Pharmacology of oleanolic acid and ursolic acid.

Oleanolic acid and ursolic acid are triterpenoid compounds that exist widely in food, medicinal herbs and other plants. This review summarizes the pharmacological studies on these two triterpenoids. Both oleanolic acid and ursolic acid are effective in protecting against chemically induced liver injury in laboratory animals. Oleanolic acid has been marketed in China as an oral drug for human liver disorders. The mechanism of hepatoprotection by these two compounds may involve the inhibition of toxicant activation and the enhancement of the body defense systems. Oleanolic acid and ursolic acid have also been long-recognized to have antiinflammatory and antihyperlipidemic properties in laboratory animals, and more research is warranted to develop a therapy for patients. Recently, both compounds have been noted for their antitumor-promotion effects, which are stimulating additional research in this field. Oleanolic acid and ursolic acid are relatively non-toxic, and have been used in cosmetics and health products. The possible mechanisms for the pharmacological effects and the prospects for these two compounds are discussed.

[1]  S. Shibata Saponins with Biological and Pharmacological Activity , 1977 .

[2]  S. Shibata Antitumor‐Promoting and Anti‐inflammatory Activities of Licorice Principles and Their Modified Compounds , 1994 .

[3]  M. Rigaud,et al.  Inhibition of lipoxygenase activity and HL60 leukemic cell proliferation by ursolic acid isolated from heather flowers (Calluna vulgaris). , 1992, Biochimica et biophysica acta.

[4]  Y. Ito,et al.  Inhibitory effects of ursolic and oleanolic acid on skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. , 1986, Cancer letters.

[5]  Y. Oshima,et al.  Analgesic and antihepatotoxic actions of dianosides, triterpenoid saponins of Dianthus superbus var. longicalycinus herbs. , 1984, Planta medica.

[6]  Y. Miyake,et al.  Inhibition of glucosyltransferase from Streptococcus mutans by oleanolic acid and ursolic acid. , 1987, Caries research.

[7]  S. Mahato,et al.  Review article number 38Triterpenoid saponins , 1988 .

[8]  Y. A. Dominic,et al.  Studies on mitochondrial lipid peroxidation in tumour-bearing rats treated with ursolic acid and ursolic acetate , 1993 .

[9]  Y. Ito,et al.  Epstein-Barr virus activation by tung oil, extracts of Aleurites fordii and its diterpene ester 12-O-hexadecanoyl-16-hydroxyphorbol-13-acetate. , 1983, Cancer letters.

[10]  A. Kapil,et al.  Anti‐complement activity of oleanolic acid: an inhibitor of C3‐convertase of the classical complement pathway , 1994, The Journal of pharmacy and pharmacology.

[11]  Y. Ito,et al.  Search for possible antitumor promoters by inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus activation; ursolic acid and oleanolic acid from an anti-inflammatory Chinese medicinal plant, Glechoma hederaceae L. , 1986, Cancer letters.

[12]  Y. Dai,et al.  [Effects of oleanolic acid on immune system and type I allergic reaction]. , 1989, Zhongguo yao li xue bao = Acta pharmacologica Sinica.

[13]  S. Choudhuri,et al.  Oleanolic acid protects against cadmium hepatotoxicity by inducing metallothionein. , 1993, The Journal of pharmacology and experimental therapeutics.

[14]  M. Hirota,et al.  Suppression of Tumor Promoter-induced Inflammation of Mouse Ear by Ursolic Acid and 4,4-Dimethylcholestane Derivatives , 1990 .

[15]  K. Lee,et al.  The Cytotoxic Principles of Prunella vulgaris, Psychotria serpens, and Hyptis capitata: Ursolic Acid and Related Derivatives1 , 1988, Planta medica.

[16]  L. Zaprutko,et al.  NITROGENOUS TRITERPENE DERIVATIVES. PART 10: HEMISUCCINATES OF SOME DERIVATIVES OF OLEANOLIC ACID AND THEIR ANTIULCER EFFECTS , 1985 .

