The fruit of Acanthopanax senticosus Harms improves arterial stiffness and blood pressure: a randomized, placebo-controlled trial

  • Oh, Eunkyoung (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Kim, Youjin (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Park, Soo-yeon (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Lim, Yeni (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Shin, Ji-yoon (Ewha Graduate School of Converging Clinical & Public Health) ;
  • Kim, Ji Yeon (Department of Food Science and Technology, Seoul National University of Science and Technology) ;
  • Kim, Ji-Hyun (Cardiovascular Center, Dongguk University Ilsan Hospital) ;
  • Rhee, Moo-Yong (Cardiovascular Center, Dongguk University Ilsan Hospital) ;
  • Kwon, Oran (Department of Nutritional Science and Food Management, Ewha Womans University)
  • Received : 2019.12.23
  • Accepted : 2020.03.24
  • Published : 2020.08.01


BACKGROUND/OBJECTIVES: Arterial stiffness and endothelial dysfunction are 2 of the independent predictors for cardiovascular disease, while Acanthopanax senticosus Harms (ASH) is a traditional medicinal plant that can improve cardiovascular health. This study aimed to investigate the efficacy of the fruit of ASH on vascular function in apparently healthy subjects. SUBJECTS/METHODS: A 12-week, randomized, double-blind, placebo-controlled design, consisting of healthy adults with at least 2 of the following 3 conditions: borderline high blood pressure (BP; 120 mmHg ≤ systolic BP ≤ 160 mmHg or 80 mmHg ≤ diastolic BP ≤ 100 mmHg), smoking (≥10 cigarettes/day), and borderline blood lipid levels (220 ≤ total cholesterol ≤ 240, 130 ≤ low density lipoprotein cholesterol ≤ 165, or 150 ≤ triglyceride ≤ 220 mg/dL). Randomly assigned 76 subjects who received a placebo or 2 doses of ASH fruit (low, 500 mg/day; high, 1,000 mg/day) completed the intervention. Brachial-ankle pulse wave velocity (baPWV), flow-mediated dilation, carotid intima-media thickness, and BP were measured both at baseline and following the 12-week intervention. Endothelial nitric oxide synthase (eNOS) phosphorylation was assessed by western blotting. RESULTS: Compared with the placebo group, the low-dose group showed more significant changes after the 12-week intervention period in terms of systolic BP (0.1 vs. -7.7 mmHg; P = 0.044), baPWV (31.3 vs. -98.7 cm/s; P = 0.007), and the ratio of phospho-eNOS/eNOS (0.8 vs. 1.22; P = 0.037). CONCLUSIONS: These results suggest that ASH fruit extract at 500 mg/day has the potential to improve BP and arterial stiffness via endothelial eNOS activation in healthy adults with smoking and the tendency of having elevated BP or blood lipid parameters.


  1. Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, Iwamoto A, Kajikawa M, Matsumoto T, Oda N, Kishimoto S, Matsui S, Hashimoto H, Aibara Y, Mohamad Yusoff F, Hidaka T, Kihara Y, Chayama K, Noma K, Nakashima A, Goto C, Tomiyama H, Takase B, Kohro T, Suzuki T, Ishizu T, Ueda S, Yamazaki T, Furumoto T, Kario K, Inoue T, Koba S, Watanabe K, Takemoto Y, Hano T, Sata M, Ishibashi Y, Node K, Maemura K, Ohya Y, Furukawa T, Ito H, Ikeda H, Yamashina A, Higashi Y. Endothelial dysfunction, increased arterial stiffness, and cardiovascular risk prediction in patients with coronary artery disease: FMD-J (flow-mediated dilation Japan) study A. J Am Heart Assoc 2018;7:e008588.
  2. Anderson TJ. Arterial stiffness or endothelial dysfunction as a surrogate marker of vascular risk. Can J Cardiol 2006;22 Suppl B:72B-80B.
  3. Santos-Parker JR, Strahler TR, Bassett CJ, Bispham NZ, Chonchol MB, Seals DR. Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailability and reducing oxidative stress. Aging (Albany NY) 2017;9:187-208.
