Ursolic acid is a kind of tritepene compound existing in natural plant with various kinds of biological effects such as sedation, antiinflammation, antibiosis, antidiabetes, antiulcer etc.. In recent years, it has been found that it has the functions of anticancer and antiangiogenesis. It possibly becomes one of the new type anticancer drugs with low toxicity and high efficiency. For strong antioxygen function, ursolic acid is widely used as material of medicine and cosmetics.
In act IV scene v of Hamlet, Ophelia says to Hamlet,'There's rosemary, that's for remembrance, pray you, love, remember'.
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Basic Instruction
Ursolic acid:Actions,Commonly Known Benefit and Research.
M.Formula:C30H48O3 M.Weight:456.3603 CAS No.:77-52-1
EINECS:201-034-0 Beilstein RN: 2228563
Solubility:Insoluble in water,soluble in ethanol, no extraneous substance after being dissolved
Melting Point:283-285 Deg C.
Specific Optical Rotation:59 (c=0.3, pyridine)
Synonyms:(3Beta)-3-hydroxyurs-12-en-28-oic acid;malol;prunol;Ursolic acid;urson,micromerol.
Pharmacological Action: Anti-Infective Agents,Antineoplastic Agents,Phytogenic; Cyclooxygenase Inhibitors.
Basic Introduction and Botanical Info:
Ursolic acid, also known as urson, prunol, micromerol, and malol, is a pentacyclic triterpenoid compound which naturally occurs in a large number of vegetarian foods, medicinal herbs, and other plants. For a long time, it was considered to be pharmacologically inactive. Thus, ursolic acid and its alkali salts (e.g. potassium or sodium ursolates) were exclusively used as emulsifying agents in pharmaceutical, cosmetic, and food preparations. However, upon closer examination, ursolic acid was found to be medicinally active both topically and internally1. Its anti-inflammatory, anti-tumor (skin cancer), and antimicrobial properties make it useful in cosmetic applications.
Definition: ursolic acid:(biochemistry) C30H48O3 A pentacyclic terpene that crystallizes from absolute alcohol solution, found in leaves and berries of plants; used in pharmaceutical and food industries as an emulsifying agent.
Use:Play down blood sugar,oxidation resisting,leave something decrepitude of Human body, antibiotic and anti-inflammation, nourish the liver and promote the function of gallbladder.
Botanical Source:
Ursolic Acid is a pentacyclic triterpenoid. It can be found in many plants including, apple, bilberry, cranberry, elder flower, peppermint, lavender, oregano, thyme, and prunes. Ursolic acid can be used both topically and internally. It is used in cosmetics for its anti-inflammatory and antimicrobial properties. It is also used to treat burns. Ursolic acid has antifungal and antibacterial activities as well.
Distribution: Ursolic acid is present in many plants, including apples, bilberries, cranberries, elder flower, peppermint, lavender, oregano, thyme, hawthorn, prunes.
Like most triterpenoids, ursolic acid is ubiquitous in the plant kingdom. Ursolic acid and its derivatives are constituents of numerous plants which are having diversified phylogenetic origin and taxonomic position. It has been isolated from the protective wax-like coatings of apples, pears, cranberries, prunes, and other fruits. Seaweed are rich in ursolic acid derivatives. Some of the more commonly known medicinal plants containing ursolic acid are shown in Table.
Table 1. Partial List of Medicinal Plants Containing Ursolic Acid
Common Name
Botanical Name
Family
Holy Basil (Tulsi)
Ocimum sanctum L.
Lamiaceae
Peppermint leaves
Mentha piperita L.
Lamiaceae
Lavender
Lavandula augustifolia Mill.
Lamiaceae
Oregano
Origanum vulgare L.
Lamiaceae
Thyme
Thymus vulgaris L.
Lamiaceae
Hawthorn
Crataegus laevigata (Poir) DC
Rosaceae
Cherry laurel leaves
Prunus laurocerasus L.
Rosaceae
Loquat Leaf.
Eriobotrya japonica(Thunb.)Lindl.L.
Rosaceae
Glossy privet leaf
Ligustrum lucidum Ait.L.
Oleaceae
Bilberry
Vaccinum myrtillus L.
