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 squal ...

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.

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 ''Phytolacca americana'', also known as American pokeweed, pokeweed, poke sallet, dragonberries, and inkberry, is a poisonous, herbaceous perennial plant in the pokeweed family Phytolaccaceae. This pokeweed grows . It has simple leaves on green ...

'' (American pokeweed), and ''

Syzygium ''Syzygium'' () is a genus of flowering plants that belongs to the myrtle family, Myrtaceae. The genus comprises about 1200 species, and has a native range that extends from Africa and Madagascar through southern Asia east through the Pacific. I ...

'' 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 ''Prosopis glandulosa'', commonly known as honey mesquite, is a species of small to medium-sized, thorny shrub or tree in the legume family (Fabaceae). Distribution The plant is primarily native to the Southwestern United States and Northern M ...

'' (leaves and twigs), '' Phoradendron juniperinum'' (whole plant), '' Syzygium claviflorum'' (leaves), '' Hyptis capitata'' (whole plant), ''

Mirabilis jalapa ''Mirabilis jalapa'', the marvel of Peru or four o'clock flower, is the most commonly grown ornamental species of ''Mirabilis'' plant, and is available in a range of colors. ''Mirabilis'' in Latin means wonderful and Jalapa (or Xalapa) is the st ...

'') 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 ''Syzygium samarangense'' is a species of flowering plant in the family Myrtaceae, native to an area that includes the Greater Sunda Islands, Malay Peninsula, and the Andaman and Nicobar Islands, but introduced in prehistoric times to a wider a ...

'') 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 Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do no ...

properties. Oleanolic acid was found to exhibit weak anti-

HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...

and weak anti- HCV activities ''

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

'', 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 Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock ...

of inducible nitric oxide synthase (iNOS) and of

cyclooxygenase 2 Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (The HUGO official symbol is PTGS2; HGNC ID, HGNC:9605), also known as cyclooxygenase-2 or COX-2, is an enzyme that in humans is encoded by the ''PTGS2'' gene ...

in mouse

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

. They are extremely potent inducers of the

phase 2 response Phase or phases may refer to: Science *State of matter, or phase, one of the distinct forms in which matter can exist *Phase (matter), a region of space throughout which all physical properties are essentially uniform *Phase space, a mathematica ...

(e.g., elevation of

NADH-quinone oxidoreductase NADH:ubiquinone reductase (non-electrogenic) (, '' NDH-2'', ''ubiquinone reductase'', ''coenzyme Q reductase'', ''dihydronicotinamide adenine dinucleotide-coenzyme Q reductase'', ''DPNH-coenzyme Q reductase'', ''DPNH-ubiquinone reductase'', ''NADH ...

and

heme oxygenase 1 ''HMOX1'' (heme oxygenase 1 gene) is a human gene that encodes for the enzyme heme oxygenase 1 (). Heme oxygenase (abbreviated HMOX or HO) mediates the first step of heme catabolism, it cleaves heme to form biliverdin. The ''HMOX'' gene is locate ...

), 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 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 charged, have an atom that carries ...

stress. A 2002 study in

Wistar rat A laboratory rat or lab rat is a brown rat of the subspecies '' Rattus norvegicus domestica'' which is bred and kept for scientific research. While less commonly used for research than mice (see laboratory mouse), rats have served as an importa ...

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 (HA). Karl Meyer classified these enzymes in 1971, into three distinct groups, a scheme based on the enzyme reaction products. The three main types of hyal ...

elastase In molecular biology, elastase is an enzyme from the class of ''proteases (peptidases)'' that break down proteins. In particular, it is a serine protease. Forms and classification Eight human genes exist for elastase: Some bacteria (includin ...

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