Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa 13133, Jordan.
Department of Medical Laboratory Sciences, Faculty of Allied Science, Zarqa University, Zarqa 13110, Jordan.
Int J Mol Sci. 2023 Mar 17;24(6):5749. doi: 10.3390/ijms24065749.
Cirsimaritin is a dimethoxy flavon that has different biological activities such as antiproliferative, antimicrobial, and antioxidant activities. This study aims to investigate the anti-diabetic effects of cirsimaritin in a high-fat diet and streptozotocin-(HFD/STZ)-induced rat model of type 2 diabetes mellitus (T2D). Rats were fed HFD, followed by a single low dose of STZ (40 mg/kg). HFD/STZ diabetic rats were treated orally with cirsimaritin (50 mg/kg) or metformin (200 mg/kg) for 10 days before terminating the experiment and collecting plasma, soleus muscle, adipose tissue, and liver for further downstream analysis. Cirsimaritin reduced the elevated levels of serum glucose in diabetic rats compared to the vehicle control group ( 0.001). Cirsimaritin abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control rats ( 0.01). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the diabetic rats treated with cirsimaritin compared to the vehicle controls. The skeletal muscle and adipose tissue protein contents of GLUT4 ( < 0.01 and < 0.05, respectively) and pAMPK-α1 ( < 0.05) were upregulated following treatment with cirsimaritin. Cirsimaritin was able to upregulate GLUT2 and AMPK protein expression in the liver ( < 0.01, <0.05, respectively). LDL, triglyceride, and cholesterol were reduced in diabetic rats treated with cirsimaritin compared to the vehicle controls ( < 0.001). Cirsimaritin reduced MDA, and IL-6 levels ( < 0.001), increased GSH levels ( < 0.001), and reduced GSSG levels ( < 0.001) in diabetic rats compared to the vehicle control. Cirsimaritin could represent a promising therapeutic agent to treat T2D.
朝藿定 C 是一种二甲氧基黄酮,具有不同的生物活性,如抗增殖、抗菌和抗氧化活性。本研究旨在研究朝藿定 C 在高脂肪饮食和链脲佐菌素(HFD/STZ)诱导的 2 型糖尿病(T2D)大鼠模型中的抗糖尿病作用。大鼠给予 HFD,随后单次给予低剂量 STZ(40mg/kg)。HFD/STZ 糖尿病大鼠在实验结束前用朝藿定 C(50mg/kg)或二甲双胍(200mg/kg)口服治疗 10 天,收集血浆、比目鱼肌、脂肪组织和肝脏进行下游分析。与 vehicle 对照组相比,朝藿定 C 降低了糖尿病大鼠升高的血清葡萄糖水平( 0.001)。与 vehicle 对照组相比,朝藿定 C 抑制了治疗糖尿病组血清胰岛素的增加( 0.01)。与 vehicle 对照组相比,朝藿定 C 治疗的糖尿病大鼠的胰岛素抵抗稳态模型评估(HOMA-IR)降低。骨骼肌和脂肪组织中 GLUT4 的蛋白含量(分别为 < 0.01 和 < 0.05)和 pAMPK-α1( < 0.05)升高。朝藿定 C 可上调肝脏中 GLUT2 和 AMPK 蛋白表达( < 0.01, < 0.05)。与 vehicle 对照组相比,糖尿病大鼠经朝藿定 C 治疗后 LDL、甘油三酯和胆固醇降低( < 0.001)。与 vehicle 对照组相比,朝藿定 C 降低糖尿病大鼠 MDA 和 IL-6 水平( < 0.001),增加 GSH 水平( < 0.001),降低 GSSG 水平( < 0.001)。朝藿定 C 可能是治疗 2 型糖尿病的一种有前途的治疗药物。