5β,19-Epoxycucurbitane Triterpenoids from Momordica charantia and Their Anti-Inflammatory and Cytotoxic Activity

Chia-Ching Liaw; Hui-Chi Huang; Ping-Chun Hsiao; Li-Jie Zhang; Zhi-Hu Lin; Syh-Yuan Hwang; Feng-Lin Hsu; Yao-Haur Kuo

doi:10.1055/s-0034-1383307

Planta Medica, Table of Contents

Planta Med 2015; 81(01): 62-70
DOI: 10.1055/s-0034-1383307

Natural Product Chemistry

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

5β,19-Epoxycucurbitane Triterpenoids from Momordica charantia and Their Anti-Inflammatory and Cytotoxic Activity

Chia-Ching Liaw^*

¹R&D Department, Starsci Biotech Co. Ltd., Taipei, Taiwan

,

Hui-Chi Huang^*

²Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan

,

Ping-Chun Hsiao

³Division of Chinese Materia Medica Development, National Research Institute of Chinese Medicine, Taipei, Taiwan

⁴Endemic Species Research Institute, Council of Agriculture, Nantou, Taiwan

,

Li-Jie Zhang

³Division of Chinese Materia Medica Development, National Research Institute of Chinese Medicine, Taipei, Taiwan

,

Zhi-Hu Lin

³Division of Chinese Materia Medica Development, National Research Institute of Chinese Medicine, Taipei, Taiwan

,

Syh-Yuan Hwang

⁴Endemic Species Research Institute, Council of Agriculture, Nantou, Taiwan

,

Feng-Lin Hsu

⁵Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan

,

Yao-Haur Kuo

³Division of Chinese Materia Medica Development, National Research Institute of Chinese Medicine, Taipei, Taiwan

⁶Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan

⁷Ph.D Program for the Clinical Drug Discovery from Botanical Herbs, School of Pharmacy, Taipei Medical University, Taipei, Taiwan

› Author Affiliations

Abstract

Five new 5β,19-epoxycucurbitane triterpenoids, taikugausins A–E (1–5), together with 5β,19-epoxy-25-methoxycucurbita-6,23-diene-3β,19-diol (6), have been isolated and characterized from the 70 % EtOH extract of the fresh fruits of Momordica charantia. The chemical structures of compounds 1–6 were elucidated on the basis of extensive spectroscopic analyses, especially 2D NMR (HMQC, HMBC, and NOESY) experiments and HRESIMS data. The relationship between NMR chemical shifts and the configuration of C-19 with an OMe group in 5β,19-epoxycucurbitane are described. Among them, compounds 3 and 4 exhibited remarkable anti-inflammatory activities by the inhibition of nitric oxide production at the concentration of 10 µg/mL. In addition, 3 and 4 also showed moderate cytotoxicity against WiDr, Hep G2, MCF-7, and HEp-2 human tumor cell lines.

Key words

Momordica charantia - Cucurbitaceae - 5β,19-epoxycucurbitane - taikuguasins - anti-inflammatory activity - cytotoxicity

