Xinyue Liu,1 Lele Chen,1 Peng Sun,1 Xiaolong Jiang,1 Pengze Li,2 Zichen Xu,3 Zhaoshuang Zhan,1 Jiafeng Wang1 

1College of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2College of Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 3College of Optometry and Ophthalmology, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China

Correspondence: Zhaoshuang Zhan; Jiafeng Wang, Email zzshuang2000@126.com; wjfeng2000@126.com

Background: Atopic Dermatitis (AD) is a common continuous inflammation dermatosis requiring efficacious therapeutic intervention. Phellodendri Chinensis Cortex-Cnidii Fructus (PC) herb pair has shown effectiveness and security in traditional Chinese medicine (TCM) clinical applications, yet its pharmacological constituents and mechanisms are not fully elucidated.
Purpose: This study used serum pharmacochemistry, network pharmacology, and validation experiments to examine the impact of PC in the treatment of AD.
Methods: Initially, ultra performance liquid chromatography-mass spectrometry (UPLC-MS) had been applied to elucidate the components of PC that were absorbed. An integrative approach combining network pharmacology and in vivo research (general index observation, skin pathological tissue staining, ELISA, immunohistochemistry, immunofluorescence, and Western blotting) was employed to validate PC’s mechanism in action after 2,4-dinitrochlorobenzene (DNCB) was used to create a mouse model of AD.
Results: Fifty-three compounds and 18 serum prototype components were characterized within PC. The therapeutic efficacy of PC in AD was notably manifested in the alleviation of pruritus, improvement of skin histopathology, and reduction of cytokines involving IgE, IL-4, TNF-α and IL-6. Based on molecular docking studies, pharmacodynamic components such as phellodendrine, xanthotoxin, nomilin, and isopimpinellin strongly favored the main targets. Comprehensive investigations integrating serum pharmacochemistry, network pharmacology, and in vivo studies had revealed that PC prevented DNCB-induced AD through adjusting the TLR4/NF-κB signaling pathway.
Conclusion: The anti-AD effects of PC may be attributed to its modulation of the TLR4/NF-κB signaling pathway, reduction of NF-кB expression in the nucleusim, downregulation of inflammatory cytokine levels, provement of skin histopathological manifestations, and reduction of skin pruritus.

Keywords: Phellodendri Chinensis Cortex, Cnidii Fructus, atopic dermatitis, serum pharmacochemistry, network pharmacology, mechanism