Download PDF
Planta Med 2021; 87(12/13): 949-963
DOI: 10.1055/a-1533-0021
Natural Product Chemistry and Analytical Studies
Reviews

Coffee Leaves: An Upcoming Novel Food?[ # ]

Andrea Montis
1   RD3 Department-Unit of Pharmacognosy, Bioanalysis and Drug Discovery, Faculty of Pharmacy, Université libre de Bruxelles, Brussels, Belgium
2   APFP Analytical platform of the faculty of pharmacy, Faculty of Pharmacy, Université libre de Bruxelles, Brussels, Belgium
,
Florence Souard
3   Département de Pharmacochimie Moléculaire, UMR 5063 CNRS, Université Grenoble Alpes, Saint-Martin dʼHères, France
4   DPP Department – Unit of Pharmacology, Pharmacotherapy and Pharmaceutical care, Faculty of Pharmacy, Université libre de Bruxelles, Brussels, Belgium
,
Cédric Delporte
1   RD3 Department-Unit of Pharmacognosy, Bioanalysis and Drug Discovery, Faculty of Pharmacy, Université libre de Bruxelles, Brussels, Belgium
2   APFP Analytical platform of the faculty of pharmacy, Faculty of Pharmacy, Université libre de Bruxelles, Brussels, Belgium
,
Piet Stoffelen
5   Meise Botanic Garden, Domein van Bouchout, Meise, Belgium
,
Caroline Stévigny‡
1   RD3 Department-Unit of Pharmacognosy, Bioanalysis and Drug Discovery, Faculty of Pharmacy, Université libre de Bruxelles, Brussels, Belgium
,
Pierre Van Antwerpen‡
1   RD3 Department-Unit of Pharmacognosy, Bioanalysis and Drug Discovery, Faculty of Pharmacy, Université libre de Bruxelles, Brussels, Belgium
2   APFP Analytical platform of the faculty of pharmacy, Faculty of Pharmacy, Université libre de Bruxelles, Brussels, Belgium
› Author Affiliations
› Further Information
   Permissions and Reprints

Abstract

Unlike those of coffee beans, the healthy properties of coffee leaves have been overlooked for a long time, even if they are consumed as a beverage by local communities of several African countries. Due to the presence of xanthines, diterpenes, xanthones, and several other polyphenol derivatives as main secondary metabolites, coffee leaves might be useful to prevent many daily disorders. At the same time, as for all bioactive molecules, careless use of coffee leaf infusions may be unsafe due to their adverse effects, such as the excessive stimulant effects on the central nervous system or their interactions with other concomitantly administered drugs. Moreover, the presence of some toxic diterpene derivatives requires careful analytical controls on manufactured products made with coffee leaves. Accordingly, knowledge about the properties of coffee leaves needs to be increased to know if they might be considered a good source for producing new supplements. The purpose of the present review is to highlight the biosynthesis, metabolism, and distribution of the 4 main classes of secondary metabolites present in coffee leaves, their main pharmacological and toxicological aspects, and their main roles in planta. Differences in coffee leaf chemical composition depending on the coffee species will also be carefully considered.

Key words

Coffea - coffee leaves - Rubiaceae - biosynthesis - metabolome - food supplement

# Dedicated to Professor Arnold Vlietinck on the occasion of his 80th birthday.




Publication History

Received: 11 December 2020

Accepted after revision: 14 June 2021

Article published online:
24 September 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Bedford E. World arabica coffee production 2021. 2020 Accessed January 13, 2021 at: https://www.statista.com/statistics/225400/world-arabica-coffee-production/
    Google Scholar
  • 2 Bedford E. World robusta coffee production 2021. 2020 Accessed January 13, 2021 at: https://www.statista.com/statistics/225402/world-robusta-coffee-production/
    Google Scholar
  • 3 Bawin Y, Ruttink T, Staelens A, Haegeman A, Stoffelen P, Mwanga JCI, Roldán-Ruiz I, Honnay O, Janssens SB. Phylogenomic analysis clarifies the evolutionary origin of Coffea arabica L. J Syst Evol 2020; DOI: 10.1111/jse.12694.
    CrossrefPubMedGoogle Scholar
  • 4 Ngamsuk S, Huang TC, Hsu JL. Determination of phenolic compounds, procyanidins, and antioxidant activity in processed Coffea arabica L. leaves. Foods Basel Switz 2019; 8: 389
    PubMedGoogle Scholar
  • 5 Belayneh A, Bussa NF. Ethnomedicinal plants used to treat human ailments in the prehistoric place of Harla and Dengego valleys, eastern Ethiopia. J Ethnobiol Ethnomedicine 2014; 10: 18 DOI: 10.1186/1746-4269-10-18.
