Pharmacology Division, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh, 160014, India.
Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences (UIPS), UGC Centre of Advanced Studies, Panjab University, Chandigarh, 160 014, India.
Neurochem Res. 2022 Aug;47(8):2431-2444. doi: 10.1007/s11064-022-03640-x. Epub 2022 Jun 4.
Cognitive dysfunction is an important complication observed in type 2 diabetes mellitus (T2DM) patients. Tetramethylpyrazine (TMP) is known to exhibit anti-diabetic and neuroprotective properties. Therefore, the present study aimed to investigate the possible therapeutic effects of TMP against type 2 diabetes-associated cognitive impairment in rats. High-fat diet (HFD) followed by a low dose of streptozotocin (35 mg/kg) was used to induce diabetes in Sprague-Dawley rats. TMP (20, 40, and 80 mg/kg) and Pioglitazone (10 mg/kg) were administered for 4 weeks. The Morris water maze (MWM) and novel objective recognition task (NOR) tests were used to assess memory function. Fasting blood glucose (FBG), lipid profile, HOMA-IR, glycosylated hemoglobin (HbA1c), and glucose tolerance were measured. Acetylcholinesterase (AChE) and choline acetytransferase (ChAT) activity, acetylcholine (ACh) levels, oxidative stress, apoptotic (Bcl-2, Bax, caspase-3), and inflammatory markers (TNF-α, IL-1β, and NF-kβ) were assessed. BDNF, p-AKT, and p-CREB levels were also measured. In the present work, we observed that treatment of diabetic rats with TMP alleviated learning and memory deficits, improved insulin sensitivity, and attenuated hyperglycemia and dyslipidemia. Furthermore, treatment with TMP increased BDNF, p-Akt, and p-CREB levels, normalized cholinergic dysfunction, and suppressed oxidative, inflammatory, and apoptotic markers in the hippocampus. Collectively, our results suggest that the TMP may be an effective neuroprotective agent in alleviating type 2 diabetes-associated cognitive deficits.
认知功能障碍是 2 型糖尿病（T2DM）患者的一种重要并发症。川芎嗪（TMP）具有抗糖尿病和神经保护作用。因此，本研究旨在探讨 TMP 对大鼠 2 型糖尿病相关认知障碍的可能治疗作用。高果糖饮食（HFD）加小剂量链脲佐菌素（35mg/kg）诱导 Sprague-Dawley 大鼠糖尿病。TMP（20、40 和 80mg/kg）和吡格列酮（10mg/kg）给药 4 周。使用 Morris 水迷宫（MWM）和新物体识别任务（NOR）测试评估记忆功能。测量空腹血糖（FBG）、血脂谱、HOMA-IR、糖化血红蛋白（HbA1c）和葡萄糖耐量。测定乙酰胆碱酯酶（AChE）和胆碱乙酰转移酶（ChAT）活性、乙酰胆碱（ACh）水平、氧化应激、凋亡（Bcl-2、Bax、caspase-3）和炎症标志物（TNF-α、IL-1β和 NF-kβ）。还测量了脑源性神经营养因子（BDNF）、p-AKT 和 p-CREB 水平。在本工作中，我们观察到 TMP 治疗糖尿病大鼠可减轻学习和记忆障碍，改善胰岛素敏感性，并减轻高血糖和血脂异常。此外，TMP 治疗可增加 BDNF、p-Akt 和 p-CREB 水平，使胆碱能功能障碍正常化，并抑制海马中的氧化、炎症和凋亡标志物。综上所述，我们的结果表明，TMP 可能是一种有效的神经保护剂，可减轻 2 型糖尿病相关的认知功能障碍。
