Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Biotechnol Appl Biochem. 2021 Jun;68(3):497-512. doi: 10.1002/bab.1956. Epub 2020 May 26.
Enzyme activity modulation by synthetic compounds provide strategies combining the inhibitory and therapeutic mode of action of the confirmed inhibitors. However, natural modulators could offer a valuable alternative for synthetic ones for the treatment of different chronic diseases (diabetes, hypertension, cancer); due to the numerous side effects of the latter. In vitro screening assays were conducted for Psidium guajava leaf methanolic extract against three metabolism-related enzymes; α-amylase, tyrosinase, and hyaluronidase. The obtained results showed that the examined extract retained weak and moderate multitarget inhibition against α-amylase, tyrosinase, and hyaluronidase, respectively; however, the leaf fractions exhibited stronger inhibitions for the three investigated enzymes. Fractionation of P. guajava leaf extract revealed that anthraquinones and ellagic acid are of the major active compounds with inhibitory activities for α-amylase, tyrosinase, and hyaluronidase. Kinetic studies showed that quinalizarin inhibition is competitive for both α-amylase and hyaluronidase, and ellagic acid inhibition for tyrosinase and hyaluronidase is competitive and un-competitive, respectively. The molecular docking studies of quinalizarin and ellagic acid with α-amylase, tyrosinase, and hyaluronidase showed high binding energies with different bonds stabilizing the ligand-protein complex. Compiling all obtained results led to conclude that both P. guajava leaf fractions, quinalizarin and ellagic acid, have multitarget activities with potential therapeutic applications in many metabolic disorders.
通过合成化合物对酶活性的调节提供了结合已确认抑制剂的抑制和治疗作用模式的策略。然而，由于后者存在许多副作用，天然调节剂可能为治疗不同慢性疾病（糖尿病、高血压、癌症）提供了一种有价值的替代合成调节剂的选择。对番石榴叶甲醇提取物进行了针对三种代谢相关酶（α-淀粉酶、酪氨酸酶和透明质酸酶）的体外筛选试验。得到的结果表明，所检查的提取物对 α-淀粉酶、酪氨酸酶和透明质酸酶分别保留了弱和中等的多靶点抑制作用；然而，叶部分对三种研究酶表现出更强的抑制作用。番石榴叶提取物的分馏表明，蒽醌和鞣花酸是具有抑制α-淀粉酶、酪氨酸酶和透明质酸酶活性的主要活性化合物。动力学研究表明，藜芦醛抑制对α-淀粉酶和透明质酸酶均为竞争性抑制，鞣花酸对酪氨酸酶和透明质酸酶的抑制分别为竞争性和非竞争性抑制。藜芦醛和鞣花酸与α-淀粉酶、酪氨酸酶和透明质酸酶的分子对接研究表明，与不同键结合具有高结合能，稳定配体-蛋白复合物。综合所有获得的结果得出结论，番石榴叶部分、藜芦醛和鞣花酸均具有多靶点活性，具有在许多代谢紊乱中应用的治疗潜力。
