Planta Med 2019; 85(18): 1553
DOI: 10.1055/s-0039-3400108
Main Congress Poster
Poster Session 2
© Georg Thieme Verlag KG Stuttgart · New York

The vitamin E derivative α-amplexichromanol as anti-inflammatory lead inspired from traditional African medicine

K Neukirch
1   Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena,, 07743, Jena Germany
,
A Rossi
2   Department of Pharmacy, School of Medicine, University of Naples Federico II,, 80131, Naples Italy
,
M Raasch
3   Institute of Biochemistry II and Center for Sepsis Control and Care, University Hospital Jena,, 07747, Jena Germany
,
S Pace
1   Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena,, 07743, Jena Germany
,
D Séraphin
4   Substances d’Origine Naturelle et Analogues Structuraux, SONAS, SFR4207 QUASAV, UNIV Angers, Université Bretagne Loire,, 49070, Beaucouzé France
,
JJ Helesbeux
4   Substances d’Origine Naturelle et Analogues Structuraux, SONAS, SFR4207 QUASAV, UNIV Angers, Université Bretagne Loire,, 49070, Beaucouzé France
,
AS Mosig
3   Institute of Biochemistry II and Center for Sepsis Control and Care, University Hospital Jena,, 07747, Jena Germany
,
F Roviezzo
2   Department of Pharmacy, School of Medicine, University of Naples Federico II,, 80131, Naples Italy
,
P Richomme
4   Substances d’Origine Naturelle et Analogues Structuraux, SONAS, SFR4207 QUASAV, UNIV Angers, Université Bretagne Loire,, 49070, Beaucouzé France
,
O Werz
1   Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena,, 07743, Jena Germany
,
A Koeberle
1   Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena,, 07743, Jena Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
20 December 2019 (online)

 

The nut seeds of Garcinia kola are traditionally used in African medicine and known for their anti-microbial, anti-oxidative and anti-inflammatory activities. Structural optimization of the anti-inflammatory ingredient and potent 5-lipoxygenase inhibitor garcinoic acid [1] yielded α-amplexichromanol (α-AC) which is a semi-synthetic analog of endogenous vitamin E metabolites that mediate immune functions of vitamin E [2]. α-AC possesses superior 5-lipoxygenase-inhibitory activity as compared to garcinoic acid and the bioactive vitamin E metabolite α-T-13ʹ-COOH. Here we show that α-AC limits inflammation in murine peritonitis and experimental asthma in vivo and address the compound’s expected higher metabolic stability using a liver-on-chip model. α-AC significantly reduced 5-lipoxygenase-derived leukotriene (LT)C4 levels along with inflammatory cell infiltration and bronchial hyperreactivity. Lipid mediator profiles in plasma, lung and bronchia are comprehensively altered and α-AC was detected in lung up to six days after the last i.p. administration in contrast to α-T-13ʹ-COOH. While α-T-13ʹ-COOH is efficiently degraded by β-oxidation, α-AC is predominantly sulfated but not truncated. Our results indicate α-AC as a promising natural product-inspired lead that is orally active and seemingly metabolically more stable as compared to garcinoic acid and endogenous vitamin E metabolites.

 
  • References

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  • 2 Pein H, Ville A, Pace S, Temml V, Garscha U, Raasch M, Alsabil K, Viault G, Dinh CP, Guilet D, Troisi F, Neukirch K, Konig S, Bilancia R, Waltenberger B, Stuppner H, Wallert M, Lorkowski S, Weinigel C, Rummler S, Birringer M, Roviezzo F, Sautebin L, Helesbeux JJ, Seraphin D, Mosig AS, Schuster D, Rossi A, Richomme P, Werz O, Koeberle A. Endogenous metabolites of vitamin E limit inflammation by targeting 5-lipoxygenase. Nat Commun 2018; 9: 3834