Ameliorative effects of Wikstroemia trichotoma 95% EtOH extract on a mouse model of DNCB-induced atopic dermatitis

J Ethnopharmacol. 2024 Oct 28:333:118398. doi: 10.1016/j.jep.2024.118398. Epub 2024 May 31.

Abstract

Ethnopharmacological relevance: The genus Wikstroemia has been extensively utilized in traditional Chinese medicine (TCM) for the management of conditions such as coughs, edema, arthritis, and bronchitis. Studies have indicated that the crude extracts of Wikstroemia exhibit anti-inflammatory, anti-allergy, anti-aging, skin psoriasis, anti-cancer, and antiviral properties. In addition, these extracts are known to contain bioactive substances, including flavonoids, coumarins, and lignans. However, few studies have investigated the anti-inflammatory or anti-allergic activities of Wikstroemia trichotoma (Thunb.) Makino against atopic dermatitis (AD).

Aim of the study: The study aimed to explore the potential of a 95% ethanol extract of W. trichotoma (WTE) on the dysfunction of skin barrier and immune system, which are primary symptoms of AD, in 2,4-dinitrochlorobenzene (DNCB)-induced SKH-1 hairless mice and phorbol 12-myristate 13-acetate (PMA)/ionomycin or immunoglobulin E (IgE) + 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulated rat basophilic leukemia cell line (RBL-2H3). Furthermore, we sought to identify the chemical contents of WTE using high-performance liquid chromatography equipped with a photodiode array detector (HPLC-PDA).

Materials and methods: An in vitro study was conducted using RBL-2H3 cells stimulated with PMA/ionomycin or IgE + DNP-BSA to assess the inhibitory effects of WTE on mast cell degranulation and interleukin-4 (IL-4) mRNA expression levels. For the in vivo study, AD was induced in SKH-1 hairless mice by applying 1% DNCB to the dorsal skin daily for 7 days. Subsequently, 0.1% DNCB solution was applied on alternate days, and mice were orally administered WTE (at 30 or 100 mg/kg/day) dissolved in 0.5% carboxymethyl cellulose (CMC) daily for 2 weeks. Transepidermal water loss (TEWL), skin hydration, skin pH, and total serum IgE levels were measured.

Results: In DNCB-stimulated SKH-1 hairless mice, WTE administration significantly improved AD symptoms and ameliorated dorsal skin inflammation. Oral administration of WTE led to a significant decrease in skin thickness, infiltration of mast cells, and level of total serum IgE, thus restoring skin barrier function in the DNCB-induced skin lesions. In addition, WTE inhibited β-hexosaminidase release and reduced IL-4 mRNA levels in RBL-2H3 cells. Chemical profile analysis of WTE confirmed the presence of three phenolic compounds, viz. chlorogenic acid, miconioside B, and matteucinol-7-O-β-apiofuranosyl (1 → 6)-β-glucopyranoside.

Conclusions: WTE ameliorates AD symptoms by modulating in the skin barrier and immune system dysfunction. This suggests that W. trichotoma extract may offer therapeutic benefits for managing AD.

Keywords: 2,4-dinitrochlorobenzene; Anti-inflammation; Atopic dermatitis; Rat basophilic leukemia cell line; Skin barrier function; Wikstroemia trichotoma.

MeSH terms

  • Animals
  • Anti-Allergic Agents / pharmacology
  • Anti-Inflammatory Agents / pharmacology
  • Cell Line, Tumor
  • Dermatitis, Atopic* / chemically induced
  • Dermatitis, Atopic* / drug therapy
  • Dinitrochlorobenzene*
  • Disease Models, Animal*
  • Ethanol* / chemistry
  • Female
  • Immunoglobulin E* / blood
  • Interleukin-4 / metabolism
  • Male
  • Mast Cells / drug effects
  • Mast Cells / metabolism
  • Mice
  • Mice, Hairless
  • Plant Extracts* / chemistry
  • Plant Extracts* / pharmacology
  • Skin / drug effects
  • Skin / metabolism
  • Skin / pathology
  • Wikstroemia* / chemistry

Substances

  • Dinitrochlorobenzene
  • Plant Extracts
  • Ethanol
  • Immunoglobulin E
  • Anti-Inflammatory Agents
  • Anti-Allergic Agents
  • Interleukin-4