Antidiabetic activities of a cucurbitane‑type triterpenoid compound from Momordica charantia in alloxan‑induced diabetic mice

Jiang,Bowen; Ji,Mingli; Liu,Wei; Chen,Lili; Cai,Zhiyu; Zhao,Yuqing; Bi,Xiuli

doi:10.3892/mmr.2016.5800

Antidiabetic activities of a cucurbitane‑type triterpenoid compound from Momordica charantia in alloxan‑induced diabetic mice

Authors:
- Bowen Jiang
- Mingli Ji
- Wei Liu
- Lili Chen
- Zhiyu Cai
- Yuqing Zhao
- Xiuli Bi
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Affiliations: College of Life Science, Liaoning University, Shenyang, Liaoning 110036, P.R. China, Department of Physiology, College of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. China
Published online on: October 5, 2016 https://doi.org/10.3892/mmr.2016.5800
Pages: 4865-4872

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Abstract

Momordica charantia has been used to treat a variety of diseases, including inflammation, diabetes and cancer. A cucurbitane‑type triterpenoid [(19R,23E)‑5β, 19‑epoxy‑19‑methoxy‑cucurbita‑6,23,25‑trien‑3 β‑o‑l] previously isolated from M. charantia was demonstrated to possess significant cytotoxicity against cancer cells. The current study investigated the effects of this compound (referred to as compound K16) on diabetes using an alloxan‑induced diabetic mouse model. C57BL/6J mice were intraperitoneally injected with alloxan (10 mg/kg body weight), and those with blood glucose concentration higher than 10 mM were selected for further experiments. Diabetic C57BL/6J mice induced by alloxan were administered 0.9% saline solution, metformine (10 mg/kg body weight), or K16 (25 or 50 mg/kg body weight) by gavage for 4 weeks, followed by analysis of blood glucose level, glucose tolerance, serum lipid levels and organ indexes. The results demonstrated that compound K16 significantly reduced blood glucose (31‑48.6%) and blood lipids (13.5‑42.8%; triglycerides and cholesterol), while improving glucose tolerance compared with diabetic mice treated with saline solution, suggesting a positive improvement in glucose and lipid metabolism following K16 treatment. Furthermore, similarly to metformine, compound K16 markedly upregulated the expression of a number of insulin signaling pathway‑associated proteins, including insulin receptor, insulin receptor substrate 1, glycogen synthase kinase 3β, Akt serine/threonine kinase, and the transcript levels of glucose transporter type 4 and AMP‑activated protein kinase α1. The results of the current study demonstrated that compound K16 alleviated diabetic metabolic symptoms in alloxan‑induced diabetic mice, potentially by affecting genes and proteins involved in insulin metabolism signaling.

