دورية أكاديمية
Berberine directly targets AKR1B10 protein to modulate lipid and glucose metabolism disorders in NAFLD.
| العنوان: | Berberine directly targets AKR1B10 protein to modulate lipid and glucose metabolism disorders in NAFLD. |
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| المؤلفون: | Yang S; School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China., Cao SJ; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China., Li CY; School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China., Zhang Q; School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China., Zhang BL; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China., Qiu F; School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin, 301617, China. Electronic address: fengqiu20070118@163.com., Kang N; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. Electronic address: kangndd@163.com. |
| المصدر: | Journal of ethnopharmacology [J Ethnopharmacol] 2024 Oct 05; Vol. 332, pp. 118354. Date of Electronic Publication: 2024 May 17. |
| 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: | Non-alcoholic Fatty Liver Disease*/drug therapy , Non-alcoholic Fatty Liver Disease*/metabolism , Berberine*/pharmacology , Berberine*/therapeutic use , Mice, Inbred C57BL* , Diet, High-Fat*/adverse effects , Lipid Metabolism*/drug effects , Aldo-Keto Reductases*/metabolism , Aldo-Keto Reductases*/genetics, Animals ; Humans ; Hep G2 Cells ; Male ; Mice ; Aldehyde Reductase/metabolism ; Aldehyde Reductase/genetics ; Glucose/metabolism ; Liver/drug effects ; Liver/metabolism ; Insulin Resistance |
| مستخلص: | Ethnopharmacological Relevance: Berberine (BBR) is the main active component from Coptidis rhizome, a well-known Chinese herbal medicine used for metabolic diseases, especially diabetes for thousands of years. BBR has been reported to cure various metabolic disorders, such as nonalcoholic fatty liver disease (NAFLD). However, the direct proteomic targets and underlying molecular mechanism of BBR against NAFLD remain less understood. Aim of the Study: To investigate the direct target and corresponding molecular mechanism of BBR on NAFLD is the aim of the current study. Materials and Methods: High-fat diet (HFD)-fed mice and oleic acid (OA) stimulated HepG2 cells were utilized to verify the beneficial impacts of BBR on glycolipid metabolism profiles. The click chemistry in proteomics, DARTS, CETSA, SPR and fluorescence co-localization analysis were conducted to identify the targets of BBR for NAFLD. RNA-seq and shRNA/siRNA were used to investigate the downstream pathways of the target. Results: BBR improved hepatic steatosis, ameliorated insulin resistance, and reduced TG levels in the NAFLD models. Importantly, Aldo-keto reductase 1B10 (AKR1B10) was first proved as the target of BBR for NAFLD. The gene expression of AKR1B10 increased significantly in the NAFLD patients' liver tissue. We further demonstrated that HFD and OA increased AKR1B10 expression in the C57BL/6 mice's liver and HepG2 cells, respectively, whereas BBR decreased the expression and activities of AKR1B10. Moreover, the knockdown of AKR1B10 by applying shRNA/siRNA profoundly impacted the beneficial effects on the pathogenesis of NAFLD by BBR. Meanwhile, the changes in various proteins (ACC1, CPT-1, GLUT2, etc.) are responsible for hepatic lipogenesis, fatty acid oxidation, glucose uptake, etc. by BBR were reversed by the knockdown of AKR1B10. Additionally, RNA-seq was used to identify the downstream pathway of AKR1B10 by examining the gene expression of liver tissues from HFD-fed mice. Our findings revealed that BBR markedly increased the protein levels of PPARα while downregulating the expression of PPARγ. However, various proteins of PPAR signaling pathways remained unaffected post the knockdown of AKR1B10. Conclusions: BBR alleviated NAFLD via mediating PPAR signaling pathways through targeting AKR1B10. This study proved that AKR1B10 is a novel target of BBR for NAFLD treatment and helps to find new targets for the treatment of NAFLD by using active natural compounds isolated from traditional herbal medicines as the probe. 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: AKR1B10; Berberine; Lipid and glucose metabolism disorder; NAFLD; PPAR signaling pathways |
| المشرفين على المادة: | 0I8Y3P32UF (Berberine) EC 1.1.1.- (Aldo-Keto Reductases) EC 1.1.1.- (AKR1B10 protein, human) EC 1.1.1.21 (Aldehyde Reductase) IY9XDZ35W2 (Glucose) |
| تواريخ الأحداث: | Date Created: 20240518 Date Completed: 20240611 Latest Revision: 20240621 |
| رمز التحديث: | 20240621 |
| DOI: | 10.1016/j.jep.2024.118354 |
| PMID: | 38762210 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1872-7573 |
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| DOI: | 10.1016/j.jep.2024.118354 |