  4. Magda SL, Ciobanu AO, Florescu M, Vinereanu D. Comparative reproducibility of the noninvasive ultrasound methods for the assessment of vascular function. Heart Vessels 2013;28:143-50.
  5. Kajikawa M, Maruhashi T, Hida E, Iwamoto Y, Matsumoto T, Iwamoto A, Oda N, Kishimoto S, Matsui S, Hidaka T, Kihara Y, Chayama K, Goto C, Aibara Y, Nakashima A, Noma K, Higashi Y. Combination of flow-mediated vasodilation and nitroglycerine-induced vasodilation is more effective for prediction of cardiovascular events. Hypertension 2016;67:1045-52.
  6. Tomiyama H, Yamashina A. Non-invasive vascular function tests: their pathophysiological background and clinical application. Circ J 2010;74:24-33.
  7. Cardoso SM, Pereira OR, Seca AM, Pinto DC, Silva AM. Seaweeds as preventive agents for cardiovascular diseases: from nutrients to functional foods. Mar Drugs 2015;13:6838-65.
  8. Alissa EM, Ferns GA. Functional foods and nutraceuticals in the primary prevention of cardiovascular diseases. J Nutr Metab 2012;2012:569486.
  9. Sikand G, Kris-Etherton P, Boulos NM. Impact of functional foods on prevention of cardiovascular disease and diabetes. Curr Cardiol Rep 2015;17:39.
  10. Kim YH, Cho ML, Kim DB, Shin GH, Lee JH, Lee JS, Park SO, Lee SJ, Shin HM, Lee OH. The antioxidant activity and their major antioxidant compounds from Acanthopanax senticosus and A. koreanum. Molecules 2015;20:13281-95.
  11. Davydov M, Krikorian AD. Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. (Araliaceae) as an adaptogen: a closer look. J Ethnopharmacol 2000;72:345-93.
  12. Han Y, Zhang A, Sun H, Zhang Y, Meng X, Yan G, Liu L, Wang X. High-throughput ultra high performance liquid chromatography combined with mass spectrometry approach for the rapid analysis and characterization of multiple constituents of the fruit of Acanthopanax senticosus (Rupr. et Maxim.) Harms. J Sep Sci 2017;40:2178-87.
  13. Saito T, Nishida M, Saito M, Tanabe A, Eitsuka T, Yuan SH, Ikekawa N, Nishida H. The fruit of Acanthopanax senticosus (Rupr. et Maxim.) Harms improves insulin resistance and hepatic lipid accumulation by modulation of liver adenosine monophosphate-activated protein kinase activity and lipogenic gene expression in high-fat diet-fed obese mice. Nutr Res 2016;36:1090-7.
  14. Fujikawa T, Yamaguchi A, Morita I, Takeda H, Nishibe S. Protective effects of Acanthopanax senticosus Harms from Hokkaido and its components on gastric ulcer in restrained cold water stressed rats. Biol Pharm Bull 1996;19:1227-30.
  15. Wang X, Hai CX, Liang X, Yu SX, Zhang W, Li YL. The protective effects of Acanthopanax senticosus Harms aqueous extracts against oxidative stress: role of Nrf2 and antioxidant enzymes. J Ethnopharmacol 2010;127:424-32.
  16. Yi JM, Hong SH, Kim JH, Kim HK, Song HJ, Kim HM. Effect of Acanthopanax senticosus stem on mast cell-dependent anaphylaxis. J Ethnopharmacol 2002;79:347-52.
  17. Jung HJ, Park HJ, Kim RG, Shin KM, Ha J, Choi JW, Kim HJ, Lee YS, Lee KT. In vivo anti-inflammatory and antinociceptive effects of liriodendrin isolated from the stem bark of Acanthopanax senticosus. Planta Med 2003;69:610-6.
  18. Lee S, Shin DS, Oh KB, Shin KH. Antibacterial compounds from the leaves of Acanthopanax senticosus. Arch Pharm Res 2003;26:40-2.
