Polyphenolische Verbindungen als Inhibitoren der Pankreaslipase

Zusammenfassung

Aktuell ist Orlistat der einzige zugelassene Pankreaslipase (PL)-Inhibitor in Europa. Seine Anwendung ist jedoch mit einer Vielzahl von unerwünschten Nebenwirkungen verbunden. Die Suche nach potenziellen Inhibitoren pflanzlichen Ursprungs ist derzeit Gegenstand zahlreicher Forschungsarbeiten. Vor allem aus Camellia sinensis (L.) Kuntze (Theaceae) konnten zahlreiche Catechin- und Epicatechinderivate als PL-Inhibitoren identifiziert und isoliert werden. Bei der Untersuchung von Phenolsäuren konnte gezeigt werden, dass Hydroxybenzoesäuren schwächer inhibieren als Hydroxyzimtsäuren. Diese Ergebnisse dienen als eine erste Grundlage für die Suche nach neuen, natürlichen Strukturen mit PL-inhibitorischer Aktivität. Durch die Verwendung von computerbasierten Modellierungsversuchen wird versucht, neue Arzneistoffe für die Behandlung von Adipositas zu identifizieren.

Summary

Polyphenolic compounds as pancreatic lipase inhibitors

Inhibition of pancreatic lipase and the associated reduction of lipid absorption is an attractive approach for the treatment of obesity. Currently, the only clinically approved pharmacologic agent as pancreatic lipase inhibitor is Orlistat. However, its usage is compromised by unpleasant gastrointestinal adverse reactions (oily stools, oily spotting, flatulence). The use of botanical materials as a potential source of new drugs is of increasing importance and application. Natural products that are interesting for obesity treatment are generally considered to have less toxic and side effects than totally synthetic drugs. One of the most important sources of potential pancreatic lipase inhibitors represents the class of polyphenols. This article summarizes most studied subclasses of polyphenols including flavonoids, hydroxycinnamic acids, hydroxybenzoic acids and lignans with pancreatic lipase inhibitory effects. A structural comparison of potent inhibitors shows an increased inhibitory effect depending on number and position of phenolic hydroxyl groups, degree of polymerization and elimination of glycosylation during digestion.

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