Klin Farmakol Farm. 2004;18(2):96-101

Biologické účinky triterpenoidů: protizánětlivé, antimikrobiální, hepatoprotektivní, analgetické a další farmakologické aktivity

Petr Džubák1, Marián Hajdúch1,2, David Vydra1, Jan Šarek3, Karel Cwiertka2
1 Laboratoř experimentální medicíny při Dětské klinice LF UP a FN Olomouc
2 Onkologická klinika FN a LF UP, Olomouc
3 Katedra organické a jaderné chemie, Přírodovědecká fakulta UK v Praze

Keywords: triterpenoids, anti-inflammatory, antiulcerogenic, antimicrobial, virostatic.

Published: December 31, 2004  Show citation

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Džubák P, Hajdúch M, Vydra D, Šarek J, Cwiertka K. Biologické účinky triterpenoidů: protizánětlivé, antimikrobiální, hepatoprotektivní, analgetické a další farmakologické aktivity. Klin Farmakol Farm. 2004;18(2):96-101.

Článek navazuje na předchozí část zaměřenou na protinádorové účinky triterpenoidů a podává podrobným způsobem přehled dalších farmakologických aktivit, které se často mezi sebou překrývají. Protizánětlivé, antiulcerózní, antimikrobiální, antiprotozoální, ale také virostatické a analgetické patří mezi ty nejvýznamnější. Vlastní mechanizmus působení je různorodý, přes ovlivnění prozánětlivých enzymů, transkripčních faktorů, blokádu uvolnění histaminu, až k inhibici enzymů důležitých pro replikaci virionu, či patogenitu baktérie. Pokročilé metody izolace a přesná identifikace přírodních triterpenoidů otevírá cestu k syntetickým modifikacím a screeningu semisyntetických sloučenin s potenciálně vyšším žádoucím a nižším nežádoucím účinkem.

BIOLOGICAL ACTIVITY OF TRITERPENOIDS: ANTIINFLAMMATORY, ANTIMICROBIAL, HEPATOPROTECTIVE, ANALGESTIC AND OTHERS PHARMACOLOGICAL ACTIVITIES

This article is the second part of the review about triterpenoids and their biological activities. The first part focuses on the anticancer effects and the second part is about other pharmacological activities. These effects have been found to often overlap. Antiinflammatory, antiulcerogenic, antimicrobial, antiprotozoal, virostatic and analgestic activity are the most significant effects. The mechanism of action is heterogenous over inhibition of pro-inflammatory enzymes, transcriptional factors to inhibition of release of histamine, and inhibition of enzymes important for the replication of viroids or pathogenicity of bacteria. Isolation and precise identification of triterpenoids occurring in nature is ongoing. Advanced analysis opens up new ways to other synthetic modifications and to the screening of more effective semi-synthetic compounds with higher activity and eliminated adverse reactions.

