دورية أكاديمية
Stigmast-4-en-3-one from Euonymus alatus (Thunb.) Siebold. improves diabetic retinopathy and angiogenesis mediated by glucocorticoids receptor.
| العنوان: | Stigmast-4-en-3-one from Euonymus alatus (Thunb.) Siebold. improves diabetic retinopathy and angiogenesis mediated by glucocorticoids receptor. |
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| المؤلفون: | Ji R; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address: jirf0527@163.com., Du Y; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address: duyutcm@163.com., Wang Y; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China; College of Life Science, Beijing University of Chinese Medicine, Beijing, 100029, China; Beijing Key Laboratory of TCM Syndrome and Formula, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address: wangyong@bucm.edu.cn., Tian J; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address: tjy6002@163.com., Wang Z; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China; Beijing Key Laboratory of TCM Syndrome and Formula, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address: 1065092305@qq.com., Peng M; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China; Beijing Key Laboratory of TCM Syndrome and Formula, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address: 1632636815@qq.com., Hao G; Basic Theory of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, 100091, China. Electronic address: haogaimei@163.com., Xing Y; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address: xxx_yeah_up@163.com., Xu Y; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China; Beijing Key Laboratory of TCM Syndrome and Formula, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address: 13051153327@163.com., Ye D; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address: yess_summer@163.com., Liu Y; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address: liuyg0228@163.com., Han J; Institute of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China; Beijing Key Laboratory of TCM Syndrome and Formula, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address: hanjing8585@163.com., Wang W; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China; Beijing Key Laboratory of TCM Syndrome and Formula, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address: wangwei26960@126.com. |
| المصدر: | Journal of ethnopharmacology [J Ethnopharmacol] 2024 Nov 15; Vol. 334, pp. 118567. Date of Electronic Publication: 2024 Jul 11. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Sequoia Country of Publication: Ireland NLM ID: 7903310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7573 (Electronic) Linking ISSN: 03788741 NLM ISO Abbreviation: J Ethnopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Limerick : Elsevier Sequoia Original Publication: Lausanne, Elsevier Sequoia. |
| مواضيع طبية MeSH: | Diabetic Retinopathy*/drug therapy , Receptors, Glucocorticoid*/metabolism , Zebrafish* , Diabetes Mellitus, Experimental*/drug therapy , Euonymus*/chemistry, Animals ; Mice ; Chick Embryo ; Male ; Molecular Docking Simulation ; Dexamethasone/pharmacology ; Mice, Inbred C57BL ; Cell Proliferation/drug effects ; Endothelial Cells/drug effects ; Endothelial Cells/metabolism ; Angiogenesis Inhibitors/pharmacology ; Triamcinolone Acetonide/pharmacology ; Angiogenesis |
| مستخلص: | Ethnopharmacological Relevance: Euonymus alatus (Thunb.) Siebold. (EA), a traditional Chinese medicine, is widely used in the treatment of diabetes. Our group has previously found that EA could treat diabetic retinopathy (DR) and stigmast-4-en-3-one (Numbered E6) is the active substance responsible for inhibiting angiogenesis in vitro by EA. However, the effects and mechanisms of E6 in the treatment of DR is still unknown. Aim of the Study: The aim of this study was to investigate the effects and mechanisms of E6 in EA on DR. Additionally, a comparison was made between the effects of E6 and triamcinolone acetonide (TA), as well as the side effects of E6 and dexamethasone. Materials and Methods: Ocular affinity assessment and pharmacokinetic parameter prediction were conducted to evaluate the potential of E6 to treat DR. Retinal endothelial cells were used to investigate the in vitro inhibitory effect of E6 on vascular proliferation. Additionally, chicken embryos, zebrafish, and mice were used to investigate the in vivo anti-vascular proliferation effect of E6. Finally, diabetic mice were used to investigate whether E6 improves diabetic retinopathy and to compare its efficacy with that of TA. We then used network pharmacology to study the targets of E6 and performed molecular docking; followed by immunofluorescence experiments, ELISA, Western blot, and tube formation experiments to further investigate its mechanism. Finally, we compared the side effects of E6 with those of dexamethasone. Results: E6 was found to have an affinity for the eye and to inhibit vascular proliferation both in vivo and in vitro. Moreover, E6 was found to be more efficacious than TA in the treatment of DR. Molecular docking experiments predicted that the glucocorticoid receptor (GR) is a potential target of E6, and immunofluorescence analyses confirmed that E6 upregulated the expression of the GR in the retina of hyperglycemic mice. In addition, western blotting results and tube formation experiments showed that E6 also attenuated angiogenesis by inhibiting the Hippo and VEGF pathways. Finally, by comparing the effects of E6 and dexamethasone on glucose regulation and osteoporosis, E6 was found to have fewer side effects. Conclusions: E6 is a highly effective drug for the treatment of DR, superior to TA and with fewer side effects than dexamethasone. Its mechanism involves the activation of glucocorticoid receptor and inhibition of Hippo and VEGF pathways to alleviate angiogenesis and inflammation. This study is the first to investigate the role and mechanism of E6 in improving DR. The findings suggest that E6 has unique advantages in the treatment of DR. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Angiogenesis; Chinese medicine; Diabetic retinopathy; Glucocorticoid receptor; Inflammation |
| المشرفين على المادة: | 0 (Receptors, Glucocorticoid) 7S5I7G3JQL (Dexamethasone) 0 (Angiogenesis Inhibitors) F446C597KA (Triamcinolone Acetonide) |
| تواريخ الأحداث: | Date Created: 20240712 Date Completed: 20240809 Latest Revision: 20240809 |
| رمز التحديث: | 20240812 |
| DOI: | 10.1016/j.jep.2024.118567 |
| PMID: | 38996951 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1872-7573 |
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| DOI: | 10.1016/j.jep.2024.118567 |