Chlorogenic acid

Chlorogenic acid
Names
IUPAC name
(1S,3R,4R,5R)-3-{[(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy}-1,4,5-trihydroxycyclohexanecarboxylic acid
Other names
3-(3,4-Dihydroxycinnamoyl)quinate
3-(3,4-Dihydroxycinnamoyl)quinic acid
3-Caffeoylquinate
3-Caffeoylquinic acid
3-CQA
3-O-Caffeoylquinic acid
Chlorogenate
Chlorogenic acid
Heriguard
3-trans-Caffeoylquinic acid
Identifiers
327-97-9 Yes
ChEBI CHEBI:16112 
ChEMBL ChEMBL284616 
ChemSpider 1405788 Yes
Jmol-3D images Image
PubChem 1794427
RTECS number GU8480000
Properties
Molecular formula
 C16H18O9
Molar mass 354.31 g·mol−1
Density 1.28 g/cm3
Melting point 207 °C (405 °F; 480 K)
Hazards
MSDS External MSDS
R-phrases -
S-phrases S24 S25 S28 S37 S45
NFPA 704
Flammability code 0: Will not burn. E.g., water Health code 1: Exposure would cause irritation but only minor residual injury. E.g., turpentine Reactivity (yellow): no hazard code Special hazards (white): no codeNFPA 704 four-colored diamond
0
1
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
  verify (what is: Yes/?)
Infobox references

Chlorogenic acid (CGA) is a natural chemical compound which is the ester of caffeic acid and (−)-quinic acid. It is an important biosynthetic intermediate.[1] Chlorogenic acid is an important intermediate in lignin biosynthesis. This compound, known as an antioxidant, may also slow the release of glucose into the bloodstream after a meal.[2]

The term chlorogenic acids can also refer to a related family of esters of hydroxycinnamic acids (caffeic acid, ferulic acid and p-coumaric acid) with quinic acid.[3]

Despite the "chloro" of the name, chlorogenic acids contain no chlorine. Instead, the name comes from the Greek χλωρός (light green) and -γένος (a suffix meaning "giving rise to"), because of the green color produced when chlorogenic acids are oxidized.

Chemical properties

Structurally, chlorogenic acid is the ester formed between caffeic acid and L-quinic acid.[4]

Isomers of chlorogenic acid include 4-O-caffeoylquinic acid (cryptochlorogenic acid or 4-CQA), 5-O-caffeoylquinic acid (neochlorogenic acid or 5-CQA). The epimer at position 1 has not yet been reported.[3]

Isomers containing two caffeic acid molecules are called isochlorogenic acid. It can be found in coffee.[5] There are several isomers such as 3,4-dicaffeoylquinic acid and 3,5-dicaffeoylquinic acid[6] Cynarine (1,5-dicaffeoylquinic acid) is an other isomer with two caffeic acid molecules..

Chlorogenic acid UV vis spectrum with a maximum of absorbance at 325 nm

Chlorogenic acid is freely soluble in ethanol and acetone.

Natural occurrences

Isomers of chlorogenic acid are found in potatoes.[7]

Chlorogenic acid can be found in bamboo Phyllostachys edulis.[8] as well as in many other plants.[9] It is one of the major phenolic compounds identified in peach[10] and in prunes.[11] It also is one of the phenols found in green coffee bean extract.[12]

Chlorogenic acid, its 3-O-glucoside, 3-O-galactoside and 3-O-arabinoside can be found in the shoots of Calluna vulgaris (heather).[13]

Food additive

Chlorogenic acid is marketed under the tradename Svetol, a standardized green coffee extract, as a food additive used in coffee products, chewing gum, and mints, and also as a stand-alone product. Dried sunflower leaves collected immediately after opening are processed into 98.38% chlorogenic acid extract and marketed in Bulgaria under the name of "Yamiagra"or "Yummyiagra".

Biological effects

Review articles in 2014[14] and 2011[15] report modest, but significant, blood pressure lowering effects from chlorogenic acid administration. No studies have appeared to assess possible interactions with antihypertensive drugs or advisability in patients being treated for low blood pressure.

Chlorogenic acid is reported to be a chemical sensitizer responsible for human respiratory allergy to certain types of plant materials.[16]

It could be involved in the laxative effect observed in prunes.[11]

One study showed that chlorogenic acid may have weak psychostimulant effects in mice.[17]

Another study showed chlorogenic acid to have a protective effect in neuroinflammatory conditions on dopaminergic neurons.[18]

Cancer prevention

Chlorogenic acid (CGA), at a level equivalent to the CGA in three cups of coffee a day for humans, added to the diet of mice in a mouse model for colon cancer, reduced colon cancer incidence from 56% to 18%.[19] To cause cancer in the model diet, a standard diet plus 0.2% deoxycholate (DOC) was used, to raise the level of DOC in the colons of the mice to the level of DOC in colons of humans on a high fat Western diet. DOC is a natural endogenous component of the digestive system in humans and is considerably increased in the human colon when a high fat diet is eaten.[20]