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References

  1. Wasserman SI. Mediators of immediate hypersensitivity. J. Allergy. Clin. Immunol. 1983; 72: 101-119. Go to original source... Go to PubMed...
  2. Ammon HP, Mack T, Singh GB, et al. Inhibition of leukotriene B4 formation in rat peritoneal neutrophils by an ethanolic extract of the gum resin exudate of Boswellia serrata. Planta Medica 1991; 57: 203-207. Go to original source... Go to PubMed...
  3. Giner-Larza EM, Manez S, Recio MC, et al. Oleanonic acid, a 3-oxotriterpene from Pistacia, inhibits leukotriene synthesis and has anti-inflammatory activity. Eur. J. Pharmacol. 2001; 28: 137-143. Go to original source... Go to PubMed...
  4. Sailer ER, Subramanian LR, Rall B, et al. Acetyl-11-keto-beta-boswellic acid (AKBA): structure requirements for binding and 5-lipoxygenase inhibitory activity. Br. J. Pharmacol. 1996; 117: 615-618. Go to original source... Go to PubMed...
  5. Sailer ER, Schweizer S, Boden SE, et al. Characterization of an acetyl-11-keto-beta-boswellic acid and arachidonate-binding regulatory site of 5-lipoxygenase using photoaffinity labeling. Eur. J. Biochem. 1998; 256: 364-368. Go to original source... Go to PubMed...
  6. Dahmen U, Gu YL, Dirsch O, et al. Boswellic acid, a potent antiinflammatory drug, inhibits rejection to the same extent as high dose steroids. Transplant. Proc. 2001; 33: 539-541. Go to original source... Go to PubMed...
  7. Bernstein PR, Edwards PD, Williams JC. Inhibitors of human leukocyte elastase. Prog. Med. Chem. 1994; 31: 59-120. Go to original source... Go to PubMed...
  8. Gupta MB, Nath R, Gupta GP, et al. Antiulcer activity of some plant triterpenoids. Indian J. Med. Res. 1981; 73: 649-652.
  9. Hirota M, Mori T, Yoshida M, et al. Suppression of tumor promoter-induced inflammation of mouse ear by ursolic acid and 4,4-dimethylcholestane derivatives. Agric. Biol. Chem. 1990; 54: 1073-1075. Go to original source...
  10. Safayhi H, Rall B, Sailer ER, et al. Inhibition by boswellic acids of human leukocyte elastase. J. Pharmacol. Exp. Ther. 1997; 281: 460-463.
  11. Elliott S, Hyas E, Mayor M, et al. The triterpenoid CDDO inhibits expression of matrix metalloproteinase-1, matrix metaloproteinase-13 and Bcl-3 in primary human chondrocytes. Arthritis Res. Ther. 2003; 5: R385-R291. Go to original source... Go to PubMed...
  12. Mix KS, Coon CI, Rosen ED, et al. Peroxisome proliferator-activated receptor-?-independent repression of collagenase gene expression by 2-cyano-3,12-dioxooleana-1.9-dien-28-oic acid and prostaglandin 15-deoxy-?(12,14)J2: a role for Smad signaling. Mol. Pharmacol. 2004; 65: 309-318. Go to original source... Go to PubMed...
  13. Reddy GK, Chandraksan G, Dhar SC. Studies on the metabolism of glycosaminoglycans under the influence of new herbal anti-inflammatory agents. Biochem. Pharm. 1989; 38: 3527-3534. Go to original source... Go to PubMed...
  14. Sander O, Herborn G, Rau R. Is H15 (resin extract of Boswellia serrata, "incense) a useful supplement to established drug therapy of chronic polyarthritis? Results of a double-blind pilot study. Z. Rheumatol. 1998; 57: 11-16. Go to original source... Go to PubMed...
  15. Gerhardt H, Seifert F, Buvari P, et al. Therapy of active Crohn disease with Boswellia serrata extract H 15. Z. Gastroenterol. 2001; 39: 11-17. Go to original source... Go to PubMed...