Full Text

References

References
1 Grover JK, Yadav SP. Pharmacological actions and potential uses of Momordica charantia: a review. J Ethnopharmacol 2004; 93: 123-132
2 Abascal K, Yarnell E. Using bitter melon to treat diabetes. J Altern Complement Med 2005; 1: 179-184
3 Bourinbaiar AS, Lee-Huang S. Potentiation of anti-HIV activity of anti-inflammatory drugs, dexamethasone and indomethacin, by MAP30, the antiviral agent from bitter melon. Biochem Biophys Res Commun 1995; 208: 779-785
4 Jilka C, Strifler B, Fortner GW, Hays EF, Takemoto DJ. In vivo antitumor activity of the bitter melon (Momordica charantia). Cancer Res 1983; 43: 5151-5155
5 Ray RB, Raychoudhuri A, Steele R, Nerurkar P. Bitter melon (Momordica charantia) extract inhibits breast cancer cell proliferation by modulating cell cycle regulatory genes and promotes apoptosis. Cancer Res 2010; 70: 1925-1931
6 Ali L, Khan AK, Mamun MI, Mosihuzzaman M, Nahar N, Nur-e-Alam M, Rokeya B. Studies on hypoglycemic effects of fruit pulp, seed, and whole plant of Momordica charantia on normal and diabetic model rats. Planta Med 1993; 59: 408-412
7 Kumar R, Balaji S, Uma TS, Sehgal PK. Fruit extracts of Momordica charantia potentiate glucose uptake and up-regulate Glut-4, PPAR gamma and PI3K. J Ethnopharmacol 2009; 126: 533-537
8 Gurbuz I, Akyuz C, Yesilada E, Sener B. Anti-ulcerogenic effect of Momordica charantia L. fruits on various ulcer models in rats. J Ethnopharmacol 2000; 71: 77-82
9 Li CK, Chen HW, Yun WT, Liu KL. Suppressive effects of wild bitter gourd (Momordica charantia Linn. var. abbreviata ser.) fruit extracts on inflammatory responses in RAW264.7 macrophages. J Ethnopharmacol 2009; 122: 227-233
10 Leung SO, Yeung HW, Leung KN. The immunosuppressive activities of two abortifacient proteins isolated from the seeds of bitter melon (Momordica charantia). Immunopharmacology 1987; 13: 159-171
11 Lee SY, Eom SH, Kim YK, Park NI, Park SU. Cucurbitane-type triterpenoids in Momordica charantia Linn. J Med Plants Res 2009; 3: 1264-1269
12 Murakami T, Emoto A, Matsuda H, Yoshikawa M. Medicinal foodstuffs. XXI. Structures of new cucurbitane-type triterpene glycosides, goyaglycosides-a, -b, -c, -d, -e, -f, -g, and -h, and new oleanane-type triterpene saponins, goyasaponins I, II, and III, from the fresh fruit of Japanese Momordica charantia L. Chem Pharm Bull 2001; 49: 54-63
13 Begum S, Ahmed M, Siddiqui BS. Triterpenes, a sterol and a monocyclic alcohol from Momordica charantia L. Phytochemistry 1997; 44: 1313-1320
14 Chen JC, Chiu MH, Nie RL, Cordell GA, Qiu SX. Cucurbitacins and cucurbitane glycosides: structures and biological activities. Nat Prod Rep 2005; 22: 386-399
15 Hsiao PC, Liaw CC, Hwang SY, Cheng HL, Zhang LJ, Shen CC, Hsu FL, Kuo YH. Antiproliferative and hypoglycemic cucurbitane-type glycosides from the fruits of Momordica charantia . J Agric Food Chem 2013; 61: 2979-2986
16 Zhang LJ, Liaw CC, Hsiao PC, Huang HC, Lin MJ, Lin ZH, Hsu FL, Kuo YH. Cucurbitane-type glycosides from the fruits of Momordica charantia and their hypoglycaemic and cytotoxic activities. J Funct Foods 2014; 564-574
17 Mulholland DA, Sewram V, Osborne R, Pegel KH, Connolly JD. Cucurbitane triterpenoids from the leaves of Momordica foetida . Phytochemistry 1997; 45: 391-395
18 Li QY, Chen HB, Liu ZM, Wang B, Zhao YY. Cucurbitane triterpenoids from Momordica charantia . Magn Reson Chem 2007; 45: 451-456
19 Akihisa T, Higo N, Tokuda H, Ukiya M, Akazawa H, Tochigi Y, Kimura Y, Suzuki T, Nishino H. Cucurbitane-type triterpenoids from the fruits of Momordica charantia and their cancer chemopreventive effects. J Nat Prod 2007; 70: 1233-1239
20 Chen JC, Liu WQ, Lu L, Qiu MH, Zheng YT, Yang LM, Zhang XM, Zhou L, Li ZR. Kuguacins F–S, cucurbitane triterpenoids from Momordica charantia . Phytochemistry 2009; 70: 133-140
21 Nguyen XN, Phan VK, Chau VM, Ninh KB, Nguyen XC, Lee MH, Bui HT, Tran HQ, Nguyen HT, Kim YH. Cucurbitane-type triterpene glycosides from the fruits of Momordica charantia . Magn Reson Chem 2010; 48: 392-396
22 Pan ZM, Cheng JT, He J, Wang YY, Peng LY, Xu G, Sun WB, Zhao QS. Splendidins A–C, three new clerodane diterpenoids from Salvia splendens . Helv Chim Acta 2011; 94: 417-422
23 Fukui S, Hochster RM. D-ribo-Hexos-3-ulose, a new dicarbonyl-sugar. J Am Chem Soc 1963; 85: 1967-1968
24 Harinantenaina L, Tanaka M, Takaoka S, Oda M, Mogami O, Uchida M, Asakawa Y. Momordica charantia constituents and antidiabetic screening of the isolated major compounds. Chem Pharm Bull 2006; 54: 1017-1021
25 Zhang LJ, Chiou CT, Cheng JJ, Huang HC, Kuo-Yang LM, Liao CC, Bastow KF, Lee KH, Kuo YH. Cytotoxic polyisoprenyl benzophenonoids from Garcinia subelliptica . J Nat Prod 2010; 73: 557-562

Supplementary Material

Supporting Information