A study on the molecular mechanisms underlying the compatibility of traditional Chinese medicines: Development of ferulic acid-tetramethylpyrazine compound patch

Abstract

Chuanxiong Rhizome (known as Chuanxiong in Chinese), is widely used in traditional Chinese medicines (TCMs) compounding patches. Ferulic acid (FA) and tetramethylpyrazine (TMP) are the main components of Chuanxiong. This paper aimed to prepare an FA-TMP compound patch with proven anti-inflammatory activity and elucidate the molecular mechanisms of transdermal behaviors of compounds. As confirmed by an anti-inflammatory study, the formulation was optimized by the employment of in vitro skin permeation. The addition of TMP increased the skin permeation amount of FA by approximately 1.9 times. Through FT-IR, XPS, and thermal analysis, it was demonstrated that FA mainly formed hydrogen bonds with TMP, which depressed the melting point (ΔM.P. = 14.6 °C) and hydrophilicity (Δlog Do/w = 0.44) of FA. As revealed by ATR-FTIR and 13C NMR, compounds increased the degree of skin lipid perturbation (ΔνasCH2 = 3.28 cm−1) and attenuated FA binding to ceramides and keratin. To sum up, the hydrogen bonding site of FA was competed by TMP, which enhanced the ability of FA to penetrate the stratum corneum (SC) and partition into the hydrophilic dermal layer, increasing the amount of skin permeation of FA. This study is the first investigation on the combined citation of FA and TMP in patches. It will not only provide a valuable reference for research on the molecular mechanism of transdermal behaviors concerning compounds but will also help to provide a theoretical basis at the molecular level for the scientific design of TCMs formulations.