Preventive effect of Eucommia leaf extract on aortic media hypertrophy in Wistar-Kyoto rats fed a high-fat diet


Eucommia ulmoides Oliver leaf extract (ELE) has been shown to have anti-hypertensive and anti-obesity effects in rats that are fed a high-fat diet (HFD). To explore the effects of chronic administration of ELE on body weight, blood pressure and aortic media thickness, 7-week-old male Wistar-Kyoto (WKY) rats were orally administered a normal diet, a 30% HFD, or a 5% ELE plus HFD ad libitum for 10 weeks. The HFD treatment caused mild obesity and hypertension in the normotensive rats, while rats receiving both ELE and the HFD had significantly lower body weights, less visceral and perirenal fat, lower blood pressure and thinner aortic media than the control rats receiving the HFD only. The plasma adiponectin/leptin ratio also improved in ELE-treated rats. Although plasma leptin levels were elevated in all HFD rats, adiponectin levels increased only in the ELE-treated rats. Anti-hypertensive and anti-obesity effects may be caused by the geniposidic acid (GEA) and/or asperuloside present in ELE. These findings suggest that chronic ELE administration prevents aortic media hypertrophy in early-stage obesity with hypertension. Long-term administration of ELE might inhibit the development of arteriosclerosis.

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  1. 1

    World Health OrganizationA Global Brief on Hypertension-Silent Killer, Global Public Health Crisis. WHO Reference Number: WHO/DCO/WHD/2013.2. WHO: Geneva, Switzerland, 2013..

  2. 2

    Hirata C, Miyai N, Idoue A, Utsumi M, Hattori S, Iwahara A, Uematsu Y, Shiba M, Arita M . Effect of metabolic syndrome components and their clustering on carotid atherosclerosis in a sample of the general Japanese population. Hypertens Res 2016; 39: 362–366.

    Article  Google Scholar 

  3. 3

    Nagai M, Ohkubo T, Murakami Y, Takashima N, Kadota A, Miyagawa N, Saito Y, Nishi N, Okuda N, Kiyohara Y, Nakagawa H, Nakamura Y, Fujiyoshi A, Abbott RD, Okamura T, Okayama A, Ueshima H, Miura K . NIPPON DATA80/90/2010 Research Group. Secular trends of the impact of overweight and obesity on hypertension in Japan, 1980-2010. Hypertens Res 2015; 38: 790–795.

    Article  Google Scholar 

  4. 4

    Matsuzawa Y . Adiponectin: identification, physiology and clinical relevance in metabolic and vascular disease. Atheroscler Suppl 2005; 6: 7–14.

    CAS  Article  Google Scholar 

  5. 5

    Dorresteijn JA, Visseren FL, Spiering W . Mechanisms linking obesity to hypertension. Obes Rev 2012; 13: 17–26.

    CAS  Article  Google Scholar 

  6. 6

    Fujii M, Ohnishi H, Saitoh S, Akasaka H, Miura T, Mori M . The combination of abdominal obesity and high-sensitivity C-reactive protein predicts new-onset hypertension in the general Japanese population: the Tanno-Sobetsu study. Hypertens Res 2015; 38: 426–432.

    CAS  Article  Google Scholar 

  7. 7

    Krzesiński P, Stańczyk A, Piotrowicz K, Gielerak G, Uziębło-Zyczkowska B, Skrobowski A . Abdominal obesity and hypertension: a double burden to the heart. Hypertens Res 2016; 39: 349–355.

    Article  Google Scholar 

  8. 8

    Guizhou Province Institute for Drug Control and Guizhou Province Chinese Medicine Research Laboratories. A hypertensive clinical study on Eucommia leaves. Chin Med Herbs Res 1978; 8: 59–63.

    Google Scholar 

  9. 9

    Namba T, Hattori M, Yie JN, Ma YH, Nomura Y, Kaneko S, Kitamura Y, Koizumi T, Katayama K, Lu W . Studies on Tu-Chung leaves (I) pharmacological effects of the water extract in vivo. Wakan Iyaku Gakkaishi 1986; 3: 89–97.

    Google Scholar 

  10. 10

    Fujikawa T, Hirata T, Wada A, Kawamura N, Yamaguchi Y, Fujimura K, Ueda T, Yurugi Y, Soya H, Nishibe S . Chronic administration of Eucommia leaf stimulates metabolic function of rats across several organs. Br J Nutr 2010; 104: 1868–1877.

