Coumarins and metabolic syndrome: Brief Report
Main Article Content
Abstract
Metabolic syndrome is defined by the presentation of a wide array of interconnected physiological, biochemical, clinical, and metabolic abnormalities that mainly increase the risk of type 2 diabetes mellitus and cardiovascular disease, which is commonly recognized as the primary clinical outcome. Pharmacological treatment for those whose risk factors are not adequately reduced with lifestyle changes remains challenging due to the polypharmacy, the risk of side effects and interactions especially in long-term treatments. The aim of this study was a systematic review of the literature published in previous years about the effects of coumarins against metabolic syndrome using in-vivo animal models. All studies included where pharmacological treatment was given to animals with obesity or diabetes mellitus. Studies included at least 75% of guidelines of the Gold Standard Publication Checklist (GSPC) for improved design, reporting and scientific quality of animal studies. Twenty studies reporting on the effects of different pharmacological treatments were included. Evidence supports that coumarins derivatives present lipid lowering and antidiabetic effects. However, only animal studies were found, so it is necessary the development of clinical studies with improved trial designs. Especially with the most promising compounds.
Keywords:
obesity, lipid, coumarins, cardiovascular disease, systematic review
Article Details
How to Cite
MARRERO, Joaquin et al.
Coumarins and metabolic syndrome: Brief Report.
Medical Research Archives, [S.l.], v. 5, n. 11, nov. 2017.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/1574>. Date accessed: 26 dec. 2024.
doi: https://doi.org/10.18103/mra.v5i11.1574.
Keywords
systematic review, cardiovascular disease, obesity, coumarin, lipid metabolism, diabetes, metabolic syndrome
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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2 Eckel RH; Grundy SM; Zimmet PZ. The metabolic syndrome. Lancet 2005; 365(9468): 1415-1428.
3 Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for The Study Of Obesity. Circulation. 2009; 120: 1640–1645.
4 O’Neill S, O’Driscoll L. Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies. Obes Rev. 2015; 16: 1-12.
5 Šimunović M, Božić J, Milić L, Unić I, Škrabić V. The prevalence of metabolic syndrome and cardiovascular risk factors in obese children and adolescents in Dalmatia: A hospital based study. Int J Endocrinol. 2016; 2016: 1823561. doi: http://dx.doi.org/10.1155 /2016/1823561
6 Kaur J. A comprehensive review on metabolic syndrome. Cardiology Research & Practice. 2014; 2014: 943162.
7 Tupper T, Gopalakrishnan G. Prevention of diabetes development in those with the metabolic syndrome. Med Clin North Am. 2007; 91: 1091-1105.
8 Welty FK, Alfaddagh A, Elajami TK. Targeting inflammation in metabolic syndrome. Transl Res. 2016; 167: 257–280.
9 Grundy SM. Drug therapy of the metabolic syndrome: minimizing the emerging crisis in polypharmacy. Nat Rev Drug Discov. 2006; 5: 295-309.
10 van Zwieten PA, Visser FC. Metabolic syndrome: pharmacological treatment. Heart & Metabolism. 2006; 30: 15–20.
11 Nguelefack-Mbuyo PE, Nguelefack TB, Dongmo AB, Afkir S, Azebaze AG, Dimo T, Legssyer A, Kamanyi A, Ziyyat A. Anti-hypertensive effects of the methanol/methylene chloride stem bark extract of Mammea africana in l-NAME- induced hypertensive rats. J Ethnopharmacol. 2008; 117(3): 446-450.
12 Gregório BM, De Souza DB, de Morais Nascimento FA, Pereira LM, Fernandes-Santos C. The potential role of antioxidants in metabolic syndrome. Curr Pharm Des. 2016; 22: 859-869.
13 Abdali D, Samson SE, Grover AK. How effective are antioxidant supplements in obesity and diabetes? Med Princ Pract. 2015; 24: 201-215.
14 Medina FG, Marrero JG, Macías-Alonso M, González MC, Córdova-Guerrero I, Teissier García AG, Osegueda-Robles S. Coumarin heterocyclic derivatives: chemical synthesis and biological activity. Nat Prod Rep. 2015; 32: 1472-507.
