[en] [en] BACKGROUND: Traditionally Momordica charantia (Bitter gourd) is known for its blood glucose lowering potential. This has been validated by many previous studies based on rodent models but human trials are less convincing and the physiological mechanisms underlying the bioactivity of Bitter gourd are still unclear. The present study compared the effects of whole fruit or stems-leaves from five different Bitter gourd cultivars on metabolic control in adult diabetic obese Göttingen Minipigs.
METHODS: Twenty streptozotocin-induced diabetic (D) obese Minipigs (body weight ~85 kg) were subdivided in mildly and overtly D pigs and fed 500 g of obesogenic diet per day for a period of three weeks, supplemented with 20 g dried powdered Bitter gourd or 20 g dried powdered grass as isoenergetic control in a cross-over, within-subject design.
RESULTS: Bitter gourd fruit from the cultivars "Palee" and "Good healthy" reduced plasma fructosamine concentrations in all pigs combined (from 450±48 to 423±53 and 490±50 to 404±48 μmol/L, both p<0.03, respectively) indicating improved glycemic control by 6% and 17%. These effects were statistically confirmed in mildly D pigs but not in overtly D pigs. In mildly D pigs, the other three cultivars of fruit showed consistent numerical but no significant improvements in glycemic control. The composition of Bitter gourd fruit was studied by metabolomics profiling and analysis identified three metabolites from the class of triterpenoids (Xuedanoside H, Acutoside A, Karaviloside IX) that were increased in the cultivars "Palee" (>3.9-fold) and "Good healthy" (>8.9-fold) compared to the mean of the other three cultivars. Bitter gourd stems and leaves from the cultivar "Bilai" increased plasma insulin concentrations in all pigs combined by 28% (from 53±6 to 67±9 pmol/L, p<0.03). The other two cultivars of stems and leaves showed consistent numerical but no significant increases in plasma insulin concentrations. The effects on plasma insulin concentrations were confirmed in mildly D pigs but not in overtly D pigs.
CONCLUSIONS: Fruits of Bitter gourd improve glycemic control and stems-leaves of Bitter gourd increase plasma insulin concentrations in an obese pig model for mild diabetes. The effects of Bitter gourd fruit on glycemic control seem consistent but relatively small and cultivar specific which may explain the varying results of human trials reported in the literature.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Koopmans, Sietse Jan ; Wageningen Livestock Research, Wageningen University & Research, Wageningen, The Netherlands
Binnendijk, Gisabeth; Wageningen Livestock Research, Wageningen University & Research, Wageningen, The Netherlands
Ledoux, Allison ; Université de Liège - ULiège > Département de pharmacie > Pharmacognosie ; Natural Products Laboratory, Institute of Biology, Leiden University, Leiden, The Netherlands
Choi, Young Hae; Natural Products Laboratory, Institute of Biology, Leiden University, Leiden, The Netherlands ; College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea
Mes, Jurriaan J; Wageningen Food & Biobased Research, Wageningen University & Research, Wageningen, The Netherlands
Guan, Xiaonan; Schothorst Feed Research, Lelystad, The Netherlands
Molist, Francesc; Schothorst Feed Research, Lelystad, The Netherlands
Thị Minh, Tâm Phạm; Department of Food crops and Horticulture, Nong Lam University, Ho Chi Minh City, Vietnam
van der Wielen, Nikkie; Department of Animal Nutrition and Division of Human Nutrition, Wageningen University & Research, Wageningen, The Netherlands
Language :
English
Title :
Momordica charantia fruit reduces plasma fructosamine whereas stems and leaves increase plasma insulin in adult mildly diabetic obese Göttingen Minipigs.