    CAS  Article  Google Scholar 

  11. 11

    Metori K, Ohashi S, Takahashi S, Tamura T . Effects of du-zhong leaf extract on serum and hepatic lipids in rats fed a high-fat diet. Biol Pharm Bull 1994; 17: 917–920.

    CAS  Article  Google Scholar 

  12. 12

    Yen GC, Hsieh CL . Reactive oxygen species scavenging activity of Du-zhong (Eucommia ulmoides Oliv.) and its active compounds. J Agric Food Chem 2000; 48: 3431–3436.

    CAS  Article  Google Scholar 

  13. 13

    Lee MK, Kim MJ, Cho SY, Park SA, Park KK, Jung UJ, Park HM, Choi MS . Hypoglycemic effect of Du-zhong (Eucommia ulmoides Oliv.) leaves in streptozotocin-induced diabetic rats. Diabetes Res Clin Pract 2005; 67: 22–28.

    Article  Google Scholar 

  14. 14

    Jin X, Amitani K, Zamami Y, Takatori S, Hobara N, Kawamura N, Hirata T, Wada A, Kitamura Y, Kawasaki H . Ameliorative effect of Eucommia ulmoides Oliv. leaves extract (ELE) on insulin resistance and abnormal perivascular innervation in fructose-drinking rats. J Ethnopharmacol 2010; 128: 672–678.

    Article  Google Scholar 

  15. 15

    Tsukamoto S, Yamaguchi Y, Ueda T, Kajimoto O, Nakagawa Y, Nakagawa S, Kajimoto Y . Hypotensive effects of beverage containing ‘Eucommia leaf glycoside’ on high normal blood pressure and mild hypertensive subjects. Int Symp Eucommia Ulmoides 2007; 1: 47–54.

    Article  Google Scholar 

  16. 16

    Hosoo S, Koyama M, Kato M, Hirata T, Yamaguchi Y, Yamasaki H, Wada A, Wada K, Nishibe S, Nakamura K . The restorative effects of Eucommia ulmoides Oliver leaf extract on vascular function in spontaneously hypertensive rats. Molecules 2015; 20: 21971–21981.

    CAS  Article  Google Scholar 

  17. 17

    Yamori Y, Horie R . Analysis of genetic factors of atherogenesis, separation of normotensive atherogenic rats (NAR). J Jpn Atheroscler Soc 1980; 8: 105–108.

    Article  Google Scholar 

  18. 18

    Fujikawa T, Hirata T, Hosoo S, Nakajima K, Wada A, Yurugi Y, Soya H, Matsui T, Yamaguchi A, Ogata M, Nishibe S . Asperuloside stimulates metabolic function in rats across several organs under high-fat diet conditions, acting like the major ingredient of Eucommia leaves with anti-obesity activity. J Nutr Sci 2012; 1: 1–11.

    Article  Google Scholar 

  19. 19

    Hirata T, Kobayashi T, Wada A, Ueda T, Fujikawa T, Miyashita H, Ikeda T, Tsukamoto S, Nohara T . Anti-obesity compounds in green leaves of Eucommia ulmoides. Bioorg Med Chem Lett 2011; 21: 1786–1791.

    CAS  Article  Google Scholar 

  20. 20

    Knight SF, Quigley JE, Yuan J, Roy SS, Elmarakby A, Imig JD . Endothelial dysfunction and the development of renal injury in spontaneously hypertensive rats fed a high-fat diet. Hypertension 2008; 51: 352–359.

    CAS  Article  Google Scholar 

  21. 21

    Heeneman S, Sluimer JC, Daemen MJ . Angiotensin-converting enzyme and vascular remodeling. Circ Res 2007; 101: 441–454.

    CAS  Article  Google Scholar 

  22. 22

    Bravo PE, Morse S, Borne DM, Aguilar EA, Reisin E . Leptin and hypertension in obesity. Vasc Health Risk Manag 2006; 2: 163–169.

    CAS  Article  Google Scholar 

  23. 23

    Simonds SE, Cowley MA . Hypertension in obesity: is leptin the culprit? Trends Neurosci 2013; 36: 121–132.