  16. Gupta I, Parihar A, Malhotra P, et al. Effects of Boswellia serrata gum resin in patients with ulcerative colitis. Eur. J. Med. Res. 1997; 2: 37-43.
  17. Gupta I, Parihar A, Malhotra P, et al. Effects of gum resin of Boswellia serrata in patients with chronic colitis. Planta Med. 2001; 67: 391-395. Go to original source... Go to PubMed...
  18. Gupta I, Gupta V, Parihar A, et al. Effects of Boswellia serrata gum resin in patients with bronchial asthma: results of a double-blind, placebo-controlled, 6-week clinical study. Eur. J. Med. Res. 1998; 17: 511-514.
  19. Bernard P, Scior T, Didier B, et al. Etnopharmacology and bioinformatic combination for leads discovery: application to phospholipase A(2) inhibitors. Phytochemistry 2001; 58: 865-874. Go to original source... Go to PubMed...
  20. Jain MK, Yu BZ, Rogers JM, et al. Specific competitive inhibitor of secreted phospholipase A2 from berries of Schinus terebinthifolius. Phytochemistry. 1995; 39: 537-547. Go to original source... Go to PubMed...
  21. Kapil A, Sharma S. Effect of oleanolic acid on complement in adjuvant- and carrageenan-induced inflammation in rats. J. Pharm. Pharmacol. 1995; 47: 585-587. Go to original source... Go to PubMed...
  22. Kapil A, Sharma S. Anti-complement activity of oleanolic acid: an inhibitor of C3-convertase of the classical complement pathway. J. Pharm. Pharmacol. 1994; 46: 922-923. Go to original source... Go to PubMed...
  23. Assefa H, Nimrod A, Walker L, et al. Enantioselective synthesis and complement inhibitory assay of A/B-ring partial analogues of oleanolic acid. Bioorg. Med. Chem. Lett. 2001; 11: 1619-1623. Go to original source... Go to PubMed...
  24. Min BS, Gao JJ, Hattori M, et al. Anticomplement activity of terpenoids from the spores of Ganoderma lucidum. Planta Med. 2001; 67: 811-814. Go to original source... Go to PubMed...
  25. Singh GB, Singh S, Bani S, et al. Anti-inflammatory activity of oleanolic acid in rats and mice. J. Pharm. Pharmacol. 1995; 47: 585-587. Go to PubMed...
  26. Kim YP, Lee EB, Kim SY, et al. Inhibition of prostaglandin E2 production by platycodin D isolated from the root of Platycodon grandiflorum.Planta Med. 2001; 67: 362-364. Go to original source... Go to PubMed...
  27. Ringbom T, Segura L, Noreen Y, et al. Ursolic acid from Plantago major, a selective inhibitor of cyclooxygenase-2 catalyzed prostaglandin biosynthesis. J. Nat. Prod. 1998; 61: 1212-1215. Go to original source... Go to PubMed...
  28. Subbaramaiah K, Michaluart P, Sporn MB, et al. Ursolic acid inhibits cyclooxygenase-2 transcription in human mammary epithelial cells. Cancer Res. 2000; 60: 2399-2404.
  29. Choi CY, You HJ, Jeong HG. Nitric oxide and tumor necrosis factor-alpha production by oleanolic acid via nuclear factor-kappaB activation in macrophages. Biochem. Biophys. Res. Commun. 2001; 288: 49-55. Go to original source... Go to PubMed...
  30. Jeong HG, Kim JY. Induction of inducible nitric oxide synthase expression by 18beta-glycyrrhetinic acid in macrophages. FEBS Lett. 2002; 513: 208-212. Go to original source... Go to PubMed...
  31. Suh N, Wang Y, Honda T, et al. A novel synthetic oleanane triterpenoid, 2-cyano3,12-dioxoolean-1,9-dien-28-oic acid, with potent differentiating, antiproliferative, and anti-inflammatory activity. Cancer Res. 1999; 59: 336-341.
  32. Yamashita K, Lu H, Lu J, et al.Effect of three triterpenoids, lupeol, betulin, and betulinic acid on the stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophils. Clin. Chim. Acta. 2002; 325: 91-96. Go to original source... Go to PubMed...