  19. Zhou AY, Song BW, Fu CY, Baranenko DD, Wang EJ, Li FY, Lu GW. Acanthopanax senticosus reduces brain injury in mice exposed to low linear energy transfer radiation. Biomed Pharmacother 2018;99:781-90.
  20. Bang JS, Chung YH, Chung SJ, Lee HS, Song EH, Shin YK, Lee YJ, Kim HC, Nam Y, Jeong JH. Clinical effect of a polysaccharide-rich extract of Acanthopanax senticosus on alcohol hangover. Pharmazie 2015;70:269-73.
  21. Lee YJ, Chung HY, Kwak HK, Yoon S. The effects of A. senticosus supplementation on serum lipid profiles, biomarkers of oxidative stress, and lymphocyte DNA damage in postmenopausal women. Biochem Biophys Res Commun 2008;375:44-8.
  22. Hwang YC, Jeong IK, Ahn KJ, Chung HY. The effects of Acanthopanax senticosus extract on bone turnover and bone mineral density in Korean postmenopausal women. J Bone Miner Metab 2009;27:584-90.
  23. Engler MB, Engler MM, Chen CY, Malloy MJ, Browne A, Chiu EY, Kwak HK, Milbury P, Paul SM, Blumberg J, Mietus-Snyder ML. Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults. J Am Coll Nutr 2004;23:197-204.
  24. Bucholz EM, Gooding HC, de Ferranti SD. Awareness of cardiovascular risk factors in U.S. young adults aged 18-39 years. Am J Prev Med 2018;54:e67-77.
  25. Nelson RH. Hyperlipidemia as a risk factor for cardiovascular disease. Prim Care 2013;40:195-211.
  26. Niva M. 'All foods affect health': understandings of functional foods and healthy eating among healthoriented Finns. Appetite 2007;48:384-93.
  27. Lim Y, Song TJ, Hwang W, Kim JY, Lee D, Kim YJ, Kwon O. Synergistic effects of Sanghuang-Danshen bioactives on arterial stiffness in a randomized clinical trial of healthy smokers: an integrative approach to in silico network analysis. Nutrients 2019;11:11.
  28. Figueroa A, Wong A, Hooshmand S, Sanchez-Gonzalez MA. Effects of watermelon supplementation on arterial stiffness and wave reflection amplitude in postmenopausal women. Menopause 2013;20:573-7.
  29. Mucalo I, Jovanovski E, Rahelic D, Bozikov V, Romic Z, Vuksan V. Effect of American ginseng (Panax quinquefolius L.) on arterial stiffness in subjects with type-2 diabetes and concomitant hypertension. J Ethnopharmacol 2013;150:148-53.
  30. Johnson SA, Figueroa A, Navaei N, Wong A, Kalfon R, Ormsbee LT, Feresin RG, Elam ML, Hooshmand S, Payton ME, Arjmandi BH. Daily blueberry consumption improves blood pressure and arterial stiffness in postmenopausal women with pre- and stage 1-hypertension: a randomized, double-blind, placebocontrolled clinical trial. J Acad Nutr Diet 2015;115:369-77.
  31. Avolio A. Arterial stiffness. Pulse (Basel) 2013;1:14-28.
  32. Otsuka K, Fukuda S, Shimada K, Suzuki K, Nakanishi K, Yoshiyama M, Yoshikawa J. Serial assessment of arterial stiffness by cardio-ankle vascular index for prediction of future cardiovascular events in patients with coronary artery disease. Hypertens Res 2014;37:1014-20.
  33. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, Ducimetiere P, Benetos A. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001;37:1236-41.
  34. Sugawara J, Hayashi K, Yokoi T, Cortez-Cooper MY, DeVan AE, Anton MA, Tanaka H. Brachial-ankle pulse wave velocity: an index of central arterial stiffness? J Hum Hypertens 2005;19:401-6.
  35. Tsuchikura S, Shoji T, Kimoto E, Shinohara K, Hatsuda S, Koyama H, Emoto M, Nishizawa Y. Brachialankle pulse wave velocity as an index of central arterial stiffness. J Atheroscler Thromb 2010;17:658-65.
  36. Hung CS, Lin JW, Hsu CN, Chen HM, Tsai RY, Chien YF, Hwang JJ. Using brachial-ankle pulse wave velocity to associate arterial stiffness with cardiovascular risks. Nutr Metab Cardiovasc Dis 2009;19:241-6.
  37. Koyama N, Suzuki K, Furukawa Y, Arisaka H, Seki T, Kuribayashi K, Ishii K, Sukegawa E, Takahashi M. Effects of safflower seed extract supplementation on oxidation and cardiovascular risk markers in healthy human volunteers. Br J Nutr 2009;101:568-75.
  38. Tomiyama H, Kohro T, Higashi Y, Takase B, Suzuki T, Ishizu T, Ueda S, Yamazaki T, Furumoto T, Kario K, Inoue T, Koba S, Watanabe K, Takemoto Y, Hano T, Sata M, Ishibashi Y, Node K, Maemura K, Ohya Y, Furukawa T, Ito H, Ikeda H, Yamashina A. Reliability of measurement of endothelial function across multiple institutions and establishment of reference values in Japanese. Atherosclerosis 2015;242:433-42.
  39. Incalza MA, D'Oria R, Natalicchio A, Perrini S, Laviola L, Giorgino F. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vascul Pharmacol 2018;100:1-19.
  40. Lessiani G, Santilli F, Boccatonda A, Iodice P, Liani R, Tripaldi R, Saggini R, Davi G. Arterial stiffness and sedentary lifestyle: role of oxidative stress. Vascul Pharmacol 2016;79:1-5.
  41. Siti HN, Kamisah Y, Kamsiah J. The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vascul Pharmacol 2015;71:40-56.
  42. Kolluru GK, Siamwala JH, Chatterjee S. eNOS phosphorylation in health and disease. Biochimie 2010;92:1186-98.
  43. Fukada K, Kajiya-Sawane M, Matsumoto Y, Hasegawa T, Fukaya Y, Kajiya K. Antiedema effects of Siberian ginseng in humans and its molecular mechanism of lymphatic vascular function in vitro. Nutr Res 2016;36:689-95.
  44. Chung BH, Kim S, Kim JD, Lee JJ, Baek YY, Jeoung D, Lee H, Choe J, Ha KS, Won MH, Kwon YG, Kim YM. Syringaresinol causes vasorelaxation by elevating nitric oxide production through the phosphorylation and dimerization of endothelial nitric oxide synthase. Exp Mol Med 2012;44:191-201.
  45. Efferth T, Koch E. Complex interactions between phytochemicals. The multi-target therapeutic concept of phytotherapy. Curr Drug Targets 2011;12:122-32.
  46. Calabrese EJ, Calabrese V, Tsatsakis A, Giordano JJ. Hormesis and Ginkgo biloba (GB): numerous biological effects of GB are mediated via hormesis. Ageing Res Rev. Forthcoming 2020.
  47. Calabrese V, Santoro A, Trovato Salinaro A, Modafferi S, Scuto M, Albouchi F, Monti D, Giordano J, Zappia M, Franceschi C, Calabrese EJ. Hormetic approaches to the treatment of Parkinson's disease: perspectives and possibilities. J Neurosci Res 2018;96:1641-62.
  48. Ozturk K, Guler AK, Cakir M, Ozen A, Demirci H, Turker T, Demirbas S, Uygun A, Gulsen M, Bagci S. Pulse wave velocity, intima media thickness, and flow-mediated dilatation in patients with normotensive normoglycemic inflammatory bowel disease. Inflamm Bowel Dis 2015;21:1314-20.
  49. EUGenMed Cardiovascular Clinical Study GroupRegitz-Zagrosek V, Oertelt-Prigione S, Prescott E, Franconi F, Gerdts E, Foryst-Ludwig A, Maas AH, Kautzky-Willer A, Knappe-Wegner D, Kintscher U, Ladwig KH, Schenck-Gustafsson K, Stangl V. Gender in cardiovascular diseases: impact on clinical manifestations, management, and outcomes. Eur Heart J 2016;37:24-34.