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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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this work, a murine model of UC with\n                      <jats:italic>C. albicans<\/jats:italic>\n                      colonization was established with dextran sodium sulfate (DSS) and\n                      <jats:italic>C. albicans<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SHD attenuated\n                      <jats:italic>C. albican<\/jats:italic>\n                      s 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-1\n                      <jats:italic>\u03b2<\/jats:italic>\n                      , NF-\u03baB, PI3K and Akt proteins were stimulated by\n                      <jats:italic>C. albican<\/jats:italic>\n                      s, and partially reversed by SHD in UC mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggested SHD could be a candidate for the treatment of fungal dysbiosis-associated UC via TLR4-NF-\u03baB and PI3K-Akt signaling pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13020-021-00487-2","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T06:04:04Z","timestamp":1628575444000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Systems pharmacology and transcriptomics reveal the mechanisms of Sanhuang decoction enema in the treatment of ulcerative colitis with additional Candida albicans infection"],"prefix":"10.1186","volume":"16","author":[{"given":"Zhijun","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofen","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiming","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changzhong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"issue":"47","key":"487_CR1","doi-asserted-by":"publisher","first-page":"6866","DOI":"10.3748\/wjg.v25.i47.6866","volume":"25","author":"S Selvaratnam","year":"2019","unstructured":"Selvaratnam S, Gullino S, Shim L, Lee E, Lee A, Paramsothy S, Leong RW. 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