Screening for food-grade anti-amyloidgenic compounds in food stuffs by using human cystatin C and improvement of their functionalities

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Cystatin C, a cysteine proteinase inhibitor, is ubiquitous in mammalian tissues and body fluids, and plays an important role in extracellular regulation of endogenous cysteine protainases. A human cystatin C has been shown to easily cause amyloid deposits in the brains of patients suffering from Alzheimer's disease or hereditary cystatin C amyloid angiopathy. Since the incidence of the incurable diseases has been steadily on the rise in developed nations, there has been an increased interest in screening for food-grade anti-amyloidgenic compounds in food stuffs. A synthetic gene encoding human cystatin C was constructed and inserted not only into a Pichia pastoris vector, pPCIZa-C (Invitrogen, Carlsbad, CA) but also into a Escherichia colt vectors pQE-30 and pQE-32. The resulting recombinant human cystatin C was used for screening of bioactive compounds with amyloidgenicity in food stuffs. As the result, it was demonstrated that flavonoids and phenolic acids from plants are capable of in vitro inhibition of amyloid-fibril formation of cystatin. Ginsenoside Rg1 with a monosaccharide from gingseng showed strong anti-amyloidgenicity towards cystatin, whereas ginsenoside Re with a disaccharide chain did not. Chlorogenic acid and its derivatives also exhibited anti-amyloidgenicity, although it may have a tendency to be attenuated over a period of digestion in the intestinal tract. These observations can be useful for novel inhibitors' design as therapeutic anents for amyloid-associated diseases.