Vacciniaceae
Devil's Claw
Harpagophytum procumbens DC
Pedaliaceae
Elder Flowers (European Variety)
Sambucus nigra L.
Caprifoliaceae
Periwinkle
Vinca minor L.
Apocynaceae
Actions and Chemistry of Ursolic Acid:
Medicinal plants containing ursolic acid have been used in folk medicine before it was known which constituents were responsible for their therapeutic effectiveness. Contemporary scientific research which led to the isolation and identification of ursolic acid revealed and confirmed that several pharmacological effects, such as, anti-tumor, hepatoprotective, anti-inflammatory (oral and topical), anti-ulcer, antimicrobial, anti-hyperlipidemic and antiviral, can be attributed to ursolic acid.
However, its anti-inflammatory (topical), anti-tumor (skin cancer), and antimicrobial properties are pertinent to the cosmetic industry.
Ursolic acid has medicinally action, both topically and internally. Ursolic acid is used in many cosmetic preparations for its anti-inflammatory, antitumor and antimicrobial properties.
Ursolic acid has antibacterial and antifungal activity. Tests have shown that Ursolic acid inhibits the growth of Candida albicans and Microsporium lenosum.
Ursolic acid has anti-inflammatory properties and is used in ointments to treat burns.
Topical application of ursolic acid inhibited TPA-induced initiation and promotion of tumor growth.
Chemistry:
Ursolic acid [(3Beta)-3-Hydroxyurs-12-en-28-oic acid] rarely occurs without its isomer oleanolic acid [(3Beta)-3-Hydroxyolean-12-en-28-oic acid] They may occur in their free acid form, as shown in Figure 1, or as aglycones for triterpenoid saponins which are comprised of a triterpenoid aglycone linked to one or more sugar moieties. Ursolic and oleanolic acids are similar in pharmacological activity.
Several ursolic acid derivatives, both natural and synthetic, have been reported. Novel ursolic acid derivatives, including ursane-type triterpenoid saponins, naturally occur as secondary metabolites through complex metabolic processes in different parts of the plants. Synthetic derivatives obtained from ursolic acid have been reported and evaluated for their pharmacological action
Commonly Known Benefit of Ursolic Acid:
1.Inhibition of Tumor Promotion in skin:
Ursolic acid (UA) and oleanolic acid (OA), isolated from Glechoma hederacea, inhibited Epstein-Barr virus activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) in mouse skin. The inhibitory effects were evaluated for 20 weeks. Continuous application of UA and OA (41 nmol of each) before TPA-treatment (4.1 nmol) delayed the formation of papillomas in mouse skin and reduced the rate (%) of papilloma bearing mice. Both UA and OA exhibited remarkable inhibitory activity against tumor promotion, which is comparable to the known tumor inhibitor, retinoic acid (RA). Compared to either RA or OA, ursolic acid inhibited tumor more effectively after a single application before initial TPA-treatment as shown in Figure 1. This suggests that the role of tumor inhibition by UA differs from that of either RA or OA. It is suggested that pretreatment of skin with UA may inhibit the first dramatic cellular event in tumor promotion caused by TPA.
Topical application of ursolic acid derived from rosemary extract inhibited TPA-induced tumor initiation and promotion, inflammation, and ornithine decarboxylase activity in mouse skin. Ursolic acid exhibited strong anti-inflammatory activity. It is even more active than of 1 or 2 mmol of ursolic acid along with 5 nmol of TPA for TPA for 20 weeks inhibited the formation of skin tumors per mouse by 45 or 61% respectively.
Lower doses (0.1 or 0.3 mmol) of ursolic acid had a similar inhibitory effect as the higher doses. Twice weekly topical application of 0.1, 0.3, 1, or 2 mmol of ursolic acid along with 5 nmol TPA for 8,12, and 18 weeks reduced the number of skin tumors per mouse by 52-86%, 49-63%, and 44-61%, respectively.
Ursolic acid and its isomer, oleanolic acid have been recommended for skin cancer therapy in China. Topical cosmetic preparations containing ursolic acid/ oleanolic acid have been patented in China for the prevention of topical skin cancer. An ursolic acid/ oleanolic acid ointment inhibited 7,12-dimethylbenz [alpha] anthracene (DMBA)-induced skin cancer in mice. Reportedly, 0% and 3% of mice developed cancer in 15 weeks and 30 weeks, respectively compared to 50% and 90% for the control mice.