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1	World Health Organization, . Diabetes Fact Sheet. World Health Organization; Geneva: 2015
2	World Health Organization, . Global health estimates: Deaths by cause, age, sex and country, 2000–2012. World Health Organization; Geneva: 2014
3	Sharma BR, Kim HJ and Rhyu DY: Caulerpa lentillifera extract ameliorates insulin resistance and regulates glucose metabolism in C57BL/KsJ-db/db mice via PI3K/AKT signaling pathway in myocytes. J Transl Med. 13:622015. View Article : Google Scholar : PubMed/NCBI
4	Grover JK and Yadav SP: Pharmacological actions and potential uses of Momordica charantia: A review. J Ethnopharmacol. 93:123–132. 2004. View Article : Google Scholar : PubMed/NCBI
5	Zhu Y, Dong Y, Qian X, Cui F, Guo Q, Zhou X, Wang Y, Zhang Y and Xiong Z: Effect of superfine grinding on antidiabetic activity of bitter melon powder. Int J Mol Sci. 13:14203–14218. 2012. View Article : Google Scholar : PubMed/NCBI
6	Iseli TJ, Turner N, Zeng XY, Cooney GJ, Kraegen EW, Yao S, Ye Y, James DE and Ye JM: Activation of AMPK by bitter melon triterpenoids involves CaMKKβ. PLoS One. 8:e623092013. View Article : Google Scholar : PubMed/NCBI
7	Tan MJ, Ye JM, Turner N, Hohnen-Behrens C, Ke CQ, Tang CP, Chen T, Weiss HC, Gesing ER, Rowland A, et al: Antidiabetic activities of triterpenoids isolated from bitter melon associated with activation of the AMPK pathway. Chem Biol. 15:263–273. 2008. View Article : Google Scholar : PubMed/NCBI
8	Chaturvedi P: Antidiabetic potentials of Momordica charantia: Multiple mechanisms behind the effects. J Med Food. 15:101–107. 2012. View Article : Google Scholar : PubMed/NCBI
9	Wang X, Sun W, Cao J, Qu H, Bi X and Zhao Y: Structures of new triterpenoids and cytotoxicity activities of the isolated major compounds from the fruit of Momordica charantia L. J Agric Food Chem. 60:3927–3933. 2012. View Article : Google Scholar : PubMed/NCBI
10	Zeng K, He YN, Yang D, Cao JQ, Xia XC, Zhang SJ, Bi XL and Zhao YQ: New compounds from acid hydrolyzed products of the fruits of Momordica charantia L. and their inhibitory activity against protein tyrosine phosphatas 1B. Eur J Med Chem. 81:176–180. 2014. View Article : Google Scholar : PubMed/NCBI
11	Li Y, Hamasaki T, Nakamichi N, Kashiwagi T, Komatsu T, Ye J, Teruya K, Abe M, Yan H, Kinjo T, et al: Suppressive effects of electrolyzed reduced water on alloxan-induced apoptosis and type 1 diabetes mellitus. Cytotechnology. 63:119–131. 2011. View Article : Google Scholar : PubMed/NCBI
12	Bi X, Fang W, Wang LS, Stoner GD and Yang W: Black raspberries inhibit intestinal tumorigenesis in apc1638+/− and Muc2−/− mouse models of colorectal cancer. Cancer Prev Res (Phila). 3:1443–1450. 2010. View Article : Google Scholar : PubMed/NCBI
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
14	Prabhakar V, Gupta D, Kanade P and Radhakrishnan M: Diabetes-associated depression: The serotonergic system as a novel multifunctional target. Indian J Pharmacol. 47:4–10. 2015. View Article : Google Scholar : PubMed/NCBI
15	Alvim RO, Cheuhen MR, Machado SR, Sousa AG and Santos PC: General aspects of muscle glucose uptake. An Acad Bras Cienc. 87:351–368. 2015. View Article : Google Scholar : PubMed/NCBI
16	Yang SJ, Choi JM, Park SE, Rhee EJ, Lee WY, Oh KW, Park SW and Park CY: Preventive effects of bitter melon (Momordica charantia) against insulin resistance and diabetes are associated with the inhibition of NF-kappaB and JNK pathways in high-fat-fed OLETF rats. J Nutr Biochem. 26:234–240. 2015. View Article : Google Scholar : PubMed/NCBI
17	Lo HY, Ho TY, Li CC, Chen JC, Liu JJ and Hsiang CY: A novel insulin receptor-binding protein from Momordica charantia enhances glucose uptake and glucose clearance in vitro and in vivo through triggering insulin receptor signaling pathway. J Agric Food Chem. 62:8952–8961. 2014. View Article : Google Scholar : PubMed/NCBI
18	Zheng D, MacLean PS, Pohnert SC, Knight JB, Olson AL, Winder WW and Dohm GL: Regulation of muscle GLUT-4 transcription by AMP-activated protein kinase. J Appl Physiol (1985). 91:1073–1083. 2001.PubMed/NCBI
19	Penumathsa SV, Thirunavukkarasu M, Zhan L, Maulik G, Menon VP, Bagchi D and Maulik N: Resveratrol enhances GLUT-4 translocation to the caveolar lipid raft fractions through AMPK/Akt/eNOS signalling pathway in diabetic myocardium. J Cell Mol Med. 12:2350–2361. 2008. View Article : Google Scholar : PubMed/NCBI
20	Turan B, Tuncay E and Vassort G: Resveratrol and diabetic cardiac function: Focus on recent in vitro and in vivo studies. J Bioenerg Biomembr. 44:281–296. 2012. View Article : Google Scholar : PubMed/NCBI
21	Dasgupta B and Milbrandt J: Resveratrol stimulates AMP kinase activity in neurons. Proc Natl Acad Sci USA. 104:7217–7222. 2007. View Article : Google Scholar : PubMed/NCBI
22	Wang X, Tian J, Jiang J, Li L, Ying X, Tian H and Nie M: Effects of green tea or green tea extract on insulin sensitivity and glycaemic control in populations at risk of type 2 diabetes mellitus: A systematic review and meta-analysis of randomised controlled trials. J Hum Nutr Diet. 27:501–512. 2014. View Article : Google Scholar : PubMed/NCBI
23	Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Görgün C, Glimcher LH and Hotamisligil GS: Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 306:457–461. 2004. View Article : Google Scholar : PubMed/NCBI
24	Embi N, Rylatt DB and Cohen P: Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur J Biochem. 107:519–527. 1980. View Article : Google Scholar : PubMed/NCBI
25	de Figueiredo Souto Padron A, Salmon AB, Bruno F, Jimenez F, Martinez HG, Halade GV, Ahuja SS, Clark RA, DeFronzo RA, Abboud HE and El Jamali A: Nox2 mediates skeletal muscle insulin resistance induced by a high-fat diet. J Biol Chem. 290:13427–13439. 2015. View Article : Google Scholar : PubMed/NCBI
26	Shih CC, Lin CH, Lin WL and Wu JB: Momordica charantia extract on insulin resistance and the skeletal muscle GLUT4 protein in fructose-fed rats. J Ethnopharmacol. 123:82–90. 2009. View Article : Google Scholar : PubMed/NCBI
27	Huang S and Czech MP: The GLUT4 glucose transporter. Cell Metab. 5:237–252. 2007. View Article : Google Scholar : PubMed/NCBI
28	Cheng HL, Huang HK, Chang CI, Tsai CP and Chou CH: A cell-based screening identifies compounds from the stem of Momordica charantia that overcome insulin resistance and activate AMP-activated protein kinase. J Agric Food Chem. 56:6835–6843. 2008. View Article : Google Scholar : PubMed/NCBI
29	McCarty MF: Does bitter melon contain an activator of AMP-activated kinase? Med Hypotheses. 63:340–343. 2004. View Article : Google Scholar : PubMed/NCBI
30	Jiang Q, Takemori AE, Sultana M, Portoghese PS, Bowen WD, Mosberg HI and Porreca F: Differential antagonism of opioid delta antinociception by [D-Ala2, Leu5, Cys6]enkephalin and naltrindole 5′-isothiocyanate: Evidence for delta receptor subtypes. J Pharmacol Exp Ther. 257:1069–1075. 1991.PubMed/NCBI