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| Status |
Public on Oct 10, 2023 |
| Title |
Fangji Dihuang formulation ameliorated DNCB-induced atopic dermatitis-like skin lesions by IL-17 signaling pathway: Integrating network analysis and experimental validation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: Fangji Dihuang formulation (FJDHF) is a well-known Traditional Chinese Medicine (TCM) formula with a reported clinical therapeutic effect in the treatment of inflammatory skin diseases. However, there is a lack of pharmacological research on its anti-atopic dermatitis (AD) activity. Methods: To investigate the potential anti-AD activity of FJDHF, DNCB was used to induce AD-like skin inflammation in the back of mice. Following successful modeling, the mice were administered FJDHF orally. The extent of the inflammatory skin lesions was recorded at day 4, 7, 14 and 28. UHPLC-Q-Exactive Orbitrap MS was used to identify and match the compounds present in FJDHF with ITCM, TCMIP and TCMSID. In silico predictions of potential target proteins of the identified compounds were obtained from SwishTargetPrediction, ITCM and TargetNet databases. AD-related genes were identified from GSE32924 data set, and FJDHF anti-AD hub genes were identified by MCODE algorithm. ClueGo enrichment analysis was employed to identify the core pathway of FJDHF's anti-AD effect. To further investigate the anti-AD effect of FJDHF, single-cell RNA sequencing data set (GSE148196) from AD patients was analyzed to determine the target cells and signaling pathways of FJDHF in AD. Finally, rt-PCR, flow cytometry, and mouse back skin RNA sequencing were utilized to validate our findings. Results: FJDHF was found to be effective in improving the degree of the AD-like lesions in the mice. Network pharmacological analysis revealed the core pathway of FJDHF to be the IL-17 signaling pathway, which is interactively associated with cytokines. Single-cell RNA sequencing analysis suggested that FJDHF may play an anti-AD role by influencing dendritic cells. Flow cytometry and rt-PCR results showed that FJDHF can reduce the influence of AD sample of IL-4, IFN-γ and the expression of IL-17. The RNA sequencing of mouse back skin also confirmed our conclusion. Conclusion: FJDHF may inhibit DNCB-induced AD-like skin inflammation in mice by inhibiting the IL-17 signaling pathway. Thus, FJDHF can be considered as a potential therapeutic agent for AD.
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| Overall design |
To investigate the potential anti-AD activity of FJDHF, DNCB was used to induce AD-like skin inflammation in the back of mice. Following successful modeling, the mice were administered FJDHF orally. The extent of the inflammatory skin lesions was recorded at day 4, 7, 14 and 28. UHPLC-Q-Exactive Orbitrap MS was used to identify and match the compounds present in FJDHF with ITCM, TCMIP and TCMSID. In silico predictions of potential target proteins of the identified compounds were obtained from SwishTargetPrediction, ITCM and TargetNet databases. AD-related genes were identified from GSE32924 data set, and FJDHF anti-AD hub genes were identified by MCODE algorithm. ClueGo enrichment analysis was employed to identify the core pathway of FJDHF's anti-AD effect. To further investigate the anti-AD effect of FJDHF, single-cell RNA sequencing data set (GSE148196) from AD patients was analyzed to determine the target cells and signaling pathways of FJDHF in AD. Finally, rt-PCR, flow cytometry, and mouse back skin RNA sequencing were utilized to validate our findings.
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| Contributor(s) |
Zeng X, Zhao W, Jiang H, Zhang W |
| Citation(s) |
38089052 |
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| Submission date |
Oct 02, 2023 |
| Last update date |
Jan 02, 2024 |
| Contact name |
chunhao cao |
| E-mail(s) |
24483222@life.hkbu.edu.hk
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| Organization name |
Hong Kong Baptist University
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| Department |
School of Chinese Medicine
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| Street address |
Hong Kong
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| City |
Hong Kong |
| ZIP/Postal code |
999077 |
| Country |
Hong Kong |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (9)
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| GSM7816028 |
Back skin of atopic dermatitis model mouse 1 |
| GSM7816029 |
Back skin of atopic dermatitis model mouse 2 |
| GSM7816030 |
Back skin of atopic dermatitis model mouse 3 |
| GSM7816031 |
Back skin of atopic dermatitis model mouse 4 |
| GSM7816032 |
Back skin of atopic dermatitis model mouse (with treated by Fangji dihuang Formulation) 1 |
| GSM7816033 |
Back skin of atopic dermatitis model mouse (with treated by Fangji dihuang Formulation) 2 |
| GSM7816034 |
Back skin of atopic dermatitis model mouse (with treated by Fangji dihuang Formulation) 3 |
| GSM7816035 |
Back skin of atopic dermatitis model mouse (with treated by Fangji dihuang Formulation) 4 |
| GSM7816036 |
Back skin of atopic dermatitis model mouse (with treated by Fangji dihuang Formulation) 5 |
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| Relations |
| BioProject |
PRJNA1023158 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE244430_gene_count_matrix.txt.gz |
655.6 Kb |
(ftp)(http) |
TXT |
| GSE244430_genes_fpkm_expression.txt.gz |
8.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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