Post-Graduate Program in Biological Sciences: Toxicological Biochemistry, Center for Natural and Exact Sciences, Federal University of Santa Maria, University Campus, Camobi District, 97105-900 Santa Maria, RS, Brazil.
Post-Graduate Program in Biological Sciences: Toxicological Biochemistry, Center for Natural and Exact Sciences, Federal University of Santa Maria, University Campus, Camobi District, 97105-900 Santa Maria, RS, Brazil.
Life Sci. 2021 Jul 15;277:119421. doi: 10.1016/j.lfs.2021.119421. Epub 2021 Mar 27.
Diabetes mellitus (DM) is a metabolic disorder characterized by a chronic hyperglycemia state, increased oxidative stress parameters, and inflammatory processes.
To evaluate the effect of caffeic acid (CA) on ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) and adenosine deaminase (ADA) enzymatic activity and expression of the A2A receptor of the purinergic system, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymatic activity and expression of the α7nAChR receptor of the cholinergic system as well as inflammatory and oxidative parameters in diabetic rats.
Diabetes was induced by a single dose intraperitoneally of streptozotocin (STZ, 55 mg/kg). Animals were divided into six groups (n = 10): control/oil; control/CA 10 mg/kg; control/CA 50 mg/kg; diabetic/oil; diabetic/CA 10 mg/kg; and diabetic/CA 50 mg/kg treated for thirty days by gavage.
CA treatment reduced ATP and ADP hydrolysis (lymphocytes) and ATP levels (serum), and reversed the increase in ADA and AChE (lymphocytes), BuChE (serum), and myeloperoxidase (MPO, plasma) activities in diabetic rats. CA treatment did not attenuate the increase in IL-1β and IL-6 gene expression (lymphocytes) in the diabetic state; however, it increased IL-10 and A2A gene expression, regardless of the animals' condition (healthy or diabetic), and α7nAChR gene expression. Additionally, CA attenuated the increase in oxidative stress markers and reversed the decrease in antioxidant parameters of diabetic animals.
Overall, our findings indicated that CA treatment positively modulated purinergic and cholinergic enzyme activities and receptor expression, and improved oxi-inflammatory parameters, thus suggesting that this phenolic acid could improve redox homeostasis dysregulation and purinergic and cholinergic signaling in the diabetic state.
评估咖啡酸（CA）对嘌呤能系统的外核苷酸三磷酸二磷酸水解酶（E-NTPDase）和腺苷脱氨酶（ADA）酶活性和 A2A 受体表达、胆碱能系统的乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）酶活性和 α7nAChR 受体表达以及糖尿病大鼠的炎症和氧化参数的影响。
通过单次腹腔注射链脲佐菌素（STZ，55mg/kg）诱导糖尿病。动物分为六组（n=10）：对照组/油；对照组/CA 10mg/kg；对照组/CA 50mg/kg；糖尿病组/油；糖尿病组/CA 10mg/kg；糖尿病组/CA 50mg/kg，通过灌胃治疗 30 天。
CA 治疗降低了 ATP 和 ADP 水解（淋巴细胞）和 ATP 水平（血清），并逆转了糖尿病大鼠 ADA 和 AChE（淋巴细胞）、BuChE（血清）和髓过氧化物酶（MPO，血浆）活性的增加。CA 治疗并没有减弱糖尿病状态下 IL-1β 和 IL-6 基因表达（淋巴细胞）的增加；然而，它增加了 IL-10 和 A2A 基因表达，无论动物的状况（健康或糖尿病）如何，以及 α7nAChR 基因表达。此外，CA 减轻了氧化应激标志物的增加，并逆转了糖尿病动物抗氧化参数的降低。
总的来说，我们的研究结果表明，CA 治疗可正向调节嘌呤能和胆碱能酶活性和受体表达，并改善氧化-炎症参数，表明这种酚酸可改善糖尿病状态下的氧化还原失衡和嘌呤能及胆碱能信号。
