Skip to main content
Top
Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

Hypoglycemic effects of Trichosanthes kirilowii and its protein constituent in diabetic mice: the involvement of insulin receptor pathway

Authors: Hsin-Yi Lo, Tsai-Chung Li, Tse-Yen Yang, Chia-Cheng Li, Jen-Huai Chiang, Chien-Yun Hsiang, Tin-Yun Ho

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

Login to get access

Abstract

Background

Diabetes is a serious chronic metabolic disorder. Trichosanthes kirilowii Maxim. (TK) is traditionally used for the treatment of diabetes in traditional Chinese medicine (TCM). However, the clinical application of TK on diabetic patients and the hypoglycemic efficacies of TK are still unclear.

Methods

A retrospective cohort study was conducted to analyze the usage of Chinese herbs in patients with type 2 diabetes in Taiwan. Glucose tolerance test was performed to analyze the hypoglycemic effect of TK. Proteomic approach was performed to identify the protein constituents of TK. Insulin receptor (IR) kinase activity assay and glucose tolerance tests in diabetic mice were further used to elucidate the hypoglycemic mechanisms and efficacies of TK.

Results

By a retrospective cohort study, we found that TK was the most frequently used Chinese medicinal herb in type 2 diabetic patients in Taiwan. Oral administration of aqueous extract of TK displayed hypoglycemic effects in a dose-dependent manner in mice. An abundant novel TK protein (TKP) was further identified by proteomic approach. TKP interacted with IR by docking analysis and activated the kinase activity of IR. In addition, TKP enhanced the clearance of glucose in diabetic mice in a dose-dependent manner.

