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.

中文翻译：

---

番石榴叶酚类化合物对三种代谢相关酶活性的影响

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，天然调节剂可以为合成调节剂提供一种有价值的替代品，用于治疗不同的慢性疾病（糖尿病、高血压、癌症）；由于后者的许多副作用。对番石榴番石榴进行了体外筛选试验叶甲醇提取物对抗三种代谢相关酶；α-淀粉酶、酪氨酸酶和透明质酸酶。所得结果表明，所检测的提取物分别对 α-淀粉酶、酪氨酸酶和透明质酸酶保留了弱和中度的多靶点抑制作用；然而，叶子部分对三种研究的酶表现出更强的抑制作用。分馏P.番石榴叶提取物显示蒽醌和鞣花酸是主要的活性化合物，对α-淀粉酶、酪氨酸酶和透明质酸酶具有抑制活性。动力学研究表明，奎尼西林的抑制作用对 α-淀粉酶和透明质酸酶均具有竞争性，而鞣花酸对酪氨酸酶和透明质酸酶的抑制作用分别具有竞争性和非竞争性。奎尼西林和鞣花酸与 α-淀粉酶、酪氨酸酶和透明质酸酶的分子对接研究表明，具有不同键的高结合能稳定了配体 - 蛋白质复合物。汇总所有获得的结果得出的结论是，番石榴叶组分、奎尼西林和鞣花酸具有多靶点活性，在许多代谢紊乱中具有潜在的治疗应用。