Manzoor Natasha, Samad Noreen, Khaliq Saima, Bin Khatab Abbasi Bakar, Ahmad Saara, Irfan Ali, Raish Mohammad, Bin Jardan Yousef A
Department of Biochemistry, Faculty of Science, Bahauddin Zakariya University, Multan 60800, Pakistan.
Department of Biochemistry, Federal Urdu University of Arts, Science and Technology, Karachi, Pakistan.
Brain Res Bull. 2025 Jun 1;225:111342. doi: 10.1016/j.brainresbull.2025.111342. Epub 2025 Apr 9.
Acipimox (ACPX), a niacin derivative, has demonstrated antioxidant activity In vitro and In vivo; however, it has not been widely used in treating neurological problems. The present study examined the effects of Acipimox on body weight, dietary intake, depressive symptoms, oxide-neuroinflammation, 5-HT metabolism, and 5-HT1A receptor expression in hypothalamus of rats. Forty eight (n = 8) male albino rats were randomly divided into six groups (i) Vehicle (Veh)+ normal diet (ND) (ii) ND + ACPX (25 mg/mL/kg; low dose) (iii) ND+ ACPX (50 mg/mL/kg; high dose) (iv) Veh +High fat rich diet (HFRD) (v) HFRD+ACPX (25 mg/mL/kg; low dose (vi) HFRD+ACPX (50 mg/mL/kg; high dose). Animals were given their respective treatment for 8 weeks. After that, behavioral tests i.e. tail suspension test (TST) and forced swim test (FST) performed for depression-like behavior assessment. Animals were decapitated and the hypothalamus was isolated from the brain for biochemical and neurochemical analysis. Results showed that, HFRD induced depression like behavior and increased body weight and food intake was prevented by repeated administration of ACPX (both doses). HFRD induced increased oxido-neuroinflammation, altered serotonin metabolism and serotonin-1A receptor relative expression in the hypothalamus were regulated by ACPX (both doses). In conclusion, HFRD-induced behavioral deficits (depression like behavior) mitigated by ACPX through its antioxidant, anti-inflammatory, and neuromodulatory properties. It is recommended that use of ACPX could be helpful for HFRD-induced behavioral impairment i.e. depression.
阿西莫司（ACPX）是一种烟酸衍生物，已在体外和体内表现出抗氧化活性；然而，它尚未广泛用于治疗神经问题。本研究考察了阿西莫司对大鼠体重、饮食摄入量、抑郁症状、氧化神经炎症、5-羟色胺（5-HT）代谢以及下丘脑5-HT1A受体表达的影响。48只（n = 8）雄性白化大鼠被随机分为六组：（i）溶剂对照组（Veh）+正常饮食（ND）；（ii）ND + ACPX（25毫克/毫升/千克；低剂量）；（iii）ND + ACPX（50毫克/毫升/千克；高剂量）；（iv）Veh +高脂肪饮食（HFRD）；（v）HFRD + ACPX（25毫克/毫升/千克；低剂量）；（vi）HFRD + ACPX（50毫克/毫升/千克；高剂量）。动物接受各自的处理8周。之后，进行行为测试，即悬尾试验（TST）和强迫游泳试验（FST），以评估抑郁样行为。动物被断头，从大脑中分离出下丘脑进行生化和神经化学分析。结果显示，重复给予ACPX（两种剂量）可预防HFRD诱导的抑郁样行为以及体重和食物摄入量增加。ACPX（两种剂量）可调节HFRD诱导的下丘脑氧化神经炎症增加、血清素代谢改变以及血清素-1A受体相对表达。总之，ACPX通过其抗氧化、抗炎和神经调节特性减轻了HFRD诱导的行为缺陷（抑郁样行为）。建议使用ACPX可能有助于改善HFRD诱导的行为损伤，即抑郁。
