Osthole relieves diabetics cardiac autonomic neuropathy associated with P2X3 receptor in ratstellate ganglia.

Diabetic cardiac autonomic neuropathy (DCAN) is a serious complication of diabetes mellitus, which often leads to cardiac dysfunction and even threatens patients' life. Osthole, a natural coumarin derivative, has anti-inflammatory, anti-oxidant and antihypertensive effects. The P2X3 receptor is related to DCAN. The objective of this study will investigate whether osthole relieves DCAN associated with the P2X3 receptor in the stellate ganglia of diabetic rats. A type 2 diabetes mellitus rat model was induced by a combination of diet and streptozotocin. Our results showed that osthole improved the abnormal changes of blood pressure, heart rate, and heart rate variability in diabetic rats and significantly reduced the up-regulated expression levels of the P2X3 receptor, tumor necrosis factor-α and interleukin-1β in stellate ganglia of diabetic rats. Meanwhile, osthole significantly decreased the elevated serum adrenaline concentration and phosphorylation level of extracellular regulated protein kinase 1/2. In addition, the molecular docking result indicated that osthole was a perfect fit for interacting with the P2X3 receptor. Overall, osthole alleviates the sympathetic relative excitation via inhibiting the expression of P2X3 receptors in the stellate ganglia, to achieve a balance between sympathetic and parasympathetic nerves, relieves the DCAN.