The antioxidant activities of Korean Red Ginseng ( Panax ginseng) and ginsenosides: A systemic review through in vivo and clinical trials

Soo Kyung Park, Sun Hee Hyun, Gyo In, Chae-Kyu Park, Yi-Seong Kwak, Young-Jin Jang, Bumseok Kim, Jong-Hoon Kim, Chang-Kyun Han, Soo Kyung Park, Sun Hee Hyun, Gyo In, Chae-Kyu Park, Yi-Seong Kwak, Young-Jin Jang, Bumseok Kim, Jong-Hoon Kim, Chang-Kyun Han

Abstract

A wide range of studies have steadily pointed out the relation of oxidative stress to the primary and secondary causes of human disease and aging. As such, there have been multiple misconceptions about oxidative stress. Most of reactive oxygen species (ROS) generated from chronic diseases cause oxidative damage to cell membrane lipids and proteins. ROS production is increased by abnormal stimulation inside and outside in the body, and even though ROS are generated in cells in response to abnormal metabolic processes such as disease, it does not mean that they directly contribute to the pathogenesis of a disease. Therefore, the focus of treatment should not be on ROS production itself but on the prevention and treatment of diseases linked to ROS production, including types 1 and 2 diabetes, cancer, heart disease, schizophrenia, Parkinson's disease, and Alzheimer's disease. In this regard, Korean Red Ginseng (KRG) has been traditionally utilized to help prevent and treat diseases such as diabetes, cancer, inflammation, nervous system diseases, cardiovascular disease, and hyperlipidemia. Therefore, this review was intended to summarize in vivo animal and human clinical studies on the antioxidant activities of KRG and its components, ginsenosides.

Keywords: Animal experiments; Antioxidant activities; Clinical trials; Korean Red Ginseng; Oxidative stress.

Conflict of interest statement

The authors have declared no conflict of interest

© 2020 The Korean Society of Ginseng. Publishing services by Elsevier B.V.

Figures

Fig. 1
Fig. 1
Chemical structures of gensenosides. Ginsenosides are classified into protopanaxadiol(PPD) and protopanaxatriol(PPT) with different groups at C3, C6, and C20.

