Topical delivery of bioactive compounds from Cortex Dictamni alleviates atopic dermatitis-like lesion by inhibiting the activation of keratinocytes, macrophages, and basophils: Dictamnine versus fraxinellone.

Autor: Chou WL; Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan., Yang SC; Department of Microbiology, Soochow University, Taipei, Taiwan., Alshetaili A; Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudi Arabia., Wei SH; Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan., Yang SH; School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan; Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan. Electronic address: dryang@mail.cgu.edu.tw., Fang JY; Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan; Research Center for Food and Cosmetic Safety and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan. Electronic address: fajy@mail.cgu.edu.tw.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 25; Vol. 143 (Pt 2), pp. 113486. Date of Electronic Publication: 2024 Oct 29.
DOI: 10.1016/j.intimp.2024.113486
Abstrakt: Dictamnine and fraxinellone constitute the primary alkaloid and limonoid components in Cortex Dictamni, respectively. Both compounds exhibit anti-inflammatory properties. This study aims to assess the ability of dictamnine and fraxinellone in treating atopic dermatitis (AD) through in silico-, cell-, and animal-based experiments. The effects of these compounds on the coordinated activation of keratinocytes, macrophages, and basophils in AD development were investigated. A dinitrochlorobenzene (DNCB)-sensitized AD model in mice was employed to examine the in vivo anti-AD effects. Dictamnine and fraxinellone effectively reduced the release of proinflammatory effectors, including interleukin (IL)-4, IL-13, chemokine (C-C motif) ligand (CCL)5, and CCL17, by suppressing extracellular signal-regulated kinase (ERK) signaling in activated keratinocytes. The conditioned medium from dictamnine-treated macrophages reduced signal transducer and activator of transcription (STAT)3 in keratinocytes by 39 %, indicating the inhibition of keratinocytes-immune cell interaction. Both compounds comparably suppressed RBL-2H3 cell degranulation by decreasing histamine production. In vitro permeation test (IVPT) demonstrated three-fold greater skin absorption of topically applied dictamnine than fraxinellone. The in silico molecular docking manifested a preferable ceramide interaction with dictamnine over fraxinellone. Topical application of dictamnine decreased the mouse skin lesion development and the overexpressed cytokines/chemokines. This attenuation is comparable to the activity of tacrolimus ointment, a standard clinical treatment. Histological analysis revealed that dictamnine inhibited epidermal proliferation, reducing thickness from 220 to 97 μm. However, dictamnine did not restore the barrier function, as evidenced by the results of filaggrin and loricrin expression and in vivo transepidermal water loss (TEWL). The findings suggest that topical dictamnine can be a promising agent for alleviating AD inflammation.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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