Iridoids are common components of plants, but the iridoid glycosides are important active components of only certain Chinese herbs, particularly rehmannia, with which cornus is frequently combined. It is thought that the glucose molecule is cleaved in the digestive system to yield the aglycone as the active compound that has anti-inflammatory actions.
Oleanolic acid (OA) and ursolic acid (UA) are isomers; they have the same chemical formula. These two pentacyclic triterpenes are of interest to scientists because of their numerous biological activities. OA can lower blood sugar, a property attributed to cornus, which is listed among the Chinese herbs used for treating diabetes. UA and OA have liver-protecting and anti-inflammatory effects; cornus is used in some herb formulas for viral hepatitis and the anti-inflammatory effects may be one reason that cornus can be recommended for low back and knee pain associated with aging.
2.Hair Growth Stimulant:
Ursolic acid and its isomer, oleanolic acid, have been used in to nics to enhance hair growth and prevent scalp irritation. Both triterpenoid compounds encourage hair growth by stimulating the peripheral blood flow in the scalp and activating the hair mother cells. They also furnish alopecia-preventing and dandruff-preventing effects.
3.Antimicrobial Activity:
Beta ursolic acid (triterpenoid sapogenin from the ursan group) inhibited the growth of several strains of staphylococci. Numerous ursolic acid containing plants from the Lamiaceae family exhibited antibacterial/ fungal activity. The minimal inhibitory concentration of Rosmarinus officinalis, Origanum majorana, and Lavandula officinalis were 500, 250, and 500 mg/cm3, respectively. Ursolic acid also inhibited the growth of Microsporium lenosum and Candida albicans at 250 mg/mL.
4.Anti-Aging Agent:
Ursolic acid treatment improves the health of skin and hair. Ursolic acid and its derivatives form oil-resistant barriers on the skin and hair as they do in the waxy coating of fruits. Ursolic acid has been used to treat photoaged skin because it prevents and improves the appearance of wrinkles and age spots by restoring the skin's collagen bundle structures and its elasticity. Concentrations of ursolic acid ranging from 0.01 to 50 mg have been reported for inclusion in skin treatment preparations
5.Anti-Inflammatory Activity:
Ursolic acid is a potent anti-inflammatory agent. Thus, it has been recommended for use in burn ointments. It not only inhibits human leucocyte elastase(HLE), but also 5-lipoxygenase and cyclooxygenase activity. Ursolic acid (1.0 mg/ear) inhibited TPA-induced mouse ear edema by 72.4%23. Hirota and coworkers24 determined that 200 mg and 50 mg applications of ursolic acid inhibited 12-O-hexadecanoyl-16-hydroxyphorbol-13-acetate (HPPA) - induced inflammation by 49% and 33%, respectively. In addition, it inhibited concanavalin A (Con A) induced histamine release, which can cause severe inflammation, by 95% at a concentration of 0.001 M.
6.Remembrance and acetylcholinesterase inhibitor:
Soundbite Molecules: Rosemary and Ursolic acid for Remembrance
Simon Cotton, teacher at Uppingham School, takes a look at those compounds that find themselves in the news or relate to our everyday lives.
That's from a Shakespeare play, isn't it?
Yes, in act IV scene v of Hamlet, Ophelia says to Hamlet,,'There's rosemary, that's for remembrance, pray you, love, remember'.
And is there any connection?
One link is that the plant symbolises remembering the dead. In act IV scene v of Romeo and Juliet, rosemary was placed on Juliet's body for her burial ('Stick your rosemary on this fair cor[p]se'). Australians wear a sprig of rosemary on Anzac day to honour the dead soldiers of World War I. The herb grows wild on the Gallipoli peninsula, Turkey, where many Anzacs died during the ill-fated Allied campaign of 1915.
Is there any evidence that rosemary helps memory?
Recent research by Dr Mark Moss and his colleagues at Northumbria University in Newcastle suggests that exposure to rosemary oil can enhance long-term memory by ca 15 per cent.
Which chemicals might be responsible for this effect?
