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<p>This study investigated the modification of blood–brain barrier (BBB) permeability of alkaloids from Phellodendri Chinensis Cortex (PC) by wine processing. Phytochemical analysis using UPLC–QqQ-MS compared raw PC (RPC) and wine-processed PC (WPC), identifying significant changes in four major alkaloids (phellodendrine, magnoflorine, berberrubine, and berberine). Subsequent in vivo experiments demonstrated enhanced brain distribution of these alkaloids in WPC-treated mice. An in vitro BBB model was established using bEnd.3 endothelial cells and astrocytes to evaluate the permeability of four major alkaloids from RPC and WPC using UPLC–QqQ-MS. Tight junction protein expression and transporter interactions were analyzed through Western blotting and ligand fishing assays. Results showed WPC treatment significantly enhanced alkaloid transport across the BBB model, with mechanistic studies demonstrating downregulation of tight junction proteins (ZO-1 and Occludin), reduced P-glycoprotein expression, and increased binding to the absorptive transporter TfRc. These findings reveal that wine processing enhances BBB penetration of PC alkaloids by coordinately modulating both paracellular and transcellular transport pathways, providing scientific validation for traditional processing methods of Chinese Materia Medica and insights for developing brain-targeted herbal medicines.</p> Graphical Abstract <p></p>

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Optimizing blood–brain barrier permeability: the effect of wine processing on alkaloids in Phellodendri Chinensis Cortex

  • 期刊论文

  • 发表日期：

    2025年9月26日

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  • Shuo Zhang,
  • Jiahui Zhao,
  • Wenjing Ren,
  • Yue Zhou,
  • Yang Chen,
  • Shiru Jiang,
  • Gui Xu,
  • Xiutong Ge,
  • Hui Gao,
  • Fan Zhang

摘要

This study investigated the modification of blood–brain barrier (BBB) permeability of alkaloids from Phellodendri Chinensis Cortex (PC) by wine processing. Phytochemical analysis using UPLC–QqQ-MS compared raw PC (RPC) and wine-processed PC (WPC), identifying significant changes in four major alkaloids (phellodendrine, magnoflorine, berberrubine, and berberine). Subsequent in vivo experiments demonstrated enhanced brain distribution of these alkaloids in WPC-treated mice. An in vitro BBB model was established using bEnd.3 endothelial cells and astrocytes to evaluate the permeability of four major alkaloids from RPC and WPC using UPLC–QqQ-MS. Tight junction protein expression and transporter interactions were analyzed through Western blotting and ligand fishing assays. Results showed WPC treatment significantly enhanced alkaloid transport across the BBB model, with mechanistic studies demonstrating downregulation of tight junction proteins (ZO-1 and Occludin), reduced P-glycoprotein expression, and increased binding to the absorptive transporter TfRc. These findings reveal that wine processing enhances BBB penetration of PC alkaloids by coordinately modulating both paracellular and transcellular transport pathways, providing scientific validation for traditional processing methods of Chinese Materia Medica and insights for developing brain-targeted herbal medicines.

Graphical Abstract