Conclusions

In conclusion, this study applied a bed-to-bench approach to elucidate the hypoglycemic efficacies and mechanisms of TK on clinical usage. In addition, we newly identified a hypoglycemic protein TKP from TK. Our findings might provide a reasonable explanation of TK on the treatment of diabetes in TCM.
Literature
1.
go back to reference American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37 Suppl:81–90.CrossRef American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37 Suppl:81–90.CrossRef
2.
go back to reference American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care. 2015;38 Suppl:8–16.CrossRef American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care. 2015;38 Suppl:8–16.CrossRef
4.
go back to reference Powers AC. Diabetes mellitus. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, editors. Harrison’s principles of internal medicine. New York: The McGraw-Hill Companies, Inc; 2012. p. 2275–304. Powers AC. Diabetes mellitus. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, editors. Harrison’s principles of internal medicine. New York: The McGraw-Hill Companies, Inc; 2012. p. 2275–304.
5.
go back to reference Xu Q, Bauer R, Hendry BM, Fan TP, Zhao Z, Duez P, Simmonds MS, Witt CM, Lu A, Robinson N, Guo DA, Hylands PJ. The quest for modernisation of traditional Chinese medicine. BMC Complement Altern Med. 2013;13:132.CrossRefPubMedPubMedCentral Xu Q, Bauer R, Hendry BM, Fan TP, Zhao Z, Duez P, Simmonds MS, Witt CM, Lu A, Robinson N, Guo DA, Hylands PJ. The quest for modernisation of traditional Chinese medicine. BMC Complement Altern Med. 2013;13:132.CrossRefPubMedPubMedCentral
6.
go back to reference Yu C, Ji K, Cao H, Wang Y, Jin HH, Zhang Z, Yang G. Effectiveness of acupuncture for angina pectoris: a systematic review of randomized controlled trials. BMC Complement Altern Med. 2015;15:90.CrossRefPubMedPubMedCentral Yu C, Ji K, Cao H, Wang Y, Jin HH, Zhang Z, Yang G. Effectiveness of acupuncture for angina pectoris: a systematic review of randomized controlled trials. BMC Complement Altern Med. 2015;15:90.CrossRefPubMedPubMedCentral
7.
go back to reference Zhang X, Wu J, Zhang B. Xuesaitong injection as one adjuvant treatment of acute cerebral infarction: a systematic review and meta-analysis. BMC Complement Altern Med. 2015;15:36.CrossRefPubMedPubMedCentral Zhang X, Wu J, Zhang B. Xuesaitong injection as one adjuvant treatment of acute cerebral infarction: a systematic review and meta-analysis. BMC Complement Altern Med. 2015;15:36.CrossRefPubMedPubMedCentral
8.
go back to reference Lo HY, Hsiang CY, Li TC, Li CC, Huang HC, Chen JC, Ho TY. A novel glycated hemoglobin A1c-lowering traditional Chinese medicinal formula, identified by translational medicine study. PLoS One. 2014;9:e104650.CrossRefPubMedPubMedCentral Lo HY, Hsiang CY, Li TC, Li CC, Huang HC, Chen JC, Ho TY. A novel glycated hemoglobin A1c-lowering traditional Chinese medicinal formula, identified by translational medicine study. PLoS One. 2014;9:e104650.CrossRefPubMedPubMedCentral
9.
go back to reference Zheng S, Zhao M, Wu Y, Wang Z, Ren Y. Suppression of pancreatic beta cell apoptosis by Danzhi Jiangtang capsule contributes to the attenuation of type 1 diabetes in rats. BMC Complement Altern Med. 2016;16:31.CrossRefPubMedPubMedCentral Zheng S, Zhao M, Wu Y, Wang Z, Ren Y. Suppression of pancreatic beta cell apoptosis by Danzhi Jiangtang capsule contributes to the attenuation of type 1 diabetes in rats. BMC Complement Altern Med. 2016;16:31.CrossRefPubMedPubMedCentral
10.
go back to reference Chinese Pharmacopoeia Commission. Pharmacopoeia of the People’s Republic of China. Beijing: China Medical Science and Technology Press; 2015. p. 56. Chinese Pharmacopoeia Commission. Pharmacopoeia of the People’s Republic of China. Beijing: China Medical Science and Technology Press; 2015. p. 56.
11.
