Rutin

Rutin

Names
IUPAC name 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-{[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-({[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy}methyl)oxan-2-yl]oxy}-4H-chromen-4-one
Preferred IUPAC name 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranosyloxy]-4H-chromen-4-one
Other names Rutoside Phytomelin Sophorin Birutan Eldrin Birutan Forte Rutin trihydrate Globularicitrin Violaquercitrin
Identifiers
CAS Number	153-18-4
ChemSpider	4444362
DrugBank	DB01698
Jmol 3D image	Interactive graph
KEGG	C05625
PubChem	5280805
RTECS number	VM2975000
UNII	5G06TVY3R7
InChI InChI=1S/C27H30O16/c1-8-17(32)20(35)22(37)26(40-8)39-7-15-18(33)21(36)23(38)27(42-15)43-25-19(34)16-13(31)5-10(28)6-14(16)41-24(25)9-2-3-11(29)12(30)4-9/h2-6,8,15,17-18,20-23,26-33,35-38H,7H2,1H3/t8-,15+,17-,18+,20+,21-,22+,23+,26+,27-/m0/s1
SMILES CC1C(C(C(C(O1)OCC2C(C(C(C(O2)OC3=C(OC4=CC(=CC(=C4C3=O)O)O)C5=CC(=C(C=C5)O)O)O)O)O)O)O)O
Properties
Chemical formula	C27H30O16
Molar mass	610.52 g·mol^−1
Appearance	Solid
Melting point	242 °C (468 °F; 515 K)
Solubility in water	12.5 mg/100 mL[1] 13 mg/100mL[2]
Pharmacology
ATC code	C05CA01 (WHO)
Hazards
NFPA 704	0 2 0
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Rutin, also called rutoside, quercetin-3-O-rutinoside and sophorin, is the glycoside between the flavonol quercetin and the disaccharide rutinose (α-L-rhamnopyranosyl-(1→6))-β-D-glucopyranose). In the fava d'anta tree, the synthesis is done via a rutin synthase activity.^[3]

Occurrences

Rutin is one of the phenolic compounds found in the invasive plant species Carpobrotus edulis and contributes to the antibacterial^[4] properties of the plant.

Its name comes from the name of Ruta graveolens, a plant that also contains rutin.

In food

Rutin is a citrus flavonoid glycoside found in many plants including buckwheat,^[5] the leaves and petioles of Rheum species, and asparagus. Tartary buckwheat seeds have been found to contain more rutin (about 0.8-1.7% dry weight) than common buckwheat seeds (0.01% dry weight).^[5] Rutin is also found in the fruit of the fava d'anta tree (from Brazil), fruits and flowers of the pagoda tree, fruits and fruit rinds (especially the citrus fruits orange, grapefruit, lemon, and lime) and apple; berries such as mulberry, ash tree fruits, aronia berries and cranberries.^[6] Rutin is one of the primary flavonols found in 'clingstone' peaches.^[7]

It is also found in green tea infusions.^[8]

Chemical relatives

Rutin (quercetin rutinoside), like quercitrin, is a glycoside of the flavonoid quercetin. As such, the chemical structures of both are very similar, with the difference existing in the hydroxyl functional group. Both quercetin and rutin are used in many countries as medications for blood vessel protection, and are ingredients of numerous multivitamin preparations and herbal remedies.

Role as ligand

It can combine with cations, supplying nutrients from the soil to the cells in plants. In humans, it attaches to the iron ion Fe²⁺, preventing it from binding to hydrogen peroxide, which would otherwise create a highly reactive free radical that may damage cells. It is also an antioxidant.

Furthermore, it has been shown to inhibit in vitro the vascular endothelial growth factor^[9] in subtoxic concentrations, so acts as an inhibitor of angiogenesis. This finding may have potential relevance for the control of some cancers.

Animal research

While a body of evidence for the effects of rutin and quercetin is available in mice,^[10] rats,^[11] hamsters,^[12] and rabbits,^[13] as well as in vitro studies,^[14] no clinical studies directly demonstrate significant, positive effects of rutin as dietary supplement in humans.

