Abstract
The modern lifestyle is characterised by various factors that cause accelerating ageing by the upregulation of oxidative stress and inflammation—two processes that are inextricably linked in an endless circle of self-propagation. Inflammation in particular is commonly accepted as aetiological factor in many chronic disease states, such as obesity, diabetes and depression. In terms of disease prevention or treatment, interventions aimed at changing dietary and/or exercise habits have had limited success in practise, mostly due to poor long-term compliance. Furthermore, other primary stimuli responsible for eliciting an oxidative stress or inflammatory response—e.g. psychological stress and anxiety—cannot always be easily addressed. Thus, preventive medicine aimed at countering the oxidative stress and/or inflammatory responses has become of interest. Especially in developing countries, such as South Africa, the option of development of effective strategies from plants warrants further investigation. A brief overview of the most relevant and promising South African plants which have been identified in the context of inflammation, oxidative stress and chronic disease is provided here. In addition, and more specifically, our group and others have shown considerable beneficial effects across many models, after treatment with products derived from grapes. Of particular interest, specific cellular mechanisms have been identified as therapeutic targets of grape-derived polyphenols in the context of inflammation and oxidative stress. The depth of these studies afforded some additional insights, related to methodological considerations pertaining to animal vs. human models in natural product research, which may address the current tendency for generally poor translation of positive animal model results into human in vivo models. The importance of considering individual data vs. group averages in this context is highlighted.
Similar content being viewed by others
References
Africa LD, Smith C (2015) Sutherlandia frutescens may exacerbate HIV-associated neuroinflammation. J Negat Results in Biomed 14(1):14. https://doi.org/10.1186/s12952-015-0031-y
Africa LD, Smith C (2015b) Using a simulated blood-brain barrier to investigate potential modulators of HIV-1-associated neuroinflammatory processes in vitro. J Res Biol 5(A):6–20
Andrade JM, Frade AC, Guimarães JB, Freitas KM, Lopes MT, Guimarães AL, de Paula AM, Coimbra CC, Santos SH (2014) Resveratrol increases brown adipose tissue thermogenesis markers by increasing SIRT1 and energy expenditure and decreasing fat accumulation in adipose tissue of mice fed a standard diet. Eur J Nutr 53(7):1503–1510. https://doi.org/10.1007/s00394-014-0655-6
Andreollo NA, Santos EF, Araújo MR, Lopes LR (2012) Rat’s age versus human’s age: what is the relationship? Arq Bras Cir Dig 25(1):49–51
Ayeleso A, Brooks N, Oguntibeju O (2014) Modulation of antioxidant status in streptozotocin-induced diabetic male Wistar rats following intake of red palm oil and/or rooibos. Asian Pac J Trop Med 7(7):536–544. https://doi.org/10.1016/S1995-7645(14)60090-0
Beltrán-Debón R, Rull A, Rodríguez-Sanabria F, Iswaldi I, Herranz-López M, Aragonès G, Camps J, Alonso-Villaverde C, Menéndez JA, Micol V, Segura-Carretero A, Joven J (2011) Continuous administration of polyphenols from aqueous rooibos (Aspalathus linearis) extract ameliorates dietary-induced metabolic disturbances in hyperlipidemic mice. Phytomedicine 18(5):414–424. https://doi.org/10.1016/j.phymed.2010.11.008
Bennett AC, Smith C (2018) Immunomodulatory effects of Sceletium tortuosum (Trimesemine™) elucidated in vitro: implications for chronic disease. J Ethnopharmacol 214:134–140. https://doi.org/10.1016/j.jep.2017.12.020