15 Liang HJ, Suk FM, Wang CK, Hung LF, Liu DZ, Chen NQ, Chen YC, Chang CC, Liang YC. Osthole, a potential antidiabetic agent, alleviates hyperglycemia in db/db mice. Chem Biol Interact. 2009; 181: 309-315.
16 Qi Z-G, Zhao X, Zhong W, Xie M-L. Osthole improves glucose and lipid metabolism via modulation of PPARα/γ-mediated target gene expression in liver, adipose tissue, and skeletal muscle in fatty liver rats. Pharm Biol. 2016; 54: 882–888.
17 Pan G, Zhao L, Xiao N, Yang K, Ma Y, Zhao X, Fan Z, Zhang Y, Yao Q, Lu K, Yu P. Total synthesis of 8-(6″-umbelliferyl)-apigenin and its analogs as anti-diabetic reagents. Eur J Med Chem. 2016; 122: 674-83.
18 Li D, Wang N, Zhang J, Ma S, Zhao Z, Ellis EM. Hepatoprotective effect of 7- hydroxycoumarin against methyl glyoxal toxicity via activation of Nrf2. Chem Biol Interact. 2017. doi: 10.1016/j.cbi.2017.02.020.
19 Vinayagam R, Xu B. 7, 8-Dihydroxycoumarin (daphnetin) protects INS-1 pancreatic β- cells against streptozotocin-induced apoptosis. Phytomedicine. 2017; 24: 119-126.
20 Zhang S, Yang J, Li H, Li Y, Liu Y, Zhang D, Zhang F, Zhou W, Chen X. Skimmin, a coumarin, suppresses the streptozotocin-induced diabetic nephropathy in wistar rats. Eur J Pharmacol. 2012; 692(1–3): 78–83.
21 Li H, Zheng X, Wang H, Zhang Y, Xin H, Chen X. XLF-III-43, a novel coumarin- aspirin compound, prevents diabetic nephropathy in rats via inhibiting advanced glycation end products. Eur J Pharmacol. 2010; 627(1-3): 340-347.
22 Meena VP, Seenu V, Sharma MC, Mallick SR, Bhalla AS, Gupta N, Mohan A, Guleria R, Pandey RM, Luthra K, Vikram NK. Relationship of adipocyte size with adiposity and metabolic risk. Factors in asian indians. PLoS One. 2014; 9(9): e108421. DOI: 10.1371/journal.pone.0108421.
23 Després JP, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E, Rodés-Cabau J, Bertrand OF, Poirier P. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol. 2008; 28: 1039–1049.
24 Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011; 11: 85–97.
25 Sashidhara KV, Kumar A, Kumar M, Srivastava A, Puri A. Synthesis and antihyperlipidemic activity of novel coumarin bisindole derivatives. Bioorg. Med. Chem. Lett. 2010; 20: 6504–6507.
26 Ferris JS, McCoy L, Neugut AI, Wrensch M, and Lai R. HMG CoA reductase inhibitors, NASIDs and risk of glioma. Int J Cancer. 2012; 131: E1031–1037.
27 Liang C, Ju W, Pei S, Tang Y, Xiao Y. Pharmacological activities and synthesis of esculetin and its derivatives: A mini-review. Molecules. 2017; 22(3). pii: E387. doi: 10.3390/molecules22030387.
28 Huang HC, Weng Y, Lee CR, Jan TR, Chen YL, Lee YT. Protection by scoparone against the alterations of plasma lipoproteins, vascular morphology and vascular reactivity in hyperlipidaemic diabetic rabbit. Br J Pharmacol. 1993; 110: 1508–1514.
29 Zhang A, Qiu S, Sun H, Zhang T, Guan Y, Han Y, Yan G, Wang X. Scoparone affects lipid metabolism in primary hepatocytes using lipidomics. Scientific Reports. 2016; 6: Article number: 28031. DOI: 10.1038/srep28031.
30 Iwase M, Yamamoto T, Nishimura K, Takahashi H, Mohri S, Li Y, Jheng HF, Nomura W, Takahashi N, Kim CS, Yu R, Taniguchi M, Baba K, Murakami S, Kawada T, Goto T. Suksdorfin promotes adipocyte differentiation and improves abnormalities in glucose metabolism via PPARγ activation. Lipids. 2017; 52: 657-664.
