Oleanolic acid

Last updated
Oleanolic acid [1]
Oleanolic acid.png
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 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 208-081-6
PubChem CID
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 Yes check.svgY
    Key: MIJYXULNPSFWEK-GTOFXWBISA-N Yes check.svgY
  • 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
AppearanceWhite
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).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

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]

Contents

Natural occurrence

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

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 Oleanolic Acid Biosynthesis.gif
Biosynthesis of Oleanolic Acid in Saccharomyces Cerevisiae

Pharmacological research

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

Related Research Articles

Saponins, also selectively referred to as triterpene glycosides, are bitter-tasting usually toxic plant-derived organic chemicals that have a foamy quality when agitated in water. They are widely distributed but found particularly in soapwort, a flowering plant, the soapbark tree, common corn-cockle, baby’s breath and soybeans. They are used in soaps, medicines, fire extinguishers, as dietary supplements, for synthesis of steroids, and in carbonated beverages. Saponins are both water and fat soluble, which gives them their useful soap properties. Some examples of these chemicals are glycyrrhizin and quillaia, a bark extract used in beverages.

<i>Gymnema sylvestre</i> Species of flowering plant

Gymnema sylvestre is a perennial woody vine native to Asia, Africa and Australia. It has been used in Ayurvedic medicine. Common names include gymnema, Australian cowplant, and Periploca of the woods, and the Hindi term gurmar, which means "sugar destroyer".

<span class="mw-page-title-main">Ambrein</span> Chemical compound

Ambrein is a triterpene alcohol that is the chief constituent of ambergris, a secretion from the digestive system of the sperm whale. It has been suggested as the possible active component producing the supposed aphrodisiac effects of ambergris. Although ambrein itself is odorless, it serves as the biological precursor for aromatic derivatives such as ambroxan and is thought to possess fixative properties for other odorants.

<i>Centella asiatica</i> Species of flowering plant in the celery family Apiaceae

Centella asiatica, commonly known as Indian pennywort, Asiatic pennywort, spadeleaf, coinwort or gotu kola, is a herbaceous, perennial plant in the flowering plant family Apiaceae. It is native to tropical regions of Africa, Asia, Australia, and islands in the western Pacific Ocean. It is consumed as a culinary vegetable and is used in traditional medicine.

<span class="mw-page-title-main">Moronic acid</span> Chemical compound

Moronic acid is a natural triterpene. Moronic acid can be extracted from Rhus javanica, a sumac plant traditionally believed to hold medicinal applications. The molecule has also been extracted from mistletoe.

<span class="mw-page-title-main">Oleanane</span> Chemical compound

Oleanane is a natural triterpenoid. It is commonly found in woody angiosperms and as a result is often used as an indicator of these plants in the fossil record. It is a member of the oleanoid series, which consists of pentacyclic triterpenoids where all rings are six-membered.

<span class="mw-page-title-main">Betulinic acid</span> Chemical compound

Betulinic acid is a naturally occurring pentacyclic triterpenoid which has antiretroviral, antimalarial, and anti-inflammatory properties, as well as a more recently discovered potential as an anticancer agent, by inhibition of topoisomerase. It is found in the bark of several species of plants, principally the white birch from which it gets its name, but also the ber tree, selfheal, the tropical carnivorous plants Triphyophyllum peltatum and Ancistrocladus heyneanus, Diospyros leucomelas, a member of the persimmon family, Tetracera boiviniana, the jambul, flowering quince, rosemary, and Pulsatilla chinensis.

<span class="mw-page-title-main">Triterpene</span> Class of chemical compounds

Triterpenes are a class of terpenes composed of six isoprene units with the molecular formula C30H48; they may also be thought of as consisting of three terpene units. Animals, plants and fungi all produce triterpenes, including squalene, the precursor to all steroids.

<span class="mw-page-title-main">Ursolic acid</span> Pentacyclic chemical compound found in fruits

Ursolic acid, is a pentacyclic triterpenoid identified in the epicuticular waxes of apples as early as 1920 and widely found in the peels of fruits, as well as in herbs and spices like rosemary and thyme.

<i>Barringtonia acutangula</i> Species of plant

Barringtonia acutangula is a species of Barringtonia native to coastal wetlands in southern Asia and northern Australasia, from Afghanistan east to the Philippines, Queensland and the Northern Territory. Common names include freshwater mangrove, itchytree and mango-pine.

<span class="mw-page-title-main">Ginsenoside</span> Class of steroids

Ginsenosides or panaxosides are a class of natural product steroid glycosides and triterpene saponins. Compounds in this family are found almost exclusively in the plant genus Panax (ginseng), which has a long history of use in traditional medicine that has led to the study of pharmacological effects of ginseng compounds. As a class, ginsenosides exhibit a large variety of subtle and difficult-to-characterize biological effects when studied in isolation.

<i>Cornus officinalis</i> Species of flowering plant

Cornus officinalis, the Japanese cornel or Japanese cornelian cherry, is a species of flowering plant in the dogwood family Cornaceae. Despite its name, it is native to China and Korea as well as Japan. It is not to be confused with C. mas, which is also known as the Cornelian cherry. It is not closely related to the true cherries of the genus Prunus.

<span class="mw-page-title-main">Hederagenin</span> Chemical compound

Hederagenin is a triterpenoid which is a chemical constituent of the Hedera helix plant.

Momordin is one of several saponins derived from oleanolic acid, a triterpenoid. These chemical compounds are found in some plants of the genus Momordica, which includes the bitter melon and the balsam apple, as well as in other Asian herbal medicine plants such as Kochia scoparia and Ampelopsis radix.

<span class="mw-page-title-main">Lupeol</span> Chemical compound

Lupeol is a pharmacologically active pentacyclic triterpenoid. It has several potential medicinal properties, like anticancer and anti-inflammatory activity.

<span class="mw-page-title-main">Amyrin</span> Chemical compound

The amyrins are three closely related natural chemical compounds of the triterpene class. They are designated α-amyrin (ursane skeleton), β-amyrin (oleanane skeleton) and δ-amyrin. Each is a pentacyclic triterpenol with the chemical formula C30H50O. They are widely distributed in nature and have been isolated from a variety of plant sources such as epicuticular wax. In plant biosynthesis, α-amyrin is the precursor of ursolic acid and β-amyrin is the precursor of oleanolic acid. All three amyrins occur in the surface wax of tomato fruit. α-Amyrin is found in dandelion coffee.

β-amyrin synthase is an enzyme with systematic name (3S)-2,3-epoxy-2,3-dihydrosqualene mutase . This enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">Oxidosqualene cyclase</span>

Oxidosqualene cyclases (OSC) are enzymes involved in cyclization reactions of 2,3-oxidosqualene to form sterols or triterpenes.

<i>Gardenia erubescens</i> Species of plant

Gardenia erubescens is a shrub or small tree species with edible fruits that occurs in the Guinea and Sudan savannah vegetation of West and Central Africa. It is within the Rubiaceae family.

References

  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. 1 2 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. 1 2 3 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. 1 2 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.