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Planta Med 2000; 66(3): 221-227
DOI: 10.1055/s-2000-8563
Original Paper
Georg Thieme Verlag Stuttgart · New York

In Vivo Studies on the Anti-Inflammatory Activity of Pachymic and Dehydrotumulosic Acids

Eva-María Giner1 , Salvador Máñez1 , María-Carmen Recio1 , Rosa-María Giner1 , Miguel Cerdá-Nicolás2 , José-Luis Ríos1,*
  • 1 Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Spain
  • 2 Departament de Patologia, Facultat de Medicina, Universitat de València, Spain
Further Information

Publication History

Publication Date:
31 December 2000 (online)

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Abstract

Pachymic and dehydrotumulosic acids were studied in different models of acute and chronic inflammation. They proved to be active in most of the methods applied. None of them were active against arachidonic acid-induced ear edema. Dehydrotumulosic acid significantly diminished the mouse ear edema induced by ethyl phenylpropiolate, while pachymic acid was ineffective. When the putative corticoid-like mechanism of both compounds was explored, pachymic acid activity was partially abolished by the glucocorticoid receptor antagonist progesterone, but dehydrotumulosic acid activity was not affected. In vivo experiments demonstrated the inhibition by both principles of the phospholipase A2 (PLA2)-induced extravasation. The previous report on the effects of both compounds in vitro against PLA2, together with the present in vivo results, support the idea that the inhibition of this enzyme probably constitutes their main mechanism of action.

Abbreviations

AA:arachidonic acidCOX:cyclooxygenaseEPP:ethyl phenylpropiolateLOX:lipoxygenaseMPO:myeloperoxidasePLA2:phospholipase A2PMNL:polymorphonuclear leukocytesTPA:12-O-tetradecanoylphorbol-13-acetate

Key words

Pachymic acid - dehydrotumulosic acid - anti-inflammatory activity - dermatitis - Poria cocos - Polyporaceae - phospholipase A2 inhibition

