Macrovascular Protecting Effects of Berberine through Anti-inflammation and Intervention of BKCa in Type 2 Diabetes Mellitus Rats

Objective: The aim of this study was to examine the effect of berberine in diabetes mellitus in vivo and in vitro, and elucidate the underlying mechanisms.

Methods: Rat models of type 2 diabetes mellitus (T2DM) were established, which were treated with berberine. Pathological changes in the thoracic aorta, and inflammatory factor and adiponectin levels were investigated. Vascular smooth muscle cells (VSMCs) of the thoracic aorta were cultured and treated with berberine. Cellular proliferation, migration, and inflammatory factor levels were investigated. Responses of vascular rings to phenylephrine (PE) and sodium nitroprusside (SNP) after berberine intervention, and the changes of relaxation responses to SNP after adding Iberiotoxin (IbTX) were investigated.

Results: Berberine ameliorated the pathological status of the thoracic aorta in the T2DM rats. Berberine significantly inhibited the C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) production, and increased the adiponectin level compared with the model group. Compared with the model group, berberine inhibited the proliferation and migration of VSMCs in vitro, and reduced tumor growth factor-β1 (TGF-β1), IL-6, and TNF-α levels. Furthermore, the contraction of thoracic aorta to PE was reduced, while the relaxation response of thoracic aorta to SNP was increased, after the berberine intervention in the T2DM rats. The relaxation of thoracic aorta to SNP in the model and berberine groups were decreased after the IbTX treatment.

Conclusions: Protective effects of berberine against macrovascular complications induced by diabetes mellitus may be attributed to inhibiting the inflammation and intervening the calcium-activated potassium (BKCa).

Keywords: BKCa; Berberine; diabetes mellitus; inflammatory factor; macrovascular complications.; vascular smooth muscle cells.