# The Therapeutic Potential of Kiwi Extract as a Source of Cysteine Protease Inhibitors on DNCB-Induced Atopic Dermatitis in Mice and Human Keratinocyte HaCaT Cells

## TL;DR

This study explores how kiwi extract can reduce inflammation in a mouse model of atopic dermatitis and human skin cells.

## Contribution

The study demonstrates the anti-inflammatory potential of kiwi extract in treating atopic dermatitis.

## Key findings

- CPKE reduced phosphorylation of MAPK and Akt in TNF-α-stimulated HaCaT cells.
- Topical CPKE application decreased dermatitis severity and epidermal thickness in DNCB-treated mice.
- CPKE inhibited cysteine protease activity and remained stable under various conditions.

## Abstract

The discovery of effective cysteine protease inhibitors with crude protein kiwi extracts (CPKEs) has created novel challenges and prospects for pharmaceutical development. Despite extensive research on CPKEs, limited research has been conducted on treating atopic dermatitis (AD). Therefore, the objective of this work was to investigate the anti-inflammatory effects of CPKEs on TNF-α activation in a HaCaT cell model and in a DNCB (1-chloro-2, 4-dinitrochlorobenzene)-induced atopic dermatitis animal model. The molecular weight of the CPKE was determined using SDS-PAGE under non-reducing (17 kDa and 22 kDa) and reducing conditions (25 kDa, 22 kDa, and 15 kDa), whereas gelatin zymography was performed to examine the CPKE’s inhibitory impact on cysteine protease (actinidin and papain) activity. Moreover, the CPKE remains stable at 60 °C, with pH levels varying from 4 to 11, as determined by the azocasein assay. CPKE treatment decreased the phosphorylation of mitogen-activated protein kinase (MAPK) and Akt, along with the activation of nuclear factor-kappa B (NF-κB)-p65 in tumor necrosis factor-α (TNF-α)-stimulated HaCaT cells. Five-week-old BALB/c mice were treated with DNCB to act as an AD-like animal model. The topical application of CPKE to DNCB-treated mice for three weeks substantially decreased clinical dermatitis severity and epidermal thickness and reduced eosinophil infiltration and mast cells into ear and skin tissues. These findings imply that CPKE derived from kiwifruit might be a promising therapy option for inflammatory skin diseases such as AD.