Top

Published in:

Open Access 01-10-2015 | Original Paper

Dipeptidyl peptidase-IV inhibitory activity of dimeric dihydrochalcone glycosides from flowers of Helichrysum arenarium

Authors: Toshio Morikawa, Kiyofumi Ninomiya, Junji Akaki, Namiko Kakihara, Hiroyuki Kuramoto, Yurie Matsumoto, Takao Hayakawa, Osamu Muraoka, Li-Bo Wang, Li-Jun Wu, Seikou Nakamura, Masayuki Yoshikawa, Hisashi Matsuda

Published in: Journal of Natural Medicines | Issue 4/2015

Abstract

A methanol extract of everlasting flowers of Helichrysum arenarium L. Moench (Asteraceae) was found to inhibit the increase in blood glucose elevation in sucrose-loaded mice at 500 mg/kg p.o. The methanol extract also inhibited the enzymatic activity against dipeptidyl peptidase-IV (DPP-IV, IC₅₀ = 41.2 μg/ml), but did not show intestinal α-glucosidase inhibitory activities. From the extract, three new dimeric dihydrochalcone glycosides, arenariumosides V–VII (2–4), were isolated, and the stereostructures were elucidated based on their spectroscopic properties and chemical evidence. Of the constituents, several flavonoid constituents, including 2–4, were isolated, and these isolated constituents were investigated for their DPP-IV inhibitory effects. Among them, chalconaringenin 2′-O-β-D-glucopyranoside (16, IC₅₀ = 23.1 μM) and aureusidin 6-O-β-D-glucopyranoside (35, 24.3 μM) showed relatively strong inhibitory activities.

Czinner E, Hagymási K, Blázovics A, Kéry Á, Szöke É, Lemberkovics É (2000) In vitro antioxidant properties of Helichrysum arenarium (L.) Moench. J Ethnopharmacol 73:437–443CrossRefPubMed

Gradinaru AC, Silion M, Trifan A, Miron A, Aprotosoaie AC (2014) Helichrysum arenarium subsp. arenarium: phenolic composition and antibacterial activity against lower respiratory tract pathogens. Nat Prod Res 28:2076–2080CrossRefPubMed

Vrkoc J, Dolejs L, Sedmera P, Vasickova S, Sorm F (1971) Structure of arenol and homoarenol, α-pyrone derivatives from Helichrysum arenarium. Therahedron Lett 3:247–250CrossRef

Morikawa T, Wang L-B, Nakamura S, Ninomiya K, Yokoyama E, Matsuda H, Muraoka O, Wu L-J, Yoshikawa M (2009) Medicinal flowers. XXVII. new flavanone and chalcone glycosides, arenariumosides I, II, III, and IV, and tumor necrosis factor-α inhibitors from everlasting, flowers of Helichrysum arenarium. Chem Pharm Bull 57:361–367CrossRefPubMed

Morikawa T, Wang L-B, Ninomiya K, Nakamura S, Matsuda H, Muraoka O, Wu L-J, Yoshikawa M (2009) Medicinal flowers. XXX. Eight new glycosides, everlastosides F–M, from the flowers of Helichrysum arenarium. Chem Pharm Bull 57:853–859CrossRefPubMed

Wang L-B, Morikawa T, Nakamura S, Ninomiya K, Matsuda H, Muraoka O, Wu L-J, Yoshikawa M (2009) Medicinal flowers. XXVIII. structures of five new glycosides, everlastosides A, B, C, D, and E, from the flowers of Helichrysum arenarium. Heterocycles 78:1235–1242CrossRef

Wang L-B, Wang J, Gan C, Wu L-J, Liu F (2011) Chemical constituents in fraction of lipid-lowering of Helichrysi arenarii flos. Shenyang Yaoke Daxue Xuebao 28(868–870):916

Wang L-B, Liu F, Gan C, Dong N, Hou Y, Wang C (2012) Isolation and identification of chemical constituents in the lipid-lowering fraction of flos Helichrysum arenarium (II). Shenyang Yaoke Daxue Xuebao 29(109–112):125

Wang L-B, Wang J-W, Wang C, Sun S-C, Xu B, Wu L-J (2012) Chemical constituents in the lipid-lowering fraction of flos Helichrysum arenarium (III). Zhongguo Yaowu Huaxue Zazhi 22(220–222):226

10.

Vrkoc J, Ubik K, Sedmera P (1973) Phenolic extractives from the achenes of Helichrysum arenarium. Phytochemistry 12:2062CrossRef

11.