References

    1. Turrens J.F. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552(Pt 2):335–344.
    1. Pillai C.K., Pillai K.S. Antioxidants in health. Indian J Physiol Pharmacol. 2002;46(1):1–5.
    1. Asmat U., Abad K., Ismail K. Diabetes mellitus and oxidative stress-A concise review. Saudi Pharm J. 2016;24(5):547–553.
    1. Warner D.S., Sheng H., Batinić-Haberle I. Oxidants, antioxidants and the ischemic brain. J Exp Biol. 2004;207(Pt 18):3221–3231.
    1. So S.H., Lee J.W., Kim Y.S., Hyun S.H., Jan C.K. Red ginseng monograph. J Ginseng Res. 2018;42(4):549–561.
    1. Zielinski Z.A.M., Pratt D.A. Lipid peroxidation: kinetics, mechanisms, and products. J Org Chem. 2017;82(6):2817–2825.
    1. Zhang J.T., Qu Z.W., Liu Y., Deng H.L. Preliminary study on antiamnestic mechanism of ginsenoside Rg1 and Rb1. Chin Med J (Engl) 1990;103(11):932–938.
    1. Deng H.L., Zhang J.T. Anti-lipid peroxilative effect of ginsenoside Rb1 and Rg1. Chin Med J (Engl) 1991;104(5):395–398.
    1. Jung J., Jang H.J., Eom S.J., Choi N.S., Lee N.K., Paik H.D. Fermentation of red ginseng extract by the probiotic Lactobacillus plantarum KCCM 11613P: ginsenoside conversion and antioxidant effects. J Ginseng Res. 2019;43:20–26.
    1. Kim J.S., Nam K., Shim K.H., Kim K.W., Im K.S., Chung H.Y. Antioxidative mechanism of total saponin of red ginseng. Korean J Life Sci. 1996;6(1):48–55.
    1. Sung K.S., Chun C., Kwon Y.H., Kim K.H., Chang C.C. Effects of red ginseng component on the antioxidative enzymes activities and lipid peroxidation in the liver of mice. J Ginseng Res. 2000;24:29–34.
    1. Sanchez-Valle V., Chavez-Tapia N.C., Uribe M., Mendez-Sanchez N. Role of oxidative stress and molecular changes in liver fibrosis: a review. Curr Med Chem. 2012;19(28):4850–4860.
    1. Al-Yahya M., Mothana R., Al-Said M., Al-Dosari M., Al-Musayeib N., Al-Sohaibani M., Parvez M.K., Syed Rafatullah. Attenuation of CCl4-induced oxidative stress and hepatonephrotoxicity by Saudi Sidr honey in rats. Evid Based Complement Alternat Med. 2013;2013:569037.
    1. Wee J.J., Heo J.N., Kim M.W., Kang D.Y. Protective effect of Korean red ginseng against oxidative damage by carbon tetrachloride in rat. Korean J Ginseng Sci. 1996;20:154–158.
    1. El Denshary E.S., Al-Gahazali M.A., Mannaa F.A., Salem H.A., Hassan N.S., Abdel-Wahhab M.A. Dietary honey and ginseng protect against carbon tetrachloride-induced hepatonephrotoxicity in rats. Exp Toxicol Pathol. 2012;64(7–8):753–760.
    1. Kim H., Lee Y.H., Kim S.I. Antihepatotoxic components of Korean ginseng: effect on lipid peroxidation. Korean Biochem J. 1989;22:12–18.
    1. Lee C.K., Kim N.Y., Han Y.N., Choi J. Effects of pretreated Korean red ginseng on carbon tetrachloride and galactosamine-induced hepatotoxicity in rats. J Ginseng Res. 2003;27:1–10.
    1. Jaeschke H., Ramachandran A. Oxidant stress and lipid peroxidation in acetaminophen hepatotoxicity. React Oxyg Species (Apex) 2018;5(15):145–158.
    1. Saba E., Lee Y.Y., Kim M., Kim S.H., Hong S.B., Rhee M.H. A comparative study on immune-stimulatory and antioxidant activities of various types of ginseng extracts in murine and rodent models. J Ginseng Res. 2018;42(4):577–584.
    1. Seong G.S., Chun S.G., Chang C.C. Hepatoprotective effects of white and red ginseng extracts of acetaminophen-induced hepatotoxicity in mice. J Ginseng Res. 2005;29:131–137.
    1. Kim Y.S., Kim Y.H., Noh J.R., Cho E.S., Park J.H., Son H.Y. Protective effect of Korean red ginseng against aflatoxin B1-induced hepatotoxicity in rat. J Ginseng Res. 2011;35(2):243–249.
    1. Abdelfattah-Hassan A., Shalaby S.I., Khater S.I., El-Shertry E.S., Fadil H.A.E., Elsayed S.A. Panax ginseng is superior to vitamin E as a hepatoprotector against cyclophosphamide-induced liver damage. Complement Ther Med. 2019;46:95–102.
    1. Kim H., Hong M.K., Choi H., Moon H.S., Lee H.J. Chemopreventive effects of Korean red ginseng extract on rat hepatocarcinogenesis. J Cancer. 2015;6(1):1–8.
    1. Wu D., Cederbaum A.I. Alcohol, oxidative stress, and free radical damage. Alcohol Res Health. 2003;27(4):277–284.
