Clinical and Experimental Hypertension (Nov 2019)

Berberine suppresses the ectopic expression of miR-133a in endothelial cells to improve vascular dementia in diabetic rats

  • Sen Yin,
  • Wenwu Bai,
  • Peng Li,
  • Xu Jian,
  • Tichao Shan,
  • Zhenyu Tang,
  • Xuejiao Jing,
  • Song Ping,
  • Quanzhong Li,
  • Zhang Miao,
  • Shuangxi Wang,
  • Wensheng Ou,
  • Jianchun Fei,
  • Tao Guo

DOI
https://doi.org/10.1080/10641963.2018.1545846
Journal volume & issue
Vol. 41, no. 8
pp. 708 – 716

Abstract

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Objective: Vascular dementia is the second leading cause of dementia, which is strongly associated with diabetes. Ectopic expression of miR-133a in endothelial cells is involved in endothelial dysfunction in diabetes. Whether berberine, as a natural product in Coptis chinensis, improves vascular dementia induced by diabetes remains unknown. Methods: Diabetes and subsequent vascular dementia were induced in rats by injecting streptozotocin (50 mg/kg/day) for five consecutive days. The expression of miR-133a was determined by fluorescence in situ hybridization. The learning and memory were evaluated by step-down, step-through, and morris water maze (MWM) tests. Results: In streptozotocin-injected rats, hyperglycemia dramatically induced miR-133a ectopic expressions in vascular endothelium, reduced GTPCH1 gene expressions and BH4 levels, which were reversed by berberine administration (1.0 g/kg/day, 8 weeks). Hyperglycemia also inhibited acetylcholine-induced vasorelaxation in middle cerebral artery and reduced blood supply to the brain, which were bypassed by berberine. Ex vivo studies indicated that miR-133a agomirs abolished these beneficial effects of berberine on acetylcholine-induced vasorelaxation, while supplement of L-sepiapterin prevented endothelial dysfunction in middle cerebral artery isolated from rats. By performing step-down, step-through, and MWM tests, we observed that hyperglycemia significantly caused the impairments of learning and memory in streptozotocin-injected rats. Importantly, these aberrant phenotypes in diabetic rats were normalized by berberine therapy. Finally, berberine reduced miR-133a expression, and increased both BH4 levels and NO production in cultured endothelial cells treated with high glucose. Conclusion: Berberine improves vascular dementia in diabetes, which is possibly related to the suppression of miR-133a ectopic expression in endothelial cells.

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