    CrossrefPubMedGoogle Scholar
  • 6 Ross IA. Medicinal Plants of the World, Volume 3: Chemical Constituents, traditional and modern medicinal Uses. Totowa, NJ: Humana Press; 2005
    Google Scholar
  • 7 European Food Safety Authority (EFSA). Technical report on the notification of infusion from coffee leaves (Coffea arabica L. and/or Coffea canephora Pierre ex A. Froehner) as a traditional food from a third country pursuant to Article 14 of Regulation (EU) 2015/2283. EFSA J 2020; DOI: 10.2903/sp.efsa.2020.EN-1783.
    CrossrefPubMedGoogle Scholar
  • 8 Lall RK, Syed DN, Adhami VM, Khan IM, Srivastava SK. Dietary polyphenols in prevention and treatment of prostate cancer. Int J Mol Sci 2015; 16: 3350-3376
    CrossrefPubMedGoogle Scholar
  • 9 Malar DS, Devi KP. Dietary polyphenols for treatment of Alzheimerʼs disease-future research and development. Curr Pharm Biotechnol 2014; 15: 330-342
    CrossrefPubMedGoogle Scholar
  • 10 Monteiro Â, Colomban S, Azinheira HG, Guerra-Guimarães L, Do Céu Silva M, Navarini L, Resmini M. Dietary antioxidants in coffee leaves: impact of botanical origin and maturity on chlorogenic acids and xanthones. Antioxid Basel Switz 2019; 9: 6
    CrossrefPubMedGoogle Scholar
  • 11 Hicks MB, Hsieh YHP, Bell LN. Tea preparation and its influence on methylxanthine concentration. Food Res Int 1996; 29: 325-330
    CrossrefPubMedGoogle Scholar
  • 12 Farah A. Coffee: Production, Quality and Chemistry. London: Royal Society of Chemistry; 2019
    Google Scholar
  • 13 Mehari B, Redi-Abshiro M, Chandravanshi BS, Atlabachew M, Combrinck S, McCrindle R. simultaneous determination of alkaloids in green coffee beans from Ethiopia: chemometric evaluation of geographical origin. Food Anal Methods 2016; 9: 1627-1637
    CrossrefPubMedGoogle Scholar
  • 14 Bicho NC, Leitão AE, Ramalho JC, Alvarenga NB, Cebola Lidon F. Identification of chemical clusters discriminators of arabica and Robusta green coffee. Int J Food Prop 2013; 16: 895-904
    CrossrefPubMedGoogle Scholar
  • 15 Silvarolla MB, Mazzafera P, de Lima MMA. Caffeine content of Ethiopian Coffea Arabica beans. Genet Mol Biol 2000; 23: 213-215
    CrossrefPubMedGoogle Scholar
  • 16 Dias RCE, Benassi MDT. Discrimination between Arabica and Robusta coffees using hydrosoluble compounds: is the efficiency of the parameters dependent on the roast degree?. Beverages 2015; 1: 127-139
    CrossrefPubMedGoogle Scholar
  • 17 Gramza-Michałowska A. Caffeine in tea Camellia sinensis-content, absorption, benefits and risks of consumption. J Nutr Health Aging 2014; 18: 143-149
    CrossrefPubMedGoogle Scholar
  • 18 Spiller GA. Caffeine. Boca Raton, FL: CRC Press; 2019
    CrossrefGoogle Scholar
  • 19 Marx F, Janssens MJJ, Urfer P, Scherer R. Caffeine and theobromine composition of mate (Ilex paraguariensis) leaves in five plantations of Misiones, Argentina. Plant Foods Hum Nutr 2003; 58: 1-8
    CrossrefPubMedGoogle Scholar
  • 20 Chen XM, Ma Z, Kitts DD. Effects of processing method and age of leaves on phytochemical profiles and bioactivity of coffee leaves. Food Chem 2018; 249: 143-153
    CrossrefPubMedGoogle Scholar
  • 21 Ky CL, Louarn J, Dussert S, Guyot B, Hamon S, Noirot M. Caffeine, trigonelline, chlorogenic acids and sucrose diversity in wild Coffea Arabica L. and C. canephora P. accessions. Food Chem 2001; 75: 223-230
    CrossrefPubMedGoogle Scholar
  • 22 Farah A, Monteiro MC, Calado V, Franca AS, Trugo LC. Correlation between cup quality and chemical attributes of Brazilian coffee. Food Chem 2006; 98: 373-380
    CrossrefPubMedGoogle Scholar
  • 23 Campa C, Mondolot L, Rakotondravao A, Bidel LPR, Gargadennec A, Couturon E, La Fisca P, Rakotomalala JJ, Jay-Allemand C, Davis AP. A survey of mangiferin and hydroxycinnamic acid ester accumulation in coffee (Coffea) leaves: biological implications and uses. Ann Bot 2012; 110: 595-613
    CrossrefPubMedGoogle Scholar
  • 24 Preedy V. Processing and Impact on Antioxidants in Beverages. Amsterdam: Elsevier; 2014
    Google Scholar