31 Taira N, Nugara RN, Inafuku M, Takara K, Ogi T, Ichiba T, Iwasaki H, Okabe T, Oku H. In vivo and in vitro anti-obesity activities of dihydropyranocoumarins derivatives from Peucedanum japonicum Thunb. J Funct Foods. 2017; 29: 19–28.
32 Choi W-S, Chang S-H, Kim J-E, Lee S-E. Hypolipidemic effects of scoparone and its coumarin analogues in hyperlipidemia rats induced by high fat diet. J Korean Soc Appl Biol Chem. 2013; 56: 647–653.
33 Li J, Li X, Li Z, Zhang L, Liu Y, Ding H, Yin S. Isofraxidin, a coumarin component improves high-fat diet induced hepatic lipid homeostasis disorder and macrophage inflammation in mice. Food & Function. 2017; 8: 2886-2896.
34 Madhavan GR, Balraju V, Mallesham B, Chakrabarti R, Lohray VB. Novel coumarin derivatives of heterocyclic compounds as lipid-lowering agents. Bioorg Med Chem Lett. 2003; 13: 2547–2551.
35 Ogawa H, Rei Nakamura, Kimiye Baba. Beneficial effect of Laserpitin, a coumarin compound from Angelica keiskei, on lipid metabolism in stroke-prone spontaneously hypertensive rats. Clin Exp Pharmacol Physiol. 2005; 32: 1104–1109.
36 Pari L, Rajarajeswari N, Saravanan S, Rathinam A. Antihyperlipidemic effect of coumarin in experimental type 2 diabetic rats. Biomed Prev Nutr. 2014; 4: 171–176.
37 Ramesh B, Pugalendi KV. Antihyperlipidemic and antidiabetic effects of umbelliferone in streptozotocin diabetic rats. Yale J Biol Med. 2005; 78: 187-194.
38 Sashidhara KV, Palnati GR, Sonkar R, Avula SR, Awasthi C, Bhatia G. Coumarin chalcone fibrates: A new structural class of lipid lowering agents. Eur J Med Chem. 2013; 64: 422-431.
39 American Diabetes Association. Standards of medical care in diabetes-2007. Diabetes Care. 2007; 30 Suppl 1:S4-S41.
40 International Diabetes Federation. IDF Diabetes Atlas, 7th edition. Available at http://www.diabetesatlas.org. Accessed July 11, 2017.
41 Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, Cavan D, Shaw JE, Makaroff LE. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017; 128: 40-50.
42 Irons BK, Minze MG. Drug treatment of type 2 diabetes mellitus in patients for whom metformin is contraindicated. Diabetes Metab Syndr Obes. 2014; 7: 15–24.
43 Veerapur VP, Prabhakar KR, Thippeswamy BS. Antidiabetic effect of Dodonaea viscosa (L). Lacq. aerial parts in high fructose-fed insulin resistant rats: a mechanism based study. Indian J Exp Biol. 2010; 48: 800-810.
44 Li H, Yao Y, Li L. Coumarins as potential antidiabetic agents. J Pharm Pharmacol. 2017. DOI: 10.1111/jphp.12774.
45 Bucolo C, Ward KW, Mazzon E, Cuzzocrea S, Drago F. Protective effects of a coumarin derivative in diabetic rats. Invest Ophthalmol Vis Sci. 2009; 50: 3846-3852.
46 Bucolo C, Leggio GM, Drago F, Salomone S. Eriodictyol prevents early retinal and plasma abnormalities in streptozotocin-induced diabetic rats. Biochem Pharmacol. 2012; 84: 88-92.
47 Kang KS, Lee W, Jung Y, Lee JH, Lee S, Eom DW, Jeon Y, Yoo HH, Jin MJ, Song KI, Kim WJ, Ham J, Kim HJ, Kim SN. Protective effect of esculin on streptozotocin- induced diabetic renal damage in mice. J Agric Food Chem. 2014; 62(9): 2069-2076.
