Jun Kawabata

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Organization: Hokkaido University

Department: Division of Applied Bioscience, Graduate School of Agriculture

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Chemicals
References

Structural confirmation of novel oligosaccharides isolated from sugar beet molasses

Co-reporter:Tatsuya Abe, Hiroto Kikuchi, Tsutomu Aritsuka, Yusuke Takata, Eri Fukushi, Yukiharu Fukushi, Jun Kawabata, Keiji Ueno, Shuichi Onodera, Norio Shiomi

Food Chemistry 2016 Volume 202() pp:284-290

Publication Date(Web):1 July 2016

DOI:10.1016/j.foodchem.2016.01.126

•Eleven oligosaccharides were isolated from sugar beet molasses.•The structures of the oligosaccharides were confirmed using NMR techniques.•Three of 11 oligosaccharides were novel.Eleven oligosaccharides were isolated from sugar beet molasses using carbon–Celite column chromatography and HPLC. The constituent sugars and linkage positions were determined using methylation analysis, MALDI–TOF-MS, and NMR measurements. The configurations of isolated oligosaccharides were confirmed based on detailed NMR analysis. Based on our results, three of the 11 oligosaccharides were novel.

Selective purification of intestinal maltase complex by affinity chromatography employing an uncompetitive inhibitor as the ligand

Co-reporter:Eisuke Kato, Hiroki Tsuji, Jun Kawabata

Tetrahedron 2015 Volume 71(Issue 9) pp:1419-1424

Publication Date(Web):4 March 2015

DOI:10.1016/j.tet.2015.01.019

Affinity chromatography of specific enzymes is limited by the presence of related enzymes and the limited selectivity of the affinity ligand. We synthesized and investigated the use of an uncompetitive inhibitor as an affinity ligand, to leverage its three-component interactions. Use of the potent α-glucosidase uncompetitive inhibitor 2-aminoresorcinol as the ligand of the affinity gel offered selective purification of maltase-glucoamylase complex from the crude mixture of intestinal α-glucosidases.

α-Amylase Inhibitory Triterpene from Abrus precatorius Leaves

Co-reporter:Ryuta Yonemoto, Miyuki Shimada, Maria D. P. T. Gunawan-Puteri, Eisuke Kato, and Jun Kawabata

Journal of Agricultural and Food Chemistry 2014 Volume 62(Issue 33) pp:8411-8414

Publication Date(Web):August 4, 2014

DOI:10.1021/jf502667z

In the screening experiments for porcine pancreatic α-amylase inhibitors in 18 plants obtained from Indonesia, a potent inhibitory activity was detected in the extract of leaves of Abrus precatorius. The enzyme assay-guided fractionation of the extract led to the isolation of a triterpene ketone, lupenone (1), as a potent α-amylase inhibitor, together with 24-methylenecycloartenone (2) and luteolin (3). The mode of inhibition of compound 1 against porcine pancreatic α-amylase was a mixed inhibition. This is the first report that describes the potent α-amylase inhibitory activity of the low-polar triterpene ketone similar to compound 1. A comparison of the activities of the isolate and related compounds indicated the importance of C-3 ketone and the lupane skeleton in the α-amylase inhibitory activity.

Identification of hydroxychavicol and its dimers, the lipase inhibitors contained in the Indonesian spice, Eugenia polyantha

Co-reporter:Eisuke Kato, Ryo Nakagomi, Maria D.P.T. Gunawan-Puteri, Jun Kawabata

Food Chemistry 2013 Volume 136(3–4) pp:1239-1242

Publication Date(Web):1–15 February 2013

DOI:10.1016/j.foodchem.2012.09.013

Inhibition of pancreatic lipase is effective for a prevention of obesity. Eugenia polyantha is a tropical tree whose leaves are known as a spice and also as an ingredient for Jamu, the traditional medicine of Indonesia. We found inhibitory activity against pancreatic lipase in the extract of E. polyantha leaves. Purification of the active principals resulted in isolation of hydroxychavicol, and two structurally new dimers. All of the isolated compounds showed inhibitory activity against the porcine pancreatic lipase and high content of hydroxychavicol (1.83 wt.%) indicated this compound to be responsible for the majority of inhibitory activity of E. polyantha extract. Furthermore, hydroxychavicol is reported to possess anti-carcinogenic, anti-oxidant, anti-microbial and anti-inflammatory activity which is related to traditional usage of this plant. These results offer this plant as an attractive material for treating various health problems including obesity.Highlights► Extract of Eugenia polyantha showed high pancreatic lipase inhibitory activity. ► Hydroxychavicol and two dimers were isolated as the pancreatic lipase inhibitor. ► Beneficial effect of E. polyantha arises from the high content of hydroxychavicol.

