Rosmarinic acid

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Structural formula
Structural formula of rosmarinic acid
General
Surname Rosmarinic acid
other names
  • ( E , R ) -3- (3,4-dihydroxyphenyl) -acrylic acid-1-carboxy-2- (3,4-dihydroxyphenyl) -ethyl ester,
  • 2- O -caffeoyl-2-hydroxy-2,3-dihydrocaffeic acid
Molecular formula C 18 H 16 O 8
Brief description

dark red to brown solid

External identifiers / databases
CAS number
  • 20283-92-5 ( E , R )
  • 537-15-5 ( E , RS )
EC number 606-487-1
ECHA InfoCard 100.123.507
PubChem 5281792
ChemSpider 4445104
Wikidata Q50380051
properties
Molar mass 360.34 g mol −1
Physical state

firmly

Melting point

171-175 ° C

solubility

something in water

safety instructions
GHS labeling of hazardous substances
no GHS pictograms
H and P phrases H: no H-phrases
P: no P-phrases
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Rosmarinic acid is the common name of a phenylacrylic acid that is widespread in the plant kingdom. From a chemical point of view, it is the ester of caffeic acid with 3- (3,4-dihydroxyphenyl) lactic acid .

history

The first isolation and characterization of rosmarinic acid took place in 1958. It was obtained that year from rosemary ( Rosmarinus officinalis ) by the two Italian chemists ML Scarpatti and G. Oriente .

Occurrence

Rosemary ( Rosmarinus officinalis )

Especially the families of the Lamiaceae , especially the subfamilies Nepetoideae and Boraginaceaen, are rich in rosmarinic acid. However, it can also be found in plant groups that are taxonomically more distant, such as ferns and hornworts , but here in lower concentrations.

use

Use in pharmacy

Rosmarinic acid has antiviral , antibacterial and anti-inflammatory properties. It is therefore used in various melissa preparations (e.g. Lomaherpan ® cream) and in some ointments against sports injuries (e.g. Traumaplant ® ).

Pure rosmarinic acid counteracts the complement-dependent stimulation of prostaglandin synthesis , has antioxidant properties, blocks opsonization and can easily be absorbed through the skin .

Other uses

Rosmarinic acid, like many other phenol carboxylic acid esters , has tanning properties . Since it occurs mainly in plant species of the Lamiaceae family , it is also known as Lamiaceae tannin or as labiate tannin - Labiatae is the outdated name for mint family. In animal studies it had chemoprotective, neuroprotective and potentially antidepressant effects.

Biological importance

Rosmarinic acid is a secondary plant substance . Plants synthesize them as a defense against fungi and bacteria . It is also believed that it protects the plant from predators . Plants store rosmarinic acid in the vacuoles separately from oxidases . If there is an injury, this compartmentalization is canceled. The phenolic hydroxyl groups of rosmarinic acid are oxidized to orthoquinones . These bind to peptides and thereby inactivate them.

biosynthesis

The biosynthesis of rosmarinic acid was first examined in detail in 1970. It begins with the two amino acids L -phenylalanine and L -yrosine . A total of eight different proteins are involved.

Rosmarinic acid biosynthesis

Biosynthesis can be divided into three different processes:

Conversion of L- phenylalanine to 4-cumaroyl-CoA

In the first step, phenylalanine is deaminated to E - cinnamic acid with the help of phenylalanine ammonium lyase (PAL) . This reaction can be observed in many biosyntheses of compounds with phenylpropane backbones. The syntheses of lignins , flavonoids and coumarins begin with this step.

In a second step, a hydroxyl group is introduced into the aromatic ring of E- cinnamic acid. This hydroxylation is catalyzed by the enzyme cinnamic acid 4- hydroxylase (CAH), 4- coumaric acid is formed . The latter is also formed during the deamination of the amino acid L- tyrosine with PAL, as this enzyme can also use this amino acid as a substrate.

In the third and last step of this general phenylpropane metabolism, 4-coumarate-CoA ligase (4CL) converts 4-coumaric acid into the corresponding CoA ester.

Conversion of L -yrosine to 4-hydroxyphenyl lactate

Parallel to the implementation of L -phenylalanine, the implementation of L -yrosine takes place . In the first step, tyrosine aminotransferase (TAT) catalyzes the transamination with 2-oxoglutarate as an amino acceptor to form 4-hydroxyphenylpyruvate and glutamate . In the second step, the pyruvate is reduced to ( R ) - (+) - 4-hydroxyphenyl lactate by the NADH / NADPH -dependent hydroxyphenylpyruvate reductase (HPPR) .