  • 25 Vignoli JA, Viegas MC, Bassoli DG, De Toledo Benassi M. Roasting process affects differently the bioactive compounds and the antioxidant activity of Arabica and Robusta coffees. Food Res Int 2014; 61: 279-285
    CrossrefPubMedGoogle Scholar
  • 26 Jeszka-Skowron M, Sentkowska A, Pyrzyńska K, Paz De Peña M. Chlorogenic acids, caffeine content and antioxidant properties of green coffee extracts: influence of green coffee bean preparation. Eur Food Res Technol 2016; 242: 1403-1409
    CrossrefPubMedGoogle Scholar
  • 27 Macheiner L, Schmidt A, Schreiner M, Mayer HK. Green coffee infusion as a source of caffeine and chlorogenic acid. J Food Compos Anal 2019; 84: 103307
    CrossrefPubMedGoogle Scholar
  • 28 Trevisan MTS, de Almeida RF, Soto G, De Melo Virginio Filho E, Ulrich CM, Owen RW. Quantitation by HPLC-UV of mangiferin and isomangiferin in coffee (Coffea Arabica) leaves from Brazil and Costa Rica after solvent extraction and infusion. Food Anal Methods 2016; 9: 2649-2655
    CrossrefPubMedGoogle Scholar
  • 29 De Almeida RF, Trevisan MTS, Thomaziello RA, Breuer A, Klika KD, Ulrich CM, Owen RW. Nutraceutical compounds: echinoids, flavonoids, xanthones and caffeine identified and quantitated in the leaves of Coffea Arabica trees from three regions of Brazil. Food Res Int 2019; 115: 493-503
    CrossrefPubMedGoogle Scholar
  • 30 Dias RCE, Campanha FG, Vieira LGE, Ferreira LP, Pot D, Marraccini P, De Toledo Benassi M. Evaluation of kahweol and cafestol in coffee tissues and roasted coffee by a new high-performance liquid chromatography methodology. J Agric Food Chem 2010; 58: 88-93
    CrossrefPubMedGoogle Scholar
  • 31 Chen X. A review on coffee leaves: Phytochemicals, bioactivities and applications. Crit Rev Food Sci Nutr 2019; 59: 1008-1025
    CrossrefPubMedGoogle Scholar
  • 32 Aneja M, Gianfagna T. Induction and accumulation of caffeine in young, actively growing leaves of cocoa (Theobroma cacao L.) by wounding or infection with Crinipellis perniciosa . Physiol Mol Plant Pathol 2001; 59: 13-16
    CrossrefPubMedGoogle Scholar
  • 33 Metro D, Cernaro V, Santoro D, Papa M, Buemi M, Benvenga S, Manasseri L. Beneficial effects of oral pure caffeine on oxidative stress. J Clin Transl Endocrinol 2017; 10: 22-27
    PubMedGoogle Scholar
  • 34 Mellbye FB, Jeppesen PB, Shokouh P, Laustsen C, Hermansen K, Gregersen S. Cafestol, a bioactive substance in coffee, has antidiabetic properties in KKAy mice. J Nat Prod 2017; 80: 2353-2359
    CrossrefPubMedGoogle Scholar
  • 35 Choi MJ, Park EJ, Oh JH, Min KJ, Yang ES, Kim YH, Lee TJ, Kim SH, Choi YH, Park JW, Kwon TK. Cafestol, a coffee-specific diterpene, induces apoptosis in renal carcinoma Caki cells through down-regulation of anti-apoptotic proteins and Akt phosphorylation. Chem Biol Interact 2011; 190: 102-108
    CrossrefPubMedGoogle Scholar
  • 36 Ashihara H, Monteiro AM, Gillies FM, Crozier A. biosynthesis of caffeine in leaves of coffee. Plant Physiol 1996; 111: 747-753
    CrossrefPubMedGoogle Scholar
  • 37 Salgado PR, Favarin JL, Leandro RA, De Lima Filho OF. Total phenol concentrations in coffee tree leaves during fruit development. Sci Agric 2008; 65: 354-359
    CrossrefPubMedGoogle Scholar
  • 38 European Food Safety Authority. Food supplements. Accessed April 7, 2021 at: https://www.efsa.europa.eu/en/topics/topic/food-supplements
    Google Scholar
  • 39 Frischknecht PM, Ulmer-Dufek J, Baumann TW. Purine alkaloid formation in buds and developing leaflets of Coffea arabica: expression of an optimal defence strategy?. Phytochemistry 1986; 25: 613-616
    CrossrefPubMedGoogle Scholar
  • 40 Ashihara H, Sano H, Crozier A. Caffeine and related purine alkaloids: biosynthesis, catabolism, function and genetic engineering. Phytochemistry 2008; 69: 841-856
    CrossrefPubMedGoogle Scholar
  • 41 McCarthy AA, McCarthy JG. The structure of two N-methyltransferases from the caffeine biosynthetic pathway. Plant Physiol 2007; 144: 879-889
    CrossrefPubMedGoogle Scholar
  • 42 Fujimori N, Ashihara H. Biosynthesis of theobromine and caffeine in developing leaves of Coffea arabica . Phytochemistry 1994; 36: 1359-1361
