Skin-Soothing Properties of Juniperus formosana Hayata Revealed by Bioactivity-Based Molecular Networking

Juniperus formosana Hayata, a Tibetan medicinal plant, has been used for over a millennium in China to treat dermatitis and itching, However, its application in cosmetic and personal care products has been limited due to a lack of scientific evidence. This study aimed to identify its active compounds and biological mechanism. Guided by bioactivity-based molecular networking, a skin-soothing active fraction, predominantly composed of the theaflavin analog (84.47%), was purified from J. formosana extract. This fraction significantly inhibited the secretion and mRNA expression of the chemokine MCP-1 in inflammatory keratinocytes, suppressed inflammation-induced monocyte recruitment and its activation marker CD86. In addition, it alleviated inflammation-induced desensitization damage of TRPA1, an ion channel associated with pain and itch. Molecular docking revealed that the theaflavin analog exhibits high binding affinity to both monomeric (-8.1 kcal/mol) and dimeric (-8.6 kcal/mol) forms of MCP-1, positioning it as a promising active compound for preventing skin inflammation J. formosana Hayata * molecular networking * skin soothing * MCP-1 * TRPA1exacerbation by interfering with the MCP-1/CCR2 axis.