Bennett AC, Van Camp A, López V, Smith C (2018) Sceletium tortuosum alkaloids may delay chronic disease progression via their anti-inflammatory and antioxidant actions. J Physiol Biochem. https://doi.org/10.1007/s13105-018-0620-6
Biais B, Krisa S, Cluzet S, Da Costa G, Waffo-Teguo P, Mérillon JM, Richard T (2017) Antioxidant and cytoprotective activities of grapevine stilbenes. J Agric Food Chem 65(24):4952–4960. https://doi.org/10.1021/acs.jafc.7b01254
Biessels GJ, van der Heide LP, Kamal A, Bleys RL, Gispen WH (2002) Ageing and diabetes: implications for brain function. Eur J Pharmacol 441(1–2):1–14
Carmeli E, Bachar A, Rom O, Aizenbud D (2016) Oxidative stress and nitric oxide in sedentary older adults with intellectual and developmental disabilities. Adv Exp Med Biol 884:21–27
Carpenter JM, Jourdan MK, Fountain EM, Ali Z, Abe N, Khan IA, Sufka KJ (2016) The effects of Sceletium tortuosum (L.) N.E. Br. extract fraction in the chick anxiety-depression model. J Ethnopharmacol 193:329–332. https://doi.org/10.1016/j.jep.2016.08.019
Cásedas G, Les F, Gómez-Serranillos MP, Smith C, López V (2017) Anthocyanin profile, antioxidant activity and enzyme inhibiting properties of blueberry and cranberry juices: a comparative study. Food Funct 8:4187–4193. https://doi.org/10.1039/c7fo01205e
Chan MM, Fong D, Ho CT, Huang HI (1997) Inhibition of inducible nitric oxide synthase gene expression and enzyme activity by epigallocatechin gallate, a natural product from green tea. Biochem Pharmacol 54(12):1281–1286
Coetzee DD, López V, Smith C (2016) High-mesembrine Sceletium extract (Trimesemine™) is a monoamine releasing agent, rather than only a selective serotonin reuptake inhibitor. J Ethnopharmacol 177:111–116. https://doi.org/10.1016/j.jep.2015.11.034
Dominguez LJ, Galioto A, Ferlisi A, Pineo A, Putignano E, Belvedere M, Costanza G, Barbagallo M (2006) Ageing, lifestyle modifications, and cardiovascular disease in developing countries. J Nutr Health Aging 10(2):143–149
Dvorakova M, Landa P (2017) Anti-inflammatory activity of natural stilbenoids: a review. Pharmacol Res 124:126–145. https://doi.org/10.1016/j.phrs.2017.08.002
Fernández-Quintela A, Milton-Laskibar I, González M, Portillo MP (2017) Antiobesity effects of resveratrol: which tissues are involved? Ann N Y Acad Sci 1403(1):118–131. https://doi.org/10.1111/nyas.13413
Fleshner M (2013) Stress-evoked sterile inflammation, danger associated molecular patterns (DAMPs), microbial associated molecular patterns (MAMPs) and the inflammasome. Brain Behav Immun 27:1–7
George MG, Tong X, Bowman BA (2017) Prevalence of cardiovascular risk factors and strokes in younger adults. JAMA Neurol 74(6):695–703. https://doi.org/10.1001/jamaneurol.2017.0020
Hadem IKH, Majaw T, Kharbuli B, Sharma R (2017) Beneficial effects of dietary restriction in aging brain. J Chem Neuroanat. https://doi.org/10.1016/j.jchemneu.2017.10.001
Hayflick L (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37(3):614–636. https://doi.org/10.1016/0014-4827(65)90211-9
Jiang J, Chuang DY, Zong Y, Patel J, Brownstein K, Lei W, Lu CH, Simonyi A, Gu Z, Cui J, Rottinghaus GE, Fritsche KL, Lubahn DB, Folk WR, Sun GY (2014) Sutherlandia frutescens ethanol extracts inhibit oxidative stress and inflammatory responses in neurons and microglial cells. PLoS One 9(2):e89748. https://doi.org/10.1371/journal.pone.0089748
Khakimov B, Engelsen SB (2017) Resveratrol in the foodomics era: 1:25,000. Ann N Y Acad Sci 1403(1):48–58. https://doi.org/10.1111/nyas.13425
Kim CS, Park S, Kim J (2017) The role of glycation in the pathogenesis of aging and its prevention through herbal products and physical exercise. J Exerc Nutr Biochem 21(3):55–61. https://doi.org/10.20463/jenb.2017.0027
Kruger MJ, Smith C (2012) Post-contusion polyphenol treatment alters inflammation and muscle regeneration. Med Sci Sports Exerc 44(5):872–880
Kruger MJ, Myburgh KH, Smith C (2014) Contusion injury with chronic in vivo polyphenol supplementation: leukocyte responses. Med Sci Sports Exerc 46(2):225–231