    CrossrefPubMedGoogle Scholar
  • 43 Zheng X, Ashihara H. Distribution, biosynthesis and function of purine and pyridine alkaloids in Coffea Arabica seedlings. Plant Sci 2004; 166: 807-813
    CrossrefPubMedGoogle Scholar
  • 44 Ashihara H, Crozier A. Biosynthesis and metabolism of caffeine and related purine alkaloids in plants. Adv Bot Res 1999; 30: 117-205
    CrossrefPubMedGoogle Scholar
  • 45 Dewick MD. Medicinal natural Products: A biosynthetic Approach. Hoboken, NJ: John Wiley & Sons; 2009
    CrossrefGoogle Scholar
  • 46 Ashihara H. Metabolism of alkaloids in coffee plants. Braz J Plant Physiol 2006; 18: 1-8
    CrossrefPubMedGoogle Scholar
  • 47 Kong H, Jones PP, Koop A, Zhang L, Duff HJ, Chen SRW. Caffeine induces Ca2+ release by reducing the threshold for luminal Ca2+ activation of the ryanodine receptor. Biochem J 2008; 414: 441-452
    CrossrefPubMedGoogle Scholar
  • 48 Boswell-Smith V, Spina D, Page CP. Phosphodiesterase inhibitors. Br J Pharmacol 2006; 147 (Suppl. 01) 252-257
    CrossrefPubMedGoogle Scholar
  • 49 Azam S, Hadi N, Khan NU, Hadi SM. Antioxidant and prooxidant properties of caffeine, theobromine and xanthine. Med Sci Monit 2003; 9: 325-330
    PubMedGoogle Scholar
  • 50 Devasagayam TPA, Kamat JP, Mohan H, Kesavan PC. Caffeine as an antioxidant: inhibition of lipid peroxidation induced by reactive oxygen species. Biochim Biophys Acta 1996; 1282: 63-70
    CrossrefPubMedGoogle Scholar
  • 51 Dulloo AG, Seydoux J, Girardier L, Chantre P, Vandermander J. Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic activity. Int J Obes 2000; 24: 252-258
    CrossrefPubMedGoogle Scholar
  • 52 Kolahdouzan M, Hamadeh MJ. The neuroprotective effects of caffeine in neurodegenerative diseases. CNS Neurosci Ther 2017; 23: 272-290
    CrossrefPubMedGoogle Scholar
  • 53 Chen JF, Xu K, Petzer JP, Staal R, Xu YH, Beilstein M, Sonsalla PK, Castagnoli K, Castagnoli jr. N, Schwarzschild MA. Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinsonʼs disease. J Neurosci Off J Soc Neurosci 2001; 21: RC143
    CrossrefPubMedGoogle Scholar
  • 54 Arendash GW, Schleif W, Rezai-Zadeh K, Jackson EK, Zacharia LC, Cracchiolo JR, Shippy D, Tan J. Caffeine protects Alzheimerʼs mice against cognitive impairment and reduces brain β-amyloid production. Neuroscience 2006; 142: 941-952
    CrossrefPubMedGoogle Scholar
  • 55 Renner B, Clarke G, Grattan T, Beisel A, Mueller C, Werner U, Kobal G, Brune K. Caffeine accelerates absorption and enhances the analgesic effect of acetaminophen. J Clin Pharmacol 2007; 47: 715-726
    CrossrefPubMedGoogle Scholar
  • 56 Dewar L, Heuberger R. The effect of acute caffeine intake on insulin sensitivity and glycemic control in people with diabetes. Diabetes Metab Syndr Clin Res Rev 2017; 11: 631-635
    CrossrefPubMedGoogle Scholar
  • 57 Richardson T, Thomas P, Ryder J, Kerr D. Influence of caffeine on frequency of hypoglycemia detected by continuous interstitial glucose monitoring system in patients with long-standing type 1 diabetes. Diabetes Care 2005; 28: 1316-1320
    CrossrefPubMedGoogle Scholar
  • 58 Robinson LE, Savani S, Battram DS, McLaren DH, Sathasivam P, Graham TE. Caffeine ingestion before an oral glucose tolerance test impairs blood glucose management in men with type 2 diabetes. J Nutr 2004; 134: 2528-2533
    CrossrefPubMedGoogle Scholar
  • 59 Krebs JD, Parry-Strong A, Weatherall M, Carroll RW, Downie M. A crossover study of the acute effects of espresso coffee on glucose tolerance and insulin sensitivity in people with type 2 diabetes mellitus. Metabolism 2012; 61: 1231-1237
    CrossrefPubMedGoogle Scholar
  • 60 James J. The influence of user status and anxious disposition on the hypertensive effects of caffeine. Int J Psychophysiol 1990; 10: 171-179
    CrossrefPubMedGoogle Scholar
  • 61 Drake C, Roehrs T, Shambroom J, Roth T. Caffeine effects on sleep taken 0, 3, or 6 hours before going to bed. J Clin Sleep Med 2013; 9: 1195-1200
    CrossrefPubMedGoogle Scholar