Substrate-like water soluble lipase inhibitors from Filipendula kamtschatica

Co-reporter:Eisuke Kato, Michitsugu Yama, Ryo Nakagomi, Toshiro Shibata, Keizo Hosokawa, Jun Kawabata

Bioorganic & Medicinal Chemistry Letters 2012 Volume 22(Issue 20) pp:6410-6412

Publication Date(Web):15 October 2012

DOI:10.1016/j.bmcl.2012.08.055

Filipendula kamtschatica is a plant utilized as a traditional medicine by Ainu people in Japan, but its chemical constituents are not much studied. Pancreatic lipase inhibitors are a promising tool for the treatment of obesity. We searched for natural lipase inhibitors from F. kamtschatica and two new compounds were isolated along with the known flavonoid glycoside. The structure elucidation of new compounds revealed these two to be 2-O-caffeoyl-4-O-galloyl-l-threonic acid and 3-O-caffeoyl-4-O-galloyl-l-threonic acid, which can be recognized as a pancreatic lipase’s substrate-like structure. The isolated compounds all showed an inhibitory activity against porcine pancreatic lipase and one of the isomer, 3-O-caffeoyl-4-O-galloyl-l-threonic acid, possessed the most potent activity with IC50 value showing an order lower value compared to others. The substrate-like structure of the new compounds seemed to be important for their activity.

α-Glucosidase inhibitors from the bulb of Eleutherine americana

Co-reporter:Tomohiro Ieyama, Maria D.P.T. Gunawan-Puteri, Jun Kawabata

Food Chemistry 2011 Volume 128(Issue 2) pp:308-311

Publication Date(Web):15 September 2011

DOI:10.1016/j.foodchem.2011.03.021

One effective way to treat diabetes is by suppressing carbohydrate digestion due to the utilisation of α-glucosidase inhibitors (AGIs). The determination of prospective herbs, done in vitro by using enzyme assay, resulted in the finding of Eleutherine americana, which showed a potent inhibitory activity. A 50% aqueous methanol-soluble extract of bulbs of E. americana was chromatographed successively and the active fractions were further purified with preparative high performance liquid chromatography (HPLC) to isolate active compounds against α-glucosidase. Structure determination by mass and NMR analysis revealed that these isolated compounds were eleutherol (1), eleutherinoside A (2), and eleuthoside B (3) based on comparisons with the reference data. Considering the amount and the inhibitory activity of each naphthalene in the whole extracts, the bulb of E. americana inhibitory activity against α-glucosidase might be a result of compound 2 (IC50 = 0.5 mM, yield = 5 mg/50 g plant sample, with a characteristic structure which has never been found in other AGIs. AGIs play an important role for the treatment of diabetes, therefore these results may suggest novel alternatives for diabetes treatment management.Highlights► Extract of the bulb of Eleutherine americana showed strong maltase-inhibitory activity. ► Eleutherinoside A with naphtopyrone structure is a unique glucosidase inhibitor. ► This is the first study of E. americana in relation to its anti-diabetic potencies.

Synthesis and α-amylase inhibitory activity of glucose–deoxynojirimycin conjugates

Co-reporter:Eisuke Kato, Naoya Iwano, Akihiko Yamada, Jun Kawabata

Tetrahedron 2011 67(40) pp: 7692-7702

Publication Date(Web):

