Natural plant-derived nanovesicles for effective psoriasis therapy via dual modulation of IL-17 and NRF2 pathway

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-04-30 DOI:10.1016/j.isci.2025.112556

Sreeram Peringattu Kalarikkal , Meghana N. Kumar , Soundaram Rajendran , Cathrine M.S. Bethi , Jahnavi Ravilla , Janakiraman Narayanan , Gopinath M. Sundaram

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Abstract

Psoriasis is an inflammatory skin disease with aberrant epidermal differentiation and chronic inflammation. Plant-derived exosome-like nanovesicles (PDNVs) are exosome-mimetic structures isolated from plants with enhanced bioavailability and solubility. Herein, we investigated the therapeutic efficacy of PDNVs for psoriasis treatment. In our initial phenotype-driven screen, PDNVs from apple, garlic, and shallot displayed both pro-differentiation and anti-inflammatory activity in vitro. In imiquimod (IMQ)-induced psoriasis-like murine model, topical application of either shallot or garlic PDNV hydrogels led to complete recovery of normal skin phenotype. In porcine skin ex vivo assay, both shallot and garlic PDNVs displayed percutaneous penetration up to the suprabasal epidermis. Using next generation sequencing and quantitative mRNA profiling in keratinocytes and murine skin, we elucidated a suppressive effect of shallot and garlic PDNVs on IL-17 signaling via modulation of upstream nuclear factor erythroid-2-related factor 2 (NRF2) pathway. Since PDNVs are economical to produce, shallot and garlic PDNVs could be natural and cost-effective topical alternative for psoriasis.

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天然植物源性纳米囊泡通过IL-17和NRF2通路的双重调节有效治疗银屑病

银屑病是一种表皮异常分化的慢性炎症性皮肤病。植物源性外泌体样纳米囊泡（pdnv）是从植物中分离出来的模拟外泌体结构，具有增强的生物利用度和溶解性。在此，我们研究了PDNVs治疗银屑病的疗效。在我们最初的表型驱动筛选中，来自苹果、大蒜和葱的pdnv在体外显示出促分化和抗炎活性。在咪喹莫特（IMQ）诱导的牛皮癣样小鼠模型中，局部应用葱或大蒜PDNV水凝胶可使正常皮肤表型完全恢复。在猪皮肤离体实验中，大葱和大蒜的pdnv均能穿透到下基底表皮。利用角化细胞和小鼠皮肤的下一代测序和定量mRNA分析，我们阐明了葱和大蒜pdnv通过调节上游核因子红细胞2相关因子2 （NRF2）通路对IL-17信号的抑制作用。由于pdnv的生产经济，葱和大蒜pdnv可能是天然的和具有成本效益的银屑病局部替代品。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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