Oleanolic acid

Oleanolic acid[1]
Oleanolic acid
Names
IUPAC name
3β-Hydroxyolean-12-en-28-oic acid
Systematic IUPAC name
(4aS,6aS,6bR,8aR,10S,12aR,12bR,14bS)-10-Hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-octadecahydropicene-4a(2H)-carboxylic acid
Other names
Oleanic acid
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.007.347 Edit this at Wikidata
EC Number
  • 208-081-6
UNII
  • InChI=1S/C30H48O3/c1-25(2)14-16-30(24(32)33)17-15-28(6)19(20(30)18-25)8-9-22-27(5)12-11-23(31)26(3,4)21(27)10-13-29(22,28)7/h8,20-23,31H,9-18H2,1-7H3,(H,32,33)/t20-,21-,22+,23-,27-,28+,29+,30-/m0/s1 checkY
    Key: MIJYXULNPSFWEK-GTOFXWBISA-N checkY
  • InChI=1S/C30H48O3/c1-25(2)14-16-30(24(32)33)17-15-28(6)19(20(30)18-25)8-9-22-27(5)12-11-23(31)26(3,4)21(27)10-13-29(22,28)7/h8,20-23,31H,9-18H2,1-7H3,(H,32,33)/t20-,21-,22+,23-,27-,28+,29+,30-/m0/s1
    Key: MIJYXULNPSFWEK-GTOFXWBIBS
  • Key: MIJYXULNPSFWEK-GTOFXWBISA-N
  • O=C(O)[C@@]54[C@H](/C3=C/C[C@H]1[C@](CC[C@@H]2[C@]1(C)CC[C@H](O)C2(C)C)(C)[C@]3(C)CC4)CC(C)(C)CC5
Properties
C30H48O3
Molar mass 456.711 g·mol−1
Appearance White
Melting point > 300 °C (572 °F; 573 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Oleanolic acid or oleanic acid is a naturally occurring pentacyclic triterpenoid related to betulinic acid. It is widely distributed in food and plants where it exists as a free acid or as an aglycone of triterpenoid saponins.[2]

Natural occurrence

[edit]

Oleanolic acid can be found in olive oil, Phytolacca americana (American pokeweed), and Syzygium spp, garlic, etc. It was first studied and isolated from several plants, including Olea europaea[3] (leaves, fruit), Rosa woodsii (leaves), Prosopis glandulosa (leaves and twigs), Phoradendron juniperinum (whole plant), Syzygium claviflorum (leaves), Hyptis capitata (whole plant), Mirabilis jalapa[4] and Ternstroemia gymnanthera (aerial part). Other Syzygium species including java apple (Syzygium samarangense) and rose apples contain it, as does Ocimum tenuiflorum (holy basil).

Biosynthesis of oleanolic acids

[edit]

Oleanolic acid biosynthesis starts with mevalonate to create squalene. Squalene monooxygenase in the next step oxidases the squalene and forms an epoxide resulting in 2,3-oxidosqualene.[5] Beta-amyrin synthase creates beta-amyrin by a ring formation cascade.[5][6] After the formation of beta amyrin, CYP716AATR2, also known as a cytochrome p450 enzyme, oxidizes carbon 28 turning it into alcohol.[6] CYP716AATR2 converts the alcohol to aldehyde and finally to a carboxylic acid forming oleanolic acid.[6]

Biosynthesis of Oleanolic Acid in Saccharomyces Cerevisiae

Pharmacological research

[edit]

Oleanolic acid is relatively non-toxic, hepatoprotective, and exhibits antitumor and antiviral properties.[7] Oleanolic acid was found to exhibit weak anti-HIV[8] and weak anti-HCV activities in vitro, but more potent synthetic analogs are being investigated as potential drugs.[9]

An extremely potent synthetic triterpenoid analog of oleanolic acid was found in 2005, that is a powerful inhibitor of cellular inflammatory processes. They work by the induction by IFN-γ of inducible nitric oxide synthase (iNOS) and of cyclooxygenase 2 in mouse macrophages. They are extremely potent inducers of the phase 2 response (e.g., elevation of NADH-quinone oxidoreductase and heme oxygenase 1), which is a major protector of cells against oxidative and electrophile stress.[10]

A 2002 study in Wistar rats found that oleanolic acid reduced sperm quality and motility, causing infertility. After withdrawing exposure, male rats regained fertility and successfully impregnated female rats.[11] Oleanolic acid is also used as standard for comparison of hyaluronidase, elastase and matrix-metalloproteinase-1 inhibition of other substances in primary research (similar to diclofenac sodium for comparison of analgesic activity).[12][13]