  33. Geetha T, Varalakshmi P, Latha RM. Effect of triterpenes from Crataeva nurvala stem bark on lipid peroxidation in adjuvant induced arthritis in rats. Pharmacol Res. 1998; 37: 191-195. Go to original source... Go to PubMed...
  34. Chen G, Lu H, Wang C, et al. Effect of five triterpenoid compounds isolated from leaves of Diospyros kaki on stimulus-induced superoxide generation and tyrosyl phosphorylation in human polymorphonuclear leukocytes. Clin. Chim. Acta. 2002; 320: 11-16. Go to original source... Go to PubMed...
  35. Huang FC, Chan WK, Moriarty KJ, et al. Novel cytokine release inhibitors. Part I: Triterpenes. Bioorg. Med. Chem. Lett. 1998; 8: 1883-1886. Go to original source... Go to PubMed...
  36. He W, Huang FC, Gavai A, et al. Novel cytokine release inhibitors. Part III: Truncated analogs of tripterine. Bioorg. Med. Chem. Lett. 1998; 15: 3659-3664. Go to original source... Go to PubMed...
  37. Takaishi Y, Wariishi N, Tateishi H, et al. Triterpenoid inhibitors of interleukin-1 secretion and tumour-promotion from Tripterygium Wilfordii var. Regelii. Phytochemistry. 1997; 45: 969-974. Go to original source...
  38. Farina C, Pinza M, Pifferi G. Synthesis and anti-ulcer activity of new derivatives of glycyrrhetic, oleanolic and ursolic acids. Farmaco. 1998; 53: 22-32. Go to original source... Go to PubMed...
  39. Rodriguéz JA, Astudillo L, Schmeda-Hirschmann G. Oleanolic acid promotes healing of acetic acid-induced chronic gastric lesions in rats. Pharm. Res. 2003; 48: 291-294. Go to original source... Go to PubMed...
  40. Zhang Z, ElSohly HN, Jacob MR, et al. Natural products inhibiting Candida albicans secreted aspartic proteases from Lycopodium cernuum. J. Nat. Prod. 2002; 65: 979-985. Go to original source... Go to PubMed...
  41. Bringmann G, Saeb W, Assi LA, et al. Betulinic acid: isolation from Triphyophyllum peltatum and Ancistrocladus heyneanus, antimalarial activity, and crystal structure of the benzyl ester. Planta Med. 1997; 63: 255-257. Go to original source... Go to PubMed...
  42. Steele JC, Warhurst DC, Kirby GC, et al. In vitro and in vivo evaluation of betulinic acid as an antimalarial. Phytother. Res. 1999; 13: 115-119. Go to original source... Go to PubMed...
  43. Majester-Savornin B, Elias R, Diaz-Lanza AM, et al. Saponins of the ivy plant, Hedera helix, and their leishmanicidic activity. Planta. Med. 1991; 57: 260-262. Go to original source... Go to PubMed...
  44. Oketch-Rabah HA, Dossaji SF, Christensen SB, et al. Antiprotozoal compounds from Asparagus africanus. J. Nat. Prod. 1997; 60: 1017-1022. Go to original source... Go to PubMed...
  45. Camacho MR, Mata R, Castaneda P, et al. Bioactive compounds from Celaenodendron mexicanum. Planta Med. 2000; 66: 463-468. Go to original source... Go to PubMed...
  46. Benoit-Vical F, Imbert C, Bonfils J. Antiplasmodial and antifungal activities of iridal a plant triterpenoid. Phytochemistry 2003; 62, 747-775. Go to original source... Go to PubMed...
  47. Cantrell ChL, Franzblau SG, Fischer NH. Antimycobacterial Plant Terpenoids. Planta Med. 2001; 67, 685-694. Go to original source... Go to PubMed...
  48. Nawaz HR, Malik A, Ali MS. Trianthenol: an antifungal tetraterpenoid from Trianthema portulacastrum (Aizoaceae). Phytochemistry 2001; 56: 99-102. Go to original source... Go to PubMed...
