Nutr Res Pract.  2014 Jun;8(3):284-291.

Anti-inflammation effect of Exercise and Korean red ginseng in aging model rats with diet-induced atherosclerosis

Affiliations
  • 1Department of Anatomy and Cell Biology, Collage of Medicine, Han-Yang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 133-791, Korea. kimwg@hanyang.ac.kr
  • 2Exercise Biochemistry Laboratory, Korea National Sport University, Seoul, 138-763, Korea.

Abstract

BACKGROUND/OBJECTIVES
The aim of this study was to investigate the effects of exercise (EX) and Korean red ginseng (KRG) on inflammation mechanism in aging model rats with diet-induced atherosclerosis.
MATERIALS/METHODS
Forty-eight male Sprague-Dawley rats were divided into 6 groups: Young control (Y-C), Aging control (A-C), A-C with HFD (AHF), AHF with EX (AHF-EX), AHF-EX with KRG (AHF-EX+RG), and AHF with KRG (AHF-RG). Aging was induced by D-gal (100mg/kg) and atherosclerosis was induced by HFD (60% fat) for 9 weeks. The experimental rats were performed swimming (60 min/day, 5 days/week) and supplied KRG orally (dose of 200 mg/kg) for 8 weeks. All rat aorta samples were harvested for biochemical and immunohistochemical analyses. REULTS: The EX and KRG supplementation significantly inhibited body weight and levels of TC, TG, LDL-C, and enhance of HDL-C compared with untreated AHF groups. AHF-EX, AHF-EX+RG, and AHF-RG group showed a decreased plasma CRP and increase plasma NO activities compared to AHF group. In addition, these groups revealed reduced 4-HNE, NF-kB, TNF-alpha, IL-6, COX-2, ICAM-1, VCAM-1 and enhanced eNOS expression in the aorta.
CONCLUSION
These results suggest that EX alone, KRG alone, and combined treatment of EX and KRG may be an effective anti-inflammatory therapeutic for the atherosclerosis, possibly acting via the decreased of CRP and pro-inflammation proteins and the increased NO and eNOS.

Keyword

Korea red ginseng; exercise; lipid profiles; inflammation; atherosclerosis

MeSH Terms

Aging*
Animals
Aorta
Atherosclerosis*
Body Weight
Humans
Inflammation
Intercellular Adhesion Molecule-1
Interleukin-6
Male
NF-kappa B
Panax*
Plasma
Rats*
Rats, Sprague-Dawley
Swimming
Tumor Necrosis Factor-alpha
Vascular Cell Adhesion Molecule-1
Intercellular Adhesion Molecule-1
Interleukin-6
NF-kappa B
Tumor Necrosis Factor-alpha
Vascular Cell Adhesion Molecule-1

Figure

  • Fig. 1 Plasma levels of CRP (A), NO levels (B) in blood of D-gal-induced aging rats with high fat diet. Y-C: Young control group, A-C: Aging control group, AHF: Aging with high fat diet group, AHF-EX: AHF with exercise training group, AHF-EX+RG: AHF-EX with Korean red ginseng, AHF-RG: AHF with Korean red ginseng. Values are means ± SEM (n = 8). *P < 0.05, **P < 0.01 vs Y-C, A-C, †P < 0.05 vs AHF

  • Fig. 2 Immunohistochemical (A) and Western blotting (B) analysis of 4-HNE expression. Densitometric analysis of Western blots (C) in aorta of D-gal-induced aging rats with high fat diet are shown. Y-C: Young control group, A-C: Aging control group, AHF: Aging with high fat diet group, AHF-EX: AHF with exercise training group, AHF-EX+RG: AHF-EX with Korean red ginseng, AHF-RG: AHF with Korean red ginseng. *P < 0.05, **P < 0.01 vs Y-C, A-C, †P < 0.05 vs AHF. Magnification = ×400, Bar = 200 µm. Values are means ± SEM (n = 8).

  • Fig. 3 Immunohistochemical (A) and Western blotting (B) analysis of NF-kB expression. Densitometric analysis of Western blots (C) in aorta of D-gal-induced aging rats with high fat diet are shown. Y-C: Young control group, A-C: Aging control group, AHF: Aging with high fat diet group, AHF-EX: AHF with exercise training group, AHF-EX+RG: AHF-EX with Korean red ginseng, AHF-RG: AHF with Korean red ginseng. *P < 0.05, **P < 0.01 vs Y-C, A-C, †P < 0.05, ††P < 0.01 vs AHF. Magnification = ×400, Bar = 200 µm. Values are means ± SEM (n = 8).

  • Fig. 4 Western blotting analysis of TNF-α, IL-6 and COX-2 (A). Densitometric analyses of western blotting (B) in aorta of D-gal-induced aging rats with high fat diet are shown. Y-C: Young control group, A-C: Aging control group, AHF: Aging with high fat diet group, AHF-EX: AHF with exercise training group, AHF-EX+RG: AHF-EX with Korean red ginseng, AHF-RG: AHF with Korean red ginseng. Values are means ± SEM (n = 8). *P < 0.05, **P < 0.01 vs Y-C, A-C, †P < 0.05, ††P < 0.01 vs AHF.

  • Fig. 5 Western blotting analysis of ICAM-1, VCAM-1 and eNOS (A). The Densitometric analyses of western blotting (B) in aorta of D-gal-induced aging rats with high fat diet are shown. Y-C: Young control group, A-C: Aging control group, AHF: Aging with high fat diet group, AHF-EX: AHF with exercise training group, AHF-EX+RG: AHF-EX with Korean red ginseng, AHF-RG: AHF with Korean red ginseng. Values are means ± SEM (n = 8). *P < 0.05, **P < 0.01 vs Y-C, A-C, †P < 0.05, ††P < 0.01 vs AHF.


Reference

1. Dice JF. Cellular and molecular mechanisms of aging. Physiol Rev. 1993; 73:149–159.
Article
2. Madamanchi NR, Vendrov A, Runge MS. Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol. 2005; 25:29–38.
Article
3. Lusis AJ. Atherosclerosis. Nature. 2000; 407:233–241.
Article
4. Libby P. Inflammation in atherosclerosis. Nature. 2002; 420:868–874.
Article
5. Ma Z, Zhang J, Du R, Ji E, Chu L. Rho kinase inhibition by fasudil has anti-inflammatory effects in hypercholesterolemic rats. Biol Pharm Bull. 2011; 34:1684–1689.
Article
6. Quan Y, Qian MZ. Effect and mechanism of gypenoside on the inflammatory molecular expression in high-fat induced atherosclerosis rats. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2010; 30:403–406.
7. Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, de Cabo R. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 2008; 8:157–168.
Article
8. Chung HY, Kim HJ, Kim KW, Choi JS, Yu BP. Molecular inflammation hypothesis of aging based on the anti-aging mechanism of calorie restriction. Microsc Res Tech. 2002; 59:264–272.
Article
9. Kim HJ, Jung KJ, Yu BP, Cho CG, Choi JS, Chung HY. Modulation of redox-sensitive transcription factors by calorie restriction during aging. Mech Ageing Dev. 2002; 123:1589–1595.
Article
10. Zou Y, Jung KJ, Kim JW, Yu BP, Chung HY. Alteration of soluble adhesion molecules during aging and their modulation by calorie restriction. FASEB J. 2004; 18:320–322.
Article
11. Yu BP, Chung HY. Adaptive mechanisms to oxidative stress during aging. Mech Ageing Dev. 2006; 127:436–443.
Article
12. Chung HY, Lee EK, Choi YJ, Kim JM, Kim DH, Zou Y, Kim CH, Lee J, Kim HS, Kim ND, Jung JH, Yu BP. Molecular inflammation as an underlying mechanism of the aging process and age-related diseases. J Dent Res. 2011; 90:830–840.
Article
13. Jin YR, Yu JY, Lee JJ, You SH, Chung JH, Noh JY, Im JH, Han XH, Kim TJ, Shin KS, Wee JJ, Yun YP. Antithrombotic and antiplatelet activities of Korean red ginseng extract. Basic Clin Pharmacol Toxicol. 2007; 100:170–175.
Article
14. Lee J, Cho HS, Park S, Kim WK. Regular exercise produced cardioprotective effects on rat's heart with hypertension induced by L-NAME administration. Clin Exp Hypertens. 2009; 31:364–375.
Article
15. Kim ND. Pharmacologic effect of red ginseng. J Ginseng Res. 2001; 25:2–10.
16. Kim JH, Hahm DH, Yang DC, Kim JH, Lee HJ, Shim I. Effect of crude saponin of Korean red ginseng on high-fat diet-induced obesity in the rat. J Pharmacol Sci. 2005; 97:124–131.
Article
17. Yun SN, Moon SJ, Ko SK, Im BO, Chung SH. Wild ginseng prevents the onset of high-fat diet induced hyperglycemia and obesity in ICR mice. Arch Pharm Res. 2004; 27:790–796.
Article
18. Haddock BL, Marshak HP, Mason JJ, Blix G. The effect of hormone replacement therapy and exercise on cardiovascular disease risk factors in postmenopausal women. Sports Med. 2000; 29:39–49.
Article
