Betulin derivatives effectively suppress inflammation in vitro and in vivo

Mirka Laavola, Raisa Haavikko, Mari Hämäläinen, Tiina Leppänen, Riina Nieminen, Sami Alakurtti, Vânia M. Moreira, Jari Yli-Kauhaluoma, Eeva Moilanen

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Betulin is a pharmacologically active triterpenoid found in the bark of the birch tree (Betula sp. L.). Betulin and betulinic acid are structurally related to anti-inflammatory steroids, but little is known about their potential anti-inflammatory properties. In the present study, the inflammatory gene expression and the anti-inflammatory properties of betulin, betulinic acid, and 16 semisynthetic betulin derivatives were investigated. Betulin derivatives 3, 4, and 5 selectively inhibited the expression of the inducible nitric oxide synthase (iNOS) in a post-transcriptional manner. They also inhibited nitric oxide (NO) production but had no effect on the other inflammatory factors studied. More interestingly, a new anti-inflammatory betulin derivative 9 with a wide-spectrum anti-inflammatory activity was discovered. Compound 9 was found to suppress the expression of cytokines interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1), as well as that of prostaglandin synthase-2 (COX-2) in addition to iNOS. The in vivo anti-inflammatory effect of compound 9 was indicated via significant suppression of the carrageenan-induced paw inflammation in mice. The results show, for the first time, that the pyrazole-fused betulin derivative (9) and related compounds have anti-inflammatory properties that could be utilized in drug development.

LanguageEnglish
Pages274-280
Number of pages7
JournalJournal of Natural Products
Volume79
Issue number2
Early online date14 Jan 2016
DOIs
Publication statusPublished - 26 Feb 2016

Fingerprint

Anti-Inflammatory Agents
Inflammation
Derivatives
Betula
Nitric Oxide Synthase Type II
Plant Bark
Chemokine CCL2
Carrageenan
Cyclooxygenase 2
In Vitro Techniques
betulin
Gene expression
Interleukin-6
Nitric Oxide
Steroids
Cytokines
Gene Expression
Pharmaceutical Preparations
betulinic acid

Keywords

  • animals
  • anti-inflammatory agents
  • betula
  • carrageenan
  • chemokine CCL2
  • cyclooxygenase 2
  • cytokines
  • dinoprostone
  • inflammation
  • interleukin-6
  • lipopolysaccharides
  • macrophages
  • male
  • mice
  • molecular structure
  • NF-kappa B
  • nitric oxide
  • nitric oxide synthase type II
  • triterpenes

Cite this

Laavola, M., Haavikko, R., Hämäläinen, M., Leppänen, T., Nieminen, R., Alakurtti, S., ... Moilanen, E. (2016). Betulin derivatives effectively suppress inflammation in vitro and in vivo. Journal of Natural Products, 79(2), 274-280. https://doi.org/10.1021/acs.jnatprod.5b00709
Laavola, Mirka ; Haavikko, Raisa ; Hämäläinen, Mari ; Leppänen, Tiina ; Nieminen, Riina ; Alakurtti, Sami ; Moreira, Vânia M. ; Yli-Kauhaluoma, Jari ; Moilanen, Eeva. / Betulin derivatives effectively suppress inflammation in vitro and in vivo. In: Journal of Natural Products. 2016 ; Vol. 79, No. 2. pp. 274-280.
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Laavola, M, Haavikko, R, Hämäläinen, M, Leppänen, T, Nieminen, R, Alakurtti, S, Moreira, VM, Yli-Kauhaluoma, J & Moilanen, E 2016, 'Betulin derivatives effectively suppress inflammation in vitro and in vivo' Journal of Natural Products, vol. 79, no. 2, pp. 274-280. https://doi.org/10.1021/acs.jnatprod.5b00709

Betulin derivatives effectively suppress inflammation in vitro and in vivo. / Laavola, Mirka; Haavikko, Raisa; Hämäläinen, Mari; Leppänen, Tiina; Nieminen, Riina; Alakurtti, Sami; Moreira, Vânia M.; Yli-Kauhaluoma, Jari; Moilanen, Eeva.

In: Journal of Natural Products, Vol. 79, No. 2, 26.02.2016, p. 274-280.

Research output: Contribution to journalArticle

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AU - Laavola, Mirka

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AU - Hämäläinen, Mari

AU - Leppänen, Tiina

AU - Nieminen, Riina

AU - Alakurtti, Sami

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AU - Yli-Kauhaluoma, Jari

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KW - chemokine CCL2

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KW - dinoprostone

KW - inflammation

KW - interleukin-6

KW - lipopolysaccharides

KW - macrophages

KW - male

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Laavola M, Haavikko R, Hämäläinen M, Leppänen T, Nieminen R, Alakurtti S et al. Betulin derivatives effectively suppress inflammation in vitro and in vivo. Journal of Natural Products. 2016 Feb 26;79(2):274-280. https://doi.org/10.1021/acs.jnatprod.5b00709