ABSTRACT
CONTEXT: There is a need for the discovery of novel natural and semi-synthetic sunscreen that is safe and effective. Piperine has a UV absorption band of 230-400 nm with high molar absorptivity. This compound has a high potential to be developed to sunscreen. OBJECTIVE: This study develops new UV protection compounds from piperine by using chemical synthesis. MATERIALS AND METHODS: Piperine was isolated from Piper nigrum L. (Piperaceae) fruits, converted to piperic acid by alkaline hydrolysis, and prepared as ester derivatives by chemical synthesis. The piperate derivatives were prepared as 5% o/w emulsion, and the SPF values were evaluated. The best compound was submitted to cytotoxicity test using MTT assay. RESULTS: Piperic acid was prepared in 86.96% yield. Next, piperic acid was reacted with alcohols using Steglich reaction to obtain methyl piperate, ethyl piperate, propyl piperate, isopropyl piperate, and isobutyl piperate in 62.39-92.79% yield. All compounds were prepared as 5% oil in water emulsion and measured its SPF and UVA/UVB values using an SPF-290S analyzer. The SPF values (n = 6) of the piperate derivatives were 2.68 ± 0.17, 8.89 ± 0.46, 6.86 ± 0.91, 16.37 ± 1.8, and 9.68 ± 1.71. The UVA/UVB ratios of all compounds ranged from 0.860 to 0.967. Cytotoxicity of isopropyl piperate was evaluated using human skin fibroblast cells and the IC50 was equal to 120.2 µM. DISCUSSION AND CONCLUSION: From the results, isopropyl piperate is an outstanding compound that can be developed into a UV protection agent.
Subject(s)
Fatty Acids, Unsaturated/isolation & purification , Fatty Acids, Unsaturated/pharmacology , Piper nigrum/chemistry , Skin/drug effects , Sunscreening Agents/isolation & purification , Sunscreening Agents/pharmacology , Cell Line , Cell Survival/drug effects , Computational Biology , Fatty Acids, Unsaturated/toxicity , Fibroblasts/drug effects , Fibroblasts/radiation effects , Humans , Hydrogen Bonding , Models, Molecular , Skin/cytology , Skin/radiation effects , Spectrophotometry, Ultraviolet , Sunscreening Agents/toxicityABSTRACT
The antioxidant alpha-lipoic acid (LA) is a naturally occurring compound that has been shown to possess promising anticancer activity because of its ability to preferentially induce apoptosis and inhibit proliferation of cancer cells relative to normal cells. However, the molecular mechanisms underlying the apoptotic effect of LA are not well understood. We report here that LA induced reactive oxygen species (ROS) generation and a concomitant increase in apoptosis of human lung epithelial cancer H460 cells. Inhibition of ROS generation by ROS scavengers or by overexpression of antioxidant enzymes glutathione peroxidase and superoxide dismutase effectively inhibited LA-induced apoptosis, indicating the role of ROS, especially hydroperoxide and superoxide anion, in the apoptotic process. Apoptosis induced by LA was found to be mediated through the mitochondrial death pathway, which requires caspase-9 activation. Inhibition of caspase activity by the pan-caspase inhibitor (z-VAD-FMK) or caspase-9-specific inhibitor (z-LEHD-FMK) completely inhibited the apoptotic effect of LA. Likewise, the mitochondrial respiratory chain inhibitor rotenone potently inhibited the apoptotic and ROS-inducing effects of LA, supporting the role of mitochondrial ROS in LA-induced cell death. LA induced down-regulation of mitochondrial Bcl-2 protein through peroxide-dependent proteasomal degradation, and overexpression of the Bcl-2 protein prevented the apoptotic effect of LA. Together, our findings indicate a novel pro-oxidant role of LA in apoptosis induction and its regulation by Bcl-2, which may be exploited for the treatment of cancer and related apoptosis disorders.