Ku SK, Kwak S, Kim Y, Bae JS (2015) Aspalathin and Nothofagin from Rooibos (Aspalathus linearis) inhibits high glucose-induced inflammation in vitro and in vivo. Inflammation 38(1):445–455. https://doi.org/10.1007/s10753-014-0049-1
Kwak S, Han MS, Bae JS (2015) Aspalathin and nothofagin from Rooibos (Aspalathus linearis) inhibit endothelial protein C receptor shedding in vitro and in vivo. Fitoterapia 100:179–186. https://doi.org/10.1016/j.fitote.2014.12.002
Ky I, Teissedre PL (2015) Characterisation of Mediterranean grape pomace seed and skin extracts: polyphenolic content and antioxidant activity. Molecules 20(2):2190–2207. https://doi.org/10.3390/molecules20022190
Lee W, Kim KM, Bae JS (2015) Ameliorative effect of Aspalathin and Nothofagin from Rooibos (Aspalathus linearis) on HMGB1-induced septic responses in vitro and in vivo. Am J Chin Med 43(5):991–1012. https://doi.org/10.1142/S0192415X15500573
Lei W, Browning JD Jr, Eichen PA, Brownstein KJ, Folk WR, Sun GY, Lubahn DB, Rottinghaus GE, Fritsche KL (2015) Unveiling the anti-inflammatory activity of Sutherlandia frutescens using murine macrophages. Int Immunopharmacol 29(2):254–262. https://doi.org/10.1016/j.intimp.2015.11.012
Lima AH, Miranda AS, Correia MA, Soares AH, Cucato GG, Sobral Filho DC, Gomes SL, Ritti-Dias RM (2015) Individual blood pressure responses to walking and resistance exercise in peripheral artery disease patients: are the mean values describing what is happening? J Vasc Nurs 33(4):150–156. https://doi.org/10.1016/j.jvn.2015.09.001
Loria MJ, Ali Z, Abe N, Sufka KJ, Khan IA (2014) Effects of Sceletium tortuosum in rats. J Ethnopharmacol 155(1):731–735. https://doi.org/10.1016/j.jep.2014.06.007
MacKenzie J, Koekemoer T, Van de Venter M, Dealtry G, Roux S (2009) Sutherlandia frutescens limits the development of insulin resistance by decreasing plasma free fatty acid levels. Phytother Res 23:1609–1614. https://doi.org/10.1002/ptr.2830
Magcwebeba T, Swart P, Swanevelder S, Joubert E, Gelderblom W (2016) Anti-inflammatory effects of Aspalathus linearis and Cyclopia spp. Extracts in a UVB/keratinocyte (HaCaT) model utilising interleukin-1α accumulation as biomarker. Molecules. 21(10).
Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79(5):727–747
Marnewick JL, Rautenbach F, Venter I, Neethling H, Blackhurst DM, Wolmarans P, Macharia M (2011) Effects of rooibos (Aspalathus linearis) on oxidative stress and biochemical parameters in adults at risk for cardiovascular disease. J Ethnopharmacol 133(1):46–52. https://doi.org/10.1016/j.jep.2010.08.061
Milbourn HR, Toomey LM, Gavriel N, Gray CGG, Gough AH, Giacci MK, Fitzgerald M (2017) Limiting oxidative stress following neurotrauma with a combination of ion channel inhibitors. Discov Med 23(129):361–369
Minamino T, Orimo M, Shimizu I, Kunieda T, Yokoyama M, Ito T, Nojima A, Nabetani A, Oike Y, Matsubara H, Ishikawa F, Komuro I (2009) A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat Med 15(9):1082–1087. https://doi.org/10.1038/nm.2014
Møller P, Danielsen PH, Karottki DG, Jantzen K, Roursgaard M, Klingberg H, Jensen DM, Christophersen DV, Hemmingsen JG, Cao Y, Loft S (2014) Oxidative stress and inflammation generated DNA damage by exposure to air pollution particles. Mutat Res Rev Mutat Res 762:133–166. https://doi.org/10.1016/j.mrrev.2014.09.001
Müller AC, Skinner MF, Kanfer I (2013) Effect of the African traditional medicine, Sutherlandia frutescens, on the bioavailability of the antiretroviral protease inhibitor Atazanavir. Evid Based Complement Alternat Med 2013:1–6. https://doi.org/10.1155/2013/324618
Murase T, Misawa K, Haramizu S, Hase T (2009) Catechin-induced activation of the LKB1/AMP-activated protein kinase pathway. Biochem Pharmacol 78(1):78–84. https://doi.org/10.1016/j.bcp.2009.03.021
