ABSTRACT
In the course of our search for new melanin synthesis inhibitors from plants, 40 new flavonoids and 11 known flavonoids were isolated from the roots of Lespedeza floribunda Bunge. The structures of the new compounds were determined by MS and NMR analyses, and the absolute configurations by CD spectra. Many of the compounds inhibited melanin synthesis in normal human epidermal melanocytes (NHEM), and compounds 3, 7, 8, 11, 16, 24, 27, 29, 33, 43, 45, and 51 were particularly inhibitory. Their activities were stronger than that of hydroquinone, which is known as a major skin-lightening drug.
Subject(s)
Flavonoids/isolation & purification , Flavonoids/pharmacology , Lespedeza/chemistry , Melanins/antagonists & inhibitors , Melanins/biosynthesis , Melanocytes/drug effects , Plants, Medicinal/chemistry , Epidermis/drug effects , Flavonoids/chemistry , Humans , Japan , Melanocytes/metabolism , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Roots/chemistrySubject(s)
Asian People/genetics , Polymorphism, Genetic , Receptor, Melanocortin, Type 1/genetics , Adult , Alleles , DNA/analysis , DNA/genetics , Female , Genetic Variation , Humans , Japan , Male , Middle Aged , Phenotype , Polymerase Chain ReactionABSTRACT
The effect of water-soluble chitosan, a natural polymer used as a dietary supplement, on human bladder-tumor cells was investigated. Apoptotic morphological change was demonstrated by nuclear staining. Chitosan-treated cells showed elevation of caspase-8-like activity, but no significant elevation of caspase-9-like activity, which suggest that proapoptotic effect of chitosan is attributable to death receptor activation and not to activation of the mitochondria-cytochrome c pathway. Chitosan increased expression of TNF-R1, but decreased Fas expression. Use of monoclonal antibodies to inhibit death-receptor signal transduction did not attenuate the proapoptotic activity of chitosan. Examination of death-ligands revealed that TNFalpha mRNA expression was markedly increased by chitosan treatment while FasL mRNA was not affected. Although the direct interaction of chitosan with death receptors remains unidentified, the results suggest that its proapoptotic effect might be related to interaction with TNFalpha or TNF-R1.