Rosemary contains hundreds of different chemicals. The herb has been used in medicine as a stimulant, possibly owing to its camphor (1) content, while cineole (eucalyptol, 2) and camphor are among the molecules that give the plant microbiocidal properties. Rosemary has long been used as a food preservative. The plant contains antioxidants such as rosemarinic acid (3) and carnosic acid (4). But possibly the most interesting chemical component that affects memory is ursolic acid (5).
How so?
Ursolic acid inhibits acetylcholinesterase. This the enzyme catalyses the breakdown of the neurotransmitter chemical acetylcholine, which is important for effective cognition and reasoning. The degeneration of acetylcholine-producing neurons in the brains of people with Alzheimer's disease (AD) has been blamed for the symptom of memory loss associated with AD. Thus, sustaining acetylcholine levels may help delay this memory loss. Ursolic acid has also been shown to slow skin tumour development.
Pentacyclic Triterpenes (PCTs) as Inhibitors of Inflammation:
Pentacyclic triterpenes (PCTs) are a subdivision of an important group of botanical active constituents known as triterpenoids; when complexed with sugar molecules PCTs are called triterpene glycosides, or saponins. Several of the PCTs have inhibitory action for the COX and/or LOX enzymes. Two of the most widely occurring and intensively investigated pentacyclic triterpenes are ursolic acid and its isomer oleanolic acid; their chemical formulas are identical, and their structures differ only by the location of a methyl group (CH3), as displayed at the top of the structure diagrams below. These substances are of considerable interest for potential health benefits, including protective effects against development of cancer, inhibition of existing tumor cells, protection against chemotherapy and radiation therapy adverse effects, anti-inflammatory activity, antioxidant activity, cardiovascular protective effects, and antiviral effects. Several medicinal herbs that contain oleanolic acid, such as ligustrum, forsythia, and swertia, are remedies employed in China for the treatment of hepatitis. Isolated oleanolic acid has already been used in China as a treatment for hepatitis for many years. Ursolic acid is known for its ability to inhibit skin inflammation; in China it is also used as a topical protectant against skin cancer.
These compounds are synthesized in plants from squalene, a compound in which there are no closed carbon rings, but which has the basis for developing five ring (pentacyclic) compounds. Ursolic acid was named after the herb Uva Ursi (bearberry; urs is the root term for bear). Oleanolic acid was named for the olive (olea is the root term for olive), which is rich in this compound; there is a plant family called the Oleanaceae, whose members usually contain oleanolic acid. In general, plants that contain ursolic acid also contain oleanolic acid and vice versa.
Ursolic acid and oleanolic acid form a waxy coating that is found on some plant leaves and fruits. For example, Ligustrum trees (in the Oleanaceae family) are commonly called wax trees because of these components. Ursolic acid is one of the main waxy components on apples that contributes to the smooth, shiny appearance (not to be confused with waxes sometimes added to aid storage of fruits). Squalene (left) is found in some foods, mainly concentrated in oils, such as olive oil, wheat germ oil, and bran oil (about 0.5% of the oil). The most abundant source of squalene is the liver of deep sea sharks (up to 85% squalene in liver oil). Squalene from shark livers is sold in capsules as a dietary supplement that is claimed by proponents to enhance immune functions and reduce inflammation.
The pentacyclic triterpenes are subdivided into several groups, such as the following:
Oleanane: oleanolic acid, ginsenosides (glycoside form), fusidic acid;
Ursane: amyrin, ursolic acid, asiatic acid, boswellic acid; and
Lupane: lupeol, betulin, betulinic acid
Of these, PCTs other than oleanolic and ursolic acid that have received considerable attention are boswellic acid (from frankincense, the resin of Boswellia serrata); asiatic acid (from gotu kola, the aerial part of Centella asiatica), and betulinic acid (from birch trees, the bark of Betula spp.). Their pharmacology is similar to that of oleanolic and ursolic acid. For example, all are being investigated for anti-inflammatory and potential anticancer effects.