• Rutin inhibits platelet aggregation,^[15] as well as decreases capillary permeability, making the blood thinner and improving circulation.
• Rutin shows anti-inflammatory activity in some animal and in vitro models.^[16][17]
• Rutin inhibits aldose reductase activity.^[18] Aldose reductase is an enzyme normally present in the eye and elsewhere in the body. It helps change glucose into the sugar alcohol sorbitol.
• Recent studies show rutin could help prevent blood clots, so could be used to treat patients at risk of heart attacks and strokes.^[19]
• Some evidence also shows rutin can be used to treat hemorrhoids, varicosis, and microangiopathy.^[20]
• Relatively high amount of rutin increases thyroid iodide uptake in rats and decreases serum T3 and T4 level. The decreased hormone level can be explained by its inhibitory effect produced on Thyroid peroxidase enzyme (TPO).^[21]
• Rutin is also an antioxidant;^[22] compared to quercetin, acacetin, morin, hispidulin, hesperidin, and naringin, it was found to be the strongest.^[23] However, in other trials, the effects of rutin were lower or negligible compared to those of quercetin.^[24][25]
• Rutin produces antinociceptive effects involving central modulation of the vlPAG descending circuit partly mediated by an opioidergic mechanism ^[26]

Hydroxyethylrutosides, synthetic hydroxyethyl acetylations of rutin, are used in the treatment of chronic venous insufficiency.

In veterinary medicine

Rutin may have a veterinary use in the management of chylothorax in dogs and cats.^[27]

Metabolism

The enzyme quercitrinase can be found in Aspergillus flavus.^[28] It is an enzyme in the rutin catabolic pathway.^[29]