DOI:10.1016/j.tet.2011.08.012

Novel α-glucosidase inhibitors from Macaranga tanarius leaves

Co-reporter:Maria D.P.T. Gunawan-Puteri, Jun Kawabata

Food Chemistry 2010 Volume 123(Issue 2) pp:384-389

Publication Date(Web):15 November 2010

DOI:10.1016/j.foodchem.2010.04.050

One of the hyperglycaemic remedies is glucose absorption reduction by suppressing carbohydrate digestion due to utilisation of α-glucosidase inhibitors (AGIs). Determination of prospecting herbs done in vitro by using enzyme assay resulted in the finding of Macaranga tanarius, which showed a potent inhibitory activity. An EtOAc-soluble extract of M. tanarius leaves was chromatographed by a Diaion HP-20 column and the active fractions were further purified with high performance liquid chromatography (HPLC) to isolate active principles against α-glucosidase. Five ellagitannins were successfully isolated and identified. Structure determination revealed that these isolated compounds were mallotinic acid (IC50 > 5.00 mM), corilagin (IC50 = 2.63 mM), chebulagic acid (IC50 = 1.00 mM), and two novel compounds named macatannins A (IC50 = 0.80 mM) and B (IC50 = 0.55 mM). AGIs play an important role for the treatment of diabetes, therefore this research results may suggest novel alternatives for diabetes treatment management.

Highly Oxygenated Monoterpene Acylglucosides from Spiraea cantoniensis

Co-reporter:Kaori Yoshida, Atsuyuki Hishida, Osamu Iida, Keizo Hosokawa and Jun Kawabata

Journal of Natural Products 2010 Volume 73(Issue 5) pp:814-817

Publication Date(Web):March 23, 2010

DOI:10.1021/np900699e

Six new monoterpene acylglucosides named kodemariosides A−F (1−6) were isolated from the leaves and flowers of Spiraea cantoniensis. Their absolute structures including a highly oxygenated monoterpene aglycon part were determined by NMR experiments and chemical derivatization.

α-Glucosidase inhibitory effect by the flower buds of Tussilago farfara L.

Co-reporter:Hong Gao, Yi-Na Huang, Bo Gao, Pei-Yu Xu, Chika Inagaki, Jun Kawabata

Food Chemistry 2008 Volume 106(Issue 3) pp:1195-1201

Publication Date(Web):1 February 2008

DOI:10.1016/j.foodchem.2007.07.064

Methanolic extracts from the medicinal parts of 50 traditional Chinese herbs were tested in screening experiments for rat intestinal α-glucosidase. The methanolic extract from flower buds of Tussilago farfara L. (Compositae) showed the highest maltase inhibitory activity, with maltose as a substrate. Enzyme assay-guided fractionation of this extract afforded 3,4-dicaffeoylquinic acid (1), 3,5-dicaffeoylquinic acid (2), 4,5-dicaffeoylquinic acid (3) and rutin (4), and the structures of these compounds were elucidated on the basis of MS and NMR data analyses. Compounds 1, 2 and 3 showed comparative maltase inhibitory activities, and the IC50 values were 0.91 mM, 0.90 mM and 0.89 mM, respectively. Comparison of the activities of 1–3, chlorogenic acid (5), quinic acid (6) and caffeic acid (7) suggested that the number of caffeoyl groups attached to a quinic acid core were important for the potency. Rutin (4) showed moderate activity and inhibited 41% of maltase activity at a concentration of 1 mM. This is the first report on mammalian α-glucosidase inhibition of T. farfara and the isolation of 1, 2 and 3 from this herb species. These results suggest a use of the extract of T. farfara for antidiabetes.

Inhibitory effect on α-glucosidase by Adhatoda vasica Nees

Co-reporter:Hong Gao, Yi-Na Huang, Bo Gao, Peng Li, Chika Inagaki, Jun Kawabata

Food Chemistry 2008 Volume 108(Issue 3) pp:965-972

Publication Date(Web):1 June 2008

DOI:10.1016/j.foodchem.2007.12.002

Methanolic extracts from the medicinal parts of 40 traditional Chinese herbs were tested in screening experiments for rat intestinal α-glucosidase. The methanolic extract from the leaves of Adhatoda vasica Nees (Acanthaceae) showed the highest sucrase inhibitory activity with sucrose as a substrate. Enzyme assay-guided fractionation of this extract afforded vasicine (1) and vasicinol (2), and the structures of these compounds were elucidated on the basis of MS and NMR analysis. Compounds 1 and 2 showed a high sucrase inhibitory activity, and the IC50 values were 125 μM and 250 μM, respectively. Both 1 and 2 were shown to be reversible inhibitors of sucrase. Kinetic data revealed that compounds 1 and 2 inhibited sucrose-hydrolysing activity of rat intestinal α-glucosidase competitively with Ki values of 82 μM and 183 μM, respectively. This is the first report on the mammalian α-glucosidase inhibition of A. vasica and the inhibitory effect on sucrase by 1 and 2 from this herb species. These results suggest a use of the extract of A. vasica as an antidiabetic agent and show a possibility that compounds 1 and 2 could be an useful treatment for metabolic disorders.

