Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, P.O. Box 1334, Durban 4000, South Africa.
Department of Pharmacology, College of Medicine, Taipei Medical University, Taiwan; School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40604, Taiwan.
Biomed Pharmacother. 2024 Oct;179:117308. doi: 10.1016/j.biopha.2024.117308. Epub 2024 Aug 23.
The continual increase in global diabetic statistics portends decreased productivity and life spans, thus making it a disease of concern requiring more effective and safe therapeutic options. While several reports on antidiabetic plants, including Hura crepitans, are available, there is still a dearth of information on the holistic antidiabetic properties of H. crepitans and its associated complications. This study evaluated the antidiabetic potential of methanolic extract of Hura crepitans using in vitro, in vivo, and in silico approaches. The extract revealed a dose-dependent in vitro effect, with a 47.97 % and 65.34 % decrease in the fasting blood sugar levels of streptozotocin (STZ) induced diabetic rats at 150 and 300 mg/kg BW, respectively. Likewise, the extract increased serum and pancreatic insulin levels, and significantly ameliorated neuronal oxidative stress and inflammation by reducing the expression levels of cholinesterase, NF-κB, and COX-2 in the brain of hyperglycemic rats. Serum dyslipidemia, liver, and kidney biomarker indices, and hematological alterations in diabetic rats were also significantly attenuated by the extract. Several constituents, mainly terpenes, were identified in the extract. To further predict the drug-likeness, pharmacokinetics, and binding properties of the compounds, in silico analysis was conducted. Ergosta-2,24-dien-26-oicacid,18-(acetyloxy)-5,6-epoxy-4, 22-dihydroxy-1-oxo-,delta.-lactone-4.beta., displayed the highest docking scores for acetylcholinesterase, butyrylcholinesterases, alpha-amylase, and nuclear factor-kB with values of -12.4, -10.9, -10.3, and -9.4 kcal/mol, while ergost-25-ene-6,12-dione,3,5-dihydroxy-, (3.beta.,5.alpha.) topped for cyclooxygenase-2 (-9.0 kcal/mol). The top-ranked compounds also presented significant oral drug-likeness, pharmacokinetics, and safety properties. Altogether, our data provide preclinical evidence of the potential of Hura crepitans in ameliorating diabetes and its associated complications.
全球糖尿病统计数据的持续增长预示着生产力和寿命的下降，因此这是一种需要更有效和安全治疗选择的疾病。虽然有关于包括 Hura crepitans 在内的抗糖尿病植物的几份报告，但关于 H. crepitans 的整体抗糖尿病特性及其相关并发症的信息仍然缺乏。本研究使用体外、体内和计算方法评估了 Hura crepitans 甲醇提取物的抗糖尿病潜力。该提取物显示出剂量依赖性的体外作用，分别在 150 和 300mg/kg BW 时，使链脲佐菌素 (STZ) 诱导的糖尿病大鼠的空腹血糖水平降低了 47.97%和 65.34%。同样，该提取物增加了血清和胰腺胰岛素水平，并通过降低大脑中乙酰胆碱酯酶、NF-κB 和 COX-2 的表达水平，显著改善了高血糖大鼠的神经元氧化应激和炎症。糖尿病大鼠的血清血脂异常、肝和肾生物标志物指数以及血液学改变也被提取物显著减轻。提取物中鉴定出几种主要为萜类化合物的成分。为了进一步预测化合物的药物相似性、药代动力学和结合特性，进行了计算分析。麦角甾-2,24-二烯-26-酸，18-(乙酰氧基)-5,6-环氧-4,22-二羟基-1-氧代-，delta.-内酯-4.beta.，对乙酰胆碱酯酶、丁酰胆碱酯酶、α-淀粉酶和核因子-kB 的对接评分最高，分别为-12.4、-10.9、-10.3 和-9.4 kcal/mol，而麦角甾-25-烯-6,12-二酮，3,5-二羟基-，(3.beta.，5.alpha.)则在环氧化酶-2 中排名最高 (-9.0 kcal/mol)。排名最高的化合物也表现出显著的口服药物相似性、药代动力学和安全性特性。总的来说，我们的数据为 Hura crepitans 改善糖尿病及其相关并发症的潜力提供了临床前证据。
