Pancreatic Lipase Inhibitory Phthalide Derivatives from the Rhizome of Cnidium officinale

Pancreatic lipase plays an important role in the digestion and absorption of fats; it has become a target of interest in the treatment of obesity. Investigations of pancreatic lipase inhibitory compounds from Cnidium officinale rhizomes have resulted in the isolation of a new phthalide derivative (1) together with ten known phthalides (2-11). Phthalide derivatives from C. officinale showed mild inhibition against pancreatic lipase with 13 - 56% inhibition at 100 mu M. Structure activity relationship suggested that the double bond in the side chain of phthalide increased its inhibitory activity, whereas the addition of hydroxyl moiety to side chain reduced activity. Lineweaver-Burk plot analysis also demonstrated that compound 2 was a noncompetitive inhibitor with an IC50 of 86.4 mu M. Taken together, C. officinale and its phthalide constituents might be beneficial for the regulation of obesity through pancreatic lipase inhibition.