Vrkoc J, Dolejs L, Budesinsky M (1975) Methylene-bis-2H-pyran-2-ones and phenolic constituents from the root of Helichrysum arenarium. Phytochemistry 14:1383–1384CrossRef

12.

Vrkoc J, Budesinsky M, Dolejs L, Vasickova S (1975) Arenophthalide A, a new phthalide glycoside from Helichrysum arenarium roots. Phytochemistry 14:1845–1848CrossRef

13.

Mericli AH, Damadyan B, Cubukcu B (1986) Flavonoids of Turkish Helichrysum arenarium (L.) Moench (Asteraceae). Sci Pharm 54:363–365

14.

Ahrén B (2008) Emerging dipeptidyl peptidase-4 inhibitors for the treatment of diabetes. Expert Opin Emerg Drugs 13:593–607CrossRefPubMed

15.

Mulakayala N, Reddy CHU, Iqbal J, Pal M (2010) Synthesis of dipeptidyl peptidase-4 inhibitors: a brief overview. Tetrahedron 66:4919–4938CrossRef

16.

Hussein GME, Matsuda H, Nakamura S, Hamao M, Akiyama T, Tamura K, Yoshikawa M (2011) Mate tea (Ilex paraguariensis) promotes satiety and body weight lowering in mice: involvement of glucagon-like peptide-1. Biol Pharm Bull 34:1849–1855CrossRefPubMed

17.

Aljančić IS, Vučković I, Jadranin M, Pešić M, Ðorđević I, Podolski-Renić A, Stojković S, Menković N, Vajs VE, Milosavljević SM (2014) Two structurally distinct chalcone dimers from Helichrysum zivojinii and their activities in cancer cell lines. Phytochemistry 98:190–196CrossRefPubMed

18.

Montaudo G, Caccamese S (1973) Structure and conformation of chalcone photodimers and related compounds. J Org Chem 38:710–716CrossRef

19.

Montaudo G, Caccamese S, Librando V (1974) Photodimers of cinnamic acid and related compounds. A stereochemical study by NMR. Org Magn Res 6:534–536CrossRef

20.

Nozaki H, Hayashi K, Kido M, Kakumoto K, Ikeda S, Matsuura N, Tani H, Takaoka D, Iinuma M, Akao Y (2007) Pauferrol A, a novel chalcone trimer with a cyclobutane ring from Caesalpinia ferrea mart exhibiting DNA topoisomerase II inhibition and apoptosis-inducing activity. Tetrahedron Lett 48:8290–8292CrossRef

21.

Morikawa T, Ninomiya K, Miyake S, Miki Y, Okamoto M, Yoshikawa M, Muraoka O (2013) Flavonol glycosides with lipid accumulation inhibitory activity and simultaneous quantitative analysis of 15 polyphenols and caffeine in the flower buds of Camellia sinensis from different regions by LCMS. Food Chem 140:353–360CrossRefPubMed

22.

Morikawa T, Ninomiya K, Imura K, Yamaguchi T, Akagi Y, Yoshikawa M, Hayakawa T, Muraoka O (2014) Hepatoprotectie triterpenes from traditional Tibetan medicine Potentilla anserina. Phytochemistry 102:169–181CrossRefPubMed

23.

Drewes SE, Hudson NA (1983) Brackenin, a dimeric dihydrochalcone from Brackenridgea zanguebarica. Phytochemistry 22:2823–2825CrossRef

24.

Masaoud M, Ripperger H, Himmelreich U, Adam G (1995) Cinnabarone, a biflavonoid from dragon’s blood of Dracaena cinnabari. Phytochemistry 38:751–753CrossRef

25.

Seidel V, Bailleul F, Waterman PG (2000) (Rel)-1β,2α-di-(2,4-dihydroxy-6-methoxybenzoyl)-3β,4α-di-(4-methoxyphenyl)-cyclobutane and other flavonoids from the aerial parts of Goniothalamus gardneri and Goniothalamus thwaitesii. Phytochemistry 55:439–446CrossRefPubMed

26.

Li Y-S, Matsunaga K, Kato R, Ohizumi Y (2001) Verbenachalcone, a novel dimeric dihydrochalcone with potentiating activity on nerve growth factor-action from Verbena littoralis. J Nat Prod 64:806–808CrossRefPubMed

27.

Patil AD, Freyer AJ, Killmer L, Offen P, Taylor PB, Votta BJ, Johnson RK (2002) A new dimeric dihydrochalcone and a new prenylated flavone from the bud covers of Artocarpus altilis: potent inhibitors of cathepsin K. J Nat Prod 65:624–627CrossRefPubMed

28.