References

  • 1 Chang  H M,, But  P PH.. Pharmacology and Applications of Chinese Materia Medica. Vol. 2. World Scientific, Singapore; 1987: 875-7
  • 2 Hikino  H.. Recent Research on Oriental Medicinal Plants. In: Wagner H, Hikino H, Farnsworth NR, editors Vol. 1. Academic Press, London; 1985: 64-5
  • 3 Hattori  T,, Hayashi  K,, Nagao  T,, Furuta  K,, Ito  M,, Suzuki  Y.. Studies of antinephritic effects of plant components (3). Effects of pachyman, a main component of Poria cocos Wolf on original-type anti-GBM nephritis in rats and its mechanisms.  Jpn. J. Pharmacol.. 1992;;  59 89-96
    PubMedGoogle Scholar
  • 4 Tai  T,, Akita  Y,, Kinoshita  K,, Koyama  K,, Takahachi  K,, Watanaba  K.. Anti-emetic principles of Poria cocos.  Planta Medica. 1995;;  61 527-30
    PubMedGoogle Scholar
  • 5 Cuéllar  M J,, Giner  R M,, Recio  M C,, Just  M C,, Máñez  S,, Ríos  J L.. Effect of the basidiomycete Poria cocos on experimental dermatitis and other inflammatory conditions.  Chem. Pharm. Bull.. 1997;;  45 492-4
    PubMedGoogle Scholar
  • 6 Tseng  J,, Chang  J G.. Suppression of tumor necrosis factor-α, interleukin-1β, interleukin-6 and granulocyte-monocyte colony stimulating factor secretion from human monocytes by an extract of Poria cocos.  Chin. J. Microbiol. Immunol.. 1992;;  25 1-11
    PubMedGoogle Scholar
  • 7 Cuéllar  M J,, Giner  R M,, Recio  M C,, Just  M J,, Máñez  S,, Ríos  J L.. Two fungal lanostane derivatives as phospholipase A2 inhibitors.  J. Nat. Prod.. 1996;;  59 977-9
    CrossrefPubMedGoogle Scholar
  • 8 Kaminaga  T,, Yasukawa  K,, Takido  M,, Tai  T,, Nunoura  Y.. Inhibitory effect of Poria cocos on 12-O-tetradecanoylphorbol-13-acetate-induced ear oedema and tumour promotion in mouse skin.  Phytother. Res.. 1996;;  10 581-4
    CrossrefPubMedGoogle Scholar
  • 9 Kaminaga  T,, Yasukawa  K,, Kanno  H,, Tai  T,, Nunoura  Y,, Takido  M.. Inhibitory effect of lanostane-type triterpene acids, the components of Poria cocos, on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.  Oncology. 1996;;  53 382-5
    PubMedGoogle Scholar
  • 10 Yasukawa  K,, Kaminaga  T,, Kitanaka  S,, Tai  T,, Nunoura  Y,, Natori  S et al.. 3β-p-Hydroxybenzoyldehydrotumulosic acid from Poria cocos, and its anti-inflammatory effect.  Phytochemistry. 1998;;  48 1357-60
    CrossrefPubMedGoogle Scholar
  • 11 Young  J M,, De Young  L M.. Cutaneous models of inflammation for the evaluation of topical and systemic pharmacological agents. In: Spector J, Back N, editors. Alan R. Liss, New York; 1989: 215-31
  • 12 Stanley  P L,, Steiner  S,, Havens  M,, Tramposch  K M.. Mouse skin inflammation induced by multiple topical applications of 12-O-tetradecanoylphorbol-13-acetate.  Skin Pharmacol.. 1991;;  4 262-71
    PubMedGoogle Scholar
  • 13 De Young  L M,, Kheifets  J B,, Ballaron  S J,, Young  J M.. Edema and cell infiltration in the phorbol ester-treated mouse ear edema are temporally separate and can be differentially modulated by pharmacological agents.  Agents Actions. 1989;;  26 335-41
    CrossrefPubMedGoogle Scholar
  • 14 Neves  P CA,, Neves  M CA,, Bella Cruz  A,, Sant'ana  A EG,, Yunes  R A,, Calixto  J B.. Differential effects of Mandevilla velutina compounds on paw oedema induced by phospholipase A2 and phospholipase C.  Eur. J. Pharmacol.. 1993;;  243 213-9
    CrossrefPubMedGoogle Scholar
  • 15 Brattsand  R,, Thalén  A,, Roempke  K,, Källström  L,, Gruvstad  E.. Influence of 16α,17α-acetal substitution and steroid nucleus fluorination on the topical to systemic activity ratio of glucocorticoids.  J. Steroid Biochem.. 1982;;  16 779-86
    CrossrefPubMedGoogle Scholar
  • 16 Sugishita  E,, Amagaya  S,, Ogihara  Y.. Studies on the mechanism of anti-inflammatory activities of Papyriogenin A and C.  J. Pharm. Dyn.. 1983;;  6 287-94
    PubMedGoogle Scholar
  • 17 Recio  M C,, Giner  R M,, Máñez  S,, Guého  J,, Julien  H R,, Hostettmann  K et al.. Investigations on the steroidal anti-inflammatory activity of triterpenoids from Diospyros leucomelas.  Planta Medica. 1995;;  61 9-12
    PubMedGoogle Scholar
  • 18 Brain  S,, Lewis  G P,, Whittle  B JR.. Actions of phospholipase-A on mast-cell histamine release and paw oedema in the rat.  Br. J. Pharmacol.. 1977;;  59 440P
    PubMedGoogle Scholar