48 Kumar A, Maurya RA, Sharma S, Ahmad P, Singh AB, Bhatia G, Srivastava AK. Pyranocoumarins: A new class of anti-hyperglycemic and anti-dyslipidemic agents. Bioorg Med Chem Lett. 2009; 19(22): 6447-6451.
49 Pari L, Rajarajeswari N. Efficacy of coumarin on hepatic key enzymes of glucose metabolism in chemical induced type 2 diabetic rats. Chem Biol Interact. 2009; 181(3): 292-296.
50 Martínez AL, Madariaga-Mazón A, Rivero-Cruz I, Bye R, Mata R. Antidiabetic and antihyperalgesic effects of a decoction and compounds from Acourtia thurberi. Planta Med. 2017; 83(6): 534-544.
51 Domínguez-Mendoza EA, Cornejo-Garrido J, Burgueño-Tapiab E, Ordaz-Pichardo C. Antidiabetic effect, antioxidant activity, and toxicity of 30,40-Di-Oacetyl-cis- khellactone in Streptozotocin-induced diabetic rats. Bioorg Med Chem Lett. 2016; 26: 4086–4091.
52 García-Galicia MC, Burgueño-Tapia E, Romero-Rojas A, García-Zebadúa JC, Cornejo-Garrido J, Ordaz-Pichardo C. Anti-hyperglycemic effect, inhibition of inflammatory cytokines expression, and histopathology profile in streptozotocin- induced diabetic rats treated with Arracacia tolucensis aerial-parts extracts. J Ethnopharmacol. 2014; 152(1): 91-98.
53 Lee SO, Choi SZ, Lee JH, Chung SH, Park SH, Kang HC, Yang EY, Cho HJ, Lee KR. Antidiabetic coumarin and cyclitol compounds from Peucedanum japonicum. Arch Pharm Res. 2004; 27: 1207-1210.
54 Murali R, Srinivasan S, Ashokkumar N. Antihyperglycemic effect of fraxetin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats. Biochimie. 2013; 95: 1848-1854.
55 Prabakaran D, Ashokkumar N. Antihyperglycemic effect of esculetin modulated carbohydrate metabolic enzymes activities in streptozotocin induced diabetic rats. J Funct Foods. 2012; 4: 776 –783.
56 Ramesh B, Pugalendi KV. Antihyperglycemic effect of umbelliferone in streptozotocin-diabetic rats. J Med Food. 2006; 9: 562-566.
57 Tchamadeu MC, Dzeufiet PD, Nouga CC, Azebaze AG, Allard J, Girolami JP, Tack I, Kamtchouing P, Dimo T. Hypoglycaemic effects of Mammea africana (Guttiferae) in diabetic rats. J Ethnopharmacol. 2010; 127:368-372.
58 Verma A, Dewangan P, Kesharwani D, Kela SP. Hypoglycemic and hypolipidemic activity of scopoletin (coumarin derivative) in streptozotocin induced diabetic rats. Int J Pharm Sci Rev Res. 2013; 22: 79-83.
2 Eckel RH; Grundy SM; Zimmet PZ. The metabolic syndrome. Lancet 2005; 365(9468): 1415-1428.
3 Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for The Study Of Obesity. Circulation. 2009; 120: 1640–1645.
4 O’Neill S, O’Driscoll L. Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies. Obes Rev. 2015; 16: 1-12.
5 Šimunović M, Božić J, Milić L, Unić I, Škrabić V. The prevalence of metabolic syndrome and cardiovascular risk factors in obese children and adolescents in Dalmatia: A hospital based study. Int J Endocrinol. 2016; 2016: 1823561. doi: http://dx.doi.org/10.1155 /2016/1823561
6 Kaur J. A comprehensive review on metabolic syndrome. Cardiology Research & Practice. 2014; 2014: 943162.
7 Tupper T, Gopalakrishnan G. Prevention of diabetes development in those with the metabolic syndrome. Med Clin North Am. 2007; 91: 1091-1105.
8 Welty FK, Alfaddagh A, Elajami TK. Targeting inflammation in metabolic syndrome. Transl Res. 2016; 167: 257–280.
9 Grundy SM. Drug therapy of the metabolic syndrome: minimizing the emerging crisis in polypharmacy. Nat Rev Drug Discov. 2006; 5: 295-309.
