.

Two atypical cyclic-type sulfides, garlicnin P (1) and garlicnin J2 (2), and one thiabicyclic-type sulfide, garlicnin Q (3), were isolated from the acetone extracts of garlic, Allium sativum, bulbs cultivated in the Kumamoto city area, and their structures characterized. Their production pathways are also discussed.

Resin glycosides from Convolvulaceae plants.

Resin glycosides are well known as purgative ingredients, which are characteristic of certain crude drugs such as Mexican Scammony Radix, Orizabae Tuber, and Jalapae Tuber, all of which originate from Convolvulaceae plants. Depending on their solubility in ether, these are roughly classified into two groups-jalapin (soluble) and convolvulin (insoluble). Almost all jalapins hitherto isolated and characterized had common intramolecular macrocyclic ester structures. These are composed of 1 mol of oligoglycoside of hydroxyl fatty acid (glycosidic acid) partially acylated by some organic acids at the sugar moiety, some examples of which are ester-type dimers. On the other hand, convolvulin is regarded as an oligomer of a variety of acylated glycosidic acids. This review describes the isolation and structural elucidation of resin glycosides from some Convolvulaceae plants, including Ipomoea operculata, Pharbitis nil, Quamoclit pennata, Calystegia soldanella, and I. muricata.

Antitumor Allium Sulfides.

We examined the sulfides in onion (Allium cepa L.), Welsh onion (A. fistulosum L.), and garlic (A. sativum L.), and obtained three new thiolane-type sulfides (onionins A1-A3) from onion; two new thiabicyclic-type sulfides (welsonins A1, A2), together with onionins A1-A3, from Welsh onion; and six new acyclic-type sulfides (garlicnins L-1-L-4, E, and F), ten new thiolane-type sulfides (garlicnins A, B1-B4, C1-C3, K1, and K2), and three new atypical cyclic-type sulfides (garlicnins G, I, and J) from garlic. Acetone extracts showed the potential of these sulfides in inhibiting the polarization of M2 activated macrophages that are capable of suppressing tumor-cell proliferation. The effect of the thiolane-type sulfide of a major component, onionin A1, on tumor progression and metastasis in both osteosarcoma and ovarian cancer-bearing mouse models was then examined. Tumor proliferation was depressed, and tumor metastasis was controlled by regulating macrophage activation. These results showed that onionin A1 is an effective agent for controlling tumors in both in vitro and in vivo models, and that the antitumor effects observed in vivo are likely caused by reversing the antitumor immune system. Activation of the antitumor immune system by onionin A1 might be an effective adjuvant therapy for patients with osteosarcoma, ovarian cancer and other malignant tumors. Based on these findings, pharmacological investigations will be conducted in the future to develop natural and healthy foods and anti-cancer agents that can prevent or combat disease.

Atypical Cyclic Sulfides, Garlicnins G, I, and J, Extracted from Allium sativum.

Newly characterized, atypical sulfides, garlicnins G (1), I (2), and J (3), were isolated from the acetone extracts of garlic bulbs, Allium sativum. Their production pathways are regarded as different from those of cyclic sulfoxides, 3,4-dimethyltetrahydrothiophene-S-oxide derivatives such as onionins A1-A3, garlicnins B1-B4 and C1-C3.

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.

Two new triterpenoids from the seeds of blackberry (Rubus fructicosus).

Two new ursane-type triterpenoids (1, 2) attached to isopropylidenedioxy group were isolated from the seeds of blackberry (Rubus fructicosus L., Rosaceae) along with two known ursane-type triterpenoids, 2,3-O-isopropylidenyl-2α,3α,19α-trihydroxyurs-12-en-28-oic acid (3) and 1ß-hydroxyeuscaphic acid (4). The chemical structures of 1 and 2 were determined to be 2,3-O-isopropylidene-1ß,2ß,3ß,19α-tetrahydroxyurs-12-en-28-oic acid and 1,2-O-isopropylidene-1ß,2α,3α,19α-tetrahydroxyurs-12-en-28-oic acid, respectively, based on spectroscopic data. Additionally, their cytotoxic activity towards HL-60 human leukaemia cells was evaluated. Among them, 3 demonstrated a clear cytotoxic activity with 72.8 µM of IC50 value.

A new triterpenoid glycoside from the leaves and stems of Duranta repens.

A new triterpenoid glycoside (1) was isolated from the methanol extract of the leaves and stems of Duranta repens L. (Verbenaceae) along with 14 known compounds consisting of eight triterpenoids, four iridoids, one phenylethanoid glycoside and one flavonoid. The chemical structure of 1 was determined to be bayogenin 3-O-[ß-D-glucopyranoside]-28-O-[α-L-rhamnopyranosyl-(1→5)-O-ß-D-apiofuranosyl-(1→4)-O-α-L-rhamnopyranosyl-(1→2)-O-α-L-arabinopyranosyl] ester, based on spectroscopic data. In addition, the inhibitory effects of the isolates on lipoxygenase activity were examined. Among them, acteoside and apigenin resulted in 94 ± 3.6% and 82 ± 4.7% inhibition, respectively, at 0.5 mM.