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Dihydrotanshinone I, a natural product, ameliorates DSS-induced experimental ulcerative colitis in mice
Guo, Yanling1; Wu, Xiaxia2; Wu, Qin1; Lu, Yuanfu1; Shi, Jingshan1; Chen, Xiuping1,2

Ulcerative colitis (UC) is a chronic and relapsing inflammatory disorder of the colon and rectum with increasing morbidity in recent years. 15,16-dihydrotanshinone I (DHT) is a natural product with multiple bioactivities. In this study, we aimed to investigate the protective effect and potential mechanisms of DHT on UC. Dextran sulfate sodium salt (DSS) was administrated in drinking water for 7 days to induce UC in mice. DHT (10 and 25 mg/kg) significantly alleviated DSS-induced body weight loss, disease activity index (DAI) scores, and improved histological alterations of colon tissues. DHT inhibited the myeloperoxidase (MPO) activity, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in colon tissues and decreased serum levels of TNF-alpha, IL-1 beta, IL-6, and high-mobility group box 1 (HMGB1). Furthermore, increased expression of kinases receptor-interacting protein 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL) and decreased expression of caspase-8 in colon tissues were partially restored by DHT. In LPS-stimulated RAW264.7 macrophages, DHT significantly inhibited generation of nitric oxide, IL-6, TNF-alpha and protein expression of iNOS, COX-2. In addition, increased expression of iNOS, COX-2, and phosphorylated RIP1, RIP3, MLKL in response to LPS plus Z-VAD (LZ) were also suppressed by DHT. DHT had no effect on TNF-alpha + BV6 + Z-VAD (TBZ) induced phosphorylation of RIPs and MLKL in HT29 cells. Especially, DHT showed no effect on LZ and TBZ-induced necroptosis in RAW264.7 and HT29 cells, respectively. In summary, DHT alleviated DSS-induced UC in mice by suppressing pro-inflammatory mediators and regulating RIPs-MLKL-caspase-8 axis.

Keyword15,16-dihydrotanshinone i Ulcerative Colitis Inflammation Necroptosis
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Indexed BySCI
WOS Research AreaPharmacology & Pharmacy ; Toxicology
WOS SubjectPharmacology & Pharmacy ; Toxicology
WOS IDWOS:000429294900004
The Source to ArticleWOS
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Cited Times [WOS]:14   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorChen, Xiuping
Affiliation1.Key Lab for Pharmacology of Ministry of Education, Department of Pharmacology, Zunyi Medical College, Zunyi, China
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Guo, Yanling,Wu, Xiaxia,Wu, Qin,et al. Dihydrotanshinone I, a natural product, ameliorates DSS-induced experimental ulcerative colitis in mice[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2018,344:35-45.
APA Guo, Yanling,Wu, Xiaxia,Wu, Qin,Lu, Yuanfu,Shi, Jingshan,&Chen, Xiuping.(2018).Dihydrotanshinone I, a natural product, ameliorates DSS-induced experimental ulcerative colitis in mice.TOXICOLOGY AND APPLIED PHARMACOLOGY,344,35-45.
MLA Guo, Yanling,et al."Dihydrotanshinone I, a natural product, ameliorates DSS-induced experimental ulcerative colitis in mice".TOXICOLOGY AND APPLIED PHARMACOLOGY 344(2018):35-45.
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