  • 19 Hambleton  P,, McMahon  S.. Investigation of phospholipases-induced paw oedema in the rat.  Br. J. Pharmacol.. 1989;;  97 543P
    PubMedGoogle Scholar
  • 20 Marshall  L A,, Chang  J Y,, Calhoun  W,, Yu  J,, Carlson  R P.. Preliminary studies on phospholipase A2-induced mouse edema as a model to evaluate anti-inflammatory agents.  J. Cell Biochem.. 1989;;  40 147-55
    CrossrefPubMedGoogle Scholar
  • 21 Cirino  G,, Peers  S H,, Wallace  J L,, Flower  R J.. A study of phospholipase A2-induced oedema in rat paw.  Eur. J. Pharmacol.. 1989;;  166 505-10
    CrossrefPubMedGoogle Scholar
  • 22 Cirino  G,, Peers  S H,, Flower  R J,, Browning  J L,, Pepinsky  R B.. Human recombinant lipocortin 1 has acute local anti-inflammatory properties in the rat paw oedema test.  Proc. Natl. Acad. Sci. USA. 1989;;  86 3428-32
    PubMedGoogle Scholar
  • 23 Safayhi  H,, Sailer  E R.. Anti-inflammatory actions of pentacyclic triterpenes.  Planta Medica. 1997;;  63 487-93
    PubMedGoogle Scholar
  • 24 Ríos  J L,, Recio  M C,, Máñez  S,, Giner  R M.. Natural triterpenoids as anti-inflammatory agents. In: Atta-Ur-Rahman, editor Vol. 21. Elsevier, Amsterdam; 2000: in press
  • 25 Nukaya  H,, Yamashiro  H,, Furazawa  H,, Ishida  H,, Tsuji  K.. Isolation of inhibitors of TPA-induced mouse ear edema from Hoelen, Poria cocos.  Chem. Pharm. Bull.. 1996;;  44 847-9
    PubMedGoogle Scholar
  • 26 Ansari  S H,, Ali  M.. Analgesic and anti-inflammatory activity of tetracyclic triterpenoids isolated from Pistacia integerrima galls.  Fitoterapia. 1996;;  67 103-5
    PubMedGoogle Scholar
  • 27 Jain  M K,, Yu  B Z,, Rogers  J M,, Smith  A E,, Boger  E TA,, Ostrander  R L et al.. Specific competitive inhibitor of secreted phospholipase A2 from berries of Schinus terebinthifolius.  Phytochemistry. 1995;;  39 537-47
    CrossrefPubMedGoogle Scholar
  • 28 Takei  M,, Umeyama  A,, Shoji  N,, Arihara  S,, Endo  K.. Mechanism of inhibition of IgE-dependent histamine release from rat mast cells by penasterol and penasterone.  J. Pharm. Sci.. 1995;;  84 228-30
    PubMedGoogle Scholar
  • 29 Hirotani  M,, Asaka  L,, Ino  C,, Furuya  T,, Shiro  M.. Studies on the metabolites of higher funge.7. Ganoderic acid derivatives and ergosta-4,7,22-triene-3,6-dione from Ganoderma lucidum.  Phytochemistry. 1987;;  26 2797-803
    CrossrefPubMedGoogle Scholar
  • 30 Young  J M,, Spires  D A,, Bedord  C J,, Wagner  B,, Ballaron  S J,, De Young  L M.. The mouse ear inflammatory response to topical arachidonic acid.  J. Invest. Dermatol.. 1984;;  82 367-71
    CrossrefPubMedGoogle Scholar
  • 31 Suzuki  K,, Ota  H,, Sasagawa  S,, Sakatani  T,, Fujikura  T.. Assay method for myeloperoxidase in human polymorphonuclear leukocytes.  Anal. Biochem.. 1983;;  132 345-52
    CrossrefPubMedGoogle Scholar
  • 32 Aldaz  C M,, Conti  C J,, Giménez  I B,, Slaga  T J,, Klein-Szanto  A JP.. Cutaneous changes during prolonged application of 12-O-tetradecanoylphorbol-13-acetate on mouse.  Cancer Res.. 1985;;  45 2753-9
    PubMedGoogle Scholar
  • 33 Baxter  C S,, Andringa  A,, Chalfin  K,, Miller  M L.. Comparative histomorphometric changes in SENCAR mouse epidermis in response to multiple treatments with complete and stage-specific tumor promoting agents.  Carcinogenesis. 1989;;  10 1855-61
    PubMedGoogle Scholar
  • 34 Schmitt  D.. Le système immunitaire cutané.  CR Soc. Biol.. 1994;;  188 207-21
    PubMedGoogle Scholar
  • 35 Chapman  J R,, Ruben  Z,, Butchko  G M.. Histology of and quantitative assays for oxazolone-induced allergic contact dermatitis in mice.  Am. J. Dermatopathol.. 1986;;  8 130-8
    PubMedGoogle Scholar
  • 36 Zang  L,, Ding  Q,, Zhang  P Y,, Zhu  R P,, Zhou  Y H.. Molecular weight and aggregation behaviour in solution of β-D-glucan from Poria cocos sclerotium.  Carbohydrate Res.. 1997;;  303 193-7
    CrossrefPubMedGoogle Scholar
  • 37 Cameron  G S,, Baldwin  J K,, Klann  K C,, Patrick  K E,, Fischer  S M.. Tumor-promoting activity of ethyl phenylpropiolate.  Cancer Res.. 1991;;  51 5642-8
    PubMedGoogle Scholar

Prof. Dr. J. L. Ríos

Departament de Farmacologia Facultat de Farmàcia Universitat de València

Avda. Vicent Andrés Esés s/n

Burjassot, 46100

Spain

Email: riosjl@uv.es

Phone: +34 963864943

Fax: +34 963864973

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