Effects of Baicalin on Diabetic Cardiac Autonomic Neuropathy Mediated by the P2Y12 Receptor in Rat Stellate Ganglia

Abstract

Background/Aims: Chronic diabetic hyperglycemia can damage various of organ systems and cause serious complications. Although diabetic cardiac autonomic neuropathy (DCAN) is the primary cause of death in diabetic patients, its pathogenesis remains to be fully elucidated. Baicalin is a flavonoid extracted from Scutellaria baicalensis root and has antibacterial, diuretic, anti-inflammatory, anti- metamorphotic, and antispasmodic effects. Our study explored the effects of baicalin on enhancing sympathoexcitatory response induced by DCAN via the P2Y12 receptor. Methods: A type 2 diabetes mellitus rat model was induced by a combination of diet and streptozotocin. Serum epinephrine was measured by enzyme-linked immunosorbent assay. Blood pressure and heart rate were measured using the indirect tail-cuff method. Heart rate variability was analyzed using the frequency-domain of electrocardiogram recordings. The expression levels of P2Y12, interleukin-1beta (IL-1β), tumor necrosis factor alpha (TNF-α), and connexin 43 (Cx43) were determined by quantitative real-time reverse transcription-polymerase chain reaction and western blotting. The interaction between baicalin and P2Y12 determined using by molecular docking. Results: Baicalin alleviated elevated blood pressure and heart rate, improved heart rate variability, and decreased the elevated expression levels of P2Y12, IL-1β, TNF-α, and Cx43 in the stellate ganglia of diabetic rats. Baicalin also reduced the elevated concentration of serum epinephrine and the phosphorylation of p38 mitogen-activated protein kinase in diabetic rats. Conclusion: Baicalin decreases sympathetic activity by inhibiting the P2Y12 receptor in stellate ganglia satellite glial cells to maintain the balance between sympathetic and parasympathetic nerves and relieves DCAN in the rat.

Baicalin Alleviates Oxidative Stress and Inflammation in Diabetic Nephropathy via Nrf2 and MAPK Signaling Pathway

“…Moreover, due to many diabetic complications share common upstream pathogenesis, published evidences have demonstrated that BAI can also improve diabetic cardiac diseases and diabetic retinopathy via inhibiting oxidative stress and MAPK-inflammation pathway. 52,53 We believe that this feature can also be deduced from other natural products with both antioxidant and anti-inflammatory properties during the treatment of diabetic complications. Additionally, these findings provided compelling evidence that Nrf2 and MAPK signaling pathways were promising targets for diabetic nephropathy.…”

The Quest to Enhance the Efficacy of Berberine for Type-2 Diabetes and Associated Diseases: Physicochemical Modification Approaches

“…Interestingly, the entire dose-response curves of berberine was shown to be shifted down in the presence of baicalin (100 µmol/L), and baicalin antagonised the effect of berberine on glucose uptake in 3T3-L1 adipocytes. Since the antioxidant flavonoid baicalein is known to improve a range of abnormalities associated with diabetes [80][81][82][83][84][85], its coadministration with berberine appear to have a favourable outcome in the specified dose range.…”

Promising influences ofScutellaria baicalensisand its two active constituents, baicalin, and baicalein, against metabolic syndrome: A review

“…The results of this study revealed that S. baicalensis augments the antidiabetic effect of metformin, probably by improving the antioxidant status (Waisundara et al, 2008). In another study, Sheng et al determined the effect of baicalin on diabetic cardiac autonomic neuropathy in high‐fat diet and streptozocin‐induced diabetic rats (Sheng et al, 2018). They suggested that baicalin (100 mg/kg, I.P.…”

“…for 14 days) diminishes the increased blood pressure, heart rate, serum epinephrine, and p38MAPK levels as well as P2Y12 receptor, interleukin (IL)‐1β, TNF‐α, and connexin 43 (Cx43) expression levels in the stellate ganglia of diabetic rats. Overall, baicalin improved diabetic cardiac autonomic neuropathy by hampering the P2Y12 receptor and sympathetic activity (Sheng et al, 2018). Ma and coworkers investigated that baicalin recuperated the diabetes‐associated cognitive deficits in rats.…”