SDH, a novel diarylheptane compound, is a potential treatment for inflammatory bowel disease by restoring epithelial barrier function
Background: The global prevalence of inflammatory bowel disease (IBD) is increasing, and mucosal healing is the preferred treatment target of IBD. Sodium (aS,9 R)− 3-hydroxy-16,17-dimethoxy-15-oxidotricyclo[12.3.1.12,6]nonadeca-1(18),2,4,6(19),14,16-hexene-9-yl sulfate hydrate (SDH) is a novel diary...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-07-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222004693 |
| _version_ | 1811336506604781568 |
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| author | Fei Yang Xiaoqiang Zhu Liu Li Yanping Wang Qing Xie Yu Cao Yunhui Yu Minjie Zhang Dong Li Ling Li Zhongtian Liu Biyan Zhang Zijun Chen Shiping Deng Yunsen Li |
| author_facet | Fei Yang Xiaoqiang Zhu Liu Li Yanping Wang Qing Xie Yu Cao Yunhui Yu Minjie Zhang Dong Li Ling Li Zhongtian Liu Biyan Zhang Zijun Chen Shiping Deng Yunsen Li |
| author_sort | Fei Yang |
| collection | DOAJ |
| description | Background: The global prevalence of inflammatory bowel disease (IBD) is increasing, and mucosal healing is the preferred treatment target of IBD. Sodium (aS,9 R)− 3-hydroxy-16,17-dimethoxy-15-oxidotricyclo[12.3.1.12,6]nonadeca-1(18),2,4,6(19),14,16-hexene-9-yl sulfate hydrate (SDH) is a novel diarylheptane compound, which is designed to treat IBD. Hence, we investigated the potent therapeutic activity of SDH against IBD and explored the underlying mechanisms, and determined if SDH is a safe and well-tolerated oral therapeutic for IBD treatment. Methods: We characterized its therapeutic properties in vitro and in vivo using Caco-2 cell monolayer and dextran sodium sulfate (DSS)- or 2,4,6-trinitro-benzene sulfonic acid (TNBS)-induced colitis models. We conducted nonclinical toxicology and safety pharmacology research, including general toxicity, toxicokinetics, pharmacokinetics, metabolism and plasma protein binding, cardiovascular safety pharmacology, central nervous system safety pharmacology, respiratory safety pharmacology, fertility and early embryonic development toxicity, reverse mutation assay, chromosomal aberration assay and micronucleus test. Results: The results showed that SDH promoted expression of tight junction proteins, and protected the integrity and permeability of the epithelial barrier in both cell and animal models. Moreover, lower doses of SDH showed the similar or better efficacy than cyclosporine A (CsA) and mesalazine in DSS- or TNBS-induced colitis animals. Furthermore, our results identified that SDH has satisfactory safety in these studies we tested. In summary, SDH restored the epithelial barrier through tight junction proteins and was expected to be a novel therapeutic agent for the treatment of IBD. |
| first_indexed | 2024-04-13T17:40:33Z |
| format | Article |
| id | doaj.art-60a1c0eae7444e08b8e0d75b828097fb |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-13T17:40:33Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-60a1c0eae7444e08b8e0d75b828097fb2022-12-22T02:37:11ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-07-01151113080SDH, a novel diarylheptane compound, is a potential treatment for inflammatory bowel disease by restoring epithelial barrier functionFei Yang0Xiaoqiang Zhu1Liu Li2Yanping Wang3Qing Xie4Yu Cao5Yunhui Yu6Minjie Zhang7Dong Li8Ling Li9Zhongtian Liu10Biyan Zhang11Zijun Chen12Shiping Deng13Yunsen Li14Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, China; Suzhou Pharmavan Co.,Ltd, Suzhou, Jiangsu 215127, ChinaSuzhou Pharmavan Co.,Ltd, Suzhou, Jiangsu 215127, ChinaInstitutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, ChinaInstitutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, ChinaInstitutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, ChinaSuzhou Pharmavan Co.,Ltd, Suzhou, Jiangsu 215127, ChinaSuzhou Pharmavan Co.,Ltd, Suzhou, Jiangsu 215127, ChinaSuzhou Pharmavan Co.,Ltd, Suzhou, Jiangsu 215127, ChinaSuzhou Pharmavan Co.,Ltd, Suzhou, Jiangsu 215127, ChinaSuzhou Pharmavan Co.,Ltd, Suzhou, Jiangsu 215127, ChinaSuzhou Pharmavan Co.,Ltd, Suzhou, Jiangsu 215127, ChinaSuzhou Pharmavan Co.,Ltd, Suzhou, Jiangsu 215127, ChinaSchool of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Corresponding authors.Suzhou Pharmavan Co.,Ltd, Suzhou, Jiangsu 215127, China; Corresponding authors.Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, China; Corresponding authors.Background: The global prevalence of inflammatory bowel disease (IBD) is increasing, and mucosal healing is the preferred treatment target of IBD. Sodium (aS,9 R)− 3-hydroxy-16,17-dimethoxy-15-oxidotricyclo[12.3.1.12,6]nonadeca-1(18),2,4,6(19),14,16-hexene-9-yl sulfate hydrate (SDH) is a novel diarylheptane compound, which is designed to treat IBD. Hence, we investigated the potent therapeutic activity of SDH against IBD and explored the underlying mechanisms, and determined if SDH is a safe and well-tolerated oral therapeutic for IBD treatment. Methods: We characterized its therapeutic properties in vitro and in vivo using Caco-2 cell monolayer and dextran sodium sulfate (DSS)- or 2,4,6-trinitro-benzene sulfonic acid (TNBS)-induced colitis models. We conducted nonclinical toxicology and safety pharmacology research, including general toxicity, toxicokinetics, pharmacokinetics, metabolism and plasma protein binding, cardiovascular safety pharmacology, central nervous system safety pharmacology, respiratory safety pharmacology, fertility and early embryonic development toxicity, reverse mutation assay, chromosomal aberration assay and micronucleus test. Results: The results showed that SDH promoted expression of tight junction proteins, and protected the integrity and permeability of the epithelial barrier in both cell and animal models. Moreover, lower doses of SDH showed the similar or better efficacy than cyclosporine A (CsA) and mesalazine in DSS- or TNBS-induced colitis animals. Furthermore, our results identified that SDH has satisfactory safety in these studies we tested. In summary, SDH restored the epithelial barrier through tight junction proteins and was expected to be a novel therapeutic agent for the treatment of IBD.http://www.sciencedirect.com/science/article/pii/S0753332222004693Inflammatory bowel diseaseEpithelial barrier functionTight junction proteinsSafety pharmacologyNonclinical toxicology |
| spellingShingle | Fei Yang Xiaoqiang Zhu Liu Li Yanping Wang Qing Xie Yu Cao Yunhui Yu Minjie Zhang Dong Li Ling Li Zhongtian Liu Biyan Zhang Zijun Chen Shiping Deng Yunsen Li SDH, a novel diarylheptane compound, is a potential treatment for inflammatory bowel disease by restoring epithelial barrier function Biomedicine & Pharmacotherapy Inflammatory bowel disease Epithelial barrier function Tight junction proteins Safety pharmacology Nonclinical toxicology |
| title | SDH, a novel diarylheptane compound, is a potential treatment for inflammatory bowel disease by restoring epithelial barrier function |
| title_full | SDH, a novel diarylheptane compound, is a potential treatment for inflammatory bowel disease by restoring epithelial barrier function |
| title_fullStr | SDH, a novel diarylheptane compound, is a potential treatment for inflammatory bowel disease by restoring epithelial barrier function |
| title_full_unstemmed | SDH, a novel diarylheptane compound, is a potential treatment for inflammatory bowel disease by restoring epithelial barrier function |
| title_short | SDH, a novel diarylheptane compound, is a potential treatment for inflammatory bowel disease by restoring epithelial barrier function |
| title_sort | sdh a novel diarylheptane compound is a potential treatment for inflammatory bowel disease by restoring epithelial barrier function |
| topic | Inflammatory bowel disease Epithelial barrier function Tight junction proteins Safety pharmacology Nonclinical toxicology |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222004693 |
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