Myburgh KH, Kruger MJ, Smith C (2012) Accelerated skeletal muscle recovery after in vivo polyphenol administration. J Nutr Biochem 23:1072–1079
Nagata C, Tamura T, Wada K, Konishi K, Goto Y, Nagao Y, Ishihara K, Yamamoto S (2017) Sleep duration, nightshift work, and the timing of meals and urinary levels of 8-isoprostane and 6-sulfatoxymelatonin in Japanese women. Chronobiol Int 21:1–10. https://doi.org/10.1080/07420528.2017.1355313
Neyroud D, Kayser B, Place N (2016) Are there critical fatigue thresholds? Aggregated vs. individual data. Front Physiol 7:376. https://doi.org/10.3389/fphys.2016.00376
Oliver E, McGillicuddy F, Phillips C, Toomey S, Roche HM (2010) The role of inflammation and macrophage accumulation in the development of obesity-induced type 2 diabetes mellitus and the possible therapeutic effects of long-chain n-3 PUFA. Proc Nutr Soc 69(2):232–243. https://doi.org/10.1017/S0029665110000042
Olivier S, Foretz M, Viollet B (2018) Promise and challenges for direct small molecule AMPK activators. Biochem Pharmacol. https://doi.org/10.1016/j.bcp.2018.01.049
Orzel J, Daszykowski M, Kazura M, de Beer D, Joubert E, Schulze AE, Beelders T, de Villiers A, Malherbe CJ, Walczak B (2014) Modeling of the total antioxidant capacity of rooibos (Aspalathus linearis) tea infusions from chromatographic fingerprints and identification of potential antioxidant markers. J Chromatogr A 1366:101–109. https://doi.org/10.1016/j.chroma.2014.09.030
Petersen KS, Smith C (2016) Ageing-associated oxidative stress and inflammation are alleviated by products from grapes. Oxidative Med Cell Longev 2016:1–12. https://doi.org/10.1155/2016/6236309
Poulose N, Raju R (2015) Sirtuin regulation in aging and injury. Biochim Biophys Acta (BBA) - Mol Basis Dis 1852(11):2442–2455. https://doi.org/10.1016/j.bbadis.2015.08.017
Prevoo D, Smith C, Swart P, Swart AC (2004) The effect of Sutherlandia frutescens on steroidogenesis: confirming indigenous wisdom. Endocr Res 30(4):745–751
Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. FASEB J 22:659–661
Richa R, Yadawa AK, Chaturvedi CM (2017) Hyperglycemia and high nitric oxide level induced oxidative stress in the brain and molecular alteration in the neurons and glial cells of laboratory mouse, Mus musculus. Neurochem Int 104:64–79. https://doi.org/10.1016/j.neuint.2016.12.008
Salminen A, Kaarniranta K, Kauppinen A (2013) Crosstalk between oxidative stress and SIRT1: impact on the aging process. Int J Mol Sci 14(2):3834–3859. https://doi.org/10.3390/ijms14023834
Schloms L, Smith C, Storbeck KH, Marnewick JL, Swart P, Swart AC (2014) Rooibos influences glucocorticoid levels and steroid ratios in vivo and in vitro: a natural approach in the management of stress and metabolic disorders? Mol Nutr Food Res 58(3):537–549. https://doi.org/10.1002/mnfr.201300463
Sergeant CA, Africander D, Swart P, Swart AC (2017) Sutherlandia frutescens modulates adrenal hormone biosynthesis, acts as a selective glucocorticoid receptor agonist (SEGRA) and displays anti-mineralocorticoid properties. J Ethnopharmacol 202:290–301. https://doi.org/10.1016/j.jep.2017.03.019
Smith C (2011) The effects of Sceletium tortuosum in an in vivo model of psychological stress. J Ethnopharmacol 133(1):31–36. https://doi.org/10.1016/j.jep.2010.08.058
Smith C, Essop MF (2009) Gender differences in metabolic risk factor prevalence in a South African student population. Cardiovasc J Africa 20(3):178–182
Smith C, Essop MF (2014) Influence of lifestyle choices on metabolic risks results in distinct gender- and age-differences. Int J Clin Exp Physiol 1(1):13–19
Smith C, Janse van Vuuren M (2014) Central and peripheral effects of Sutherlandia frutescens on the response to acute psychological stress. Exp Biol Med 239:123–128
Smith C, Krygsman A (2014) Hoodia gordonii extract targets both adipose and muscle tissue to achieve weight loss in rats. J Ethnopharmacol 155(2):1284–1290. https://doi.org/10.1016/j.jep.2014.07.018
