1. Academic Validation
  2. Isorhynchophylline improves lipid metabolism disorder by mediating a circadian rhythm gene Bmal1 in spontaneously hypertensive rat

Isorhynchophylline improves lipid metabolism disorder by mediating a circadian rhythm gene Bmal1 in spontaneously hypertensive rat

  • Phytother Res. 2023 Sep 26. doi: 10.1002/ptr.8015.
Xialin Zhu 1 2 Qingqing Hou 3 Ling Zhang 3 Danyang Wang 1 Zhenhua Tian 4 Yuecheng Liu 5 Yu Wang 6 Yunlun Li 1 6 7 8 Haiqiang Jiang 1 7 8
Affiliations

Affiliations

  • 1 Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.
  • 2 Research Center of Basic Medicine, Jinan Central Hospital, Shandong First Medical University, Jinan, China.
  • 3 College of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan, China.
  • 4 Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, China.
  • 5 Shandong Academy of Chinese Medicine, Jinan, China.
  • 6 Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
  • 7 Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, China.
  • 8 Shandong Provincial Key Laboratory of Traditional Chinese Medicine for Basic Research, Shandong University of Traditional Chinese Medicine, Jinan, China.
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.

Keywords

Bmal1; circadian rhythm; hypertension; isorhynchophylline; lipid metabolism.

Figures
Products