Activation of Local 11β‐Hydroxysteroid Dehydrogenase Type 1 by Diosmetin Enhances Endogenous Glucocorticoid Levels to Alleviate Skin Inflammation: Insights Into a Novel Therapeutic Strategy for Atopic Dermatitis
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| Format: | Artículo Open Access |
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2025
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| _version_ | 1867009118026334208 |
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| author | Hyun Kang Hyun Jee Hwang Eunjung Kim Sung Ha Lim Eung Ho Choi |
| author_facet | Hyun Kang Hyun Jee Hwang Eunjung Kim Sung Ha Lim Eung Ho Choi Hyun Kang Hyun Jee Hwang Eunjung Kim Sung Ha Lim Eung Ho Choi |
| collection | Wiley Open Access |
| contents | Activation of Local 11β‐Hydroxysteroid Dehydrogenase Type 1 by Diosmetin Enhances Endogenous Glucocorticoid Levels to Alleviate Skin Inflammation: Insights Into a Novel Therapeutic Strategy for Atopic Dermatitis Hyun Kang Hyun Jee Hwang Eunjung Kim Sung Ha Lim Eung Ho Choi Experimental Dermatology ABSTRACTGlucocorticoids (GCs) are synthesised de novo by peripheral tissues and the adrenal cortex of the hypothalamic–pituitary–adrenal axis. Skin expresses an enzyme called 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1), which reduces cortisone to the active hormone cortisol which activates GC receptors. 11β‐HSD1 plays a significant role in alleviating atopic inflammation through the elevation of the concentrations of active GC in the skin. This study aimed to investigate the role of diosmetin as an activator of 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1). In human keratinocytes, diosmetin was found to upregulate 11β‐HSD1 protein expression and cortisol levels, as well as the transcriptional expression of 11β‐HSD1 mRNA. However, this upregulation of 11β‐HSD1 mRNA was abrogated in keratinocytes transfected with 11β‐HSD1 small interfering RNA (siRNA). In an atopic dermatitis (AD) murine model, topical administration of diosmetin significantly attenuated basal transepidermal water loss (TEWL) and the Eczema Area and Severity Index (EASI), while enhancing stratum corneum (SC) hydration. Diosmetin also increased corticosterone levels in the SC and upregulated 11β‐HSD1 expression in both the serum and epidermis. Furthermore, diosmetin treatment led to a marked reduction in serum immunoglobulin E (IgE) and tumour necrosis factor‐α (TNF‐α) levels, and suppressed mRNA expression of thymic stromal lymphopoietin (TSLP), interleukin‐1β (IL‐1β), IL‐4, and IL‐13 in the epidermis. Collectively, these findings suggest that diosmetin promotes the endogenous activation of glucocorticoids via local 11β‐HSD1 activation, underscoring its potential as a novel topical therapeutic agent for the management of inflammatory skin disorders, such as AD. 10.1111/exd.70039 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1111/exd.70039 |
| format | Artículo Open Access |
| id | wiley_oa_10_1111_exd_70039 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Activation of Local 11β‐Hydroxysteroid Dehydrogenase Type 1 by Diosmetin Enhances Endogenous Glucocorticoid Levels to Alleviate Skin Inflammation: Insights Into a Novel Therapeutic Strategy for Atopic Dermatitis Hyun Kang Hyun Jee Hwang Eunjung Kim Sung Ha Lim Eung Ho Choi Experimental Dermatology Activation of Local 11β‐Hydroxysteroid Dehydrogenase Type 1 by Diosmetin Enhances Endogenous Glucocorticoid Levels to Alleviate Skin Inflammation: Insights Into a Novel Therapeutic Strategy for Atopic Dermatitis Hyun Kang Hyun Jee Hwang Eunjung Kim Sung Ha Lim Eung Ho Choi Experimental Dermatology ABSTRACTGlucocorticoids (GCs) are synthesised de novo by peripheral tissues and the adrenal cortex of the hypothalamic–pituitary–adrenal axis. Skin expresses an enzyme called 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1), which reduces cortisone to the active hormone cortisol which activates GC receptors. 11β‐HSD1 plays a significant role in alleviating atopic inflammation through the elevation of the concentrations of active GC in the skin. This study aimed to investigate the role of diosmetin as an activator of 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1). In human keratinocytes, diosmetin was found to upregulate 11β‐HSD1 protein expression and cortisol levels, as well as the transcriptional expression of 11β‐HSD1 mRNA. However, this upregulation of 11β‐HSD1 mRNA was abrogated in keratinocytes transfected with 11β‐HSD1 small interfering RNA (siRNA). In an atopic dermatitis (AD) murine model, topical administration of diosmetin significantly attenuated basal transepidermal water loss (TEWL) and the Eczema Area and Severity Index (EASI), while enhancing stratum corneum (SC) hydration. Diosmetin also increased corticosterone levels in the SC and upregulated 11β‐HSD1 expression in both the serum and epidermis. Furthermore, diosmetin treatment led to a marked reduction in serum immunoglobulin E (IgE) and tumour necrosis factor‐α (TNF‐α) levels, and suppressed mRNA expression of thymic stromal lymphopoietin (TSLP), interleukin‐1β (IL‐1β), IL‐4, and IL‐13 in the epidermis. Collectively, these findings suggest that diosmetin promotes the endogenous activation of glucocorticoids via local 11β‐HSD1 activation, underscoring its potential as a novel topical therapeutic agent for the management of inflammatory skin disorders, such as AD. 10.1111/exd.70039 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Activation of Local 11β‐Hydroxysteroid Dehydrogenase Type 1 by Diosmetin Enhances Endogenous Glucocorticoid Levels to Alleviate Skin Inflammation: Insights Into a Novel Therapeutic Strategy for Atopic Dermatitis |
| topic | Experimental Dermatology |
| url | https://onlinelibrary.wiley.com/doi/10.1111/exd.70039 |