Adeyomoye Olorunsola Israel, Adetunji Juliana Bunmi, Olaniyan Olugbemi Temitope, Adetunji Charles Oluwaseun, Ebenezer Ogunmiluyi Oluwafunmbi
Department of Physiology, University of Medical Sciences, Ondo City, Nigeria.
Department of Biochemistry, Osun State University, Osogbo, Nigeria.
Metabol Open. 2024 Nov 26;24:100333. doi: 10.1016/j.metop.2024.100333. eCollection 2024 Dec.
Diabetes mellitus, a chronic metabolic disorder, has significant global health implications, particularly due to its neurological complications, such as diabetic neuropathy. This condition increases the risk of neurodegenerative diseases by affecting peripheral nerves and cognition. , known for its neuroprotective properties, shows promise as a therapeutic option for addressing these complications. This study evaluates the effects of methanol extract of (MEFE) on neurotransmission and the expression of Tau, brain-derived neurotrophic factor (BDNF), acetylcholinesterase (ACHE), and Beta-Site Amyloid Precursor Protein Cleaving Enzyme (BACE) in alloxan-induced diabetic Wistar rats. The controlled experimental design involved 20 Wistar rats divided into four groups (n = 5): control, diabetic untreated, diabetes + MEFE (200 mg/kg), and diabetes + insulin (0.3 IU). The methanol extract was prepared using cold maceration, and an aliquot was subjected to gas chromatography-mass spectrometry. Constituents of MEFE were docked with neurologic receptors. Blood glucose levels were measured using the glucose oxidase method, and neurotransmitter levels, antioxidants, oxidative stress markers, and the expression of Tau, BDNF, ACHE, and BACE were assessed using standard procedures and qRT-PCR. Data were analyzed using one-way ANOVA at P < 0.05. Results indicated that MEFE significantly reduced fasting blood glucose levels compared to untreated diabetic rats. docking identified kaur-16-ene, a constituent of MEFE, as having the highest binding affinity for NMDA, TrkB, mAchR and nAchR receptors, indicating its neuroprotective potential. MEFE also enhanced antioxidant enzyme levels (SOD, GPx, catalase) while reducing oxidative stress markers (MDA, 8-OHdG). Gene expression analysis revealed that MEFE modulates the expression of Tau, BDNF, ACHE, and BACE, suggesting its potential to influence neurodegenerative pathways associated with diabetic neuropathy. demonstrates significant therapeutic potential in managing diabetic neuropathy and related cognitive impairments by modulating neurotransmission, protein expression, and antioxidant defenses.
糖尿病是一种慢性代谢紊乱疾病，对全球健康有着重大影响，尤其是因其神经并发症，如糖尿病性神经病变。这种病症通过影响外周神经和认知功能，增加了神经退行性疾病的风险。[物质名称]以其神经保护特性而闻名，显示出作为解决这些并发症的治疗选择的潜力。本研究评估了[物质名称]的甲醇提取物（MEFE）对四氧嘧啶诱导的糖尿病Wistar大鼠神经传递以及 Tau、脑源性神经营养因子（BDNF）、乙酰胆碱酯酶（ACHE）和β-分泌酶（BACE）表达的影响。对照实验设计涉及将20只Wistar大鼠分为四组（n = 5）：对照组、未治疗的糖尿病组、糖尿病 + MEFE（200 mg/kg）组和糖尿病 + 胰岛素（0.3 IU）组。甲醇提取物采用冷浸法制备，并取一份进行气相色谱 - 质谱分析。MEFE的成分与神经受体进行对接。使用葡萄糖氧化酶法测量血糖水平，并使用标准程序和qRT - PCR评估神经递质水平、抗氧化剂、氧化应激标志物以及 Tau、BDNF、ACHE和BACE的表达。数据使用单向方差分析在P < 0.05水平进行分析。结果表明，与未治疗的糖尿病大鼠相比，MEFE显著降低了空腹血糖水平。对接分析确定MEFE的成分贝壳杉 - 16 - 烯对NMDA、TrkB、mAchR和nAchR受体具有最高的结合亲和力，表明其神经保护潜力。MEFE还提高了抗氧化酶水平（超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶），同时降低了氧化应激标志物（丙二醛、8 - 羟基脱氧鸟苷）。基因表达分析表明，MEFE调节Tau、BDNF、ACHE和BACE的表达，表明其有可能影响与糖尿病性神经病变相关的神经退行性途径。[物质名称]通过调节神经传递、蛋白质表达和抗氧化防御，在管理糖尿病性神经病变和相关认知障碍方面显示出显著的治疗潜力。
