Effect of a Novel Ascorbic Derivative, Disodium Isostearyl 2-O-L-Ascorbyl Phosphate on Human Dermal Fibroblasts: Increased Collagen Synthesis and Inhibition of MMP-1

• Published in: Biological & Pharmaceutical Bulletin Vol. 31; no. 4; pp. 563 - 568
• Main Authors: Shibayama, Hiroharu, Hisama, Masayoshi, Matsuda, Sanae, Ohtsuki, Mamitaro, Iwaki, Masahiro
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.04.2008; Pharmaceutical Society of Japan
• Subjects: amphiphilic vitamin C derivative; Ascorbic Acid - analogs & derivatives; Ascorbic Acid - metabolism; Ascorbic Acid - pharmacology; Cell Proliferation - drug effects; Cells, Cultured; Chromatography, High Pressure Liquid; Collagen - antagonists & inhibitors; Collagen - biosynthesis; collagen synthesis; disodium isostearyl 2-O-L-ascorbyl phosphate; Extracellular Matrix - metabolism; Fibroblasts - drug effects; Fibroblasts - metabolism; human skin fibroblast; Humans; Magnetic Resonance Spectroscopy; Matrix Metalloproteinase Inhibitors; Skin - cytology; Skin - drug effects; Skin - metabolism; VCP-IS-2Na
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.31.563

The effects of a novel amphiphilic vitamin C derivative, disodium isostearyl 2-O-L-ascorbyl phosphate (disodium 2-(1,3,3-trimethyl-n-butyl)-5,7,7-trimethyl-n-octyl-L-ascorbyl phosphate, VCP-IS-2Na), possessing a C18 alkyl chain attached to a stable sodium L-ascorbic acid 2-phosphate (VCP-Na), on the proliferation of fibroblasts and collagen synthesis, and inhibition of matrix metalloproteinase-1 (MMP-1) in normal human fibroblasts, NHDFs and NB1RGBs, were evaluated. Compared with proliferation of non-treated fibroblasts, VCP-IS-2Na at 50 μM increased proliferation to 123 and 135% of that in NHDFs and NB1RGBs. On the other hand, L-ascorbic acid (vitamin C) and VCP-Na had little effect on proliferation. At a concentration of 5.0—50 μM, VCP-IS-2Na stimulated collagen synthesis with an effectiveness comparable to that of vitamin C and VCP-Na. The amount of type I collagen in the culture medium was increased by treatment with VCP-IS-2Na for 72 h, in a concentration-dependent manner. Maximum increases of 126 and 1067% were seen with VCP-IS-2Na at 50 μM in NHDFs and NB1RGBs, respectively, whereas vitamin C and VCP-Na only had a small effect. VCP-IS-2Na had a small inhibitory effect on MMP-1, but vitamin C did not inhibit MMP-1, and VCP-Na had very little effect. VCP-IS-2Na exerted its collagen synthesis-promoting activity after being converted to vitamin C by phosphatase. This vitamin C promoted proliferation, collagen synthesis and inhibition of MMP-1, which are prolonged through sustained conversion of VCP-IS-2Na.