Oleanolic acid activates telomerase in peripheral blood mononuclear cells (PBMCs) 5.9-fold, more than any other compounded tested, with the exception of Centella asiatica (8.8-fold).[14] Less telomerase activation is seen for Astragalus extract 4.3-fold, TA-65 2.2-fold, and maslinic acid 2-fold.[14]

See also

[edit]

References

[edit]
  1. ^ "Oleanolic acid". Sigma-Aldrich. Merck. Retrieved November 29, 2018.
  2. ^ Pollier J, Goossens A (May 2012). "Oleanolic acid". Phytochemistry. 77: 10–15. doi:10.1016/j.phytochem.2011.12.022. PMID 22377690.
  3. ^ "Oleanolic acid (HMDB0002364)". HMDB. Canadian Institutes of Health Research. Retrieved November 29, 2018.
  4. ^ Siddiqui S, Siddiqui BS, Adil Q, Begum S (1990). "Constituents of Mirabilis jalapa". Fitoterapia. 61 (5): 471. Archived from the original on 2014-01-04.)
  5. ^ a b Fukushima EO, Seki H, Ohyama K, Ono E, Umemoto N, Mizutani M, et al. (December 2011). "CYP716A subfamily members are multifunctional oxidases in triterpenoid biosynthesis". Plant & Cell Physiology. 52 (12): 2050–2061. doi:10.1093/pcp/pcr146. PMID 22039103.
  6. ^ a b c Dale MP, Moses T, Johnston EJ, Rosser SJ (2020-05-01). "A systematic comparison of triterpenoid biosynthetic enzymes for the production of oleanolic acid in Saccharomyces cerevisiae". PLOS ONE. 15 (5): e0231980. Bibcode:2020PLoSO..1531980D. doi:10.1371/journal.pone.0231980. PMC 7194398. PMID 32357188.
  7. ^ Liu J (December 1995). "Pharmacology of oleanolic acid and ursolic acid". Journal of Ethnopharmacology. 49 (2): 57–68. doi:10.1016/0378-8741(95)90032-2. PMID 8847885.
  8. ^ Mengoni F, Lichtner M, Battinelli L, Marzi M, Mastroianni CM, Vullo V, Mazzanti G (February 2002). "In vitro anti-HIV activity of oleanolic acid on infected human mononuclear cells". Planta Medica. 68 (2): 111–114. doi:10.1055/s-2002-20256. PMID 11859458.
  9. ^ Yu F, Wang Q, Zhang Z, Peng Y, Qiu Y, Shi Y, et al. (June 2013). "Development of oleanane-type triterpenes as a new class of HCV entry inhibitors". Journal of Medicinal Chemistry. 56 (11): 4300–4319. doi:10.1021/jm301910a. PMID 23662817.
  10. ^ Dinkova-Kostova AT, Liby KT, Stephenson KK, Holtzclaw WD, Gao X, Suh N, et al. (March 2005). "Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stress". Proceedings of the National Academy of Sciences of the United States of America. 102 (12): 4584–4589. Bibcode:2005PNAS..102.4584D. doi:10.1073/pnas.0500815102. PMC 555528. PMID 15767573.
  11. ^ Mdhluli MC, van der Horst G (October 2002). "The effect of oleanolic acid on sperm motion characteristics and fertility of male Wistar rats". Laboratory Animals. 36 (4): 432–437. doi:10.1258/002367702320389107. PMID 12396287. S2CID 34990111.
  12. ^ Maity N, Nema NK, Sarkar BK, Mukherjee PK (2012). "Standardized Clitoria ternatea leaf extract as hyaluronidase, elastase and matrix-metalloproteinase-1 inhibitor". Indian Journal of Pharmacology. 44 (5): 584–587. doi:10.4103/0253-7613.100381. PMC 3480789. PMID 23112418.
  13. ^ Nema NK, Maity N, Sarkar BK, Mukherjee PK (September 2013). "Matrix metalloproteinase, hyaluronidase and elastase inhibitory potential of standardized extract of Centella asiatica". Pharmaceutical Biology. 51 (9): 1182–1187. doi:10.3109/13880209.2013.782505. PMID 23763301. S2CID 24453413.
  14. ^ a b Tsoukalas D, Fragkiadaki P, Calina D (2019). "Discovery of potent telomerase activators: Unfolding new therapeutic and anti-aging perspectives". Molecular Medicine Reports. 20 (4): 3701–3708. doi:10.3892/mmr.2019.10614. PMC 6755196. PMID 31485647.
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