Evaluation of skin response treated by bioactive and toxic compounds using different experimental platforms: magnolol/honokiol and phthalates as the permeants

• Main Authors: Yi Yun Hung, 洪宜筠
• Other Authors: Y. L. Leu
• Format: Others
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/49281301110231835287

碩士 === 長庚大學 === 中醫學系天然藥物 === 101 === This study was established on the topical delivery by a series of different experimental platforms which investigated absorption ability and toxicity between similar structure compounds, including bioactive compound (magnolol/honokiol) and toxic chemical (phthalates) as model drugs to evaluate the skin response. In the first research, magnolol and honokiol, predominant active compounds in the family Magnoliaceae, are known to exhibit strong anti-inflammatory activities against dermal disorders. We attempted to modify the structures of magnolol and honokiol by methylation to optimize the skin delivery ability. Superoxide anion and elastase released from human neutrophils were the biomarkers used to examine anti-inflammatory potencies of these permeants. The safety of the permeants was evaluated by keratinocyte viability and in vivo bioengineering techniques. Methylation significantly enhanced their skin absorption. Contrary to the skin accumulation results, the transdermal penetration across skin decreased following methylation. Methylated permeants demonstrated selective absorption into follicles. The relative order of anti-inflammatory activities was honokiol > 2-O-methylmagnolol > dimethylhonokiol > magnolol. Daily administration of methylated permeants, especially dimethylhonokiol, produced no skin irritation for up to 7 days. Methylated magnolol and honokiol can be efficient and safe candidates for treating inflammatory skin disorders. In the second research, the toxicity of phthalates is an important concern in the fields of environmental health and toxicology. Dermal exposure via skin care products, soil, and dust is a main route for phthalate delivery. We had explored the effect of topically-applied phthalates on skin absorption and toxicity. Immunohistology, functional proteomics, and Western blot were employed as methodologies for validating phthalate toxicity. Among 5 phthalates tested, di(2-ethylhexyl)phthalate (DEHP) showed the highest skin reservoir. Only diethyl phthalate (DEP) and dibutyl phthalate (DBP) could penetrate across skin. The accumulation of DEHP was significantly greater than DBP and DEP in hair follicles. DBP induced apoptosis of keratinocytes and fibroblasts via caspase-3 activation. This result was confirmed by downregulation of 14-3-3 protein sigma and immunohistology of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). On the other hand, the HSP60 overexpression and immunostaining of COX-2 suggested inflammatory response induced by DEP and DEHP. The proteomic profiling verified the role of calcium homeostasis on skin inflammation. This work provided novel platforms for examining phthalate toxicity on skin.