Joseph B, Jini D. Antidiabetic effects of Momordica charantia (bitter melon) and its medicinal potency. Asian pacific journal of tropical disease. 2013;Apr 1; 3(2):93–102. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027280/?swcfpc=1. https://doi.org/10.1016/S2222-1808(13)60052-3
Grover J, Yadav S. Pharmacological actions and potential uses of Momordica charantia: a review. Journal of ethnopharmacology. 2004; 93(1), 123–132. https://doi.org/10.1016/j.jep.2004.03.035 PMID: 15182917
Zhu Y, Dong Y, Qian X, Cui F, Guo Q, Zhou X, et al. Effect of superfine grinding on antidiabetic activity of bitter melon powder. International journal of molecular sciences. 2012; 13(11), 14203–14218. https://doi.org/10.3390/ijms131114203 PMID: 23203059
Peter EL, Kasali FM, Deyno S, Mtewa A, Nagendrappa PB, Tolo CU, et al. Momordica charantia L. lowers elevated glycaemia in type 2 diabetes mellitus patients: Systematic review and meta-analysis. Journal of ethnopharmacology. 2019; 231, 311–324. https://doi.org/10.1016/j.jep.2018.10.033 PMID: 30385422
Peter EL, Mtewa AG, Nagendrappa PB, Kaligirwa A, Sesaazi CD. Systematic review and meta-analysis protocol for efficacy and safety of Momordica charantia L. on animal models of type 2 diabetes mellitus. Systematic Reviews. 2020; 9(1), 1–9. https://doi.org/10.1186/s13643-019-1265-4 PMID: 31915054
Roura E, Koopmans SJ, Lallès JP, Le Huerou-Luron I, de Jager N, Schuurman T, et al. Critical review evaluating the pig as a model for human nutritional physiology. Nutr Res Rev. 2016; 29: p. 60–90. https://doi.org/10.1017/S0954422416000020 PMID: 27176552
Gutierrez K, Dicks N, Glanzner W, Agellon L, Bordignon V. Efficacy of the porcine species in biomedical research. Frontiers in Genetics. 2015; 6. URL = https://www.frontiersin.org/article/10.3389/fgene.2015. 00293. https://doi.org/10.3389/fgene.2015.00293 ISSN = 1664–8021. PMID: 26442109
Koopmans SJ, Schuurman T. Considerations on pig models for appetite, metabolic syndrome and obese type 2 diabetes: From food intake to metabolic disease. Eur J Pharmacol. 2015; 759: p. 231–239. https://doi.org/10.1016/j.ejphar.2015.03.044 PMID: 25814261
Coelho PG, Pippenger B, Tovar N, Koopmans SJ, Plana NM, Graves DT, et al. Effect of obesity or metabolic syndrome and diabetes on osseointegration of dental implants in a miniature swine model: a pilot study. Journal of Oral and Maxillofacial Surgery. 2018;Aug1; 76(8):1677–87. https://doi.org/10.1016/j.joms.2018.02.021 PMID: 29572133
Ahima RS, Antwi DA. Brain regulation of appetite and satiety. Endocrinol Metab Clin North Am. 2008; Dec; 37(4):811–23. https://doi.org/10.1016/j.ecl.2008.08.005 PMID: 19026933; PMCID: PMC2710609.
Halford JC, Harrold JA. Satiety-enhancing products for appetite control: science and regulation of functional foods for weight management. Proceedings of the Nutrition Society. 2012;May; 71(2):350–62. https://doi.org/10.1017/S0029665112000134 PMID: 22401600
Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010; 8(6):e1000412. https://www.research.fsu.edu/media/1876/arrive-guidelines-for-publications.pdf. https://doi.org/10.1371/journal.pbio.1000412 PMID: 20613859
Christoffersen BO, Grand N, Golozoubova V, Svendsen O, Raun K. Gender-associated differences in metabolic syndrome-related parameters in Göttingen minipigs. Comp Med. 2007;Oct; 57(5):493–504. PMID: 17974133.
Centraal Veevoeder Bureau 2011, CVB table pigs, Product Board Animal Feed, The Hague, The Netherlands. https://www.cvbdiervoeding.nl/bestand/10741/cvb-feed-table-2021.pdf.ashx.