[17]  U. Sankawa,et al.  Biologically active constituents of Melaleuca leucadendron: inhibitors of induced histamine release from rat mast cells. , 1991, Chemical & pharmaceutical bulletin.

[18]  A. Favel,et al.  In vitro antifungal activity of triterpenoid saponins. , 1994, Planta medica.

[19]  Liu Zhan-bia Oleanolic acid in decreasing hyperglycemia , 1994 .

[20]  C. Lin,et al.  Novel antihepatotoxic principles of Solanum incanum. , 1988, Planta medica.

[21]  E. O. Bregman,et al.  The Present Status. , 1926 .

[22]  M. Rigaud,et al.  Characterization of ursolic acid as a lipoxygenase and cyclooxygenase inhibitor using macrophages, platelets and differentiated HL60 leukemic cells , 1992, FEBS letters.

[23]  O. N. Tolkachev,et al.  Preparation of Some Ursolic Acid Derivatives and Their Antimicrobial Activity. , 1987 .

[24]  B. Carté,et al.  In vitro antiviral activity of dammar resin triterpenoids. , 1987, Journal of natural products.

[25]  H. Bille,et al.  [Acute hepatitis]. , 1975, Ugeskrift for laeger.

[26]  Jie Liu,et al.  The effects of 10 triterpenoid compounds on experimental liver injury in mice. , 1994, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[27]  Hiking Hiroshi,et al.  Antihepatotoxic actions of papyriogenins and papyriosides, triterpenoids of Tetrapanax papyriferum leaves☆ , 1984 .

[28]  T. Yamamoto,et al.  Studies on bioactive substances in crude drugs used for arthritic diseases in traditional Chinese medicine. III. Isolation and identification of anti-inflammatory and analgesic principles from the whole herb of Pyrola rotundifolia L. , 1985, Chemical & pharmaceutical bulletin.

[29]  G. B. Singh,et al.  Anti‐inflammatory activity of oleanolic acid in rats and mice , 1992, The Journal of pharmacy and pharmacology.

[30]  M. Pinza,et al.  Antiviral activity of new triterpenic derivatives. , 1994, Pharmacological research.

[31]  S. Simon,et al.  Inhibition of human leucocyte elastase by ursolic acid. Evidence for a binding site for pentacyclic triterpenes. , 1991, The Biochemical journal.

[32]  M. Niikawa,et al.  Isolation of substances from glossy privet (Ligustrum lucidum Ait.) inhibiting the mutagenicity of benzo[a]pyrene in bacteria. , 1993, Mutation research.

[33]  H. Wagner,et al.  New Natural Products and Plant Drugs with Pharmacological, Biological or Therapeutical Activity , 1977, Proceedings in Life Sciences.

[34]  E. Park,et al.  Anti-inflammatory activities of hederagenin and crude saponin isolated from Sapindus mukorossi Gaertn. , 1980, Chemical & pharmaceutical bulletin.

[35]  M. Rajasekaran,et al.  Antifertility effect in male rats of oleanolic acid, a triterpene from Eugenia jambolana flowers. , 1988, Journal of ethnopharmacology.

[36]  Y. Liu,et al.  Protective effects of oleanolic acid on acetaminophen-induced hepatotoxicity in mice. , 1993, The Journal of pharmacology and experimental therapeutics.

[37]  M. M. Anisimov,et al.  Chemical structure and antifungal activity of a number of triterpenoids. , 1979, Biology bulletin of the Academy of Sciences of the USSR.

[38]  U. Wrzeciono,et al.  Stickstoffhaltige Triterpenderivate. X: Hemisuccinate einiger Oleanolsäurederivate und deren Antiulkuswirkung , 1985 .

[39]  P. Moore,et al.  Constituents of Eriobotrya japonica. A study of their antiviral properties. , 1992, Journal of natural products.

