Seong Su Hui, Roy Anupom, Jung Hyun Ah, Jung Hee Jin, Choi Jae Sue
Department of Food and Life Science, Pukyong National University, Busan 608-737, Republic of Korea.
Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju 561-756, Republic of Korea.
J Ethnopharmacol. 2016 Dec 24;194:706-716. doi: 10.1016/j.jep.2016.10.007. Epub 2016 Oct 18.
Pueraria lobata root was used to treat wasting-thirst regarded as diabetes mellitus and was included in the composition of Okcheonsan, which is prescribed for thirst-waste in traditional Chinese medicine.
The objective of this study was to evaluate the anti-diabetic potential of the root of Pueraria lobata and its constituents via protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase inhibitory activities.
In this study, anti-diabetic activities of the 70% ethanolic (EtOH) extract from P. lobata roots and its solvent soluble fractions with the isolated compounds were investigated by evaluating in vitro PTP1B and α-glucosidase inhibitory activities. We also examined the potentials of active compounds as PTP1B and α-glucosidase inhibitors via enzyme kinetics and in silico molecular docking simulation between the enzymes and active compounds.
Triterpenoids lupeol and lupenone were potent PTP1B inhibitors with IC values of 38.89±0.17 and 15.11±1.23μM. Kinetic study using the Lineweaver-Burk and Dixon plots demonstrated that these compounds showed a noncompetitive-type inhibition against PTP1B with respective K values of 13.88μM and 21.24μM. In addition, molecular docking simulation showed lupeol and lupenone has negative binding energy values of -8.03 and -8.56kcal/mol. Considering the α-glucosidase inhibitory potential, daidzein, genistein, and calycosin exhibited the most potent α-glucosidase inhibition with IC values of 8.58±0.94, 2.37±0.52 and 6.84±1.58μM, respectively. Kinetic study demonstrated that these 3 compounds showed a noncompetitive-type inhibition against α-glucosidase with respective K values of 17.64μM, 5.03μM and 13.83μM. Moreover, molecular docking simulation showed daidzein, genistein and calycosin has more lower binding energy (-7.16kcal/mol, -7.42kcal/mol and -7.31kcal/mol) with higher binding affinity and tight binding capacity in the molecular docking studies than standard ligand α-D-glucose (-6.74kcal/mol).
Our results of the present study clearly demonstrate the potential of P. lobata extract and its constituents to inhibit PTP1B and α-glucosidase, contributing to the development of therapeutic or preventive agents that can be used in the treatment of diabetes.
葛根被用于治疗被视为糖尿病的消渴症，并且被纳入了中药中用于治疗消渴的玉泉散的配方中。
本研究的目的是通过蛋白酪氨酸磷酸酶1B（PTP1B）和α-葡萄糖苷酶抑制活性来评估葛根及其成分的抗糖尿病潜力。
在本研究中，通过评估体外PTP1B和α-葡萄糖苷酶抑制活性，研究了葛根根的70%乙醇提取物及其溶剂可溶部分与分离出的化合物的抗糖尿病活性。我们还通过酶动力学以及酶与活性化合物之间的计算机模拟分子对接，研究了活性化合物作为PTP1B和α-葡萄糖苷酶抑制剂的潜力。
三萜类化合物羽扇豆醇和羽扇豆酮是强效的PTP1B抑制剂，IC值分别为38.89±0.17和15.11±1.23μM。使用Lineweaver-Burk和Dixon图进行的动力学研究表明，这些化合物对PTP1B表现出非竞争性抑制类型，各自的K值分别为13.88μM和21.24μM。此外，分子对接模拟显示羽扇豆醇和羽扇豆酮的负结合能值分别为-8.03和-8.56kcal/mol。考虑到α-葡萄糖苷酶抑制潜力，大豆苷元、染料木黄酮和毛蕊异黄酮表现出最强的α-葡萄糖苷酶抑制作用，IC值分别为8.58±0.94、2.37±0.52和6.84±1.58μM。动力学研究表明，这3种化合物对α-葡萄糖苷酶表现出非竞争性抑制类型，各自的K值分别为17.64μM、5.03μM和13.83μM。此外，分子对接模拟显示，在分子对接研究中，大豆苷元、染料木黄酮和毛蕊异黄酮与标准配体α-D-葡萄糖（-6.74kcal/mol）相比，具有更低的结合能（-7.16kcal/mol、-7.42kcal/mol和-7.31kcal/mol），结合亲和力更高且结合能力更强。
我们本研究的结果清楚地证明了葛根提取物及其成分抑制PTP1B和α-葡萄糖苷酶的潜力，有助于开发可用于治疗糖尿病的治疗或预防药物。