Yuwai KE, Rao KS, Kaluwin C, Jones GP, Rivett DE. Chemical composition of Momordica charantia L. fruits. J. Agric. Food Chem. 1991; 39,1762–1763. https://doi.org/10.1021/jf00010a013
Xiang C, Wu CY, Wang LP. Analysis and utilization of nutrient composition in bitter gourd (Momordica charantia). J. Huazhong Agr Univ. 2000; 19,388–390. https://www.cabdirect.org/cabdirect/abstract/ 20013150139.
Zhang M, Hettiarachchy NS, Horax R, Chen P, Over KF. Effect of maturity stages and drying methods on the retention of selected nutrients and phytochemicals in Bitter Melon (Momordica charantia). Leaf. J. of Food Sc. 2009;Vol. 74 (6), 441–448. https://doi.org/10.1111/j.1750-3841.2009.01222.x PMID: 19723180
Koopmans SJ, Mroz Z, Dekker R, Corbijn H, Ackermans M, Sauerwein H. Association of insulin resistance with hyperglycemia in streptozotocin-diabetic pigs. Effects of metformin at isoenergetic feeding in a type 2-like diabetic pig model. Metabolism. 2006; 55:960–971. https://doi.org/10.1016/j.metabol.2006.03.004 PMID: 16784971
Gerrity RG, Natarajan R, Nadler JL, Kimsey T. Diabetes-induced accelerated atherosclerosis in swine. Diabetes. 2001; 50:1654–65. https://doi.org/10.2337/diabetes.50.7.1654 PMID: 11423488
Wallace TM, Levy JC, Matthews DR. "Use and abuse of HOMA modeling". Diabetes Care. 2004; 27 (6):1487–95. https://doi.org/10.2337/diacare.27.6.1487 PMID: 15161807
Pluskal T, Castillo S, Villar-Briones A, Orešič M. MZmine 2: modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC bioinformatics. 2010;Dec; 11 (1):1–1. https://doi.org/10.1186/1471-2105-11-395 PMID: 20650010
Myers OD, Sumner SJ, Li S, Barnes S, Du X. One step forward for reducing false positive and false negative compound identifications from mass spectrometry metabolomics data: new algorithms for constructing extracted ion chromatograms and detecting chromatographic peaks. Analytical chemistry. 2017;Sep 5; 89(17):8696–703. https://doi.org/10.1021/acs.analchem.7b00947 PMID: 28752754
Jin Y, Zhou X, Yang J, Xu X, Zhang J, Ma G. Bioactive triterpenoid saponins from the tubers of Hemsleya amabilis Diels. Fitoterapia. 2019;Nov 1; 139:104404. https://doi.org/10.1016/j.fitote.2019.104404 PMID: 31676394
Li Z, Chen M, Chen F, Li W, Huang G, Xu X, et al. Cucurbitane triterpenoid entities derived from Hemsleya penxianensis triggered glioma cell apoptosis via ER stress and MAPK signalling cross-talk. Bioorganic Chemistry. 2022;Oct 1; 127:106013. https://doi.org/10.1016/j.bioorg.2022.106013 PMID: 35841667
Perera WH, Shivanagoudra SR, Pérez JL, Kim DM, Sun YK, Jayaprakasha G, et al. Anti-inflammatory, antidiabetic properties and in silico modeling of cucurbitane-type triterpene glycosides from fruits of an Indian cultivar of Momordica charantia L. Molecules. 2021;Feb 16; 26(4):1038. https://doi.org/10.3390/ molecules26041038 PMID: 33669312
Nagao T, Tanaka R, Iwase Y, Hanazono H, Okabe H. Studies on the constituents of Luffa acutangula Roxb. I. Structures of acutosides AG, oleanane-type triterpene saponins isolated from the herb. Chemical and pharmaceutical bulletin. 1991;Mar 25; 39(3):599–606. https://doi.org/10.1248/cpb.39.599 PMID: 1863290
Ul Haq F, Ali A, Khan MN, Shah SM, Kandel RC, Aziz N, et al. Metabolite profiling and quantitation of cucurbitacins in Cucurbitaceae plants by liquid chromatography coupled to tandem mass spectrometry. Scientific Reports. 2019;Nov 5; 9(1):15992. https://doi.org/10.1038/s41598-019-52404-1 PMID: 31690753
Higgins PJ, Garlick RL, Bunn HF. Glycosylated hemoglobin in human and animal red cells: role of glucose permeability. Diabetes. 1982;Sep1; 31(9):743–8. https://doi.org/10.2337/diab.31.9.743 PMID: 7160543
Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018;AHA/ACC/ AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice.