  49. Hada S, Hattori T, Namba T. Dental caries prevention by traditional medicines. Effect of components of Ganoderma lucidum on glucosyltransferase from Streptococcus mutans. Chemical Abstracts 1990; 113, 91423f.
  50. Kozai K, Miyake, Kohda H, et al. Inhibition of glucosyltransferase from Streptococcus mutans by oleanolic acid and ursolic acid. Caries Research 1987; 21, 104-108. Go to original source... Go to PubMed...
  51. Steinberg D, Sgan-Cohen HD, Stabholz A, et al. The anticariogenic activity of glycyrrhizin: preliminary clinical trials. Isr. J. Dent. Sci. 1989; 2: 153-157. Go to PubMed...
  52. Kashiwada Y, Hashimoto F, Cosentino LM, et al. Betulinic acid and dihydrobetulinic acid derivatives as potent anti-HIV agents. J. Med. Chem. 1996; 39: 1016-1017. Go to original source... Go to PubMed...
  53. Kashiwada Y, Wang HK, Nagao T, et al. Anti-AIDS agents. 30. Anti-HIV activity of oleanolic acid, pomolic acid, and structurally related triterpenoids. J. Nat. Prod. 1998; 61: 1090-1095. Go to original source... Go to PubMed...
  54. Hashimoto F, Kashiwada Y, Cosentino LM, et al. Anti-AIDS agents-XXVII. Synthesis and anti-HIV activity of betulinic acid and dihydrobetulinic acid derivatives. Bioorg. Med. Chem. 1997; 5: 2133-2143. Go to original source... Go to PubMed...
  55. Baltina LA, Flekhter OB, Nigmatullina LR. Lupane triterpenes and derivatives with antiviral activity. Bioorganic and Medic. Chem. Lett. 2003; 13: 3549-3552. Go to original source... Go to PubMed...
  56. Cichewicz RH, Kouzi SA. Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection. Medicinal Research Reviews 2004; 24: 90-114. Go to original source... Go to PubMed...
  57. Mayaux JF, Bousseau A, Pauwels R, et al. Triterpene derivatives that block entry of human immunodeficiency virus type 1 into cells. Proc. Natl. Acad. Sci. USA 1994; 91: 3564-3568. Go to original source... Go to PubMed...
  58. Holz-Smith SL, Sun IC, Jin L, et al. Role of human immunodeficiency virus (HIV) type 1 envelope in the anti-HIV activity of the betulinic acid derivative IC9564. Antimicrob. Agents. Chemother. 2001; 45: 60-66. Go to original source... Go to PubMed...
  59. Kashiwada Y, Chiyo J, Ikeshiro Y, et al. 3,28-Di-O-(dimethylsuccinyl)betulin isomers as anti-HIV agents. Bioorganic & Medicinal Chemistry Letters 2001; 11: 183-185. Go to original source... Go to PubMed...
  60. Sun IC, Shen JK, Wang HK, et al. Anti-AIDS agents. 32. Synthesis and anti-HIV activity of betulin derivatives. Bioorg. Med. Chem. Lett. 1998; 8: 1267-1272. Go to original source... Go to PubMed...
  61. Sun IC, Wang HK, Kashiwada Y, et al. Anti-AIDS agents. 34. Synthesis and structure-activity relationships of betulin derivatives as anti-HIV agents. J. Med. Chem. 1998; 41: 4648-4657. Go to original source... Go to PubMed...
  62. Zhu YM, Shen JK, Wang HK, et al. Synthesis and anti-HIV activity of oleanolic acid derivatives. Bioorg. Med. Chem. Lett. 2001; 11: 3115-3118. Go to original source... Go to PubMed...
  63. Akihisa T, Ogihara J, Kato J, et al. Inhibitory effects of triterpenoids and sterols on human immunodeficiency virus-1 reverse transcriptase. Lipids 2001; 36: 505-512. Go to original source... Go to PubMed...
  64. Quere L, Wenger T, Schramm HJ. Triterpenes as potential dimerization inhibitors of HIV-1 protease. Biochem. Biophys. Res. Commun. 1996; 227: 484-488. Go to original source... Go to PubMed...