    1. Lee C.K., Choi J.W., Kim S.H., Kim H., Han Y.N. Biological activity of acidic polysaccharide of Korean red ginseng I.-Effects on alcohol detoxification system in the liver of alcohol-intoxicated rats. J Ginseng Res. 1998;22:260–266.
    1. Giacco F., Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010;107(9):1058–1070.
    1. Ryu J.K., Lee T., Kim D.J., Park I.S., Yoon S.M., Lee H.S., Song S.U., Suh J.K. Free radical-scavenging activity of Korean red ginseng for erectile dysfunction in non-insulin-dependent diabetes mellitus rats. Urology. 2005;65(3):611–615.
    1. Jung C.H., Seog H.M., Choi I.W., Choi H.D., Cho H.Y. Effects of wild ginseng (Panax ginseng C.A. Meyer) leaves on lipid peroxidation levels and antioxidant enzyme activities in streptozotocin diabetic rats. J Ethnopharmacol. 2005;98(3):245–250.
    1. Cho W.C., Chung W.S., Lee S.K., Leung A.W., Cheng C.H., Yue K.K. Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2006;550(1–3):173–179.
    1. Lim S.W., Jin L., Luo K., Jin J., Yang C.W. Ginseng extract reduces tacrolimus-induced oxidative stress by modulating autophagy in pancreatic beta cells. Lab Invest. 2017;97(11):1271–1281.
    1. Krata N., Zagożdżon R., Foroncewicz B., Mucha K. Oxidative stress in kidney diseases: the cause or the consequence? Arch Immunol Ther Exp (Warsz) 2018;66(3):211–220.
    1. Yokozawa T., Liu Z.W., Dong E. A study of ginsenoside-Rd in a renal ischemia-reperfusion model. Nephron. 1998;78(2):201–206.
    1. Yokozawa T., Liu Z.W. The role of ginsenoside-Rd in cisplatin-induced acute renal failure. Ren Fail. 2000;22(2):115–127.
    1. Sayre L.M., Perry G., Smith M.A. Oxidative stress and neurotoxicity. Chem Res Toxicol. 2008;21(1):172–188.
    1. Dinis-Oliveira R.J., Duarte J.A., Sanchez-Navarro A., Remiao F., Bastos M.L., Carvalho F. Paraquat poisonings: mechanisms of lung toxicity, clinical features, and treatment. Crit Rev Toxicol. 2008;38(1):13–71.
    1. Somayajulu-Niţu M., Sandhu J.K., Cohen J., Sikorska M., Sridhar T.S., Matei A., Borowy-Borowski H., Pandey S. Paraquat induces oxidative stress, neuronal loss in substantia nigra region and parkinsonism in adult rats: neuroprotection and amelioration of symptoms by water-soluble formulation of coenzyme Q10. BMC Neurosci. 2009;10:88.
    1. Liou H.H., Chen R.C., Tsai Y.F., Chen W.P., Chang Y.C., Tsai M.C. Effects of paraquat on the substantia nigra of the wistar rats: neurochemical, histological, and behavioral studies. Toxicol Appl Pharmacol. 1996;137(1):34–41.
    1. Liou H.H., Tsai M.C., Chen C.J., Jeng J.S., Chang Y.C., Chen S.Y., Chen R.C. Environmental risk factors and Parkinson’s disease: a case-control study in Taiwan. Neurology. 1997;48(6):1583–1588.
    1. Morano A., Jimenez-Jimenez F.J., Molina J.A., Antolin M.A. Risk-factors for Parkinson’s disease: case-control study in the province of Cáceres, Spain. Acta Neurol Scand. 1994;89(3):164–170.
    1. Thiruchelvam M., McCormack A., Richfield E.K., Baggs R.B., Tank A.W., Di Monte D.A., Cory-Slechta D.A. Age-related irreversible progressive nigrostriatal dopaminergic neurotoxicity in the paraquat and maneb model of the Parkinson’s disease phenotype. Eur J Neurosci. 2003;18(3):589–600.
    1. Lee J.J. Antioxidant effects of Korean red ginseng extracts on the glutathione and lipid peroxidation in the liver of mouse treated with paraquat. Korean J Biomed Lab Sci. 2000;6:45–53.
    1. Hamid I., Kim S.K., Cha K.M., Jeong M.S., Prachetash G., Rhee D.K. Korean Red Ginseng alleviates neuroinflammation and promotes cell survival in the intermittent heat stress-induced rat brain by suppressing oxidative stress via estrogen receptor beta and brain-derived neurotrophic factor upregulation. J Ginseng Res. 2020;44:593–602.
    1. Kim D.H., Kim D.W., Jung B.H., Lee J.H., Heesu Lee H., Hwang G.S., Sung Ki, Kang K.S., Lee J.W. Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells. J Ginseng Res. 2019;43:326–334.
    1. Chen X.C., Zhou Y.C., Chen Y., Zhu Y.G., Fang F., Chen L.M. Ginsenoside Rg1 reduces MPTP-induced substantia nigra neuron loss by suppressing oxidative stress. Acta Pharmacol Sin. 2005;26(1):56–62.