19. Husain K. Physical conditioning modulates rat cardiac vascular endothelial growth factor gene expression in nitric oxide-deficient hypertension. Biochem Biophys Res Commun. 2004; 320:1169–1174.
Article
20. Colbert LH, Visser M, Simonsick EM, Tracy RP, Newman AB, Kritchevsky SB, Pahor M, Taaffe DR, Brach J, Rubin S, Harris TB. Physical activity, exercise, and inflammatory markers in older adults: findings from the Health, Aging and Body Composition Study. J Am Geriatr Soc. 2004; 52:1098–1104.
Article
21. Leaf DA. The effect of physical exercise on reverse cholesterol transport. Metabolism. 2003; 52:950–957.
Article
22. Förstermann U, Boissel JP, Kleinert H. Expressional control of the 'constitutive' isoforms of nitric oxide synthase (NOS I and NOS III). FASEB J. 1998; 12:773–790.
Article
23. Furchgott RF. Role of endothelium in responses of vascular smooth muscle. Circ Res. 1983; 53:557–573.
Article
24. Tanner FC, Meier P, Greutert H, Champion C, Nabel EG, Lüscher TF. Nitric oxide modulates expression of cell cycle regulatory proteins: a cytostatic strategy for inhibition of human vascular smooth muscle cell proliferation. Circulation. 2000; 101:1982–1989.
Article
25. Barton M. Obesity and aging: determinants of endothelial cell dysfunction and atherosclerosis. Pflugers Arch. 2010; 460:825–837.
Article
26. Song X, Bao M, Li D, Li YM. Advanced glycation in D-galactose induced mouse aging model. Mech Ageing Dev. 1999; 108:239–251.
Article
27. Bailey-Downs LC, Sosnowska D, Toth P, Mitschelen M, Gautam T, Henthorn JC, Ballabh P, Koller A, Farley JA, Sonntag WE, Csiszar A, Ungvari Z. Growth hormone and IGF-1 deficiency exacerbate high-fat diet-induced endothelial impairment in obese Lewis dwarf rats: implications for vascular aging. J Gerontol A Biol Sci Med Sci. 2012; 67:553–564.
Article
28. Lei M, Hua X, Xiao M, Ding J, Han Q, Hu G. Impairments of astrocytes are involved in the d-galactose-induced brain aging. Biochem Biophys Res Commun. 2008; 369:1082–1087.
Article
29. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972; 18:499–502.
Article
30. Dawson TM, Dawson VL. Nitric oxide: actions and pathological roles. Neuroscientist. 1995; 1:7–18.
31. Batetta B, Mulas MF, Petruzzo P, Putzolu M, Bonatesta RR, Sanna F, Cappai A, Brotzu G, Dessì S. Opposite pattern of MDR1 and caveolin-1 gene expression in human atherosclerotic lesions and proliferating human smooth muscle cells. Cell Mol Life Sci. 2001; 58:1113–1120.
Article
32. Runge MS, Molnar K, Madamanchi NR. "Old" hearts and arteries: the role of oxidative stress. Trans Am Clin Climatol Assoc. 2010; 121:52–58.
33. Long J, Wang X, Gao H, Liu Z, Liu C, Miao M, Cui X, Packer L, Liu J. D-galactose toxicity in mice is associated with mitochondrial dysfunction: protecting effects of mitochondrial nutrient R-alpha-lipoic acid. Biogerontology. 2007; 8:373–381.
Article
34. Barton M, Cosentino F, Brandes RP, Moreau P, Shaw S, Lüscher TF. Anatomic heterogeneity of vascular aging: role of nitric oxide and endothelin. Hypertension. 1997; 30:817–824.
35. Stranahan AM, Cutler RG, Button C, Telljohann R, Mattson MP. Diet-induced elevations in serum cholesterol are associated with alterations in hippocampal lipid metabolism and increased oxidative stress. J Neurochem. 2011; 118:611–615.
Article
36. Fernandez ML, Webb D. The LDL to HDL cholesterol ratio as a valuable tool to evaluate coronary heart disease risk. J Am Coll Nutr. 2008; 27:1–5.
Article
37. Pang J, Xu Q, Xu X, Yin H, Xu R, Guo S, Hao W, Wang L, Chen C, Cao JM. Hexarelin suppresses high lipid diet and vitamin D3-induced atherosclerosis in the rat. Peptides. 2010; 31:630–638.
Article
38. Mazzeo RS, Horvath SM. Effects of training on weight, food intake, and body composition in aging rats. Am J Clin Nutr. 1986; 44:732–738.
Article
