Oleanolic acid or oleanic acid is a naturally occurring pentacyclic

triterpenoid Triterpenes are a class of chemical compounds composed of three terpene units with the molecular formula C30H48; they may also be thought of as consisting of six isoprene units. Animals, plants and fungi all produce triterpenes, including squale ...

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. I ...

. It is widely distributed in food and plants where it exists as a free acid or as an aglycone of triterpenoid saponins.

Natural occurrence

Oleanolic acid can be found in

olive oil Olive oil is a liquid fat obtained from olives (the fruit of ''Olea europaea''; family Oleaceae), a traditional tree crop of the Mediterranean Basin, produced by pressing whole olives and extracting the oil. It is commonly used in cooking: f ...

, '' Phytolacca americana'' (American pokeweed), and '' Syzygium'' spp, garlic, etc. It was first studied and isolated from several plants, including ''

Olea europaea The olive, botanical name ''Olea europaea'', meaning 'European olive' in Latin, is a species of small tree or shrub in the family Oleaceae, found traditionally in the Mediterranean Basin. When in shrub form, it is known as ''Olea europaea'' ...

'' (leaves, fruit), ''

Rosa woodsii ''Rosa woodsii'' is a species of wild rose known by the common names Woods' rose, interior rose, common wild rose, mountain rose, pear-hip rose, and prairie rose. Distribution and habitat It is native to North America including much of Canada an ...

'' (leaves), '' Prosopis glandulosa'' (leaves and twigs), ''

Phoradendron juniperinum ''Phoradendron juniperinum'' is a species of flowering plant in the sandalwood family known by the common name juniper mistletoe. It is native to the southwestern United States and northern Mexico, where it grows in various types of woodland hab ...

'' (whole plant), '' Syzygium claviflorum'' (leaves), ''

Hyptis capitata ''Hyptis capitata'', also known as false ironwort or knobweed, is a species of erect annual shrubs, of the plant family Lamiaceae. It is native to Florida, Mexico, Central America, the West Indies, and South America but naturalized in Australia, ...

'' (whole plant), '' Mirabilis jalapa'') and ''

Ternstroemia gymnanthera ''Ternstroemia gymnanthera'' is a species of flowering plant in the family Pentaphylacaceae which grows on elevations of in Japan, China and on elevation of in Himalayas The Himalayas, or Himalaya (; ; ), is a mountain range in Asia, se ...

'' (aerial part). Other ''Syzygium'' species including java apple ('' Syzygium samarangense'') and rose apples contain it, as does ''

Ocimum tenuiflorum ''Ocimum tenuiflorum'', commonly known as holy basil, ''tulsi'' or ''tulasi'', is an aromatic perennial plant in the family Lamiaceae. It is native to the Indian subcontinent and widespread as a cultivated plant throughout the Southeast Asian ...

'' (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. 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 Hepatoprotection or antihepatotoxicity is the ability of a chemical substance to prevent damage to the liver. This is opposite to hepatotoxicity. Hepatoprotective molecules used in emergency medicine * Acetylcysteine is considered the hepatopro ...

, and exhibits

antitumor Cancer can be treated by surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy (including immunotherapy such as monoclonal antibody therapy) and synthetic lethality, most commonly as a series of separate treatments (e.g. ...

and antiviral properties. Oleanolic acid was found to exhibit weak anti- HIV and weak anti- HCV activities '' in vitro'', but more potent synthetic

analogs Analog or analogue may refer to: Computing and electronics * Analog signal, in which information is encoded in a continuous variable ** Analog device, an apparatus that operates on analog signals *** Analog electronics, circuits which use analog ...

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 Nitric oxide synthases () (NOSs) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule. It helps modulate vascular tone, insulin secretion, airway tone, and perista ...

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

and electrophile stress. 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. 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).

References

{{Authority control Triterpenes Secondary alcohols Hydroxy acids

Natural occurrence

Biosynthesis of oleanolic acids

Pharmacological research

See also

References