Ursolic acid (sometimes referred to as urson, prunol, malol, or 3β-hydroxyurs-12-en-28-oic acid), is a 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 ...

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 ''Salvia rosmarinus'' (), commonly known as rosemary, is a shrub with fragrant, evergreen, needle-like leaves and white, pink, purple, or blue flowers, native plant, native to the Mediterranean Region, Mediterranean region. Until 2017, it was kn ...

and

thyme Thyme () is the herb (dried aerial parts) of some members of the genus ''Thymus'' of aromatic perennial evergreen herbs in the mint family Lamiaceae. Thymes are relatives of the oregano genus ''Origanum'', with both plants being mostly indigenou ...

Natural occurrence

Ursolic acid is present in many plants, such as '' Mirabilis jalapa'', as well as in many fruits and herbs used in daily life (e.g.

apple An apple is an edible fruit produced by an apple tree (''Malus domestica''). Apple fruit tree, trees are agriculture, cultivated worldwide and are the most widely grown species in the genus ''Malus''. The tree originated in Central Asia, wh ...

s, basil and

holy basil ''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 ...

, bilberries,

cranberries Cranberries are a group of evergreen dwarf shrubs or trailing vines in the subgenus ''Oxycoccus'' of the genus ''Vaccinium''. In Britain, cranberry may refer to the native species ''Vaccinium oxycoccos'', while in North America, cranberry m ...

elder flower ''Sambucus'' is a genus of flowering plants in the family Adoxaceae. The various species are commonly called elder or elderberry. The genus was formerly placed in the honeysuckle family, Caprifoliaceae, but was reclassified as Adoxaceae due to g ...

peppermint Peppermint (''Mentha'' × ''piperita'') is a hybrid species of mint, a cross between watermint and spearmint. Indigenous to Europe and the Middle East, the plant is now widely spread and cultivated in many regions of the world.Euro+Med Plantbas ...

, lavender,

oregano Oregano (, ; ''Origanum vulgare'') is a species of flowering plant in the mint family Lamiaceae. It was native to the Mediterranean region, but widely naturalised elsewhere in the temperate Northern Hemisphere. Oregano is a woody perennial pla ...

hawthorn Hawthorn or Hawthorns may refer to: Plants * '' Crataegus'' (hawthorn), a large genus of shrubs and trees in the family Rosaceae * ''Rhaphiolepis'' (hawthorn), a genus of about 15 species of evergreen shrubs and small trees in the family Rosace ...

, and

prunes A prune is a dried plum, most commonly from the European plum (''Prunus domestica''). Not all plum species or varieties can be dried into prunes. A prune is the firm-fleshed fruit (plum) of ''Prunus domestica'' varieties that have a high solu ...

). Apple peels contain large quantities of ursolic acid and related compounds.

Potential biochemical effects

A number of potential biochemical effects of ursolic acid have been investigated, but there has been no clinical study demonstrating benefits to human health. ''

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 ...

'', ursolic acid inhibits the proliferation of various cancer cell types by inhibiting the STAT3 activation pathway, and may also decrease proliferation of cancer cells and induce

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

. Ursolic acid has also been shown to inhibit

JNK c-Jun N-terminal kinases (JNKs), were originally identified as kinases that bind and phosphorylate c-Jun on Ser-63 and Ser-73 within its transcriptional activation domain. They belong to the mitogen-activated protein kinase family, and are ...

expression and

IL-2 The Ilyushin Il-2 (Russian language, Russian: Илью́шин Ил-2) is a Ground attack aircraft, ground-attack plane that was produced by the Soviet Union in large numbers during the World War II, Second World War. The word ''shturmovík'' (C ...

activation of

JURKAT Jurkat cells are an immortalized line of human T lymphocyte cells that are used to study acute T cell leukemia, T cell signaling, and the expression of various chemokine receptors susceptible to viral entry, particularly HIV. Jurkat cells can prod ...