10 van Zwieten PA, Visser FC. Metabolic syndrome: pharmacological treatment. Heart & Metabolism. 2006; 30: 15–20.
11 Nguelefack-Mbuyo PE, Nguelefack TB, Dongmo AB, Afkir S, Azebaze AG, Dimo T, Legssyer A, Kamanyi A, Ziyyat A. Anti-hypertensive effects of the methanol/methylene chloride stem bark extract of Mammea africana in l-NAME- induced hypertensive rats. J Ethnopharmacol. 2008; 117(3): 446-450.
12 Gregório BM, De Souza DB, de Morais Nascimento FA, Pereira LM, Fernandes-Santos C. The potential role of antioxidants in metabolic syndrome. Curr Pharm Des. 2016; 22: 859-869.
13 Abdali D, Samson SE, Grover AK. How effective are antioxidant supplements in obesity and diabetes? Med Princ Pract. 2015; 24: 201-215.
14 Medina FG, Marrero JG, Macías-Alonso M, González MC, Córdova-Guerrero I, Teissier García AG, Osegueda-Robles S. Coumarin heterocyclic derivatives: chemical synthesis and biological activity. Nat Prod Rep. 2015; 32: 1472-507.
15 Liang HJ, Suk FM, Wang CK, Hung LF, Liu DZ, Chen NQ, Chen YC, Chang CC, Liang YC. Osthole, a potential antidiabetic agent, alleviates hyperglycemia in db/db mice. Chem Biol Interact. 2009; 181: 309-315.
16 Qi Z-G, Zhao X, Zhong W, Xie M-L. Osthole improves glucose and lipid metabolism via modulation of PPARα/γ-mediated target gene expression in liver, adipose tissue, and skeletal muscle in fatty liver rats. Pharm Biol. 2016; 54: 882–888.
17 Pan G, Zhao L, Xiao N, Yang K, Ma Y, Zhao X, Fan Z, Zhang Y, Yao Q, Lu K, Yu P. Total synthesis of 8-(6″-umbelliferyl)-apigenin and its analogs as anti-diabetic reagents. Eur J Med Chem. 2016; 122: 674-83.
18 Li D, Wang N, Zhang J, Ma S, Zhao Z, Ellis EM. Hepatoprotective effect of 7- hydroxycoumarin against methyl glyoxal toxicity via activation of Nrf2. Chem Biol Interact. 2017. doi: 10.1016/j.cbi.2017.02.020.
19 Vinayagam R, Xu B. 7, 8-Dihydroxycoumarin (daphnetin) protects INS-1 pancreatic β- cells against streptozotocin-induced apoptosis. Phytomedicine. 2017; 24: 119-126.
20 Zhang S, Yang J, Li H, Li Y, Liu Y, Zhang D, Zhang F, Zhou W, Chen X. Skimmin, a coumarin, suppresses the streptozotocin-induced diabetic nephropathy in wistar rats. Eur J Pharmacol. 2012; 692(1–3): 78–83.
21 Li H, Zheng X, Wang H, Zhang Y, Xin H, Chen X. XLF-III-43, a novel coumarin- aspirin compound, prevents diabetic nephropathy in rats via inhibiting advanced glycation end products. Eur J Pharmacol. 2010; 627(1-3): 340-347.
22 Meena VP, Seenu V, Sharma MC, Mallick SR, Bhalla AS, Gupta N, Mohan A, Guleria R, Pandey RM, Luthra K, Vikram NK. Relationship of adipocyte size with adiposity and metabolic risk. Factors in asian indians. PLoS One. 2014; 9(9): e108421. DOI: 10.1371/journal.pone.0108421.
23 Després JP, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E, Rodés-Cabau J, Bertrand OF, Poirier P. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol. 2008; 28: 1039–1049.
24 Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011; 11: 85–97.
25 Sashidhara KV, Kumar A, Kumar M, Srivastava A, Puri A. Synthesis and antihyperlipidemic activity of novel coumarin bisindole derivatives. Bioorg. Med. Chem. Lett. 2010; 20: 6504–6507.