In mice on diet plus DOC, as in humans progressing to colon cancer, 8-OH-dG was substantially increased, DNA repair protein ERCC1 was strongly decreased, autophagy protein beclin-1 was strongly increased and, in the stem cell region at the base of crypts there was substantial nuclear localization of beta-catenin as well as considerably increased cytoplasmic beta-catenin.[20] However, in mice with both CGA and DOC added to their diet (with reduced frequency of cancer), mouse tissue showed almost complete amelioration of the aberrancies in ERCC1, beclin-1 and beta-catenin (8-OH-dG was not measured), suggesting that chlorogenic acid is protective at the molecular level against colon cancer.

As reviewed by Scott et al.,[21] the DNA damage 8-OH-dG is carcinogenic. In a rat model leading to tongue cancer, in which the oxygen radical forming carcinogen 4-NQO was added to drinking water, 8-OH-dG increased with carcinogen treatment. However, also adding chlorogenic acid to the rat diet brought the 8-OH-dG level back to normal.[22] In another report, feeding of chlorogenic acid starting one week before exposure to 4-NQO significantly reduced the incidences of tongue neoplasms (squamous cell papilloma and carcinoma) and preneoplastic lesions (hyperplasia and dysplasia).[23]

DNA damages are a major primary cause of cancer.[24] If a compound increases DNA repair, this would indicate a likely protective role against cancer. In a study of 19 antioxidants applied to cells in vitro, only chlorogenic acid and three metabolic by-products of chlorogenic acid [ m-coumaric acid, 3-(m-hydroxyphenyl) propionic acid and caffeic acid] increased the protein expression of two tested DNA repair enzymes, PARP and PMS2.[25]