go back to reference Zhang H, Tan C, Wang H, Xue S, Wang M. Study on the history of traditional Chinese medicine to treat diabetes. J Integr Med. 2010;2:41–6.CrossRef Zhang H, Tan C, Wang H, Xue S, Wang M. Study on the history of traditional Chinese medicine to treat diabetes. J Integr Med. 2010;2:41–6.CrossRef
12.
go back to reference Hikino H, Yoshizawa M, Suzuki Y, Oshima Y, Konno C. Isolation and hypoglycemic activity of trichosans A, B, C, D, and E: glycans of Trichosanthes kirilowii roots. Planta Med. 1989;55:349–50.CrossRefPubMed Hikino H, Yoshizawa M, Suzuki Y, Oshima Y, Konno C. Isolation and hypoglycemic activity of trichosans A, B, C, D, and E: glycans of Trichosanthes kirilowii roots. Planta Med. 1989;55:349–50.CrossRefPubMed
13.
go back to reference Li Q, Ye XL, Zeng H, Chen X, Li XG. Study on the extraction technology and hypoglycemic activity of lectin from Trichosanthes kirilowi. Zhong Yao Cai. 2012;35:475–9.PubMed Li Q, Ye XL, Zeng H, Chen X, Li XG. Study on the extraction technology and hypoglycemic activity of lectin from Trichosanthes kirilowi. Zhong Yao Cai. 2012;35:475–9.PubMed
14.
go back to reference Ng TB, Wong CM, Li WW, Yeung HW. Effect of Trichosanthes kirilowii lectin on lipolysis and lipogenesis in isolated rat and hamster adipocytes. J Ethnopharmacol. 1985;14:93–8.CrossRefPubMed Ng TB, Wong CM, Li WW, Yeung HW. Effect of Trichosanthes kirilowii lectin on lipolysis and lipogenesis in isolated rat and hamster adipocytes. J Ethnopharmacol. 1985;14:93–8.CrossRefPubMed
15.
go back to reference Nakamura T, Terajima T, Ogata T, Ueno K, Hashimoto N, Ono K, Yano S. Establishment and pathophysiological characterization of type 2 diabetic mouse model produced by streptozotocin and nicotinamide. Biol Pharm Bull. 2006;29:1167–74.CrossRefPubMed Nakamura T, Terajima T, Ogata T, Ueno K, Hashimoto N, Ono K, Yano S. Establishment and pathophysiological characterization of type 2 diabetic mouse model produced by streptozotocin and nicotinamide. Biol Pharm Bull. 2006;29:1167–74.CrossRefPubMed
16.
go back to reference Lo HY, Ho TY, Lin C, Li CC, Hsiang CY. Momordica charantia and its novel polypeptide regulate glucose homeostasis in mice via binding to insulin receptor. J Agric Food Chem. 2013;61:2461–8.CrossRefPubMed Lo HY, Ho TY, Lin C, Li CC, Hsiang CY. Momordica charantia and its novel polypeptide regulate glucose homeostasis in mice via binding to insulin receptor. J Agric Food Chem. 2013;61:2461–8.CrossRefPubMed
17.
go back to reference Lo HY, Li CC, Ho TY, Hsiang CY. Identification of the bioactive and consensus peptide motif from Momordica charantia insulin receptor-binding protein. Food Chem. 2016;204:298–305.CrossRefPubMed Lo HY, Li CC, Ho TY, Hsiang CY. Identification of the bioactive and consensus peptide motif from Momordica charantia insulin receptor-binding protein. Food Chem. 2016;204:298–305.CrossRefPubMed
18.
go back to reference Lo HY, Ho TY, Li CC, Chen JC, Liu JJ, 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. 2014;62:8952–61. Lo HY, Ho TY, Li CC, Chen JC, Liu JJ, 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. 2014;62:8952–61.
19.
go back to reference Lee DH, Seong S, Kim SS, Han JB. A case of stage IV non-small cell lung cancer treated with Korean medicine therapy alone. Case Rep Oncol. 2013;6:574–8.CrossRefPubMedPubMedCentral Lee DH, Seong S, Kim SS, Han JB. A case of stage IV non-small cell lung cancer treated with Korean medicine therapy alone. Case Rep Oncol. 2013;6:574–8.CrossRefPubMedPubMedCentral
20.
go back to reference Ni L, Zhu X, Gong C, Luo Y, Wang L, Zhou W, Zhu S, Li Y. Trichosanthes kirilowii fruits inhibit non-small cell lung cancer cell growth through mitotic cell-cycle arrest. Am J Chin Med. 2015;43:349–64.CrossRefPubMed Ni L, Zhu X, Gong C, Luo Y, Wang L, Zhou W, Zhu S, Li Y. Trichosanthes kirilowii fruits inhibit non-small cell lung cancer cell growth through mitotic cell-cycle arrest. Am J Chin Med. 2015;43:349–64.CrossRefPubMed
21.