    CAS  Article  Google Scholar 

  24. 24

    Ghantous CM, Azrak Z, Hanache S, Abou-Kheir W, Zeidan A . Differential role of leptin and adiponectin in cardiovascular system. Int J Endocrinol 2015; 2015: 534320.

    CAS  Article  Google Scholar 

  25. 25

    Wang ZV, Scherer PE . Adiponectin, cardiovascular function, and hypertension. Hypertension 2008; 51: 8–14.

    CAS  Article  Google Scholar 

  26. 26

    Balsan GA, Vieira JL, Oliveira AM, Portal VL . Relationship between adiponectin, obesity and insulin resistance. Rev Assoc Med Bras 2015; 61: 72–80.

    Article  Google Scholar 

  27. 27

    Ebrahimi-Mamaeghani M, Mohammadi S, Arefhosseini SR, Fallah P, Bazi Z . Adiponectin as a potential biomarker of vascular disease. Vasc Health Risk Manag 2015; 11: 55–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Matsuzawa Y, Funahashi T, Kihara S, Shimomura I . Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol 2004; 24: 29–33.

    CAS  Article  Google Scholar 

  29. 29

    Beltowski J . Leptin and atherosclerosis. Atherosclerosis 2006; 189: 47–60.

    CAS  Article  Google Scholar 

  30. 30

    Satoh N, Naruse M, Usui T, Tagami T, Suganami T, Yamada K, Kuzuya H, Shimatsu A, Ogawa Y . Leptin-to-adiponectin ratio as a potential atherogenic index in obese type 2 diabetic patients. Diabetes Care 2004; 27: 2488–2490.

    CAS  Article  Google Scholar 

  31. 31

    Kappelle PJ, Dullaart RP, van Beek AP, Hillege HL, Wolffenbuttel BH . The plasma leptin/adiponectin ratio predicts first cardiovascular event in men: a prospective nested case-control study. Eur J Intern Med 2012; 23: 755–759.

    CAS  Article  Google Scholar 

  32. 32

    Ferder L, Inserra F, Martínez-Maldonado M . Inflammation and the metabolic syndrome: role of angiotensin II and oxidative stress. Curr Hypertens Rep 2006; 8: 191–198.

    CAS  Article  Google Scholar 

  33. 33

    Nakazawa Y . Studies on Functionality and Application of Eucommia leaf to Preservation of Health, PhD thesis Kyushu University, Fukuoka, Japan. 1998.

    Google Scholar 

  34. 34

    Tang S, Wang Z, Ma C, Hattori M . Simultaneous determination of ten bioactive constituents in Eucommia ulmoides leaves and Tochu tea products by high-performance liquid chromatography-diode array detector-mass spectrometry (HPLC-DAD-MS). J Trad Med 2008; 25: 112–118.

    CAS  Google Scholar 

  35. 35

    Hirata T, Ikeda T, Fujikawa T, Nishibe S . The chemistry and bioactivity of Eucommia ulmoides Oliver leaves. Studies Nat Prod Chem 2014; 41: 225–260.

    CAS  Article  Google Scholar 

  36. 36

    Kawasaki T, Uezono K, Nakazawa Y . Antihypertensive mechanism of food for specified health use: ‘Eucommia leaf glycoside’ and its clinical application. J Health Sci 2000; 22: 29–36.

    Google Scholar 

  37. 37

    Suzuki A, Yamamoto N, Jokura H, Yamamoto M, Fujii A, Tokimitsu I, Saito I . Chlorogenic acid attenuates hypertension and improves endothelial function in spontaneously hypertensive rats. J Hypertens 2006; 24: 1065–1073.

    CAS  Article  Google Scholar 

  38. 38

    Billaud M, Johnstone SR, Isakson BE . Loss of compliance in small arteries, but not in conduit arteries, after 6 weeks exposure to high fat diet. J Cardiovasc Transl Res 2012; 5: 256–263.

    Article  Google Scholar 

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We thank Dr Sansei Nishibe, Emeritus Professor of Health Sciences University of Hokkaido, for his valuable suggestions and discussions on ELE.

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Correspondence to Kozo Nakamura.

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Hosoo, S., Koyama, M., Watanabe, A. et al. Preventive effect of Eucommia leaf extract on aortic media hypertrophy in Wistar-Kyoto rats fed a high-fat diet. Hypertens Res 40, 546–551 (2017).

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