Author:
Han Zhijun,Tan Xiaofen,Sun Juan,Wang Tianming,Yan Guiming,Wang Changzhong,Ma Kelong
Abstract
Abstract
Background
Ulcerative colitis (UC) is an important inflammatory phenotype in bowel disease (IBD), which is caused by multiple potential factors, including fungal dysbiosis. Candida albicans (C. albicans) was confirmed to be an important factor promoting the occurrence and development of UC. Sanhuang decoction (SHD) has been used for UC therapy in China for thousand of years, although its core active constituents and pharmacological mechanism remain undefined.
Methods
In this work, a murine model of UC with C. albicans colonization was established with dextran sodium sulfate (DSS) and C. albicans intragastric administration. The major bioactive constituents and potential mechanism of SHD against UC with fungal dysbiosis were comprehensively examined by combining systems pharmacology and in vivo transcriptomics.
Results
SHD attenuated C. albicans burden, reduced DAI, increased mucosal integrity and relived systemic inflammation in UC mice. Systems pharmacology analysis identified 9 core bioactive ingredients and 45 hub targets of SHD against UC. Transcriptomics analysis confirmed 370 differentially expressed genes (DEGs) after SHD treatment, which were mainly enriched in inflammatory and immune response related signaling pathways. Toll-like receptor and PI3K-Akt signaling pathway were screened out as the candidate targets involved in the action of SHD on fungal dysbiosis-associated UC, which were consistent with the findings in systems pharmacology. The expression of TLR4, IL-1β, NF-κB, PI3K and Akt proteins were stimulated by C. albicans, and partially reversed by SHD in UC mice.
Conclusion
These findings suggested SHD could be a candidate for the treatment of fungal dysbiosis-associated UC via TLR4-NF-κB and PI3K-Akt signaling pathways.
Funder
National Natural Science Foundation of China
Outstanding Youth Project of Anhui Institution of Higher Education
Natural Science Foundation of Anhui Institution of Higher Education
Discipline Construction Key Program of Anhui University of Chinese Medicine
Publisher
Springer Science and Business Media LLC
Subject
Complementary and alternative medicine,Pharmacology
Cited by
8 articles.
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