Jacobsen A, Savji N, Blumenthal R. Hypertriglyceridemia Management According to the 2018 AHA/ ACC Guideline-American College of Cardiology. Washington, DC: American College of Cardiology. 2019. https://www.acc.org/latest-in-cardiology/articles/2019/01/11/07/39/hypertriglyceridemiamanagement-according-to-the-2018-aha-acc-guideline.
Nichols TC, Merricks EP, Bellinger DA, Raymer RA, Yu J, Lam D, et al. Oxidized LDL and fructosamine associated with severity of coronary artery atherosclerosis in insulin resistant pigs fed a high fat/high NaCl diet. PloS one. 2015;Jul 6; 10(7):e0132302. https://doi.org/10.1371/journal.pone.0132302 PMID: 26147990
Tavares Ribeiro R, Paula Macedo M, Filipe Raposo J. HbA1c, fructosamine, and glycated albumin in the detection of dysglycaemic conditions. Current diabetes reviews. 2016;Mar1; 12(1):14–9. https://www.ingentaconnect.com/content/ben/cdr/2016/00000012/00000001/art00005#Refs. https://doi.org/10.2174/1573399811666150701143112 PMID: 26126638
Fonseca-Correa JI, Correa-Rotter R. Sodium-Glucose Cotransporter 2 Inhibitors Mechanisms of Action: A Review. Front Med (Lausanne). 2021;Dec 20; 8:777861. https://doi.org/10.3389/fmed.2021. 777861 PMID: 34988095; PMCID: PMC8720766.
Liu J, Rajendram R, Zhang L. Chapter 158—Effects of Oleanolic Acid and Maslinic Acid on Glucose and Lipid Metabolism: Implications for the Beneficial Effects of Olive Oil on Health. In book: Olives and Olive Oil in Health and Disease Prevention, Academic Press, Editor(s): Victor R. Preedy, Ronald Ross Watson. 2010;1423–1429, ISBN 9780123744203, https://doi.org/10.1016/B978-0-12-374420-3.00158-3
Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia. 2017;Sep; 60 (9):1577–85. https://link.springer.com/article/10.1007/s00125-017-4342-z. https://doi.org/10.1007/ s00125-017-4342-z PMID: 28776086
Zhou J, Massey S, Story D, Li L. Metformin: an old drug with new applications. International journal of molecular sciences. 2018;Oct; 19(10):2863. https://doi.org/10.3390/ijms19102863 PMID: 30241400
Jeon JY, Lee SJ, Lee S, Kim SJ, Han SJ, Kim HJ, et al. Failure of monotherapy in clinical practice in patients with type 2 diabetes: The Korean National Diabetes Program. Journal of diabetes investigation. 2018;Sep; 9(5):1144–52. https://doi.org/10.1111/jdi.12801 PMID: 29328551
Goff HD, Repin N, Fabek H, El Khoury D, Gidley MJ. Dietary fibre for glycaemia control: Towards a mechanistic understanding. Bioactive carbohydrates and dietary fibre. 2018;Apr 1; 14:39–53.
Tesseraud S, Métayer S, Duchêne S, Bigot K, Grizard J, Dupont J. Regulation of protein metabolism by insulin: value of different approaches and animal models. Domestic animal endocrinology. 2007;Aug;1; 33(2):123–42. https://doi.org/10.1016/j.domaniend.2006.06.002 PMID: 16876379
Guan X, Santos RR, Koopmans SJ, Molist F. Effects of the Inclusion of Dietary Bitter Gourd (Momordica charantia) on the Performance and Carcass Characteristics of Pigs: Potential Application in the Feed Chain. Animals. 2023;Jun 30; 13(13):2159. https://doi.org/10.3390/ani13132159 PMID: 37443956