Smith C, Krygsman A (2014) Hoodia gordonii: to eat, or not to eat. J Ethnopharmacol 155(2):987–991. https://doi.org/10.1016/j.jep.2014.06.033
Smith C, Myburgh KH (2004) Treatment with Sutherlandia frutescens subs. microphylla alters the corticosterone response to chronic intermittent immobilisation stress in rats. S Afr J Sci 100:229–232
Smith T, Engelbrecht L, Smith C (2018) Anti-inflammatory cellular targets on neutrophils elucidated using a novel cell migration model and confocal microscopy: a clinical supplementation study. J Inflamm (Lond) 15:2. https://doi.org/10.1186/s12950-017-0177-0
Soubry A, Schildkraut JM, Murtha A, Wang F, Huang Z, Bernal A, Kurtzberg J, Jirtle RL, Murphy SK, Hoyo C (2013) Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort. BMC Med 11:29. https://doi.org/10.1186/1741-7015-11-29
Suzuki T, Pervin M, Goto S, Isemura M, Nakamura Y (2016) Beneficial effects of tea and the green tea catechin epigallocatechin-3-gallate on obesity. Molecules. 21(10):1305. https://doi.org/10.3390/molecules21101305
Swart AC, Smith C (2016) Modulation of glucocorticoid, mineralocorticoid and androgen production in H295 cells by Trimesemine™, a mesembrine-rich Sceletium extract. J Ethnopharmacol 177:35–45. https://doi.org/10.1016/j.jep.2015.11.033
Thangaraj K, Vaiyapuri M (2017) Orientin, a C-glycosyl dietary flavone, suppresses colonic cell proliferation and mitigates NF-κB mediated inflammatory response in 1,2-dimethylhydrazine induced colorectal carcinogenesis. Biomed Pharmacother 96:1253–1266. https://doi.org/10.1016/j.biopha.2017.11.088
Thosar SS, Bielko SL, Wiggins CC, Klaunig JE, Mather KJ, Wallace JP (2015) Antioxidant vitamin C prevents decline in endothelial function during sitting. Med Sci Monit 21:1015–1021. https://doi.org/10.12659/MSM.893192
Tobwala S, Fan W, Hines CJ, Folk WR, Ercal N (2014) Antioxidant potential of Sutherlandia frutescens and its protective effects against oxidative stress in various cell cultures. BMC Complement Altern Med 14:271 http://www.biomedcentral.com/1472-6882/14/271
Tsutsui A, Pradipta AR, Kitazume S, Taniguchi N, Tanaka K (2017) Effect of spermine-derived AGEs on oxidative stress and polyamine metabolism. Org Biomol Chem 15(32):6720–6724. https://doi.org/10.1039/c7ob01346a
Verpoorte R, Choi YH, Kim HK (2005) Ethnopharmacology and systems biology: a perfect holistic match. J Ethnopharmacol 100(1–2):53–56
Von Zglinicki T, Serra V, Lorenz M et al (2000) Short telomeres in patients with vascular dementia: an indicator of low antioxidative capacity and a possible risk factor? Lab Investig 80(11):1739–1747. https://doi.org/10.1038/labinvest.3780184
Waisundara VY, Hoon LY (2015) Free radical scavenging ability of Aspalathus linearis in two in vitro models of diabetes and cancer. J Tradit Complement Med 5(3):174–178. https://doi.org/10.1016/j.jtcme.2014.11.009
Williams S, Roux S, Koekemoer T, Van de Venter M, Dealtry G (2013) Sutherlandia frutescens prevents changes in diabetes-related gene expression in a fructose-induced insulin resistant cell model. J Ethnopharmacol 146(2):482–489
Zhang B, Leung WK, Zou Y, Mabusela W, Johnson Q, Michaelsen TE, Paulsen BS (2014) Immunomodulating polysaccharides from Lessertia frutescens leaves: isolation, characterization and structure activity relationship. J Ethnopharmacol 152(2):340–348. https://doi.org/10.1016/j.jep.2014.01.017
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The author declares that she has no conflict of interest.
Rights and permissions
About this article
Cite this article
Smith, C. Natural antioxidants in prevention of accelerated ageing: a departure from conventional paradigms required. J Physiol Biochem 74, 549–558 (2018). https://doi.org/10.1007/s13105-018-0621-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13105-018-0621-5