Abdulrasheed-Adeleke Tawakaltu, Lawal Bashir, Agwupuye Eyuwa Ignatius, Kuo Yucheng, Eni Amarachi Mary, Ekoh Okwukwe Faith, Lukman Halimat Yusuf, Onikanni Amos S, Olawale Femi, Saidu Sani, Ibrahim Yunusa O, Al Ghamdi Maliha Abdullah Saleh, Aggad Sarah S, Alsayegh Abdulrahman A, Aljarba Nada H, Batiha Gaber El-Saber, Wu Alexander T H, Huang Hsu-Shan
Department of Biochemistry, Federal University of Technology P.M.B. 65, Minna 920001, Niger State, Nigeria.
Graduate Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; Department of Medical Laboratory Science, Faculty of Medical and Health Sciences, Newgate University Minna, Nigeria.
Biomed Pharmacother. 2023 Jun;162:114582. doi: 10.1016/j.biopha.2023.114582. Epub 2023 Mar 28.
In the present study, in vitro, in vivo, and in silico models were used to evaluate the therapeutic potential of Pulmeria alba methanolic (PAm) extract, and we identified the major phytocompound, apigetrin. Our in vitro studies revealed dose-dependent increased glucose uptake and inhibition of α-amylase (50% inhibitory concentration (IC)= 217.19 µg/mL), antioxidant (DPPH, ferric-reducing activity of plasma (FRAP), and lipid peroxidation (LPO) [IC = 103.23, 58.72, and 114.16 µg/mL respectively]), and anti-inflammatory potential (stabilizes human red blood cell (HRBC) membranes, and inhibits proteinase and protein denaturation [IC = 143.73, 131.63, and 198.57 µg/mL]) by the PAm extract. In an in vivo model, PAm treatment reversed hyperglycemia and attenuated insulin deficiency in rats with streptozotocin (STZ)-induced diabetes. A post-treatment tissue analysis revealed that PAm attenuated neuronal oxidative stress, neuronal inflammation, and neuro-cognitive deficiencies. This was evidenced by increased levels of antioxidants enzymes (superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)), and decreased malondialdehyde (MDA), proinflammatory markers (cyclooxygenase 2 (COX2), nuclear factor (NF)-κB and nitric oxide (NOx)), and acetylcholinesterase (AChE) activities in the brain of PAm-treated rats compared to the STZ-induced diabetic controls. However, no treatment-related changes were observed in levels of neurotransmitters, including serotonin and dopamine. Furthermore, STZ-induced dyslipidemia and alterations in serum biochemical markers of hepatorenal dysfunction were also reversed by PAm treatment. Extract characterization identified apigetrin (retention time: 21,227 s, 30.48%, m/z: 433.15) as the major bioactive compound in the PAm extract. Consequently, we provide in silico insights into the potential of apigetrin to target AChE/COX-2/NOX/NF-κB Altogether the present study provides preclinical evidence of the therapeutic potential of the apigetrin-enriched PAm extract for treating oxidative stress and neuro-inflammation associated with diabetes.
在本研究中，采用体外、体内和计算机模拟模型评估了白鸡蛋花甲醇提取物（PAm）的治疗潜力，并鉴定出主要的植物化合物芹菜素。我们的体外研究表明，PAm提取物可使葡萄糖摄取呈剂量依赖性增加，并抑制α-淀粉酶（50%抑制浓度（IC）=217.19µg/mL）、抗氧化剂（二苯基苦味酰基自由基（DPPH）、血浆铁还原能力（FRAP）和脂质过氧化（LPO）[IC分别为103.23、58.72和114.16µg/mL]），以及具有抗炎潜力（稳定人类红细胞（HRBC）膜，并抑制蛋白酶和蛋白质变性[IC分别为143.73、131.63和198.57µg/mL]）。在体内模型中，PAm治疗可逆转链脲佐菌素（STZ）诱导的糖尿病大鼠的高血糖症并减轻胰岛素缺乏。治疗后组织分析表明，PAm减轻了神经元氧化应激、神经元炎症和神经认知缺陷。与STZ诱导的糖尿病对照组相比，PAm处理的大鼠大脑中抗氧化酶（超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和还原型谷胱甘肽（GSH））水平升高，丙二醛（MDA）、促炎标志物（环氧合酶2（COX2）、核因子（NF）-κB和一氧化氮（NOx））以及乙酰胆碱酯酶（AChE）活性降低，证明了这一点。然而，在包括血清素和多巴胺在内的神经递质水平上未观察到与治疗相关的变化。此外，PAm治疗还逆转了STZ诱导的血脂异常以及肝肾功障碍血清生化标志物的改变。提取物表征鉴定芹菜素（保留时间：21227s，30.48%，m/z：433.15）为PAm提取物中的主要生物活性化合物。因此，我们通过计算机模拟深入了解了芹菜素靶向AChE/COX-2/NOX/NF-κB的潜力。总之，本研究提供了富含芹菜素的PAm提取物治疗与糖尿病相关的氧化应激和神经炎症的治疗潜力的临床前证据。
