ABSTRACT
Sesamin, sesamolin (lignans) and sesamol--from sesame seed (Sesamum indicum L.)--are known for their health promoting properties. We examined the inhibition effect of sesamol, a phenolic degradation product of sesamolin, on the key enzyme in melanin synthesis, viz. tyrosinase, in vitro. Sesamol inhibits both diphenolase and monophenolase activities with midpoint concentrations of 1.9 µM and 3.2 µM, respectively. It is a competitive inhibitor of diphenolase activity with a K(i) of 0.57 µM and a non-competitive inhibitor of monophenolase activity with a K(i) of 1.4 µM. Sesamol inhibits melanin synthesis in mouse melanoma B16F10 cells in a concentration dependant manner with 63% decrease in cells exposed to 100 µg/mL sesamol. Apoptosis is induced by sesamol, limiting proliferation. This study of the chemistry and biology of lignans, in relation to the mode of action of bioactive components, may open the door for drug applications targeting enzymes.
Subject(s)
Benzodioxoles/metabolism , Benzodioxoles/pharmacology , Enzyme Inhibitors/metabolism , Enzyme Inhibitors/pharmacology , Melanins/biosynthesis , Monophenol Monooxygenase/antagonists & inhibitors , Monophenol Monooxygenase/metabolism , Phenols/metabolism , Phenols/pharmacology , Agaricales/enzymology , Animals , Apoptosis/drug effects , Catalytic Domain/drug effects , Cell Line, Tumor , Cooking , Copper/metabolism , Lignans/pharmacology , Mice , Monophenol Monooxygenase/chemistry , Oxidoreductases/antagonists & inhibitors , Protein Binding , Sesame Oil/chemistry , Spectrum AnalysisABSTRACT
Pectic polysaccharides from dietary sources such as Decalepis hamiltonii--swallow root (SRPP), Hemidesmus indicus (HPP), Nigella sativa--black cumin (BCPP), Andrographis serpyllifolia-(APP), Zingiber officinale--ginger (GRPP) and, citrus pectin (CPP) were examined for galectin inhibitory activity. Inhibition of (a) galectin-3 of MDA-MB-231 cells induced hemagglutination of red blood cells; (b) galectin-3 mediated interaction between normal/metastatic human buccal cells (NBC)/(MBC) and; (c) invasion of MDA-MB-231 and MBC in the invasive chamber was assessed. Results indicated that SRPP inhibited hemagglutination at Minimum Inhibitory Concentration (MIC) of 1.86 microg ml(-1) equivalent of carbohydrate as apposed to those of BCPP (130 microg ml(-1)), APP (40 microg ml(-1)), HPP (40 microg ml(-1)) and CPP (25 microg ml(-1)). GRPP even at concentration >1-6 mg ml(-1) did not inhibit agglutination. Also SRPP showed approximately 15 and 2 fold potent anti hemagglutination activity relative to that of galectin-3 specific sugars-galactose (MIC-27.1 microg ml(-1)) and lactose (MIC-4.16 microg ml(-1)) respectively. Further, SRPP at 10 microg ml(-1) inhibited agglutination of NBC by galectin-3 of MDA-MB-231 cells. Modified swallow root pectic polysaccharide (MSRPP) of 50 kDa retained anti hemagglutination activity (MIC of 1.03 microg ml(-1)) and inhibited MDA-MB-231 and MBC invasion by 73 and 50% with an IC(50) of 136 and 200 microg ml(-1) respectively. Both SRPP and MSRPP induced apoptosis up to 80% at 100 microg ml(-1) concentration by activating approximately 2 and 8 folds of Caspase-3 activity. Sugar composition analysis and its correlation with the galectin inhibitory property indicated that pectic polysaccharides with higher arabinose and galactose content-arabinogalactan inhibited hemagglutination significantly.