Sources of Oleanolic Acid and Ursolic Acid:
Chinese natural products manufacturers are now making high concentrations of oleanolic acid and ursolic acid for formulation in various internal and topical remedies. The technical extracts contain from 25% to 99% pure compound. By contrast, standard herb extracts (e.g., hot water extracts) have up to 2.0-2.5% of ursolic or oleanolic acid (commonly obtained from holy basil, Ocimum sanctum, a common ingredient in Ayurvedic formulas). Plants rich in ursolic acid include Greek sage (Salvia triloba), oleander, rosemary, lavender, and thyme (each having at least 1% ursolic acid in the leaf or whole plant)
Safety and Toxicity for Ursolic Acid:
Notwithstanding its numerous cosmetic properties, ursolic acid is an ideal cosmetic ingredient because its overall toxicity (both chronic and acute) is low. It is not a primary irritant or sensitizer. In fact, it has been termed dermatologically innocuous.
Chronic toxicity:Ursolic acid
Hypodermic Injection:Rodent-mouse.3500mg/kg.No Death in 72 hours.
Hypodermic Injection:Rodent-Rat.Dose/Period:0.5 gram/kg.30days.No distinctive effect on body weight, blood, cardiogram, liver,and kidney functions. No pathology changes for important organs,result prove ursolic acid low toxicity and safe enough.
Administration and Dosage:
Clinical use of ursolic acid as an isolate is new, but oleanolic acid, which is nearly identical in structure but apparently milder in action, has been used for some time. Effective daily doses of oleanolic acid, based on its application in treatment of hepatitis, are reported in the range of 75-300 mg/day.
For a standard dried hot water extract of an herb, which may contain about 2% of the PCTs, that dosage corresponds to use of about 4-15 grams of the extract, a large amount. Additional information on dosage of compounds of this type (see: Platycodon and other herbs with triterpene glycosides) indicates that a daily dose of about 300 mg is safe and potentially useful for long term applications and 600 mg is safe at least for short term dosage.
Dr. Acharan Narula describes use of 300-500 mg or oleanolic acid as an intestinal anti-inflammatory and recommends Olenoate, a product of oleanolic acid in capsules of 100 mg each. For ursolic acid, in vitro studies have shown that it is about twice as effective as an anti-inflammatory compared to indomethacin, a potent NSAID that is administered in doses of just 50-100 mg/day; however, when converted to actual human use, the dose of ursolic acid needed may prove higher.
Boswellic acid, another PCT that inhibits 5-LOX, and is used as an anti-inflammatory for arthritis, Crohn's disease, and asthma, is administered in doses of 400 mg 3 times a day of an extract standardized to contain 37.5% boswellic acids, which corresponds to 450 mg/day of boswellic acid.
In general, the PCT dosage for anti-inflammatory effects appears similar to the dosage of NSAIDS.
Scientific References:
1.Ursolic acid:Actions,Commonly Known Benefit and Research.
Claims & Warning:
Claims: Information this web site presented is meant for Nutritional Benefit and as an educational starting point only, for use in maintenance and promotion good health in cooperation with a common knowledge base reference...Furthermore,it based solely on the traditional and historic use or legend of a given herb from the garden of Adonis. Although every effort has been made to ensure its accurate, please note that some info may be outdated by more recent scientific developments......
Pharmakon Warning: The order of knowledge is not the transparent order of forms and ideas,as one might be tempted retrospectively to interpret it; it is the antidote....(Dissemination,Plato's Pharmacy,II.The Ingredients:Phantasms,Festivals,and Paints;138cf. Jacques Derrida.).
And as it happens,the technique of imitation,along with the production of the simulacrum,has always been in Plato's eyes manifestly magical,thaumaturgical:......and the same things appear bent and straight to those who view them in water and out,or concave and convex,owing to similar errors of vision about colors, and there is obviously every confusion of this sort in our souls.And so scene painting (skiagraphia) in its exploitation of this weakness of four nature falls nothing short of witchcraft (thaumatopoia), and so do jugglery and many other such contrivances.(Republic X,602c-d;cf.also 607c).
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seminal trace...Ursolic acid.C30H48O3.CAS No.77-52-1.malol;prunol;Ursolic acid;urson,micromerol,Loquat Leaf extract.Glossy privet leaf Extract.Ursolic acid.25%50%95%HPLC.Pentacyclic Triterpenes....
Botanical Source:
Scientific References:
Claims & Warning:
