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Dihydrocoumarin is a compound found in Melilotus officinalis. Dihydrocoumarin is a yeast Sir2p inhibitor. Dihydrocoumarin also inhibits human SIRT1 and SIRT2 with IC50s of 208 μM and 295 μM, respectively[1].

Dihydrocoumarin induces a concentration-dependent inhibition of SIRT1 (IC50 of 208 μM) in an in vitro enzymatic assay. A decrease in SIRT1 deacetylase activity is observed even at micromolar doses (85±5.8 and 73±13.7% activity at 1.6 μM and 8 μM, respectively). The microtubule SIRT2 deacetylase is also inhibited with a similar dose dependency (IC50 of 295 μM)[1].Dihydrocoumarin (1-5 mM) increases cytotoxicity in the TK6 cell line in a dose-dependent manner following a 24-h exposure. Dihydrocoumarin (1-5 mM) increases apoptosis in a dose-dependent manner in the TK6 cell line at the 6-h time point. A 5-mM dose of Dihydrocoumarin increases apoptosis at the 6-h time point in the TK6 cell line[1].Dihydrocoumarin (1-5 mM) increases p53 lysine 373 and 382 acetylation in a dose-dependent manner in the TK6 cell line following a 24-h exposure period[1].

[1]. Olaharski AJ, et al. The flavoring agent Dihydrocoumarin reverses epigenetic silencing and inhibits sirtuindeacetylases. PLoS Genet. 2005 Dec;1(6):e77.

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