39. Motoyama M, Sunami Y, Kinoshita F, Irie T, Sasaki J, Arakawa K, Kiyonaga A, Tanaka H, Shindo M. The effects of long-term low intensity aerobic training and detraining on serum lipid and lipoprotein concentrations in elderly men and women. Eur J Appl Physiol Occup Physiol. 1995; 70:126–131.
Article
40. Shinoda M, Latour MG, Lavoie JM. Effects of physical training on body composition and organ weights in ovariectomized and hyperestrogenic rats. Int J Obes Relat Metab Disord. 2002; 26:335–343.
Article
41. Lee J, Cho HS, Kim DY, Cho JY, Chung JS, Lee HK, Seong NH, Kim WK. Combined effects of exercise and soy isoflavone diet on paraoxonase, nitric oxide and aortic apoptosis in ovariectomized rats. Appetite. 2012; 58:462–469.
Article
42. Chen X. Experimental study on the cardiovascular effects of ginsenosides. Zhonghua Xin Xue Guan Bing Za Zhi. 1982; 10:147–150.
43. Yamamoto M, Kumagai A, Yamamura Y. Plasma lipid-lowering action of ginseng saponins and mechanism of the action. Am J Chin Med. 1983; 11:84–87.
Article
44. Csiszar A, Wang M, Lakatta EG, Ungvari Z. Inflammation and endothelial dysfunction during aging: role of NF-kappaB. J Appl Physiol (1985). 2008; 105:1333–1341.
45. Kowalski J, Okopien B, Madej A, Makowiecka K, Zielinski M, Kalina Z, Herman ZS. Levels of sICAM-1, sVCAM-1 and MCP-1 in patients with hyperlipoproteinemia IIa and -IIb. Int J Clin Pharmacol Ther. 2001; 39:48–52.
Article
46. Mallat Z, Gojova A, Sauzeau V, Brun V, Silvestre JS, Esposito B, Merval R, Groux H, Loirand G, Tedgui A. Rho-associated protein kinase contributes to early atherosclerotic lesion formation in mice. Circ Res. 2003; 93:884–888.
Article
47. Ning Y, Bai Q, Lu H, Li X, Pandak WM, Zhao F, Chen S, Ren S, Yin L. Overexpression of mitochondrial cholesterol delivery protein, StAR, decreases intracellular lipids and inflammatory factors secretion in macrophages. Atherosclerosis. 2009; 204:114–120.
Article
48. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999; 340:115–126.
49. Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen AN, Skinhøj P, Pedersen BK. A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J Gerontol A Biol Sci Med Sci. 1999; 54:M357–M364.
50. Wannamethee SG, Lowe GD, Whincup PH, Rumley A, Walker M, Lennon L. Physical activity and hemostatic and inflammatory variables in elderly men. Circulation. 2002; 105:1785–1790.
Article
51. Okabe TA, Shimada K, Hattori M, Murayama T, Yokode M, Kita T, Kishimoto C. Swimming reduces the severity of atherosclerosis in apolipoprotein E deficient mice by antioxidant effects. Cardiovasc Res. 2007; 74:537–545.
Article
52. Kim HJ, Yoon KH, Kang MJ, Yim HW, Lee KS, Vuksan V, Sung MK. A six-month supplementation of mulberry, korean red ginseng, and banaba decreases biomarkers of systemic low-grade inflammation in subjects with impaired glucose tolerance and type 2 diabetes. Evid Based Complement Alternat Med. 2012; 2012:735191.
Article
53. Joo KR, Shin HP, Cha JM, Nam S, Huh Y. Effect of Korean red ginseng on superoxide dismutase inhibitor-induced pancreatitis in rats: a histopathologic and immunohistochemical study. Pancreas. 2009; 38:661–666.
Article
54. Sena CM, Nunes E, Louro T, Proença T, Fernandes R, Boarder MR, Seiça RM. Effects of alpha-lipoic acid on endothelial function in aged diabetic and high-fat fed rats. Br J Pharmacol. 2008; 153:894–906.
Article
55. Tanaka H, Dinenno FA, Monahan KD, Clevenger CM, DeSouza CA, Seals DR. Aging, habitual exercise, and dynamic arterial compliance. Circulation. 2000; 102:1270–1275.
Article
56. Hambrecht R, Adams V, Erbs S, Linke A, Kränkel N, Shu Y, Baither Y, Gielen S, Thiele H, Gummert JF, Mohr FW, Schuler G. Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation. 2003; 107:3152–3158.
Article
57. Jeon BH, Kim CS, Kim HS, Park JB, Nam KY, Chang SJ. Effect of Korean red ginseng on blood pressure and nitric oxide production. Acta Pharmacol Sin. 2000; 21:1095–1100.
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