    1. Ban J.Y., Kang S.W., Lee J.S., Chung J.H., Ko Y.G., Choi H.S. Korean red ginseng protects against neuronal damage induced by transient focal ischemia in rats. Exp Ther Med. 2012;3(4):693–698.
    1. Lim K.H., Cho J.Y., Kim B., Bae B.S., Kim J.H. Red ginseng (Panax ginseng) decreases isoproterenol-induced cardiac injury via antioxidant properties in porcine. J Med Food. 2014;17(1):111–118.
    1. Cui H., Kong Y., Zhang H. Oxidative stress, mitochondrial dysfunction, and aging. J Signal Transduct. 2012;2012:646354.
    1. Yokozawa T., Satoh A., Cho E.J. Ginsenoside-Rd attenuates oxidative damage related to aging in senescence-accelerated mice. J Pharm Pharmacol. 2004;56(1):107–113.
    1. Oh M.H., Chung H.Y., Young H.S., Kim K.W., Chung H.Y., Oura H., Yokozawa T. Effects of ginsenoside Rb2 on the antioxidants in SAM-R/1 mice. Korean Biochem J. 1992;25:492–497.
    1. Kim K.H., Sung K.S., Chang C.C. Effects of the antioxidative components to ginsenoside in the liver of 40-week-old mice. J Ginseng Res. 2000;24:162–167.
    1. Ramesh T., Kim S.W., Hwang S.Y., Sohn S.H., Yoo S.K., Kim S.K. Panax ginseng reduces oxidative stress and restores antioxidant capacity in aged rats. Nutr Res. 2012;32(9):718–726.
    1. Kopalli S.R., Hwang S.Y., Won Y.J., Kim S.W., Cha K.M., Han C.K., Hong J.Y., Kim S.K. Korean red ginseng extract rejuvenates testicular ineffectiveness and sperm maturation process in aged rats by regulating redox proteins and oxidative defense mechanisms. Exp Gerontol. 2015;69:94–102.
    1. Kim D.J., Chang C.C. The effects of red ginseng extracts of antioxidant enzyme activities and lipid peroxidation of the kidney in γ-postirradiated mice. Korean J Ginseng Sci. 1994;18:25–31.
    1. Kim D.Y., Chang J.C. Radioprotective effect of ginseng components on antioxidant enzymes, glutathione and lipid peroxidation of liver in γ-irradiated mice. Korean J Ginseng Sci. 1998;22:1–10.
    1. Jeon B.H., Seong G.S., Chun S.G., Sung J.H., Chang C.C. Antioxidative effects of white ginseng and red ginseng on liver of high fat diet-treated mice. J Ginseng Res. 2005;29:138–144.
    1. Song Y.B., Kwak Y.S., Park K.H., Chang S.K. Effect of total saponin from red ginseng on activities of antioxidant enzymes in pregnant rats. J Ginseng Res. 2002;26:139–144.
    1. Kim S.H., Park K.S., Chang M.J., Sung J.H. Effects of Panax ginseng extract on exercise-induced oxidative stress. J Sports Med Phys Fitness. 2005;45(2):178–182.
    1. Kim S.H., Park K.S. Effects of Panax ginseng extract on lipid metabolism in humans. Pharmacol Res. 2003;48(5):511–513.
    1. Kim H.G., Yoo S.R., Park H.J., Lee N.H., Shin J.W., Sathyanath R., Cho J.H., Son C.G. Antioxidant effects of Panax ginseng C.A. Meyer in healthy subjects: a randomized, placebo-controlled clinical trial. Food Chem Toxicol. 2011;49(9):2229–2235.
    1. Lee B.M., Lee S.K., Kim H.S. Inhibition of oxidative DNA damage, 8-OHdG, and carbonyl contents in smokers treated with antioxidants (vitamin E, vitamin C, beta-carotene and red ginseng) Cancer Lett. 1998;132(1–2):219–227.
    1. Seo S.K., Hong Y., Yun B.H., Chon S.J., Jung Y.S., Park J.H., Cho S.H., Choi Y.S., Lee B.S. Antioxidative effects of Korean red ginseng in postmenopausal women: a double-blind randomized controlled trial. J Ethnopharmacol. 2014;154(3):753–757.
    1. Kawamura T., Muraoka I. Exercise-induced oxidative stress and the effects of antioxidant intake from a physiological viewpoint. Antioxidants (Basel) 2018;7(9)
    1. Choi J., Kim Y., Lee K.M., Kim H.J. The effects of red-ginseng intaking on free radical produced during aerobic exercise in the elderly. J Ginseng Res. 2004;28:27–32.
    1. Lee C.M., Kim R.T. Effects of the red-ginseng administration on the antioxidant enzyme and malondialdehyde following exercise. Exerc Sci. 1999;8:473–483.
    1. Park H.S., Kim S.K. The effect of aerobic exercise training and taking Red Panax Ginseng on antioxidant enzymes and lipid superoxides in diabetics. J Sport Leisure Stud. 2004;22:471–484.
    1. Liguori I., Russo G., Curcio F., Bulli G., Aran L., Della-Morte D., Gargiulo G., Testa G., Cacciatore F., Bonaduce D. Oxidative stress, aging, and diseases. Clin Interv Aging. 2018;13:757–772.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться