Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan; Graduate Institute for Cancer Biology & Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
Department of Biochemistry and Molecular Biology, Faculty of Sciences, Federal University Ndufu-Alike Ikwo, P.M.B 1010, Abakaliki, Ebonyi State, Nigeria.
Biomed Pharmacother. 2022 Aug;152:113196. doi: 10.1016/j.biopha.2022.113196. Epub 2022 Jun 3.
The quest for novel anti-diabetic medication from medicinal plants is very important since they contain bioactive phytochemicals that offer better activity and safety compared to conventional therapy. In the present study, in vitro, in vivo and in silico approaches were explored to evaluate the anti-inflammatory, antioxidants, and hypoglycemic activities of the crude methanol extract of Azanza garckeana pulp. Our in vitro analysis revealed that the extract contains total phenols (260.80 ± 2.23 mg/100 g) and total flavonoids (10.28 ± 1.29 mg/100 g) contents, and demonstrated dose-dependent in vitro antioxidants activities in; DPPH (IC =141.30 ± 1.64 µg/mL), FRAP (IC =155.07 ± 1.03 µg/mL), LPO (IC =184.96 ± 2.01 µg/mL), and ABTS (IC =162.56 ± 1.14 µg/mL) assays; anti-inflammatory activities in: membrane stabilization (IC =141.34 ± 0.46 µg/mL), protein denaturation (IC =203.61 ± 2.35 µg/mL) and proteinase activities (ICf 171.35 ± 1.56 µg/mL) assays; and hypoglycemic activities in: α- amylase (IC 277.85 ± 2.51 µg/mL), and glucose uptake by yeast cells assays. In vivo analysis revealed that the extract exhibited dose-dependent anti-inflammatory, hypoglycemic activities and improved the weight gain in STZ-induced diabetic rats. In addition, the extract attenuated oxidative stress and increased the activities of SOD, catalase, GSH while depleting the level of LPO in STZ induced diabetic rats. Consequently, the liquid chromatography mass spectrometry (LC-MS) characterization of A. garckeana pulp, revealed the presence of 2-Hexadecen-1-ol,3,7,11,15-tetramethyl-,(2E,7 R,11 R)-, nonyl flavanone, testolactone and 6-(Benzyloxy)- 4,4-Dimethyl-2-Chromanone. These compounds were subjected to pharmacoinformatics analysis among which testolactone and 6-(Benzyloxy)- 4,4-Dimethyl-2-Chromanone demonstrated the best drug-likeness, pharmacokinetics, and also exhibited potential hypoglycemic and anti-inflammatory properties. Altogether, the present study provides preclinical evidence of the antioxidant, anti-inflammatory and antidiabetic activities of A. garckeana extract suggesting its potential applications for the development of alternative therapy for diabetes and its associated inflammatory condition.
从药用植物中寻找新型抗糖尿病药物非常重要，因为它们含有生物活性植物化学物质，与传统疗法相比，具有更好的活性和安全性。在本研究中，我们探索了从 Azanza garckeana 果肉的甲醇粗提物中评估抗炎、抗氧化和降血糖活性的体外、体内和计算方法。我们的体外分析表明，该提取物含有总酚（260.80 ± 2.23 mg/100 g）和总类黄酮（10.28 ± 1.29 mg/100 g），并表现出剂量依赖性的体外抗氧化活性; DPPH（IC = 141.30 ± 1.64 µg/mL）、FRAP（IC = 155.07 ± 1.03 µg/mL）、LPO（IC = 184.96 ± 2.01 µg/mL）和 ABTS（IC = 162.56 ± 1.14 µg/mL）测定；抗炎活性在膜稳定（IC = 141.34 ± 0.46 µg/mL）、蛋白质变性（IC = 203.61 ± 2.35 µg/mL）和蛋白酶活性（ICf 171.35 ± 1.56 µg/mL）测定中；和体内活性在α-淀粉酶（IC 277.85 ± 2.51 µg/mL）和酵母细胞葡萄糖摄取测定中。体内分析表明，该提取物表现出剂量依赖性的抗炎、降血糖活性，并改善了 STZ 诱导的糖尿病大鼠的体重增加。此外，该提取物减轻了氧化应激，增加了 SOD、过氧化氢酶、GSH 的活性，同时降低了 STZ 诱导的糖尿病大鼠中 LPO 的水平。因此，Azanza garckeana 果肉的液相色谱-质谱（LC-MS）表征显示存在 2-十六烯-1-醇，3,7,11,15-四甲基-，（2E,7 R,11 R）-，壬基黄烷酮，testolactone 和 6-（苄氧基）-4,4-二甲基-2-色满酮。这些化合物进行了药物信息学分析，其中 testolactone 和 6-（苄氧基）-4,4-二甲基-2-色满酮表现出最佳的类药性、药代动力学特性，并且表现出潜在的降血糖和抗炎特性。总之，本研究提供了 Azanza garckeana 提取物的抗氧化、抗炎和抗糖尿病活性的临床前证据，表明其在开发糖尿病及其相关炎症疾病替代疗法方面具有潜在应用。
