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DOI: 10.1055/s-0039-3400108
The vitamin E derivative α-amplexichromanol as anti-inflammatory lead inspired from traditional African medicine
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.
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References
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