JOURNAL OF COSMETIC SCIENCE 50 relative to control) (Figure 1A–D). In addition, fi brillin-1 and fi brillin-2 were stimulated by nicotinamide and 2,6-dihydroxynicotinamide at 0.01% in nonirradiated fi broblasts ( p 0.05, relative to control) (Figure 1C and D). In nonirradiated fi broblasts, the elastin protein levels (70 ng/ml as 100%)/elastin promoter activity (400 pg/ml as 100%) were stimulated by nicotinamide, 2,6- dihydroxynicotinamide, 2,4,5,6-tetrahydroxynicotinamide, and 3-hydroxypicolinamide upto 308/222%, 413/719%, 243/358%, and 224/183% of nonirradiated controls, re- spectively ( p 0.05) (Figure 1A and B). The expression of fi brillin-1 (0.5 μg/ml as 100%)/ fi brillin-2 (35 ng/ml as 100%) was stimulated by nicotinamide, 2,6-dihydroxynicotinamide, 2,4,5,6-tetrahydroxynicotinamide, and 3-hydroxypicolinamide upto 614/578%, 601/533%, 402/234%, and 336/290% of nonirradiated controls, respectively ( p 0.05) (Figure 1C and D). STIMULATION OF EXPRESSION OF ELASTIN, ELASTIN PROMOTER, FIBRILLIN-1, AND FIBRILLIN-2 BY NICOTINAMIDE, 2,6-DIHYDROXYNICOTINAMIDE, 2,4,5,6-TETRAHYDROXYNICOTINAMIDE, AND 3-HYDROXYPICOLINAMIDE IN UVA RADIATED FIBROBLASTS UVA-radiation stimulated elastin protein level to 185% (±14%) of control, and elastin promoter activity to 125% (±8%) of control (p 0.05). UVA-radiation signifi cantly in- hibited fi brillin-1 and fi brillin-2 to 65% (±4%) of control and 73% (±7%) of control ( p 0.05). The effects of the niacin derivatives on UVA-radiated fi broblasts were similar Figure 1. Stimulation of elastin protein (A), elastin promoter activity (B), fi brillin-1 protein (C), and fi bril- lin-2 protein (D) by nicotinamide (green line), 2,6-dihydroxynicotinamide (red line), 2,4,5,6-tetrahy- droxynicotinamide (violet line), and 3-hydroxypicolinamide (blue line) in non-irradiated dermal fi broblasts * = p 0.05, relative to control, error bars (A–D) represent standard deviation, n = 4.

REGULATION OF EXTRACELLULAR MATRIX BY NICOTINAMIDE AND ITS DERIVATIVES 51 to those on non-irradiated fi broblasts, except for the lack of regulation of fi brillin expres- sion by 0.01% nicotinamide and 2,6-dihydroxynicotinamide. Relative to UVA-radiated controls, the expression of elastin protein/promoter was stimu- lated by nicotinamide, 2,6-dihydroxynicotinamide, 2,4,5,6-tetrahydroxynicotinamide, and 3-hydroxypicolinamide upto 348/268%, 365/708%, 230/547%, and 221/214%, respec- tively ( p 0.05) (Figure 2A and B). The expression of fi brillin-1/fi brillin-2 protein levels was stimulated by nicotinamide, 2,6-dihydroxynicotinamide, 2,4,5,6-tetrahydroxynicotinamide, and 3-hydroxypicolinamide upto 524/482%, 859/563%, 347/312%, and 253/227% of UVA-radiated controls, respectively ( p 0.05) (Figure 2C and D). DIRECT INHIBITION OF MMP-1, MMP-3, MMP-9, AND ELASTASE ACTIVITIES BY NICOTINAMIDE, 2,6-DIHYDROXYNICOTINAMIDE, 2,4,5,6-TETRAHYDROXYNICOTINAMIDE, AND 3-HYDROXYPICOLINAMIDE The MMP-1 and MMP-3 activities were signifi cantly inhibited by nicotinamide and 2,6-dihydroxynicotinamide MMP-9 activity by nicotinamide, and elastase activity by nicotinamide, 2,6-dihydroxynicotinamide, 2,4,5,6-tetrahydroxynicotinamide, and 3-hydroxypicolinamide ( p 0.05) (Figure 3). The MMP-1/MMP-3 activities were significantly inhibited by nicotinamide upto 43/36%, and by 2,6-dihydroxynicotinamide upto 70/57%, of respective controls ( p 0.05) Figure 2 . Stimulation of elastin protein (A), elastin promoter activity (B), fi brillin-1 protein (C), and fi brillin-2 protein (D) by nicotinamide (green line), 2,6-dihydroxynicotinamide (red line), 2,4,5,6-tetrahydroxynicotin- amide (violet line), and 3-hydroxypicolinamide (blue line) in UVA-radiated dermal fi broblasts * = p 0.05, relative to UVA radiated control cells, error bars (A–D) represent standard deviation, n = 4.