  • 62 Bonnet M, Tancer M, Uhde T, Yeragani VK. Effects of caffeine on heart rate and QT variability during sleep. Depress Anxiety 2005; 22: 150-155
    CrossrefPubMedGoogle Scholar
  • 63 Caprioli G, Cortese M, Maggi F, Minnetti C, Odello L, Sagratini G, Vittori S. Quantification of caffeine, trigonelline and nicotinic acid in espresso coffee: The influence of espresso machines and coffee cultivars. Int J Food Sci Nutr 2014; 65: 465-469
    CrossrefPubMedGoogle Scholar
  • 64 Zhou J, Zhou S, Zeng S. Experimental diabetes treated with trigonelline: Effect on β cell and pancreatic oxidative parameters. Fundam Clin Pharmacol 2013; 27: 279-287
    CrossrefPubMedGoogle Scholar
  • 65 Hong BN, Yi TH, Kim SY, Kang TH. High-dosage pyridoxine-induced auditory neuropathy and protection with coffee in mice. Biol Pharm Bull 2009; 32: 597-603
    CrossrefPubMedGoogle Scholar
  • 66 Mirzaie M, Khalili M, Kiasalari Z, Roghani M. Neuroprotective and Antiapoptotic potential of trigonelline in a striatal 6-hydroxydopamine rat model of Parkinsonʼs disease. Neurophysiology 2016; 48: 176-183
    CrossrefPubMedGoogle Scholar
  • 67 Tice R. Trigonelline: review of toxicological literature. 1997 Accessed June 10, 2020 at: https://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/trigonelline_508.pdf
    Google Scholar
  • 68 Carmona-Hernandez JC, Taborda-Ocampo G, Valdez JC, Bolling BW, Gonzalez-Correa CH. Polyphenol extracts from three Colombian passifloras (passion fruits) prevent inflammation-induced barrier dysfunction of caco-2 cells. Molecules 2019; 24: 4614
    CrossrefPubMedGoogle Scholar
  • 69 Boudet AM. Evolution and current status of research in phenolic compounds. Phytochemistry 2007; 68: 2722-2735
    CrossrefPubMedGoogle Scholar
  • 70 Eyles A, Bonello P, Ganley R, Mohammed C. Induced resistance to pests and pathogens in trees. New Phytol 2010; 185: 893-908
    CrossrefPubMedGoogle Scholar
  • 71 Orians CM. The effects of hybridization in plants on secondary chemistry: Implications for the ecology and evolution of plant-herbivore interactions. Am J Bot 2000; 87: 1749-1756
    CrossrefPubMedGoogle Scholar
  • 72 Clifford MN, Jaganath IB, Ludwig IA, Crozier A. Chlorogenic acids and the acyl-quinic acids: Discovery, biosynthesis, bioavailability and bioactivity. Nat Prod Rep 2017; 34: 1391-1421
    CrossrefPubMedGoogle Scholar
  • 73 Rodríguez-Gómez R, Vanheuverzwjin J, Souard F, Delporte C, Stevigny C, Stoffelen P, De Braekeleer K, Kauffmann JM. Determination of three main chlorogenic acids in water extracts of coffee leaves by liquid chromatography coupled to an electrochemical detector. Antioxid Basel Switz 2018; 7: 143
    CrossrefPubMedGoogle Scholar
  • 74 Hanson KR. Chlorogenic acid biosynthesis. Chemical synthesis and properties of the mono-o-cinnamoylquinic acids*. Biochemistry 1965; 4: 2719-2731
    CrossrefPubMedGoogle Scholar
  • 75 Niggeweg R, Michael AJ, Martin C. Engineering plants with increased levels of the antioxidant chlorogenic acid. Nat Biotechnol 2004; 22: 746-754
    CrossrefPubMedGoogle Scholar
  • 76 Lukitasari M, Nugroho DA, Widodo N. Chlorogenic acid: The conceivable chemosensitizer leading to cancer growth suppression. J Evid-Based Integr Med 2018; 23: 1-6
    CrossrefPubMedGoogle Scholar
  • 77 Lu Z, Xu S. ERK1/2 MAP kinases in cell survival and apoptosis. IUBMB Life 2006; 58: 621-631
    CrossrefPubMedGoogle Scholar
  • 78 Yan Y, Li J, Han J, Hou N, Song Y, Dong L. Chlorogenic acid enhances the effects of 5-fluorouracil in human hepatocellular carcinoma cells through the inhibition of extracellular signal-regulated kinases. Anticancer Drugs 2015; 26: 540-546
    CrossrefPubMedGoogle Scholar
  • 79 Masri J, Bernath A, Martin J, Jo OD, Vartanian R, Funk A, Gera J. mTORC2 Activity is elevated in gliomas and promotes growth and cell motility via overexpression of Rictor. Cancer Res 2007; 67: 11712-11720
    CrossrefPubMedGoogle Scholar
  • 80 Chantaravisoot N, Wongkongkathep P, Loo JA, Mischel PS, Tamanoi F. Significance of filamin A in mTORC2 function in glioblastoma. Mol Cancer 2015; 14: 127 DOI: 10.1186/s12943-015-0396-z.