Implementation of 4-cumaroyl-CoA with 4-hydroxyphenyl lactate and subsequent hydroxylation

The lactate is esterified by rosmarinic acid synthase (RAS) on the aliphatic hydroxyl group with the 4-cumaryl-CoA formed in the first step to give 4-cumaroyl-4'-hydroxyphenyl lactate. This ester is hydroxylated in two stages at the 3 and 3 'positions on the aromatic rings. These reactions are catalyzed by two membrane-bound, cytochrome P450-dependent hydroxylases. First, caffeoyl-4'-hydroxyphenyl lactate or 4-cumaroyl-3 ', 4'-dihydroxyphenyl lactate and finally rosmarinic acid are formed as an intermediate.

literature

  • Ying Ying Gao, Hans-Ullrich Siehl, Heike Petzold, Dieter Sicker, Klaus-Peter Zeller, Prof. Dr. Stefan Berger: About rosemary and rosmarinic acid: remedies against the plague and Mediterranean spices , in: Chemistry in our time, Volume 49, Issue 5, pages 302–311, October 2015.

Individual evidence

  1. ↑ a b c d Data sheet Rosmarinic acid from Sigma-Aldrich , accessed on February 7, 2019 ( PDF ).
  2. ↑ Abdelkarim Aydi, Carlos Alberto Claumann a. a .: Differential Scanning Calorimetry Data and Solubility of Rosmarinic Acid in Different Pure Solvents and in Binary Mixtures (Methyl Acetate + Water) and (Ethyl Acetate + Water) from 293.2 to 313.2 K. In: Journal of Chemical & Engineering Data. 61, 2016, p. 3718, doi : 10.1021 / acs.jced.6b00008 .
  3. ↑ ML Scarpati, G. Oriente: Isolamento e costituzione dell 'acido rosmarinico (dal rosmarinus off. ). In: Ric.Sci. , 28, 1958, pp. 2329-2333.
  4. ↑ JA Pedersen: Distribution and taxonomic implications of some phenolics in the family Lamiaceae determined by ESR spectroscopy . In: Biochemical Systematics and Ecology , 28, 2000, pp. 229-253.
  5. ↑ E. Häusler u. a .: Rosmarinic acid in Blechmum species In: Botanikertagung 1992 Berlin, HP Haschek, C. Schnarrenberger (Eds.): Akademie Verlag, Berlin, p. 507.
  6. ↑ HD Zinsmeister u. a .: Moss, a source of biologically active natural substances? In: Angewandte Chemie , 103, 1991, pp. 134-151.
  7. ^ MJ Parnham, K. Kesselring: Rosmarinic acid. In: Drugs of the Future , 10, 1985, pp. 756-757.
  8. ↑ G. May, G. Willuhn: Antiviral effects of aqueous plant extracts in tissue cultures. In: Arzneimittel.Forsch. , 28, 1978, pp. 1-7.
  9. ↑ M. Rampart et al. a .: Complement-dependent stimulation of prostacyclin biosynthesis: Inhibition by rosmarinic acid. In: Biochem. Pharmacol. 35, 1986, pp. 1397-1400.
  10. ↑ KP Van Kessel u. a .: Rosmarinic acid inhibits external oxidative effects of human polymorphonuclear granulocytes. In: Agent Actions , 17, 1986, pp. 375-376.
  11. ↑ AMJJ Verweij-van Vught and a .: Influence of Rosmarinic acid on opsonization and intracellular killing of Esherishia coli and Staphylococcus aureus by porcine and human polymorphonuclear leucocytes. In: Agents Actions , 22, 1987, pp. 288-294.
  12. ↑ WA Ritschel et al. a .: Percutaneous absorption of rosmarinic acid in the rat. In: Meth. Exp. Clin. Pharmacol. , 11, 1989, pp. 345-353.
  13. ^ R Domitrović, I Potočnjak, Z Crnčević-Orlić, M. Skoda: Nephroprotective activities of rosmarinic acid against cisplatin-induced kidney injury in mice . In: Food Chem Toxicol. , February 8, 2014, PMID 24518541 .
  14. ↑ N Braidy, A Matin, F Rossi, M Chinain, D Laurent, GJ. Guillemin: Neuroprotective effects of rosmarinic acid on ciguatoxin in primary human neurons . In: Neurotox Res. , February 25, 2014, PMID 24097334
  15. ↑ X Jin, P Liu, F Yang, YH Zhang, D. Miao: Rosmarinic acid ameliorates depressive-like behaviors in a rat model of CUS and Up-regulates BDNF levels in the hippocampus and hippocampal-derived astrocytes . In: Neurochem Res. , September 25, 2013, PMID 23756732
  16. ↑ E. Häusler, M. Petersen: Isolation of protoplasts and vacuoles from cell suspension cultures of Coleus blumei. In: Benth. Plant Cell Rep. , 12, 1993, pp. 510-512.
  17. ↑ J. Koukol, EE Conn: Metabolism of aromatic compounds in higher plants. In: J. Biol. Chem. 236, 1961, pp. 2692-2698.
  18. ↑ M. Petersen, AW Alfermann: Two new enzymes of rosmarinic acid biosynthesis from cell cultures of Coleus blumei: hydroxyphenylpyruvate reductase and rosmarinic acid synthase. In: Z. Naturfosch. , 43c, 1988, pp. 501-504.
  19. ↑ M. Petersen u. a .: Proposed biosynthetic pathway for rosmarinic acid synthase from cell cultures of Coleus blumei. In: Benth. Planta , 189, 1993, pp. 10-14.