leukemic T Cells leading to the reduction in proliferation and T cell activation. Ursolic acid is a weak aromatase

inhibitor Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

(IC₅₀ = 32 μM), and has been shown to increase the amount of muscle and brown fat and decrease

white fat White is the lightest color and is achromatic (having no hue). It is the color of objects such as snow, chalk, and milk, and is the opposite of black. White objects fully reflect and scatter all the visible wavelengths of light. White on ...

obesity and associated conditions when added to diets fed to mice. Under physiological concentrations, ursolic acid also induces

eryptosis Eryptosis (''Erythrocyte apoptosis'' or ''Red blood cell programmed death'') is a type of apoptosis that occurs in injured erythrocytes (RBCs) due to various factors including hyperosmolarity, oxidative stress, energy depletion, heavy metals exp ...

(the

-like suicidal cell death in defective red blood cells). It has been found to reduce

muscle atrophy Muscle atrophy is the loss of skeletal muscle mass. It can be caused by immobility, aging, malnutrition, medications, or a wide range of injuries or diseases that impact the musculoskeletal or nervous system. Muscle atrophy leads to muscle weakness ...

and to stimulate muscular growth in mice, also shows a potential cardioprotection. In mice, ursolic acid induces

neural regeneration Neuroregeneration refers to the regrowth or repair of nervous tissues, cell (biology), cells or cell products. Such mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. Neuroregeneration differs between the periphera ...

after sciatic nerve injuries and recently found to have COVID preventative capabilities. More research in this recent finding is underway. In mice with chronic

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...

, ursolic acid has reduced further damage to neurons and helped rebuild the protective sheaths covering neurons, apparently by suppressing

Th17 T helper 17 cells (Th17) are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that cause Th17s to differentiate actually inhibit Treg different ...

immune cells and activating precursor cells that mature into myelin-sheath-making cells, called oligodendrocytes. Ursolic acid improves domoic acid-induced cognitive deficits in mice. Ursolic acid improves high fat diet-induced cognitive impairments by blocking endoplasmic reticulum stress and IκB kinase β/

nuclear factor-κB Nuclear may refer to: Physics Relating to the nucleus of the atom: *Nuclear engineering *Nuclear physics *Nuclear power *Nuclear reactor *Nuclear weapon *Nuclear medicine *Radiation therapy *Nuclear warfare Mathematics * Nuclear space *Nuclear ...

-mediated inflammatory pathways in mice. Ursolic acid attenuates

lipopolysaccharide Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...

-induced cognitive deficits in

mouse brain The mouse brain refers to the brain of Mus musculus. Various brain atlases exist. For reasons of reproducibility, genetically characterized, stable strains like C57BL/6 were chosen to produce high-resolution images and databases. Well known onli ...

through suppressing p38/ NF-κB mediated inflammatory pathways. Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of

senescent Senescence () or biological aging is the gradual deterioration of functional characteristics in living organisms. The word ''senescence'' can refer to either cellular senescence or to senescence of the whole organism. Organismal senescence invol ...

mice induced by D-galactose. Ursolic acid enhances mouse liver regeneration after partial hepatectomy. Ursolic acid enhances the

cellular immune system Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in ...

and pancreatic

beta-cell Beta cells (β-cells) are a type of cell (biology), cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and fun ...

function in streptozotocin-induced diabetic mice fed a high-fat diet. Ursolic acid increased skeletal muscle mass, as well as grip strength and exercise capacity, improved endurance, reduced the expression of the genes involved in the development of muscle atrophy, and decreased indicators of accumulated fatigue and exercise-induced stress. In rats, ursolic acid ameliorated high-fat diet-induced

hepatic steatosis Fatty liver disease (FLD), also known as hepatic steatosis, is a condition where excess fat builds up in the liver. Often there are no or few symptoms. Occasionally there may be tiredness or pain in the upper right side of the abdomen. Complicat ...

and improved metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease.

Uses

Ursolic acid can be found in plants that are used for cosmetics additives. It can serve as a starting material for synthesis of more potent bioactive derivatives, such as experimental antitumor agents.

References

{{reflist Triterpenes Hydroxy acids

Natural occurrence

Potential biochemical effects

Uses

See also

References