    CrossrefPubMedGoogle Scholar
  • 81 Jacinto E, Loewith R, Schmidt A, Lin S, Ruegg MA, Hall A, Hall MN. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 2004; 6: 1122-1128
    CrossrefPubMedGoogle Scholar
  • 82 Tan S, Dong X, Liu D, Hao S, He F. Anti-tumor activity of chlorogenic acid by regulating the mTORC2 signaling pathway and disrupting F-actin organization. Int J Clin Exp Med 2019; 12: 4818-4828
    PubMedGoogle Scholar
  • 83 Cho AS, Jeon SM, Kim MJ, Yeo J, Seo KI, Choi MS, Lee MK. Chlorogenic acid exhibits anti-obesity property and improves lipid metabolism in high-fat diet-induced-obese mice. Food Chem Toxicol 2010; 48: 937-943
    CrossrefPubMedGoogle Scholar
  • 84 Naveed M, Hejazi V, Abbas M, Kamboh AA, Khan GJ, Shumzaid M, Ahmad F, Babazadeh D, FangFang X, Modarresi-Ghazani F, WenHua L, XiaoHui Z. Chlorogenic acid (CGA): A pharmacological review and call for further research. Biomed Pharmacother Biomedecine Pharmacother 2018; 97: 67-74
    CrossrefPubMedGoogle Scholar
  • 85 Huang K, Liang X, Zhong Y, He W, Wang Z. 5-Caffeoylquinic acid decreases diet-induced obesity in rats by modulating PPARα and LXRα transcription. J Sci Food Agric 2015; 95: 1903-1910
    CrossrefPubMedGoogle Scholar
  • 86 Suzuki A, Kagawa D, Ochiai R, Tokimitsu I, Saito I. Green coffee bean extract and its metabolites have a hypotensive effect in spontaneously hypertensive rats. Hypertens Res Off J Jpn Soc Hypertens 2002; 25: 99-107
    CrossrefPubMedGoogle Scholar
  • 87 Tom ENL, Girard-Thernier C, Demougeot C. The Janus face of chlorogenic acid on vascular reactivity: a study on rat isolated vessels. Phytomedicine Int J Phytother Phytopharm 2016; 23: 1037-1042
    PubMedGoogle Scholar
  • 88 Chaube S, Swinyard CA. Teratological and toxicological studies of alkaloidal and phenolic compounds from Solanum Tuberosum L. Toxicol Appl Pharmacol 1976; 36: 227-237
    CrossrefPubMedGoogle Scholar
  • 89 Hagiwara A, Hirose M, Takahashi S, Ogawa K, Shirai T, Ito N. Forestomach and kidney carcinogenicity of caffeic acid in F344 rats and C57BL/6N x C3H/HeN F1 mice. Cancer Res 1991; 51: 5655-5660
    PubMedGoogle Scholar
  • 90 Tice R. Chlorogenic acid and caffeic acid: Review of toxicological literature. 1998 Accessed June 13, 2020 at: https://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/chlorogenicacid_508.pdf
    Google Scholar
  • 91 Yoshiyuki K, Hiromichi O, Takuo O, Tsutomu H, Isao A, Shigeru A. Studies on the activities of tannins and related compounds from medicinal plants and drugs. VI. Inhibitory Effects of caffeoylquinic acids on histamine release from rat peritoneal mast cells. Chem Pharm Bull (Tokyo) 1985; 33: 690-696
    CrossrefPubMedGoogle Scholar
  • 92 Cardona ML, Fernández I, Pedro JR, Serrano A. Xanthones from Hypericum reflexum . Phytochemistry 1990; 29: 3003-3006
    CrossrefPubMedGoogle Scholar
  • 93 Schmidt W, Beerhues L. Alternative pathways of xanthone biosynthesis in cell cultures of Hypericum androsaemum L. FEBS Lett 1997; 420: 143-146
    CrossrefPubMedGoogle Scholar
  • 94 Wezeman T, Bräse S, Masters KS. Xanthone dimers: a compound family which is both common and privileged. Nat Prod Rep 2015; 32: 6-28
    CrossrefPubMedGoogle Scholar
  • 95 Yang C, Ma L, Wei Z, Han F, Gao J. Advances in isolation and synthesis of xanthone derivatives. Chinese Herbal Medicines 2012; 4: 87-102
    PubMedGoogle Scholar
  • 96 Stoffelen P, Noirot M, Couturon E, Bontems S, De Block P, Anthony F. Coffea anthonyi, a new self-compatible Central African coffee species, closely related to an ancestor of Coffea Arabica . Taxon 2009; 58: 133-140
    CrossrefPubMedGoogle Scholar
  • 97 Prabhu S, Jainu M, Sabitha KE, Devi CSS. Cardioprotective effect of mangiferin on isoproterenol induced myocardial infarction in rats. Indian J Exp Biol 2006; 44: 209-215
    PubMedGoogle Scholar