[40]  M. B. Gupta,et al.  Antiulcer activity of some plant triterpenoids. , 1981, The Indian journal of medical research.

[41]  Takuji Tanaka,et al.  Modifying Effects of Fungal and Herb Metabolites on Azoxymethane‐induced Intestinal Carcinogenesis in Rats , 1992, Japanese journal of cancer research : Gann.

[42]  Y. Muto,et al.  Present status of research on cancer chemoprevention in Japan. , 1990, Japanese journal of clinical oncology.

[43]  Tan Li-wu Anti-inflammatory effect of oleanolic acid , 1989 .

[44]  K. Umehara,et al.  Studies on differentiation-inducing activities of triterpenes. , 1992, Chemical & pharmaceutical bulletin.

[45]  Y. Dai,et al.  [Inhibition of hypersensitivity reactions by oleanolic acid]. , 1988, Zhongguo yao li xue bao = Acta pharmacologica Sinica.

[46]  M. Sela,et al.  The anticariogenic activity of glycyrrhizin: preliminary clinical trials. , 1989, Israel journal of dental sciences.

[47]  X. Ma,et al.  [Studies on the preventive and therapeutic effects of ursolic acid (UA) on acute hepatic injury in rats]. , 1986, Yao xue xue bao = Acta pharmaceutica Sinica.

[48]  Y. Lou,et al.  Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid. , 1994, Cancer research.

[49]  S. Balanehru,et al.  Protective effect of oleanolic acid and ursolic acid against lipid peroxidation. , 1991, Biochemistry international.

[50]  B. Shukla,et al.  Hepatoprotective activity in the rat of ursolic acid isolated from eucalyptus hybrid , 1992 .

[51]  E. Asif,et al.  New steroidal alkaloids from the roots of Buxus papillosa , 1992 .

[52]  T. Konoshima,et al.  Studies on inhibitors of skin-tumor promotion, I. Inhibitory effects of triterpenes from Euptelea polyandra on Epstein-Barr virus activation. , 1987, Journal of natural products.

[53]  Yinping Lei,et al.  STUDIES ON THE EFFECT OF OLEANOLIC ACID ON EXPERIMENTAL LIVER INJURY , 1982 .

[54]  I. Johnson,et al.  The chemistry and biological significance of saponins in foods and feedingstuffs. , 1987, Critical reviews in food science and nutrition.

[55]  Y. Peng,et al.  65 cases of urinary tract infection treated by total acid of Achillea alpina. , 1983, Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan.

[56]  H. P. Charles,et al.  Antimicrobial activity of Carnosol and Ursolic acid: two anti-oxidant constituents of Rosmarinus officinalis L. , 1987 .

[57]  M. B. Gupta,et al.  Anti-inflammatory activity of natural products. I. Triterpenoids. , 1969, European journal of pharmacology.

[58]  Y. Kiso,et al.  Antihepatotoxic actions of papyriogenins and papyriosides, triterpenoids of Tetrapanax papyriferum leaves. , 1984, Journal of ethnopharmacology.

[59]  S. Balanehru,et al.  Triterpenes intervene in adriamycin-induced histamine release in rodents , 1994 .

[60]  H. Nishino,et al.  Inhibition of the tumor-promoting action of 12-O-tetradecanoylphorbol-13-acetate by some oleanane-type triterpenoid compounds. , 1988, Cancer research.

[61]  C. K. Lee,et al.  Ursolic acid inhibits aflatoxin B1-induced mutagenicity in a Salmonella assay system. , 1994, Biological & pharmaceutical bulletin.

[62]  Y. Liu,et al.  The effect of Chinese hepatoprotective medicines on experimental liver injury in mice. , 1994, Journal of ethnopharmacology.

[63]  Jie Liu,et al.  Effect of oleanolic acid on hepatic toxicant-activating and detoxifying systems in mice. , 1995, The Journal of pharmacology and experimental therapeutics.