α-Glucosidase and α-amylase inhibitory activities of Nepalese medicinal herb Pakhanbhed (Bergenia ciliata, Haw.)

Co-reporter:Megh Raj Bhandari, Nilubon Jong-Anurakkun, Gao Hong, Jun Kawabata

Food Chemistry 2008 Volume 106(Issue 1) pp:247-252

Publication Date(Web):1 January 2008

DOI:10.1016/j.foodchem.2007.05.077

Herbal medicine has been used for many years by different cultures around the world for the treatment of diabetes. The Nepalese herb Pakhanbhed, is one of the traditional remedies used for diabetes since prehistoric times. In this study, we examined the anti-diabetic activity using an in vitro model and isolated the active compounds from Pakhanbhed. Extraction and fractionation of the extract lead to the isolation of two active compounds, (−)-3-O-galloylepicatechin and (−)-3-O-galloylcatechin and these are reported from this plant species for the first time. These isolated compounds demonstrated significant dose dependent enzyme inhibitory activities against rat intestinal α-glucosidase and porcine pancreatic α-amylase. IC50 value for sucrose, maltase and α-amylase were 560, 334 and 739 μM, respectively for [(−)-3-O-galloylepicatechin] and 297, 150 and 401 μM, respectively for [(−)-3-O-galloylcatechin]. Our study, for the first time, revealed the anti-diabetic potential of Pakhanbhed and this study could be helpful to develop medicinal preparations or nutraceutical and functional foods for diabetes and related symptoms.

Flavonol Caffeoylglycosides as α-Glucosidase Inhibitors from Spiraea cantoniensis Flower

Co-reporter:Kaori Yoshida, Atsuyuki Hishida, Osamu Iida, Keizo Hosokawa and Jun Kawabata

Journal of Agricultural and Food Chemistry 2008 Volume 56(Issue 12) pp:4367-4371

Publication Date(Web):May 23, 2008

DOI:10.1021/jf8007579

In the screening experiments for rat intestinal α-glucosidase inhibitors in 218 plants cultivated in the Japanese temperate region, potent maltase-inhibiting activity was found in the extract of flowers of Spiraea cantoniensis. The enzyme assay guided fractionation of the extract led to the isolation of three flavonol caffeoylglycosides, quercetin 3-O-(6-O-caffeoyl)-β-galactoside (1), kaempferol 3-O-(6-O-caffeoyl)-β-galactoside (2), and kaempferol 3-O-(6-O-caffeoyl)-β-glucoside (3), as rat intestinal maltase inhibitors. This is the first report on the α-glucosidase-inhibitory activity of those flavonol caffeoylglycosides. Comparison in the activity of the isolates indicated the importance of caffeoyl substructures in the molecule for the α-glucosidase-inhibiting activity. The relatively high contents of the active isolates in the plant suggest that S. cantoniensis could be physiologically useful for treatment of diabetes.

α-Glucosidase inhibitors from Devil tree (Alstonia scholaris)

Co-reporter:Nilubon Jong-Anurakkun, Megh Raj Bhandari, Jun Kawabata

Food Chemistry 2007 Volume 103(Issue 4) pp:1319-1323

Publication Date(Web):2007

DOI:10.1016/j.foodchem.2006.10.043

α-Glucosidase inhibitors are used in the treatment of non-insulin-dependent diabetes mellitus. We attempt to isolate α-glucosidase inhibitors from 24 traditional Thai medicinal plant samples. Potent α-glucosidase inhibitory activity was found in aqueous methanol extract of dried Devil tree (Alstonia scholaris) leaves. Active principles against α-glucosidase, prepared from rat small intestine acetone powder, were isolated and identified. The structures of these isolated compounds were found to be quercetin 3-O-β-d-xylopyranosyl (1‴ → 2″)-β-d-galactopyranoside and (−)-lyoniresinol 3-O-β-d-glucopyranoside on the basis of chemical and spectral evidence. The latter exhibited an inhibitory activity against both sucrase and maltase with IC50 values of 1.95 and 1.43 mM, respectively, whereas the former inhibited only maltase with IC50 values of 1.96 mM. This preliminary observation will provide the basis for further examination of the suitability of Alstonia scholaris as a medicinal supplement that contributes toward the treatment and prevention of diabetes.

