Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2020.135
Diosmetin and Its Glycoside, Diosmin, Improve Atopic Dermatitis-Like Lesions in 2,4-Dinitrochlorobenzene-Induced Murine Models
Sang-a Park1,†, Sim-Kyu Bong1,2,†, Jin Woo Lee1, No-June Park1, Yongsoo Choi1, Sang Moo Kim2, Min Hye Yang3, Yong Kee Kim4 and Su-Nam Kim1,*
1Natural Products Research Institute, Korea Institute of Science and Technology, Gangneung 25451,
2Department of Marine Food Science and Technology, Gangneung-Wonju National University, Gangneung 25457,
3College of Pharmacy, Pusan National University, Busan 46241,
4College of Pharmacy, Sookmyung Women’s University, Seoul 04610, Republic of Korea
*E-mail: snkim@kist.re.kr
Tel: +82-33-650-3503, Fax: +82-33-650-3529
The first two authors contributed equally to this work.
Received: July 31, 2020; Revised: August 19, 2020; Accepted: August 25, 2020; Published online: September 17, 2020.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Naturally derived diosmetin and its glycoside diosmin are known to be effective in treating inflammatory disease. This study was performed to determine whether diosmin and diosmetin have the effect of improving atopic dermatitis in a 2,4-dinitrochlorobenzen (DNCB)-induced atopic dermatitis (AD) model. DNCB was used to establish AD model in hairless mice. Skin moisture, serum immunoglobulin E (IgE), interleukin 4 (IL-4), and histological analysis were performed to measure the effectiveness of diosmin and diosmetine to improve AD. IL-4 levels were also measured in RBL-2H3 cells. Administration of diometin or diosmin orally inhibited the progress of DNCB-induced AD-like lesions in murine models by inhibiting transdermal water loss (TEWL) and increasing skin hydration. Diosmetin or diosmin treatment also reduced IgE and IL-4 levels in AD-induced hairless mouse serum samples. However, in the in vitro assay, only diosmetin, not diosmin, reduced the expression level of IL-4 mRNA in RBL-2H3 cells. Diosmin and diosmetine alleviated the altered epidermal thickness and immune cell infiltration in AD. Diosmin is considered effective in the cure of AD and skin inflammatory diseases by being converted into diosmetin in the body by pharmacokinetic metabolism. Thus, oral administration of diosmetin and diosmin might be a useful agent for the treatment of AD and cutaneous inflammatory diseases.
Keywords: Diosmetin, Diosmin, Atopic dermatitis, IL-4, DNCB


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