  • 98 Ghosal S, Rao G, Saravanan V, Misra N, Rana D. A plausible chemical mechanism of the bioactivities of mangiferin. Indian J Chem Sect B 1996; 35: 561-566
    PubMedGoogle Scholar
  • 99 Jiang DJ, Tan GS, Ye F, Du YH, Xu KP, Li YJ. Protective effects of xanthones against myocardial ischemia-reperfusion injury in rats. Acta Pharmacol Sin 2003; 24: 175-180
    PubMedGoogle Scholar
  • 100 Kavitha M, Nataraj J, Essa MM, Memon MA, Manivasagam T. Mangiferin attenuates MPTP induced dopaminergic neurodegeneration and improves motor impairment, redox balance and Bcl-2/Bax expression in experimental Parkinsonʼs disease mice. Chem Biol Interact 2013; 206: 239-247
    CrossrefPubMedGoogle Scholar
  • 101 Han J, Yi J, Liang F, Jiang B, Xiao Y, Gao S, Yang N, Hu H, Xie WF, Chen W. X-3, a mangiferin derivative, stimulates AMP-activated protein kinase and reduces hyperglycemia and obesity in db/db mice. Mol Cell Endocrinol 2015; 405: 63-73
    CrossrefPubMedGoogle Scholar
  • 102 Pal PB, Sinha K, Sil PC. Mangiferin attenuates diabetic nephropathy by inhibiting oxidative stress mediated signaling cascade, TNFα related and mitochondrial dependent apoptotic pathways in streptozotocin-induced diabetic rats. PloS One 2014; 9: e115364
    CrossrefPubMedGoogle Scholar
  • 103 Jeong JJ, Jang SE, Hyam SR, Han MJ, Kim DH. Mangiferin ameliorates colitis by inhibiting IRAK1 phosphorylation in NF-κB and MAPK pathways. Eur J Pharmacol 2014; 740: 652-661
    CrossrefPubMedGoogle Scholar
  • 104 Imran M, Arshad MS, Butt MS, Kwon JH, Arshad MU, Sultan MT. Mangiferin: a natural miracle bioactive compound against lifestyle related disorders. Lipids Health Dis 2017; 16: 84
    CrossrefPubMedGoogle Scholar
  • 105 Kanokporn C, Patamaporn S, Thanaporn P, Kanjana K. Acute and subchronic oral toxicity of xanthones extracted from the pericarp of Garcinia mangostana Linn.in rat. 2015 Accessed September 11, 2020 at: https://www.asianarchpath.com/view/57
    Google Scholar
  • 106 Khaw KY, Chong CW, Murugaiyah V. LC-QTOF-MS analysis of xanthone content in different parts of Garcinia mangostana and its influence on cholinesterase inhibition. J Enzyme Inhib Med Chem 2020; 35: 1433-1441
    CrossrefPubMedGoogle Scholar
  • 107 Speer K, Kölling-Speer I. The lipid fraction of the coffee bean. Braz J Plant Physiol 2006; 18: 201-216
    CrossrefPubMedGoogle Scholar
  • 108 Singh B, Sharma RA. Plant terpenes: defense responses, phylogenetic analysis, regulation and clinical applications. 3 Biotech 2015; 5: 129-151
    CrossrefPubMedGoogle Scholar
  • 109 Singsaas EL. Terpenes and the thermotolerance of photosynthesis. New Phytol 2000; 146: 1-2
    CrossrefPubMedGoogle Scholar
  • 110 Pot D, Ferreira L, Dias RCE, Noel D, Guyot B, Ramos J, Perthuis B, Sandrin P, Benassi MT, Marraccini P, Perreira LFP, Leroy T, Vieira LGE. Genetic and molecular determinism of diterpenes metabolism in Coffea spp. 14–19.09.2008. Accessed June 12, 2020 at: https://www.researchgate.net/publication/311518539_Genetic_and_molecular_determinism_of_diterpenes_metabolism_in_Coffea_spp/link/596f4cf8aca27227101360db/download
    Google Scholar
  • 111 Ferreira Lucia P, Dias Rafael C, Noel D, Bernard G, Juliana R, Perthuis B, Sandrin-Garcia P, Benassi MT, Marraccini P, Pereira LF, Leroy T, Vieira LG, Pot D. Determinismo génetico e molecular do metabolismo de diterpenos em Coffea spp. 02. 05.06.2009 Accessed June 12, 2020 at: https://agritrop.cirad.fr/551318/
    Google Scholar
  • 112 Souard F, Delporte C, Stoffelen P, Thévenot EA, Noret N, Dauvergne B, Kauffmann JM, Van Antwerpen P, Stévigny C. Metabolomics fingerprint of coffee species determined by untargeted-profiling study using LC-HRMS. Food Chem 2018; 245: 603-612
    CrossrefPubMedGoogle Scholar
