PMID- 26915998
OWN - NLM
STAT- MEDLINE
DCOM- 20160722
LR  - 20221207
IS  - 1520-6025 (Electronic)
IS  - 0163-3864 (Linking)
VI  - 79
IP  - 2
DP  - 2016 Feb 26
TI  - Betulin Derivatives Effectively Suppress Inflammation in Vitro and in Vivo.
PG  - 274-80
LID - 10.1021/acs.jnatprod.5b00709 [doi]
AB  - 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.
FAU - Laavola, Mirka
AU  - Laavola M
AD  - The Immunopharmacology Research Group, University of Tampere School of Medicine 
      and Tampere University Hospital , FI-33014 Tampere, Finland.
FAU - Haavikko, Raisa
AU  - Haavikko R
AD  - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, 
      University of Helsinki , FI-00014 Helsinki, Finland.
FAU - Hamalainen, Mari
AU  - Hamalainen M
AD  - The Immunopharmacology Research Group, University of Tampere School of Medicine 
      and Tampere University Hospital , FI-33014 Tampere, Finland.
FAU - Leppanen, Tiina
AU  - Leppanen T
AD  - The Immunopharmacology Research Group, University of Tampere School of Medicine 
      and Tampere University Hospital , FI-33014 Tampere, Finland.
FAU - Nieminen, Riina
AU  - Nieminen R
AD  - The Immunopharmacology Research Group, University of Tampere School of Medicine 
      and Tampere University Hospital , FI-33014 Tampere, Finland.
FAU - Alakurtti, Sami
AU  - Alakurtti S
AD  - Process Chemistry and Environmental Engineering, VTT Technical Research Centre of 
      Finland , FI-02044 Espoo, Finland.
FAU - Moreira, Vania M
AU  - Moreira VM
AD  - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, 
      University of Helsinki , FI-00014 Helsinki, Finland.
FAU - Yli-Kauhaluoma, Jari
AU  - Yli-Kauhaluoma J
AD  - Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, 
      University of Helsinki , FI-00014 Helsinki, Finland.
FAU - Moilanen, Eeva
AU  - Moilanen E
AD  - The Immunopharmacology Research Group, University of Tampere School of Medicine 
      and Tampere University Hospital , FI-33014 Tampere, Finland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160114
PL  - United States
TA  - J Nat Prod
JT  - Journal of natural products
JID - 7906882
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Pentacyclic Triterpenes)
RN  - 0 (Triterpenes)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 6W70HN7X7O (betulin)
RN  - 9000-07-1 (Carrageenan)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - 4G6A18707N (Betulinic Acid)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/chemistry/*pharmacology
MH  - Betula
MH  - Carrageenan/pharmacology
MH  - Chemokine CCL2/antagonists & inhibitors
MH  - Cyclooxygenase 2/drug effects/metabolism
MH  - Cytokines/metabolism
MH  - Dinoprostone/metabolism
MH  - Inflammation/chemically induced/*drug therapy
MH  - Interleukin-6/antagonists & inhibitors/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/drug effects
MH  - Male
MH  - Mice
MH  - Molecular Structure
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type II/drug effects
MH  - Pentacyclic Triterpenes
MH  - Triterpenes/chemistry/*pharmacology
MH  - Betulinic Acid
EDAT- 2016/02/27 06:00
MHDA- 2016/07/23 06:00
CRDT- 2016/02/27 06:00
PHST- 2016/02/27 06:00 [entrez]
PHST- 2016/02/27 06:00 [pubmed]
PHST- 2016/07/23 06:00 [medline]
AID - 10.1021/acs.jnatprod.5b00709 [doi]
PST - ppublish
SO  - J Nat Prod. 2016 Feb 26;79(2):274-80. doi: 10.1021/acs.jnatprod.5b00709. Epub 
      2016 Jan 14.