go back to reference Bhattacharya S, Haldar PK. Protective role of the triterpenoid-enriched extract of Trichosanthes dioica root against experimentally induced pain and inflammation in rodents. Nat Prod Res. 2012;26:2348–52.CrossRefPubMed Bhattacharya S, Haldar PK. Protective role of the triterpenoid-enriched extract of Trichosanthes dioica root against experimentally induced pain and inflammation in rodents. Nat Prod Res. 2012;26:2348–52.CrossRefPubMed
22.
go back to reference Jung YB, Roh KJ, Jung JA, Jung K, Yoo H, Cho YB, Kwak WJ, Kim DK, Kim KH, Han CK. Effect of SKI 306X, a new herbal anti-arthritic agent, in patients with osteoarthritis of the knee: a double-blind placebo controlled study. Am J Chin Med. 2001;29:485–91.CrossRefPubMed Jung YB, Roh KJ, Jung JA, Jung K, Yoo H, Cho YB, Kwak WJ, Kim DK, Kim KH, Han CK. Effect of SKI 306X, a new herbal anti-arthritic agent, in patients with osteoarthritis of the knee: a double-blind placebo controlled study. Am J Chin Med. 2001;29:485–91.CrossRefPubMed
23.
go back to reference Lee E, Kim SG, Park NY, Park HH, Jeong KT, Choi J, Lee IH, Lee H, Kim KJ, Lee E. KOTMIN13, a Korean herbal medicine alleviates allergic inflammation in vivo and in vitro. BMC Complement Altern Med. 2016;16:169.CrossRefPubMedPubMedCentral Lee E, Kim SG, Park NY, Park HH, Jeong KT, Choi J, Lee IH, Lee H, Kim KJ, Lee E. KOTMIN13, a Korean herbal medicine alleviates allergic inflammation in vivo and in vitro. BMC Complement Altern Med. 2016;16:169.CrossRefPubMedPubMedCentral
25.
go back to reference Patel D, Prasad S, Kumar R, Hemalatha S. An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pac J Trop Biomed. 2012;2:320–30.CrossRefPubMedPubMedCentral Patel D, Prasad S, Kumar R, Hemalatha S. An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pac J Trop Biomed. 2012;2:320–30.CrossRefPubMedPubMedCentral
26.
go back to reference Teugwa CM, Boudjeko T, Tchinda BT, Mejiato PC, Zofou D. Anti-hyperglycaemic globulins from selected Cucurbitaceae seeds used as antidiabetic medicinal plants in Africa. BMC Complement Altern Med. 2013;13:63.CrossRefPubMedPubMedCentral Teugwa CM, Boudjeko T, Tchinda BT, Mejiato PC, Zofou D. Anti-hyperglycaemic globulins from selected Cucurbitaceae seeds used as antidiabetic medicinal plants in Africa. BMC Complement Altern Med. 2013;13:63.CrossRefPubMedPubMedCentral
27.
go back to reference Mukherjee PK, Nema NK, Maity N, Sarkar BK. Phytochemical and therapeutic potential of cucumber. Fitoterapia. 2013;84:227–36.CrossRefPubMed Mukherjee PK, Nema NK, Maity N, Sarkar BK. Phytochemical and therapeutic potential of cucumber. Fitoterapia. 2013;84:227–36.CrossRefPubMed
28.
go back to reference Yadav M, Jain S, Tomar R, Prasad GB, Yadav H. Medicinal and biological potential of pumpkin: an updated review. Nutr Res Rev. 2012;23:184–90.CrossRef Yadav M, Jain S, Tomar R, Prasad GB, Yadav H. Medicinal and biological potential of pumpkin: an updated review. Nutr Res Rev. 2012;23:184–90.CrossRef
29.
go back to reference Adams GG, Imran S, Wang S, Mohammad A, Kok MS, Gray DA, Channell GA, Harding SE. The hypoglycemic effect of pumpkin seeds, trigonelline (TRG), nicotinic acid (NA), and D-chiro-inositol (DCI) in controlling glycemic levels in diabetes mellitus. Crit Rev Food Sci Nutr. 2014;54:1322–9.CrossRefPubMed Adams GG, Imran S, Wang S, Mohammad A, Kok MS, Gray DA, Channell GA, Harding SE. The hypoglycemic effect of pumpkin seeds, trigonelline (TRG), nicotinic acid (NA), and D-chiro-inositol (DCI) in controlling glycemic levels in diabetes mellitus. Crit Rev Food Sci Nutr. 2014;54:1322–9.CrossRefPubMed
30.
go back to reference Singh N, Gupta M. Regeneration of beta cells in islets of Langerhans of pancreas of alloxan diabetic rats by acetone extract of Momordica charantia (Linn.) (bitter gourd) fruits. Indian J Exp Biol. 2007;45:1055–62.PubMed Singh N, Gupta M. Regeneration of beta cells in islets of Langerhans of pancreas of alloxan diabetic rats by acetone extract of Momordica charantia (Linn.) (bitter gourd) fruits. Indian J Exp Biol. 2007;45:1055–62.PubMed
31.
