Isorhynchophylline improves lipid metabolism disorder by mediating a circadian rhythm gene Bmal1 in spontaneously hypertensive rat
Xialin Zhu
Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
Research Center of Basic Medicine, Jinan Central Hospital, Shandong First Medical University, Jinan, China
Contribution: Funding acquisition, Investigation, Project administration, Writing - original draft, Writing - review & editing
Search for more papers by this authorQingqing Hou
College of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan, China
Contribution: Data curation, Investigation, Writing - original draft
Search for more papers by this authorLing Zhang
College of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan, China
Contribution: Data curation, Methodology, Supervision
Search for more papers by this authorDanyang Wang
Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
Contribution: Conceptualization, Project administration, Visualization
Search for more papers by this authorZhenhua Tian
Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, China
Contribution: Data curation, Investigation
Search for more papers by this authorYuecheng Liu
Shandong Academy of Chinese Medicine, Jinan, China
Contribution: Data curation, Funding acquisition, Software, Writing - review & editing
Search for more papers by this authorCorresponding Author
Yu Wang
Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
Correspondence
Haiqiang Jiang, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
Email: [email protected]
Yunlun Li, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
Email: [email protected]
Yu Wang, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, China.
Email: [email protected]
Contribution: Conceptualization, Software, Writing - review & editing
Search for more papers by this authorCorresponding Author
Yunlun Li
Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, China
Shandong Provincial Key Laboratory of Traditional Chinese Medicine for Basic Research, Shandong University of Traditional Chinese Medicine, Jinan, China
Correspondence
Haiqiang Jiang, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
Email: [email protected]
Yunlun Li, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
Email: [email protected]
Yu Wang, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, China.
Email: [email protected]
Contribution: Data curation, Supervision, Visualization, Writing - review & editing
Search for more papers by this authorCorresponding Author
Haiqiang Jiang
Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, China
Shandong Provincial Key Laboratory of Traditional Chinese Medicine for Basic Research, Shandong University of Traditional Chinese Medicine, Jinan, China
Correspondence
Haiqiang Jiang, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
Email: [email protected]
Yunlun Li, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
Email: [email protected]
Yu Wang, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, China.
Email: [email protected]
Contribution: Funding acquisition, Project administration, Resources, Supervision, Writing - review & editing
Search for more papers by this authorXialin Zhu
Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
Research Center of Basic Medicine, Jinan Central Hospital, Shandong First Medical University, Jinan, China
Contribution: Funding acquisition, Investigation, Project administration, Writing - original draft, Writing - review & editing
Search for more papers by this authorQingqing Hou
College of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan, China
Contribution: Data curation, Investigation, Writing - original draft
Search for more papers by this authorLing Zhang
College of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan, China
Contribution: Data curation, Methodology, Supervision
Search for more papers by this authorDanyang Wang
Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
Contribution: Conceptualization, Project administration, Visualization
Search for more papers by this authorZhenhua Tian
Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, China
Contribution: Data curation, Investigation
Search for more papers by this authorYuecheng Liu
Shandong Academy of Chinese Medicine, Jinan, China
Contribution: Data curation, Funding acquisition, Software, Writing - review & editing
Search for more papers by this authorCorresponding Author
Yu Wang
Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
Correspondence
Haiqiang Jiang, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
Email: [email protected]
Yunlun Li, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
Email: [email protected]
Yu Wang, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, China.
Email: [email protected]
Contribution: Conceptualization, Software, Writing - review & editing
Search for more papers by this authorCorresponding Author
Yunlun Li
Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, China
Shandong Provincial Key Laboratory of Traditional Chinese Medicine for Basic Research, Shandong University of Traditional Chinese Medicine, Jinan, China
Correspondence
Haiqiang Jiang, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
Email: [email protected]
Yunlun Li, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
Email: [email protected]
Yu Wang, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, China.
Email: [email protected]
Contribution: Data curation, Supervision, Visualization, Writing - review & editing
Search for more papers by this authorCorresponding Author
Haiqiang Jiang
Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, China
Shandong Provincial Key Laboratory of Traditional Chinese Medicine for Basic Research, Shandong University of Traditional Chinese Medicine, Jinan, China
Correspondence
Haiqiang Jiang, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
Email: [email protected]
Yunlun Li, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
Email: [email protected]
Yu Wang, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, China.
Email: [email protected]
Contribution: Funding acquisition, Project administration, Resources, Supervision, Writing - review & editing
Search for more papers by this authorXialin Zhu and Qingqing Hou contributed equally to this work.
Abstract
Hypertension is a progressive metabolic disease characterized by circadian regulation of lipid metabolism disorder. Identifying specific lipid components and maintaining circadian homeostasis of lipid metabolism might be a promising therapeutic strategy for hypertension. Isorhynchophylline (IRP) can regulate lipid metabolism; however, the underlying mechanism of IRP in improving lipid metabolism rhythm disorder is still unclear. The lipid circadian biomarkers and abnormal metabolic pathways intervened by IRP were investigated using diurnal lipidomic research methods. The 24-h circadian changes in mRNA and protein expression levels of circadian genes, including Bmal1, Clock, Cry1, Cry2, Per1, and Per2, and lipid metabolism-related factors (PPARα and LPL) were determined using RT-PCR and western blot analyses, respectively. The underlying mechanisms were intensively investigated by inhibiting Bmal1. Molecular docking and drug affinity responsive target stability analyses were performed to assess the binding affinity of IRP and Bmal1. IRP treatment could effectively improve 24-h blood pressure, ameliorate the lipid metabolic rhythm disorder, reverse the expression levels of circadian rhythm genes, and regulate lipid metabolism-related genes (PPARα and LPL) by mediating Bmal1. This study highlighted the potential effects of IRP in maintaining the circadian homeostasis of lipid metabolism and the treatment of hypertension.
CONFLICT OF INTEREST STATEMENT
The authors declare that there are no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| ptr8015-sup-0001-Supinfo.docxWord 2007 document , 1.5 MB | Data S1. Supporting Information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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