Docking information and results

Streptozotocin (STZ) induces hyperglycaemia associated with inflammatory disorders and is currently found in the methanolic extract from leaves of Onopordum acanthium (OAE). OAE has been discovered to treat diabetic complications. The objective of this study is to evaluate the ameliorative role of OAE on pancreatic islets injury and myocardial inflammation in diabetic rats. The steam extract of OAE contains six compounds (catechin, kaempferol, syringic acid, p-coumaric acid and epicatechin). The binding site affinity was done between extract compounds with antidiabetic receptors: insulin-like growth factor 1 kinase (PDB ID: 1K3A), glycogen phosphorylase (PDB ID: 1NOI), α-amylase, α-glucosidase (PDB ID: 1OSE), sulphonyl urease (PDB ID: 2E5Z) and glucagon-like peptide-1 (PDB ID: 3IOL). The energy required by syringic acid to bind with insulin-like growth factor 1 kinase (PDB ID: 1K3A) was the lowest at −5.2 kcal/mol, followed by the free energy required by p-coumaric acid (−5.3 kcal/mol), gallic acid (−5.8 kcal/mol), epicatechin (−7.0 kcal/mol), kaempferol (−7.1 kcal/mol) and glibenclamide (−8.0 kcal/mol). All compounds showed binding values of energy from −8.8 to −4.6 kcal/mol. The highest energy was found for catechin (Table 6) (Figure 8) and epicatechin binding with α-glucosidase (PDB ID: 1UOK) and α- amylase (PDB ID: 1OSE) of −8.4 kcal/mol and −7.7 kcal/mol, respectively. Amino acids involved in the formation of a catechin complex with α-glucosidase were GLU387 (H-bond), pHE163, ALA143, LYS293, ASP 285 (H-bond), GLN 330 (H-bond) and ARG415. Kaempferol showed the highest binding site energy interaction with glycogen phosphorylase (−8.1 kcal/mol) (Table 6) (Figure 8) compared to the rest of the naturally extracted compounds after glibenclamide (−8.8 kcal/mol). Amino acids involved were GLU124, 654, ARG93, LYS655, 544 and PRO658. Similar binding site energy (−6.0 kcal/mol) has been observed for the interaction of catechin, kaempferol, epicatechin and glibenclamide with sulphonyl urease (PDB ID: 2E5Z). The amino acids involved in the interaction of glibenclamide with sulphonyl urease are ALA 48, SER 3, ARG 47 and GLY 7. Glucagon-like peptide-1 (PDB ID: 3IOL) interaction with glibenclamide showed the highest binding site energy of (−7.6 kcal/mol) followed by kaempferol (−6.5 kcal/mol), catechin and epicatechin (−6.3 kcal/mol), respectively (Table 6). selective NSAID for COX-1, COX-2) 1CVU, 1IQM, 3FCU, 3LN1 and 3N8Y. Kaempferol has shown the highest binding site of −8.5 and −9.3 kcal/mol with the receptors of integrin αIIbβ3 (PDB ID: 3FCU) and COX-1(PDB ID: 3N8Y) respectively, with amino acids of PHE171, 419, 21, ALA359, ILE360, LEU421, ARG422 and SER420 in 3FCU and CYS36, 47, ILE46, GLY45, PRO153, GLN461, LEU152, GLU465, GLY45 in COX-1 (PDB ID: 3N8Y) (). The interaction of epicatechin with amino acid residue in COX-2 (PDB ID:3LN1) ar链脲佐菌素（Streptozotocin, STZ）可诱导伴随炎症性疾病的高血糖症，目前已从大翅蓟（Onopordum acanthium）叶甲醇提取物（OAE）中检出该物质。现有研究发现OAE可用于治疗糖尿病并发症。本研究旨在评估OAE对糖尿病大鼠胰岛损伤及心肌炎症的改善作用。 OAE的水蒸气提取物含有六种成分：儿茶素（catechin）、山奈酚（kaempferol）、丁香酸（syringic acid）、对香豆酸（p-coumaric acid）及表儿茶素（epicatechin）。本研究针对提取物成分与多个抗糖尿病靶点受体的结合位点亲和力展开分析，涉及的受体包括：胰岛素样生长因子1激酶（insulin-like growth factor 1 kinase, PDB编号：1K3A）、糖原磷酸化酶（glycogen phosphorylase, PDB编号：1NOI）、α-淀粉酶、α-葡萄糖苷酶（α-glucosidase, PDB编号：1OSE）、磺酰脲酶（sulphonyl urease, PDB编号：2E5Z）以及胰高血糖素样肽-1（glucagon-like peptide-1, GLP-1, PDB编号：3IOL）。 丁香酸与胰岛素样生长因子1激酶（PDB编号：1K3A）结合所需的自由能最低，为-5.2 kcal/mol；其次为对香豆酸（-5.3 kcal/mol）、没食子酸（gallic acid, -5.8 kcal/mol）、表儿茶素（-7.0 kcal/mol）、山奈酚（-7.1 kcal/mol）及格列本脲（glibenclamide, -8.0 kcal/mol）。所有受试成分的结合能范围为-8.8至-4.6 kcal/mol。结合能最高的成分为儿茶素（表6，图8）与表儿茶素，前者与α-葡萄糖苷酶（PDB编号：1UOK）的结合能为-8.4 kcal/mol，后者与α-淀粉酶（PDB编号：1OSE）的结合能为-7.7 kcal/mol。 儿茶素与α-葡萄糖苷酶形成复合物所涉及的氨基酸残基包括：GLU387（氢键，hydrogen bond, H-bond）、PHE163、ALA143、LYS293、ASP285（H-bond）、GLN330（H-bond）及ARG415。 相较于格列本脲（-8.8 kcal/mol）以外的其余天然提取物成分，山奈酚与糖原磷酸化酶的结合位点相互作用结合能最高，达-8.1 kcal/mol（表6，图8），所涉及的氨基酸残基为GLU124、654、ARG93、LYS655、544及PRO658。 儿茶素、山奈酚、表儿茶素与格列本脲和磺酰脲酶（PDB编号：2E5Z）的结合能相近，均为-6.0 kcal/mol。格列本脲与磺酰脲酶相互作用所涉及的氨基酸残基包括：ALA48、SER3、ARG47及GLY7。 胰高血糖素样肽-1（PDB编号：3IOL）与格列本脲的结合位点结合能最高，为-7.6 kcal/mol；其次依次为山奈酚（-6.5 kcal/mol）、儿茶素与表儿茶素（-6.3 kcal/mol）（表6）。 针对环氧合酶1（COX-1, cyclooxygenase-1）、环氧合酶2（COX-2, cyclooxygenase-2）的选择性非甾体抗炎药（NSAID, non-steroidal anti-inflammatory drug）相关靶点，其PDB编号为1CVU、1IQM、3FCU、3LN1及3N8Y。 山奈酚与整合素αIIbβ3（integrin αIIbβ3, PDB编号：3FCU）、COX-1（PDB编号：3N8Y）的结合能分别达-8.5 kcal/mol与-9.3 kcal/mol，为最高结合能；其所涉及的氨基酸残基在整合素αIIbβ3（PDB编号：3FCU）中包括PHE171、419、21、ALA359、ILE360、LEU421、ARG422及SER420，在COX-1（PDB编号：3N8Y）中包括CYS36、47、ILE46、GLY45、PRO153、GLN461、LEU152、GLU465、GLY45。 表儿茶素与COX-2（PDB编号：3LN1）中氨基酸残基的相互作用为