  • 113 Oh JH, Lee JT, Yang ES, Chang JS, Lee DS, Kim SH, Choi YH, Park JW, Kwon TK. The coffee diterpene kahweol induces apoptosis in human leukemia U937 cells through down-regulation of Akt phosphorylation and activation of JNK. Apoptosis Int J Program Cell Death 2009; 14: 1378-1386
    CrossrefPubMedGoogle Scholar
  • 114 Kim HG, Hwang YP, Jeong HG. Kahweol blocks STAT3 phosphorylation and induces apoptosis in human lung adenocarcinoma A549 cells. Toxicol Lett 2009; 187: 28-34
    CrossrefPubMedGoogle Scholar
  • 115 Ekert PG, Silke J, Vaux DL. Caspase inhibitors. Cell Death Differ 1999; 6: 1081-1086
    CrossrefPubMedGoogle Scholar
  • 116 Moeenfard M, Cortez A, Machado V, Costa R, Luís C, Coelho P, Soares R, Alves A, Borges N, Santos A. Anti-angiogenic properties of cafestol and kahweol palmitate diterpene esters. J Cell Biochem 2016; 117: 2748-2756
    CrossrefPubMedGoogle Scholar
  • 117 Wattenberg LW, Lam LK. Protective effects of coffee constituents on carcinogenesis in experimental animals. Banbury Rep 1984; 17: 137-145
    PubMedGoogle Scholar
  • 118 Cavin C, Holzhäuser D, Constable A, Huggett AC, Schilter B. The coffee-specific diterpenes cafestol and kahweol protect against aflatoxin B1-induced genotoxicity through a dual mechanism. Carcinogenesis 1998; 19: 1369-1375
    CrossrefPubMedGoogle Scholar
  • 119 Baek JH, Kim NJ, Song JK, Chun KH. Kahweol inhibits lipid accumulation and induces Glucose-uptake through activation of AMP-activated protein kinase (AMPK). BMB Rep 2017; 50: 566-571
    CrossrefPubMedGoogle Scholar
  • 120 Weusten-Van der Wouw MP, Katan MB, Viani R, Huggett AC, Liardon R, Lund-Larsen PG, Thelle DS, Ahola I, Aro A, Meyboom S, Beynen AC. Identity of the cholesterol-raising factor from boiled coffee and its effects on liver function enzymes. J Lipid Res 1994; 35: 721-733
    CrossrefPubMedGoogle Scholar
  • 121 Hutchings A, Terblanche SE. Observations on the use of some known and suspected toxic Liliiflorae in Zulu and Xhosa medicine. South Afr Med J Suid-Afr Tydskr Vir Geneeskd 1989; 75: 62-69
    PubMedGoogle Scholar
  • 122 Santi R, Luciani S. Atractyloside: Chemistry, Biochemistry and Toxicology. Padova: Piccin Editore; 1978
    Google Scholar
  • 123 Lang R, Fromme T, Beusch A, Wahl A, Klingenspor M, Hofmann T. 2-O-β-D-Glucopyranosyl-carboxyatractyligenin from Coffea L. inhibits adenine nucleotide translocase in isolated mitochondria but is quantitatively degraded during coffee roasting. Phytochemistry 2013; 93: 124-135
    CrossrefPubMedGoogle Scholar
  • 124 Obatomi DK, Bach PH. Biochemistry and Toxicology of the Diterpenoid Glycoside Atractyloside. Food Chem Toxicol 1998; 36: 335-346
    CrossrefPubMedGoogle Scholar
  • 125 Chen LY, Hu A, Chang CJ. The degradation mechanism of toxic atractyloside in herbal medicines by decoction. Molecules 2013; 18: 2018-2028
    CrossrefPubMedGoogle Scholar
  • 126 Buscemi S, Rosselli S, Bruno M, Vivona N, Piozzi F. Photoinduced functionalization of diterpenes: transformation of the C-20 methyl of atractyligenin into a carbomethoxymethyl or carbamoylmethyl group. J Photochem Photobiol Chem 2003; 155: 145-149
    CrossrefPubMedGoogle Scholar
  • 127 Segheto L, Santos BCS, Werneck AFL, Pinto Vilela FM, Vieira de Sousa O, Pereira Rodarte M. Antioxidant extracts of coffee leaves and its active ingredient 5-caffeoylquinic acid reduce chemically-induced inflammation in mice. Ind Crops Prod 2018; 126: 48-57
    CrossrefPubMedGoogle Scholar
  • 128 Galam NZ, Gambo IM, Rabiu A, Chinelo N, Dami S. Anti-inflammatory effect of aqueous extract of coffee plant leaves (Coffea canephora) in rats. J Nat Sci Res 2013; 3: 191-193
    PubMedGoogle Scholar
  • 129 Chiang HM, Lin TJ, Chiu CY, Chang CW, Hsu KC, Fan PC, Wen KC. Coffea arabica extract and its constituents prevent photoaging by suppressing MMPs expression and MAP kinase pathway. Food Chem Toxicol 2011; 49: 309-318
    CrossrefPubMedGoogle Scholar