Inhibitory effect on α-glucosidase by the fruits of Terminalia chebula Retz.

Co-reporter:Hong Gao, Yi-Na Huang, Pei-Yu Xu, Jun Kawabata

Food Chemistry 2007 Volume 105(Issue 2) pp:628-634

Publication Date(Web):2007

DOI:10.1016/j.foodchem.2007.04.023

Mammalian α-glucosidase inhibitory activity by Terminalia chebula Retz. fruits was investigated. The aqueous methanolic extract was found to have potent rat intestinal maltase inhibitory activity, whereas neither intestinal sucrase nor isomaltase activity was inhibited by this extract. Using bioassay-guided separation, three active ellagitannins were identified as chebulanin (1), chebulagic acid (2) and chebulinic acid (3) and were shown to possess potent intestinal maltase inhibitory activity, with the IC50 values of 690 μM, 97 μM and 36 μM, respectively. The intestinal maltase inhibitory activities of 2 and 3 were even higher than that of 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG) (4, IC50=140 μM), which is a known potent α-glucosidase inhibitor. Comparison of the activities of 1–4, 1,2,3-O-trigalloyl-β-d-glucose (5), neochebulagic acid (6) and corilagin (7) suggested that the positions of chebulloyl and galloyl groups mostly affected the potency. Kinetic studies revealed that 2, 3, and 4 inhibited maltose-hydrolyzing activity of intestinal α-glucosidase, noncompetitively. This is the first report on mammalian α-glucosidase inhibition by 1, 2 and 3 isolated from T. chebula fruits. These results suggest a use of the extract of T. chebula fruits for managing Type 2 diabetes.

DPPH (= 2,2-Diphenyl-1-picrylhydrazyl = 2,2-Diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl) Radical-Scavenging Reaction of Protocatechuic Acid Esters (= 3,4-Dihydroxybenzoates) in Alcohols: Formation of Bis-alcohol Adduct

Co-reporter:Shizuka Saito;Hong Gao

Helvetica Chimica Acta 2006 Volume 89(Issue 4) pp:821-831

Publication Date(Web):19 APR 2006

DOI:10.1002/hlca.200690074

Protocatechuic acid esters (= 3,4-dihydroxybenzoates) scavenge ca. 5 equiv. of radical in alcoholic solvents, whereas they consume only 2 equiv. of radical in nonalcoholic solvents. While the high radical-scavenging activity of protocatechuic acid esters in alcoholic solvents as compared to that in nonalcoholic solvents is due to a nucleophilic addition of an alcohol molecule at C(2) of an intermediate o-quinone structure, thus regenerating a catechol (= benzene-1,2-diol) structure, it is still unclear why protocatechuic acid esters scavenge more than 4 equiv. of radical (C(2) refers to the protocatechuic acid numbering). Therefore, to elucidate the oxidation mechanism beyond the formation of the C(2) alcohol adduct, 3,4-dihydroxy-2-methoxybenzoic acid methyl ester (4), the C(2) MeOH adduct, which is an oxidation product of methyl protocatechuate (1) in MeOH, was oxidized by the DPPH radical (= 2,2-diphenyl-1-picrylhydrazyl) or o-chloranil (= 3,4,5,6-tetrachlorocyclohexa-3,5-diene-1,2-dione) in CD₃OD/(D₆)acetone 3 : 1). The oxidation mixtures were directly analyzed by NMR. Oxidation with both the DPPH radical and o-chloranil produced a C(2),C(6) bis-methanol adduct (7), which could scavenge additional 2 equiv. of radical. Calculations of LUMO electron densities of o-quinones corroborated the regioselective nucleophilic addition of alcohol molecules with o-quinones. Our results strongly suggest that the regeneration of a catechol structure via a nucleophilic addition of an alcohol molecule with a o-quinone is a key reaction for the high radical-scavenging activity of protocatechuic acid esters in alcoholic solvents.