References

1. Merck Index, 12th Edition, 8456
2. Krewson CF, Naghski J (Nov 1952). "Some physical properties of rutin". Journal of the American Pharmaceutical Association. American Pharmaceutical Association 41 (11): 582–7. doi:10.1002/jps.3030411106. PMID 12999623.
3. Lucci N, Mazzafera P (2009). "Rutin synthase in fava d'anta: Purification and influence of stressors". Canadian Journal of Plant Science 89 (5): 895–902. doi:10.4141/CJPS09001.
4. Purification and identification of active antibacterial components in Carpobrotusedulis L. Elmarie van der Watt and Johan C Pretorius, Journal of Ethnopharmacology, Volume 76, Issue 1, June 2001, Pages 87–91, doi:10.1016/S0378-8741(01)00197-0
5. Kreft S, Knapp M, Kreft I (Nov 1999). "Extraction of rutin from buckwheat (Fagopyrum esculentumMoench) seeds and determination by capillary electrophoresis". Journal of Agricultural and Food Chemistry 47 (11): 4649–52. doi:10.1021/jf990186p. PMID 10552865.
6. Curbing Clots, Sept, 2012
7. Chang S, Tan C, Frankel EN, Barrett DM (Feb 2000). "Low-density lipoprotein antioxidant activity of phenolic compounds and polyphenol oxidase activity in selected clingstone peach cultivars". Journal of Agricultural and Food Chemistry 48 (2): 147–51. doi:10.1021/jf9904564. PMID 10691607.
8. Determination of Rutin in Green Tea Infusions Using Square‐Wave Voltammetry with a Rigid Carbon‐Polyurethane Composite Electrode. Andréa R. Malagutti, Vânia Zuin, Éder T. G. Cavalheiro and Luiz Henrique Mazo, Electroanalysis, April 2006k 18(10), pages 1028-1034, doi:10.1002/elan.200603496
9. Luo H, Jiang BH, King SM, Chen YC (2008). "Inhibition of cell growth and VEGF expression in ovarian cancer cells by flavonoids". Nutrition and Cancer 60 (6): 800–9. doi:10.1080/01635580802100851. PMID 19005980.
10. Enkhmaa B, Shiwaku K, Katsube T, Kitajima K, Anuurad E, Yamasaki M, Yamane Y (Apr 2005). "Mulberry (Morus alba L.) leaves and their major flavonol quercetin 3-(6-malonylglucoside) attenuate atherosclerotic lesion development in LDL receptor-deficient mice". The Journal of Nutrition 135 (4): 729–34. PMID 15795425.
11. Santos KF, Oliveira TT, Nagem TJ, Pinto AS, Oliveira MG (Dec 1999). "Hypolipidaemic effects of naringenin, rutin, nicotinic acid and their associations". Pharmacological Research 40 (6): 493–6. doi:10.1006/phrs.1999.0556. PMID 10660947.
12. Auger C, Teissedre PL, Gérain P, Lequeux N, Bornet A, Serisier S, Besançon P, Caporiccio B, Cristol JP, Rouanet JM (Mar 2005). "Dietary wine phenolics catechin, quercetin, and resveratrol efficiently protect hypercholesterolemic hamsters against aortic fatty streak accumulation". Journal of Agricultural and Food Chemistry 53 (6): 2015–21. doi:10.1021/jf048177q. PMID 15769129.
13. Juźwiak S, Wójcicki J, Mokrzycki K, Marchlewicz M, Białecka M, Wenda-Rózewicka L, Gawrońska-Szklarz B, Droździk M (2005). "Effect of quercetin on experimental hyperlipidemia and atherosclerosis in rabbits". Pharmacological Reports 57 (5): 604–9. PMID 16227643.
14. Shen SC, Lee WR, Lin HY, Huang HC, Ko CH, Yang LL, Chen YC (Jun 2002). "In vitro and in vivo inhibitory activities of rutin, wogonin, and quercetin on lipopolysaccharide-induced nitric oxide and prostaglandin E(2) production". European Journal of Pharmacology 446 (1-3): 187–94. doi:10.1016/S0014-2999(02)01792-2. PMID 12098601.
15. Navarro-Núñez L, Lozano ML, Palomo M, Martínez C, Vicente V, Castillo J, Benavente-García O, Diaz-Ricart M, Escolar G, Rivera J (May 2008). "Apigenin inhibits platelet adhesion and thrombus formation and synergizes with aspirin in the suppression of the arachidonic acid pathway". Journal of Agricultural and Food Chemistry 56 (9): 2970–6. doi:10.1021/jf0723209. PMID 18410117.
16. Guardia T, Rotelli AE, Juarez AO, Pelzer LE (Sep 2001). "Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat". Farmaco 56 (9): 683–7. doi:10.1016/S0014-827X(01)01111-9. PMID 11680812.
17. Jung CH, Lee JY, Cho CH, Kim CJ (2007). "Anti-asthmatic action of quercetin and rutin in conscious guinea-pigs challenged with aerosolized ovalbumin". Archives of Pharmacal Research 30 (12): 1599–607. doi:10.1007/BF02977330. PMID 18254248.
18. Reddy GB, Muthenna P, Akileshwari C, Saraswat M, Petrash JM. "Inhibition of aldose reductase and sorbitol accumulation by dietary rutin". Current Science 101 (9): 1191–1197.
19. Reporter, Daily Mail (9 May 2012). "Chemical found in apples, onions and green tea can help beat blood clots". London: Mail Online. Retrieved 11 May 2012.
20. http://www.naturalstandard.com/index-abstract.asp?create-abstract=/monographs/herbssupplements/patient-rutin.asp
21. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0073908
22. Metodiewa D, Kochman A, Karolczak S (1997). "Evidence for antiradical and antioxidant properties of four biologically active N,N-Diethylaminoethyl ethers of flavaone oximes: A comparison with natural polyphenolic flavonoid rutin action". IUBMB Life 41 (5): 1067–1075. doi:10.1080/15216549700202141.
23. http://www.diet-and-health.net/Supplements/Rutin.html
24. Bando N, Muraki N, Murota K, Terao J, Yamanishi R (Jul 2010). "Ingested quercetin but not rutin increases accumulation of hepatic beta-carotene in BALB/c mice". Molecular Nutrition & Food Research. 54 Suppl 2: S261–7. doi:10.1002/mnfr.200900329. PMID 20373287.
25. Chow JM, Shen SC, Huan SK, Lin HY, Chen YC (Jun 2005). "Quercetin, but not rutin and quercitrin, prevention of H2O2-induced apoptosis via anti-oxidant activity and heme oxygenase 1 gene expression in macrophages". Biochemical Pharmacology 69 (12): 1839–51. doi:10.1016/j.bcp.2005.03.017. PMID 15876423.
26. http://www.ncbi.nlm.nih.gov/pubmed/25919941
27. Kopko SH (Aug 2005). "The use of rutin in a cat with idiopathic chylothorax". The Canadian Veterinary Journal. La Revue Vétérinaire Canadienne 46 (8): 729–31. PMC 1180424. PMID 16187718.
28. quercitrinase on www.brenda-enzymes.org
29. Tranchimand S, Brouant P, Iacazio G (Nov 2010). "The rutin catabolic pathway with special emphasis on quercetinase". Biodegradation 21 (6): 833–59. doi:10.1007/s10532-010-9359-7. PMID 20419500.