  65. Kanamoto T, Kashiwada Y, Kanbara K, et al. Anti-human immunodeficiency virus activity of YK-FH312 (a betulinic acid derivative), a novel compound blocking viral maturation. Antimicrob. Agents. Chemother. 2001; 45: 1225-1230. Go to original source... Go to PubMed...
  66. Hunan Med. Inst. Pharmacological studied of hepatoprotective compounds from Swertia mileensis. Traditional Medicine. 1975; 6: 47-62.
  67. Liu J. Pharmacology of oleanolic acid and ursolic acid. J. Ethnopharmacol. 1995; 49: 57-68. Go to original source... Go to PubMed...
  68. Jeong HG. Inhibition of cytochrome P450 2E1 expression by oleanolic acid: hepatoprotective effects against carbon tetrachloride-induced hepatic injury. Toxicol. Lett. 1999; 105: 215-222. Go to original source... Go to PubMed...
  69. Liu J, Liu Y, Madhu C, et al. Protective effects of oleanolic acid on acetaminophen-induced hepatotoxicity in mice. J. Pharmacol. Exp. Ther. 1993; 266: 1607-1613.
  70. Liu Y, Kreppel H, Liu J, et al. Oleanolic acid protects against cadmium hepatotoxicity by inducing metallothionein. J. Pharmacol. Exp. Ther. 1993; 266: 400-406.
  71. Liu J, Liu Y, Parkinson A, et al. Effect of oleanolic acid on hepatic toxicant-activating and detoxifying systems in mice. J. Pharmacol. Exp. Ther. 1995; 275: 768-774.
  72. Matsuda H, Samukawa K, Kubo M. Anti-hepatitic activity of ginsenoside Ro. Planta Med. 1991; 57: 523-526. Go to original source... Go to PubMed...
  73. Liu J, Liu Y, Mao Q, et al. The effects of 10 triterpenoid compounds on experimental liver injury in mice. Fundam. Appl. Toxicol. 1994; 22: 34-40. Go to original source... Go to PubMed...
  74. Miura N, Matsumoto Y, Miyairi S, et al. Protective effects of triterpene compounds against the cytotoxicity of cadmium in HepG2 cells. Mol. Pharmacol. 1999; 56: 1324-1328. Go to original source... Go to PubMed...
  75. Shim SB, Kim NJ, Kim DH. Beta-glucuronidase inhibitory activity and hepatoprotective effect of 18 beta-glycyrrhetinic acid from the rhizomes of Glycyrrhiza uralensis. Planta Med. 2000; 66: 40-43. Go to original source... Go to PubMed...
  76. Sunitha S, Nagaraj M, Varalakshmi P. Hepatoprotective effect of lupeol and lupeol linoleate on tissue antioxidant defence system in cadmium-induced hepatotoxicity in rats. Fitoterapia. 2001; 72: 516-523. Go to original source... Go to PubMed...
  77. Beirith A, Santos AR, Calixto JB, et al. Study of the antinociceptive action of the ethanolic extract and the triterpene 24-hydroxytormentic acid isolated from the stem bark of Ocotea suaveolens. Planta Med. 1999; 65: 50-55. Go to original source... Go to PubMed...
  78. Menon MK, Kar A. Analgesic and psychopharmacological effects of the gum resin of Boswellia serrata. Planta Medica 1971; 19: 333-341. Go to original source... Go to PubMed...
  79. Bhalla TN, Gupta MB, Bhargava KP. Antipyretic and analgesic activity of some natural products. Ind. J. Pharmac. 1971; 3: 194-196.
  80. Tapondjou LA, Lontsi D, Sondengam BL, et al. In vivo anti-nociceptive and anti-inflammatory effect of the two triterpenes, ursolic acid and 23-hydroxyursolic acid, from Cussonia bancoensis. Arch. Pharm. Res. 2003; 26: 143-146. Go to original source... Go to PubMed...
  81. Fernandes AMS, Baker EA, Martin JT. Studies on plant cuticle VI. Isolation and fractionation of cuticular waxes. Ann. appl. Biol. 1964; 53, 43-58. Go to original source...
  82. Džubák P, Šarek J, Hajdúch M. Biologické účinky triterpenoidů: protinádorová aktivita. Klin. Farmakol. Farm. 2004; 18: 14-21.




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