PDF(Pubmed)
Abstract：
Diabetes, a multifactorial metabolic disorder, demands the discovery of multi-targeting drugs with minimal side effects. This study investigated the multi-targeting antidiabetic potential of quercetin and kaempferol. The druggability and binding affinities of both compounds towards multiple antidiabetic targets were explored using pharmacokinetic and docking software (AutoDock Vina 1.1.2). Our findings showed that quercetin and kaempferol obey Lipinski\'s rule of five and exhibit desirable ADMET (absorption, distribution, metabolism excretion, and toxicity) profiles. Both compounds showed higher binding affinities towards C-reactive protein (CRP), interleukin-1 (IL-1), dipeptidyl peptidase-4 (DPP-IV), peroxisome proliferator-activated receptor gamma (PPARG), protein tyrosine phosphatase (PTP), and sodium-glucose co-transporter-1 (SGLT-1) compared to metformin (the positive control). Both quercetin and kaempferol inhibited α-amylase activity (in vitro) up to 20.30 ± 0.49 and 37.43 ± 0.42%, respectively. Their oral supplementation significantly reduced blood glucose levels (p < 0.001), improved lipid profile (p < 0.001), and enhanced total antioxidant status (p < 0.01) in streptozotocin-nicotinamide (STZ-NA)-induced diabetic mice. Additionally, both compounds significantly inhibited the proliferation of Huh-7 and HepG2 (cancer cells) (p < 0.0001) with no effect on the viability of Vero cell line (non-cancer). In conclusion, quercetin and kaempferol demonstrated higher binding affinities towards multiple targets than metformin. In vitro and in vivo antidiabetic potential along with the anticancer activities of both compounds suggest promise for further development in diabetes management. The combination of both drugs did not show a synergistic effect, possibly due to their same target on the receptors.
摘要：
糖尿病,多因素代谢紊乱,需要发现副作用最小的多靶向药物。这项研究调查了槲皮素和山奈酚的多靶向抗糖尿病潜力。使用药代动力学和对接软件（AutoDockVina1.1.2）探索了两种化合物对多种抗糖尿病靶标的可药用性和结合亲和力。我们的发现表明槲皮素和山奈酚遵守Lipinski的5法则，并表现出理想的ADMET(吸收，分布，代谢排泄，和毒性)概况。两种化合物对C反应蛋白（CRP）均显示出较高的结合亲和力，白细胞介素-1（IL-1），二肽基肽酶-4（DPP-IV），过氧化物酶体增殖物激活受体γ（PPARG），蛋白酪氨酸磷酸酶（PTP），和钠-葡萄糖共转运蛋白-1(SGLT-1)与二甲双胍(阳性对照)相比。槲皮素和山奈酚均抑制α-淀粉酶活性（体外）高达20.30±0.49和37.43±0.42％，分别。他们的口服补充剂显着降低了血糖水平（p<0.001），改善血脂状况（p<0.001），并且在链脲佐菌素-烟酰胺(STZ-NA)诱导的糖尿病小鼠中总抗氧化状态增强(p<0.01)。此外,两种化合物均显著抑制Huh-7和HepG2(癌细胞)的增殖(p<0.0001),而对Vero细胞系(非癌症)的活力没有影响。总之,槲皮素和山奈酚对多个靶标的结合亲和力高于二甲双胍。两种化合物的体外和体内抗糖尿病潜力以及抗癌活性表明有望在糖尿病管理中进一步发展。两种药物的组合没有显示出协同作用，可能是由于它们在受体上的相同目标。