References

  1. ↑ Boerjan, Wout; Ralph, John; Baucher, Marie (2003). "Lignin biosynthesis". Annu. Rev. Plant Biol. 54: 519–46. doi:10.1146/annurev.arplant.54.031902.134938. PMID 14503002.
  2. ↑ Johnston, K. L.; Clifford, M. N.; Morgan, L. M. (October 2003). "Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans: glycemic effects of chlorogenic acid and caffeine". Am. J. Clin. Nutrit. 78 (4): 728–733. PMID 14522730.
  3. ↑ 3.0 3.1 Clifford, M. N.; Johnston, K. L.; Knigh, S.; Kuhnert, N. (2003). "Hierarchical Scheme for LC-MSn Identification of Chlorogenic Acids". Journal of Agricultural and Food Chemistry 51 (10): 2900–2911. doi:10.1021/jf026187q. PMID 12720369.
  4. ↑ Clifford, M. N. (1999). "Chlorogenic acids and other cinnamates – nature, occurrence and dietary burden". J. Sci. Food Agr. 79 (3): 362–372. doi:10.1002/(SICI)1097-0010(19990301)79:3<362::AID-JSFA256>3.0.CO;2-D.
  5. ↑ Isochlorogenic Acid. Isolation from Coffee and Structure Studies. H. M. Barnes, J. R. Feldman and W. V. White, J. Am. Chem. Soc., 1950, volume 72, issue 9, pages 4178–4182, doi:10.1021/ja01165a095
  6. ↑ Corse, J.; Lundin, R. E.; Waiss, A. C. (May 1965). "Identification of several components of isochlorogenic acid". Phytochem. 4 (3): 527–529. doi:10.1016/S0031-9422(00)86209-3.
  7. ↑ Mendel Friedman (1997). "Chemistry, Biochemistry, and Dietary Role of Potato Polyphenols. A Review". Journal of Agricultural and Food Chemistry 45 (5): pp 1523–1540. doi:10.1021/jf960900s.
  8. ↑ Kweon, Mee-Hyang; Hwang, Han-Joon; Sung, Ha-Chin (2001). "Identification and Antioxidant Activity of Novel Chlorogenic Acid Derivatives from Bamboo (Phyllostachys edulis)". Journal of Agricultural and Food Chemistry 49 (20): 4646–46552. doi:10.1021/jf010514x.
  9. ↑ Clifford, M. N. (2003). "14. The analysis and characterization of chlorogenic acids and other cinnamates". In C. Santos-Buelga & G. Williamson (Eds.). Methods in Polyphenol Analysis. Cambridge: Royal Society of Chemistry. pp. 314–337. ISBN 0-85404-580-5.
  10. ↑ Cheng, G. W.; Crisosto, C. H. (September 1995). "Browning Potential, Phenolic Composition, and Polyphenoloxidase Activity of Buffer Extracts of Peach and Nectarine Skin Tissue" (PDF). J. Amer. Soc. Hort. Sci. 120 (5): 835–838.
  11. ↑ 11.0 11.1 Stacewicz-Sapuntzakis, M; Bowen, PE; Hussain, EA; Damayanti-Wood, BI; Farnsworth, NR (2001). "Chemical composition and potential health effects of prunes: a functional food?". Crit. Rev. Food Sci. Nutr. 41 (4): 251–86. doi:10.1080/20014091091814. PMID 11401245.
  12. ↑ Igho Onakpoya, Rohini Terry, and Edzard Ernst (2010). "The Use of Green Coffee Extract as a Weight Loss Supplement: A Systematic Review and Meta-Analysis of Randomised Clinical Trials". Complementary Medicine: 1.
  13. ↑ Jalal, Mahbubul A.F.; Read, David J.; Haslam, E. (1982). "Phenolic composition and its seasonal variation in Calluna vulgaris". Phytochem. 21 (6): 1397–1401. doi:10.1016/0031-9422(82)80150-7.
  14. ↑ Onakpoya, I J; Spencer, E A; Thompson, M J; Heneghan, C J (19 June 2014). "The effect of chlorogenic acid on blood pressure: a systematic review and meta-analysis of randomized clinical trials". Journal of Human Hypertension 29: 77–81. doi:10.1038/jhh.2014.46. PMID 24943289. Retrieved 5 October 2014.
  15. ↑ Zhao, Y.; Wang, J.; Ballevre, O.; Luo, H.; Zhang, W. (2011). "Antihypertensive effects and mechanisms of chlorogenic acids". Hypertension Research = Hypertens Res 35 (4): 370–4. doi:10.1038/hr.2011.195. PMID 22072103.
  16. ↑ Freedman, Samuel O.; Shulman, Robert; Krupey, John; Sehon, A.H. (1964). "Antigenic properties of chlorogenic acid". J. Allergy 35 (2): 97–107. doi:10.1016/0021-8707(64)90023-1.
  17. ↑ "Effects of chlorogenic acid and its metabolites on spontaneous locomotor activity in mice.". Biosci Biotechnol Biochem 70 (10): 2560–3. 2006. doi:10.1271/bbb.60243. PMID 17031047.
  18. ↑ "Chlorogenic acid inhibits LPS-induced microglial activation and improves survival of dopaminergic neurons.". Brain Res Bull 88 (5): 487–94. 2012. doi:10.1016/j.brainresbull.2012.04.010. PMID 22580132.
  19. ↑ Bernstein C, Holubec H, Bhattacharyya AK, Nguyen H, Payne CM, Zaitlin B et al. (2011). "Carcinogenicity of deoxycholate, a secondary bile acid". Arch. Toxicol. 85 (8): 863–71. doi:10.1007/s00204-011-0648-7. PMC 3149672. PMID 21267546.
  20. ↑ 20.0 20.1 Prasad AR, Prasad S, Nguyen H, Facista A, Lewis C, Zaitlin B et al. (2014). "Novel diet-related mouse model of colon cancer parallels human colon cancer". World J Gastrointest Oncol 6 (7): 225–43. doi:10.4251/wjgo.v6.i7.225. PMC 4092339. PMID 25024814.
  21. ↑ Scott TL, Rangaswamy S, Wicker CA, Izumi T (2014). "Repair of oxidative DNA damage and cancer: recent progress in DNA base excision repair". Antioxid. Redox Signal. 20 (4): 708–26. doi:10.1089/ars.2013.5529. PMC 3960848. PMID 23901781.
  22. ↑ Kasai H, Fukada S, Yamaizumi Z, Sugie S, Mori H (2000). "Action of chlorogenic acid in vegetables and fruits as an inhibitor of 8-hydroxydeoxyguanosine formation in vitro and in a rat carcinogenesis model". Food Chem. Toxicol. 38 (5): 467–71. doi:10.1016/s0278-6915(00)00014-4. PMID 10762733.
  23. ↑ Tanaka T, Kojima T, Kawamori T, Wang A, Suzui M, Okamoto K et al. (1993). "Inhibition of 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis by the naturally occurring plant phenolics caffeic, ellagic, chlorogenic and ferulic acids". Carcinogenesis 14 (7): 1321–5. doi:10.1093/carcin/14.7.1321. PMID 8330344.
  24. ↑ Bernstein C, Prasad AR, Nfonsam V, Bernstein H. (2013). DNA Damage, DNA Repair and Cancer, New Research Directions in DNA Repair, Prof. Clark Chen (Ed.), ISBN 978-953-51-1114-6, InTech, http://www.intechopen.com/books/new-research-directions-in-dna-repair/dna-damage-dna-repair-and-cancer
  25. ↑ Bernstein H, Crowley-Skillicorn C, Bernstein C, Payne CM, Dvorak K, Garewal H (2007). Dietary compounds that enhance DNA repair and their relevance to cancer and aging. In “New Research on DNA Repair” (Breehn R. Landseer, editor), Chapter IV, 99-113. ISBN 978-1-60021-385-4 https://www.novapublishers.com/catalog/product_info.php?products_id=43814