go back to reference Habicht SD, Ludwig C, Yang RY, Krawinkel MB. Momordica charantia and type 2 diabetes: from in vitro to human studies. Curr Diabetes Rev. 2014;10:48–60. Habicht SD, Ludwig C, Yang RY, Krawinkel MB. Momordica charantia and type 2 diabetes: from in vitro to human studies. Curr Diabetes Rev. 2014;10:48–60.
32.
go back to reference Zeng K, He YN, Yang D, Cao JQ, Xia XC, Zhang SJ, Bi XL, 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. 2014;81:176–80.CrossRefPubMed Zeng K, He YN, Yang D, Cao JQ, Xia XC, Zhang SJ, Bi XL, 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. 2014;81:176–80.CrossRefPubMed
33.
34.
go back to reference Fang EF, Zhang CZ, Zhang L, Wong JH, Chan YS, Pan WL, Dan XL, Yin CM, Cho CH, Ng TB. Trichosanthin inhibits breast cancer cell proliferation in both cell lines and nude mice by promotion of apoptosis. PLoS One. 2012;7:e41592.CrossRefPubMedPubMedCentral Fang EF, Zhang CZ, Zhang L, Wong JH, Chan YS, Pan WL, Dan XL, Yin CM, Cho CH, Ng TB. Trichosanthin inhibits breast cancer cell proliferation in both cell lines and nude mice by promotion of apoptosis. PLoS One. 2012;7:e41592.CrossRefPubMedPubMedCentral
35.
go back to reference Sha O, Niu J, Ng TB, Cho EY, Fu X, Jiang W. Anti-tumor action of trichosanthin, a type 1 ribosome-inactivating protein, employed in traditional Chinese medicine: a mini review. Cancer Chemother Pharmacol. 2013;71:1387–93.CrossRefPubMedPubMedCentral Sha O, Niu J, Ng TB, Cho EY, Fu X, Jiang W. Anti-tumor action of trichosanthin, a type 1 ribosome-inactivating protein, employed in traditional Chinese medicine: a mini review. Cancer Chemother Pharmacol. 2013;71:1387–93.CrossRefPubMedPubMedCentral
36.
go back to reference Song L, Chang J, Li Z. A serine protease extracted from Trichosanthes kirilowii induces apoptosis via the PI3K/AKT-mediated mitochondrial pathway in human colorectal adenocarcinoma cells. Food Funct. 2016;7:843–54.CrossRefPubMed Song L, Chang J, Li Z. A serine protease extracted from Trichosanthes kirilowii induces apoptosis via the PI3K/AKT-mediated mitochondrial pathway in human colorectal adenocarcinoma cells. Food Funct. 2016;7:843–54.CrossRefPubMed
37.
go back to reference Wong KL, Wong RN, Zhang L, Liu WK, Ng TB, Shaw PC, Kwok PC, Lai YM, Zhang ZJ, Zhang Y, Tong Y, Cheung HP, Lu J, Sze SC. Bioactive proteins and peptides isolated from Chinese medicines with pharmaceutical potential. Chin Med. 2014;9:19.CrossRefPubMedPubMedCentral Wong KL, Wong RN, Zhang L, Liu WK, Ng TB, Shaw PC, Kwok PC, Lai YM, Zhang ZJ, Zhang Y, Tong Y, Cheung HP, Lu J, Sze SC. Bioactive proteins and peptides isolated from Chinese medicines with pharmaceutical potential. Chin Med. 2014;9:19.CrossRefPubMedPubMedCentral
38.
go back to reference Iseli TJ, Turner N, Zeng XY, Cooney GJ, Kraegen EW, Yao S, Ye Y, James DE, Ye JM. Activation of AMPK by bitter melon triterpenoids involves CaMKKβ. PLoS One. 2013;8:e62309.CrossRefPubMedPubMedCentral Iseli TJ, Turner N, Zeng XY, Cooney GJ, Kraegen EW, Yao S, Ye Y, James DE, Ye JM. Activation of AMPK by bitter melon triterpenoids involves CaMKKβ. PLoS One. 2013;8:e62309.CrossRefPubMedPubMedCentral
39.
go back to reference Wang HY, Kan WC, Cheng TJ, Yu SH, Chang LH, Chuu JJ. Differential anti-diabetic effects and mechanism of action of charantin-rich extract of Taiwanese Momordica charantia between type 1 and type 2 diabetic mice. Food Chem Toxicol. 2014;69:347–56.CrossRefPubMed Wang HY, Kan WC, Cheng TJ, Yu SH, Chang LH, Chuu JJ. Differential anti-diabetic effects and mechanism of action of charantin-rich extract of Taiwanese Momordica charantia between type 1 and type 2 diabetic mice. Food Chem Toxicol. 2014;69:347–56.CrossRefPubMed
Metadata
Title
Hypoglycemic effects of Trichosanthes kirilowii and its protein constituent in diabetic mice: the involvement of insulin receptor pathway
Authors
Hsin-Yi Lo
Tsai-Chung Li
Tse-Yen Yang
Chia-Cheng Li
Jen-Huai Chiang
Chien-Yun Hsiang
Tin-Yun Ho
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-017-1578-6

Other articles of this Issue 1/2017

BMC Complementary Medicine and Therapies 1/2017 Go to the issue