DPPH (= 2,2-Diphenyl-1-picrylhydrazyl) Radical-Scavenging Reaction of Protocatechuic Acid (= 3,4-Dihydroxybenzoic Acid): Difference in Reactivity between Acids and Their Esters

Co-reporter:Jun Kawabata;Shizuka Saito

Helvetica Chimica Acta 2006 Volume 89(Issue 7) pp:1395-1407

Publication Date(Web):26 JUL 2006

DOI:10.1002/hlca.200690139

Protocatechuic acid (= 3,4-dihydroxybenzoic acid; 1) exhibits a significantly slow DPPH (= 2,2-diphenyl-1-picrylhydrazyl) radical-scavenging reaction compared to its esters in alcoholic solvents. The present study is aimed at the elucidation of the difference between the radical-scavenging mechanisms of protocatechuic acid and its esters in alcohol. Both protocatechuic acid (1) and its methyl ester 2 rapidly scavenged 2 equiv. of radical and were converted to the corresponding o-quinone structures 1a and 2a, respectively (Scheme). Then, a regeneration of catechol (= benzene-1,2-diol) structures occurred via a nucleophilic addition of a MeOH molecule to the o-quinones to yield alcohol adducts 1f and 2c, respectively, which can scavenge additional 2 equiv. of radical. However, the reaction of protocatechuic acid (1) beyond the formation of the o-quinone was much slower than that of its methyl ester 2. The results suggest that the slower radical-scavenging reaction of 1 compared to its esters is due to a dissociation of the electron-withdrawing carboxylic acid function to the electron-donating carboxylate ion, which decreases the electrophilicity of the o-quinone, leading to a lower susceptibility towards a nucleophilic attack by an alcohol molecule.

Organic acid, phenolic content and antioxidant activity of wild yam (Dioscorea spp.) tubers of Nepal

Co-reporter:Megh Raj Bhandari, Jun Kawabata

Food Chemistry 2004 Volume 88(Issue 2) pp:163-168

Publication Date(Web):November 2004

DOI:10.1016/j.foodchem.2003.12.027

Four wild yam (Dioscorea spp.) tubers available in Nepal were analyzed for their individual organic acids, total phenolic contents and antioxidant activities. Succinic acid was predominant with an average value of 1316 mg/100 g fresh weight (FW). Citric acid was the second most abundant, with an average value of 274 mg/100 g FW. Average values recorded for malic and oxalic acids were 147 and 110 mg/100 g FW, respectively. Total polyphenol content (as phenol) ranged from 13 to 166 mg/100 g FW. Wild yam tubers were found to have significant antioxidant activities, as evaluated by different methods such as DPPH free radical scavenging, ferrous ion chelating, reducing power and total antioxidant activity tests. Consumption of fresh yam tubers may thus serve as a good source of antioxidant in its natural form; and may have role in prevention of human diseases, in which free radicals are involved, such as cancer and cardiovascular diseases.

Nutritional evaluation of wild yam (Dioscorea spp.) tubers of Nepal

Co-reporter:Megh Raj Bhandari, Takanori Kasai, Jun Kawabata

Food Chemistry 2003 Volume 82(Issue 4) pp:619-623

Publication Date(Web):September 2003

DOI:10.1016/S0308-8146(03)00019-0

Wild yams make a significant contribution to diets of tribal people in Nepal. However, there is insufficient study of their nutritional value. In this paper, four wild yam species: Dioscorea bulbifera, D. versicolor, D. deltoidea and D. triphylla, were studied. The dry matter ranged from 19.8 to 30.5% on a fresh weight basis. The ranges of crude protein, ash, crude fat and crude fibre contents were 1.6–3.1, 0.5–1.2, 0.2–0.3 and 0.6–1.5% of fresh weight, respectively. The ranges of minerals in mg per 100 g fresh weight were K (250–560), Na (4.15–17.8), P (33.1–61.6), Ca (14.3–46.9), Mg (18.3–27.3), Cu (0.10–0.21), Fe (0.39–2.92), Mn (0.14–0.35) and Zn (0.22–0.53). Sulfur-containing amino acids and lysine were the most limiting in all species studied. Nutritional compositions of wild yams were similar to those reported for most cultivated yams in several parts of the world except for the higher value of crude fibre found in our samples.