Oleanolic acid or oleanic acid is a naturally occurring pentacyclic

triterpenoid 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 pre ...

related to

betulinic acid 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 widely distributed in food and plants where it exists as a free acid or as an

aglycone An aglycone (aglycon or genin) is the chemical compound remaining after the glycosyl group on a glycoside is replaced by a hydrogen atom. For example, the aglycone of a cardiac glycoside would be a steroid A steroid is an organic compoun ...

of triterpenoid

saponin Saponins (Latin ''sapon'', 'soap' + ''-in'', 'one of') are bitter-tasting, usually toxic plant-derived secondary metabolites. They are organic chemicals that become foamy when agitated in water and have high molecular weight. They are present ...

Natural occurrence

Oleanolic acid can be found in

olive oil Olive oil is a vegetable oil obtained by pressing whole olives (the fruit of ''Olea europaea'', a traditional Tree fruit, tree crop of the Mediterranean Basin) and extracting the oil. It is commonly used in cooking for frying foods, as a cond ...

, '' Phytolacca americana'' (American pokeweed), and '' Syzygium'' spp, garlic, etc. It was first studied and isolated from several plants, including '' Olea europaea'' (leaves, fruit), '' Rosa woodsii'' (leaves), '' Prosopis glandulosa'' (leaves and twigs), '' Phoradendron juniperinum'' (whole plant), '' Syzygium claviflorum'' (leaves), '' Hyptis capitata'' (whole plant), '' Mirabilis jalapa'') 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 is an organic compound. It is a triterpene with the formula C30H50. It is a colourless oil, although impure samples appear yellow. It was originally obtained from shark liver oil (hence its name, as '' Squalus'' is a genus of sharks). ...

Squalene monooxygenase Squalene monooxygenase (also called squalene epoxidase) is a eukaryotic enzyme that uses NADPH and diatomic oxygen to oxidize squalene to 2,3-oxidosqualene (squalene epoxide). Squalene epoxidase catalyzes the first oxygenation step in sterol b ...

in the next step oxidases the squalene and forms an epoxide resulting in

2,3-oxidosqualene (''S'')-2,3-Oxidosqualene ((''S'')-2,3-epoxysqualene) is an intermediate in the synthesis of the cell membrane sterol precursors lanosterol and cycloartenol, as well as saponins. It is formed when squalene is oxidized by the enzyme squale ...

. Beta-amyrin synthase creates beta-amyrin by a ring formation cascade. After the formation of beta amyrin, CYP716AATR2, also known as a cytochrome p450 enzyme, oxidizes carbon 28 turning it into alcohol. CYP716AATR2 converts the alcohol to aldehyde and finally to a carboxylic acid forming oleanolic acid. Oleanolic Acid Biosynthesis

Pharmacological research

Oleanolic acid is relatively non-toxic, hepatoprotective, and exhibits antitumor and antiviral properties. Oleanolic acid was found to exhibit weak anti- HIV and weak anti- HCV activities ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'', but more potent synthetic analogs are being investigated as potential drugs. 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 Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

. 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 Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...

and

electrophile In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively Electric charge, charged, have an ...

stress. A 2002 study in

Wistar rat Laboratory rats or lab rats are strain (biology), strains of the rat subspecies ''Rattus norvegicus domestica'' (Domestic Norwegian rat) which are bred and kept for scientific research. While Animal testing on rodents, less commonly used for re ...

s found that oleanolic acid reduced sperm quality and motility, causing infertility. After withdrawing exposure, male rats regained fertility and successfully impregnated female rats. Oleanolic acid is also used as standard for comparison of

hyaluronidase Hyaluronidases are a family of enzymes that catalyse the degradation of hyaluronic acid. Karl Meyer classified these enzymes in 1971, into three distinct groups, a scheme based on the enzyme reaction products. The three main types of hyaluroni ...

, elastase and matrix-metalloproteinase-1 inhibition of other substances in primary research (similar to diclofenac sodium for comparison of analgesic activity). Oleanolic acid activates

telomerase Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most euka ...

peripheral blood mononuclear cell A peripheral blood mononuclear cell (PBMC) is any peripheral blood cell having a round Cell nucleus, nucleus. These cells consist of lymphocytes (T cells, B cells, NK cells) and monocytes, whereas erythrocytes and platelets have no nuclei, and gr ...

s (PBMCs) 5.9-fold, more than any other compounded tested, with the exception of '' Centella asiatica'' (8.8-fold). Less telomerase activation is seen for ''Astragalus'' extract 4.3-fold, TA-65 2.2-fold, and maslinic acid 2-fold.

References

{{Authority control Triterpenes Secondary alcohols Hydroxy acids

Natural occurrence

Biosynthesis of oleanolic acids

Pharmacological research

See also

References