Department of Pharmacy, R. P. Shaha University, Naryanganj, Bangladesh.
Department of Microbiology, Primeasia University, Banani, Bangladesh.
PLoS One. 2024 Aug 19;19(8):e0304521. doi: 10.1371/journal.pone.0304521. eCollection 2024.
Zanthoxylum rhetsa (ZR) is used traditionally to manage a variety of ailments, including diabetes. Oxidative stress may accelerate the diabetic condition. The available antidiabetic and antioxidant drugs have many shortcomings including resistance, inefficiency, higher dose, side effects and costs. The goal of the current investigation was to assess the antioxidant capacity and antidiabetic activity of an ethanolic extract of Zanthoxylum rhetsa root bark (ZRRB) through in vitro, in vivo, and in silico methods. The antioxidant capacity of the ZRRB extract was measured using both the DPPH radical assay and the total antioxidant activity test. The oral glucose tolerance test (OGTT) and alloxan-induced diabetic mice model were also used to examine in vivo antidiabetic efficacy. Phytochemicals identification was done by GCMS analysis. Additionally, computational methods such as molecular docking, ADMET analysis, and molecular dynamics (MD) modeling were performed to determine the above pharmacological effects. The extract demonstrated significant DPPH scavenging activity (IC50 = 42.65 μg/mL). In the OGTT test and alloxan-induced diabetes mice model, the extract effectively lowered blood glucose levels. Furthermore, in vitro inhibition of pancreatic α-amylase studies demonstrated the ZRRB extract as a good antidiabetic crude drug (IC50 = 81.45 μg/mL). GCMS investigation confirmed that the crude extract contains 16 major phytoconstituents, which were docked with human peroxiredoxin-5, α-amylase, and sulfonylurea receptor 1. Docking and pharmacokinetic studies demonstrated that among 16 phytoconstituents, 6H-indolo[3,2,1-de] [1,5]naphthyridin-6-one (CID: 97176) showed the highest binding affinity to targeted enzymes, and imitated Lipinski's rule of five. Furthermore, MD simulation data confirmed that the aforementioned compound is very steady to the binding site of α-amylase and sulfonylurea receptor 1 receptors. Findings from in vitro, in vivo and in silico investigation suggest that ZRRB extract contains a lead compound that could be a potent source of antidiabetic drug candidate.
花椒（ZR）传统上用于治疗多种疾病，包括糖尿病。氧化应激可能会加速糖尿病的发生。现有的抗糖尿病和抗氧化药物存在许多缺点，包括耐药性、低效性、高剂量、副作用和成本。本研究的目的是通过体外、体内和计算机模拟方法评估花椒根皮乙醇提取物（ZRRB）的抗氧化能力和抗糖尿病活性。使用 DPPH 自由基测定法和总抗氧化活性试验测定 ZRRB 提取物的抗氧化能力。还使用口服葡萄糖耐量试验（OGTT）和链脲佐菌素诱导的糖尿病小鼠模型来检测体内抗糖尿病功效。通过 GCMS 分析进行植物化学成分鉴定。此外，还进行了分子对接、ADMET 分析和分子动力学（MD）建模等计算方法，以确定上述药理作用。提取物表现出显著的 DPPH 清除活性（IC50 = 42.65 μg/mL）。在 OGTT 试验和链脲佐菌素诱导的糖尿病小鼠模型中，提取物有效降低了血糖水平。此外，体外抑制胰腺α-淀粉酶研究表明，ZRRB 提取物是一种良好的抗糖尿病粗提物（IC50 = 81.45 μg/mL）。GCMS 研究证实，粗提物含有 16 种主要的植物化学成分，这些成分与人类过氧化物酶-5、α-淀粉酶和磺酰脲受体 1 对接。对接和药代动力学研究表明，在 16 种植物成分中，6H-吲哚[3,2,1-de] [1,5]萘啶-6-酮（CID：97176）对靶酶表现出最高的结合亲和力，并模仿了 Lipinski 的五规则。此外，MD 模拟数据证实，上述化合物对α-淀粉酶和磺酰脲受体 1 受体的结合位点非常稳定。体外、体内和计算机模拟研究的结果表明，ZRRB 提取物含有一种可能成为抗糖尿病药物候选物的先导化合物。