26 Ferris JS, McCoy L, Neugut AI, Wrensch M, and Lai R. HMG CoA reductase inhibitors, NASIDs and risk of glioma. Int J Cancer. 2012; 131: E1031–1037.
27 Liang C, Ju W, Pei S, Tang Y, Xiao Y. Pharmacological activities and synthesis of esculetin and its derivatives: A mini-review. Molecules. 2017; 22(3). pii: E387. doi: 10.3390/molecules22030387.
28 Huang HC, Weng Y, Lee CR, Jan TR, Chen YL, Lee YT. Protection by scoparone against the alterations of plasma lipoproteins, vascular morphology and vascular reactivity in hyperlipidaemic diabetic rabbit. Br J Pharmacol. 1993; 110: 1508–1514.
29 Zhang A, Qiu S, Sun H, Zhang T, Guan Y, Han Y, Yan G, Wang X. Scoparone affects lipid metabolism in primary hepatocytes using lipidomics. Scientific Reports. 2016; 6: Article number: 28031. DOI: 10.1038/srep28031.
30 Iwase M, Yamamoto T, Nishimura K, Takahashi H, Mohri S, Li Y, Jheng HF, Nomura W, Takahashi N, Kim CS, Yu R, Taniguchi M, Baba K, Murakami S, Kawada T, Goto T. Suksdorfin promotes adipocyte differentiation and improves abnormalities in glucose metabolism via PPARγ activation. Lipids. 2017; 52: 657-664.
31 Taira N, Nugara RN, Inafuku M, Takara K, Ogi T, Ichiba T, Iwasaki H, Okabe T, Oku H. In vivo and in vitro anti-obesity activities of dihydropyranocoumarins derivatives from Peucedanum japonicum Thunb. J Funct Foods. 2017; 29: 19–28.
32 Choi W-S, Chang S-H, Kim J-E, Lee S-E. Hypolipidemic effects of scoparone and its coumarin analogues in hyperlipidemia rats induced by high fat diet. J Korean Soc Appl Biol Chem. 2013; 56: 647–653.
33 Li J, Li X, Li Z, Zhang L, Liu Y, Ding H, Yin S. Isofraxidin, a coumarin component improves high-fat diet induced hepatic lipid homeostasis disorder and macrophage inflammation in mice. Food & Function. 2017; 8: 2886-2896.
34 Madhavan GR, Balraju V, Mallesham B, Chakrabarti R, Lohray VB. Novel coumarin derivatives of heterocyclic compounds as lipid-lowering agents. Bioorg Med Chem Lett. 2003; 13: 2547–2551.
35 Ogawa H, Rei Nakamura, Kimiye Baba. Beneficial effect of Laserpitin, a coumarin compound from Angelica keiskei, on lipid metabolism in stroke-prone spontaneously hypertensive rats. Clin Exp Pharmacol Physiol. 2005; 32: 1104–1109.
36 Pari L, Rajarajeswari N, Saravanan S, Rathinam A. Antihyperlipidemic effect of coumarin in experimental type 2 diabetic rats. Biomed Prev Nutr. 2014; 4: 171–176.
37 Ramesh B, Pugalendi KV. Antihyperlipidemic and antidiabetic effects of umbelliferone in streptozotocin diabetic rats. Yale J Biol Med. 2005; 78: 187-194.
38 Sashidhara KV, Palnati GR, Sonkar R, Avula SR, Awasthi C, Bhatia G. Coumarin chalcone fibrates: A new structural class of lipid lowering agents. Eur J Med Chem. 2013; 64: 422-431.
39 American Diabetes Association. Standards of medical care in diabetes-2007. Diabetes Care. 2007; 30 Suppl 1:S4-S41.
40 International Diabetes Federation. IDF Diabetes Atlas, 7th edition. Available at http://www.diabetesatlas.org. Accessed July 11, 2017.
41 Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, Cavan D, Shaw JE, Makaroff LE. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017; 128: 40-50.
42 Irons BK, Minze MG. Drug treatment of type 2 diabetes mellitus in patients for whom metformin is contraindicated. Diabetes Metab Syndr Obes. 2014; 7: 15–24.