Katerere DR, Gray AI, Kennedy AR, Nash RJ, Waigh RD (2004) Cyclobutanes from Combretum albopunctatum. Phytochemistry 65:433–438CrossRefPubMed

29.

Kamara BI, Manong DTL, Brandt EV (2005) Isolation and synthesis of a dimeric dihydrochalcone from Agapanthus africanus. Phytochemistry 66:1126–1132CrossRefPubMed

30.

Kumar M, Rawat P, Rahuja N, Srivastava AK, Maurya R (2009) Antihyperglycemic activity of phenylpropanoyl esters of catechol glycoside and its dimers from Dodecadenia grandiflora. Phytochemistry 70:1448–1455CrossRefPubMed

31.

Morikawa T, Chaipech S, Matsuda H, Hamao M, Umeda Y, Sato H, Tamura H, Kon’i H, Ninomiya K, Yoshikawa M, Pongpiriyadacha Y, Hayakawa T, Muraoka O (2012) Antidiabetogenic oligostilbenoids and 3-ethyl-4-phenyl-3,4-dihydroisocoumarins from the bark of Shorea roxburghii. Bioorg Med Chem 20:832–840CrossRefPubMed

32.

Morikawa T, Ninomiya K, Imamura M, Akaki J, Fujikura S, Pan Y, Yuan D, Yoshikawa M, Jia X, Li Z, Muraoka O (2014) Acylated phenylethanoid glycosides, echinacoside and acteoside from Cistanche tubulosa, improve glucose tolerance in mice. J Nat Med 68:561–566CrossRefPubMed

33.

Muraoka O, Morikawa T, Miyake S, Akaki J, Ninomiya K, Yoshikawa M (2010) Quantitative determination of potent α-glucosidase inhibitors, salacinol and kotalanol, in Salacia species using liquid chromatography-mass spectrometry. J Pharm Biomed Anal 52:770–773CrossRefPubMed

34.

Muraoka O, Morikawa T, Miyake S, Akaki J, Ninomiya K, Pongpiriyadacha Y, Yoshikawa M (2011) Quantitative analysis of neosalacinol and neokotalanol, another two potent α-glucosidase inhibitors from Salacia species, by LC-MS with ion pair chromatography. J Nat Med 65:142–148CrossRefPubMed

35.

Akaki J, Morikawa T, Miyake S, Ninomiya K, Okada M, Tanabe G, Pongpiriyadacha Y, Yoshikawa M, Muraoka O (2014) Evaluation of Salacia species as anti-diabetic natural resources based on quantitative analysis of eight sulphonium constituents: a new class of α-glucosidase inhibitors. Phytochem Anal 25:544–550CrossRefPubMed

Title: Dipeptidyl peptidase-IV inhibitory activity of dimeric dihydrochalcone glycosides from flowers of Helichrysum arenarium
Authors: Toshio Morikawa
Kiyofumi Ninomiya
Junji Akaki
Namiko Kakihara
Hiroyuki Kuramoto
Yurie Matsumoto
Takao Hayakawa
Osamu Muraoka
Li-Bo Wang
Li-Jun Wu
Seikou Nakamura
Masayuki Yoshikawa
Hisashi Matsuda
Publication date: 01-10-2015
Publisher: Springer Japan
Published in: Journal of Natural Medicines / Issue 4/2015
Print ISSN: 1340-3443
Electronic ISSN: 1861-0293
DOI: https://doi.org/10.1007/s11418-015-0914-8

At a glance: The STEP trials

Springer Medicine

Dipeptidyl peptidase-IV inhibitory activity of dimeric dihydrochalcone glycosides from flowers of Helichrysum arenarium

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2015

A bibenzyl from Dendrobium ellipsophyllum inhibits migration in lung cancer cells

Antidepressant-like activity of Tagetes lucida Cav. is mediated by 5-HT1A and 5-HT2A receptors

Oxomollugin, a potential inhibitor of lipopolysaccharide-induced nitric oxide production including nuclear factor kappa B signals

Protective effects of aloperine on neonatal rat primary cultured hippocampal neurons injured by oxygen–glucose deprivation and reperfusion

Myrtucommulone-A treatment decreases pluripotency- and multipotency-associated marker expression in bladder cancer cell line HTB-9

Manadodioxans A−E: polyketide endoperoxides from the marine sponge Plakortis bergquistae