43 Veerapur VP, Prabhakar KR, Thippeswamy BS. Antidiabetic effect of Dodonaea viscosa (L). Lacq. aerial parts in high fructose-fed insulin resistant rats: a mechanism based study. Indian J Exp Biol. 2010; 48: 800-810.
44 Li H, Yao Y, Li L. Coumarins as potential antidiabetic agents. J Pharm Pharmacol. 2017. DOI: 10.1111/jphp.12774.
45 Bucolo C, Ward KW, Mazzon E, Cuzzocrea S, Drago F. Protective effects of a coumarin derivative in diabetic rats. Invest Ophthalmol Vis Sci. 2009; 50: 3846-3852.
46 Bucolo C, Leggio GM, Drago F, Salomone S. Eriodictyol prevents early retinal and plasma abnormalities in streptozotocin-induced diabetic rats. Biochem Pharmacol. 2012; 84: 88-92.
47 Kang KS, Lee W, Jung Y, Lee JH, Lee S, Eom DW, Jeon Y, Yoo HH, Jin MJ, Song KI, Kim WJ, Ham J, Kim HJ, Kim SN. Protective effect of esculin on streptozotocin- induced diabetic renal damage in mice. J Agric Food Chem. 2014; 62(9): 2069-2076.
48 Kumar A, Maurya RA, Sharma S, Ahmad P, Singh AB, Bhatia G, Srivastava AK. Pyranocoumarins: A new class of anti-hyperglycemic and anti-dyslipidemic agents. Bioorg Med Chem Lett. 2009; 19(22): 6447-6451.
49 Pari L, Rajarajeswari N. Efficacy of coumarin on hepatic key enzymes of glucose metabolism in chemical induced type 2 diabetic rats. Chem Biol Interact. 2009; 181(3): 292-296.
50 Martínez AL, Madariaga-Mazón A, Rivero-Cruz I, Bye R, Mata R. Antidiabetic and antihyperalgesic effects of a decoction and compounds from Acourtia thurberi. Planta Med. 2017; 83(6): 534-544.
51 Domínguez-Mendoza EA, Cornejo-Garrido J, Burgueño-Tapiab E, Ordaz-Pichardo C. Antidiabetic effect, antioxidant activity, and toxicity of 30,40-Di-Oacetyl-cis- khellactone in Streptozotocin-induced diabetic rats. Bioorg Med Chem Lett. 2016; 26: 4086–4091.
52 García-Galicia MC, Burgueño-Tapia E, Romero-Rojas A, García-Zebadúa JC, Cornejo-Garrido J, Ordaz-Pichardo C. Anti-hyperglycemic effect, inhibition of inflammatory cytokines expression, and histopathology profile in streptozotocin- induced diabetic rats treated with Arracacia tolucensis aerial-parts extracts. J Ethnopharmacol. 2014; 152(1): 91-98.
53 Lee SO, Choi SZ, Lee JH, Chung SH, Park SH, Kang HC, Yang EY, Cho HJ, Lee KR. Antidiabetic coumarin and cyclitol compounds from Peucedanum japonicum. Arch Pharm Res. 2004; 27: 1207-1210.
54 Murali R, Srinivasan S, Ashokkumar N. Antihyperglycemic effect of fraxetin on hepatic key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats. Biochimie. 2013; 95: 1848-1854.
55 Prabakaran D, Ashokkumar N. Antihyperglycemic effect of esculetin modulated carbohydrate metabolic enzymes activities in streptozotocin induced diabetic rats. J Funct Foods. 2012; 4: 776 –783.
56 Ramesh B, Pugalendi KV. Antihyperglycemic effect of umbelliferone in streptozotocin-diabetic rats. J Med Food. 2006; 9: 562-566.
57 Tchamadeu MC, Dzeufiet PD, Nouga CC, Azebaze AG, Allard J, Girolami JP, Tack I, Kamtchouing P, Dimo T. Hypoglycaemic effects of Mammea africana (Guttiferae) in diabetic rats. J Ethnopharmacol. 2010; 127:368-372.
58 Verma A, Dewangan P, Kesharwani D, Kela SP. Hypoglycemic and hypolipidemic activity of scopoletin (coumarin derivative) in streptozotocin induced diabetic rats. Int J Pharm Sci Rev Res. 2013; 22: 79-83.