The Study Of The Mechanism Of Active Substance From Dendrobium With The Function Of Treatmenting Diabetic Cataract

Objectives:To explore the mechanism of active substance from Dendrobium. with the function of treatmenting diabetic cataract and provide a basic theory for its exploitation.Methods:1. Using enzyme inhibition kinetics to detect the inhibition and inhibition type of gigantol and syringic acid to AR and iNOS.2. Using the molecular docking software Sybyl17.3 and MOE to forecastthe receptor sites for amino acids and the fore of gigantol and AR, syringicacid and AR and the synergy of gigantol and syringic acid and research the Pharmacophore of gigantol and syringic acid.Using the Amber10 to further verify the stability of the docking results of gigantol and syringic acid and AR.3. By CSI-MS to research the non-covalent binding of gigantol, syringic acid and AR.4. To study the druggability of Dendrobium, by Discover Studio2. land Gaussian03W to prediction the ADMET properties of gigantol and syringic Acid.Results:1. Active substance of gigantol to AR:1.1 the IC50 of gigantol on AR is 2.12mmol/l, the inhibition type is non-competitive inhibibion.1.2 The relationship of their role in the size and concentration is a dose-response. The role of residues of gigantol and AR are Trp111,His110, Tyr48, Trp20, the mainly binding mode is hydrophobic,hydrogen bonding and Vander Waals. Pharmacophore results show that hydrogen bond donoris the 4-hydroxy phenyl phenolleft in the hydrogen atom. The hydrogen bond acceptor is the 3'place on the hydroxyl hydrogen atom. The trajectory of molecular dynamics simulation results showed that the RMSD for the trajectory calculation is stability. Gigantol with one of the amino acid residues His11 with RMSD values of the track is also within the normal range which is further validate the docking results stability and reliability.2. Active substance of syringic acid to AR:2.1the IC50 of syringic acid on AR is 13.6mmol/l, the inhibition type is non-competitive inhibibion.2.2 The relationship of their role in the size and concentration is a dose-response. The role of residues of syringic acid and AR are Trplll, His110, Tyr48, the mainly binding mode is hydrophobic and hydrogen bonding. Pharmacophore results show that The hydrogen bond acceptor is in 8-hydroxy hydrogen atoms and 7-hydrogen atoms in the carbonyl. The trajectory of molecular dynamics simulation results showed that the RMSD for the trajectory calculation is stability3. Gigantol and iNOS docking results shows that the role of amino acids are lle195 and Gln257, the mainly binding mode is hydrogen bonds.4. The docking results of gigantol and syringic acid combined with the AR showed that the two hot spots between the main binding residues include Asn160 and the formation ofπ-πconjugation which are more stable, the mainly binding mode is hydrogen bonds. The pharmacophore results of gigantol, syringic acid show the hydrogen bond donor and the hydrogen bond donor are is syringic acid 3-benzeneln the hydrogen atom, 5'bit of right -phenyl of Dendrobium methoxy hydrogen atoms.5. CSI-MS show that when the molar ratio of gigantol and AR is 27:1, the molar ratio of syringic acid and AR is 27:1, the two largest molecular weight binding complex. If the concentration of gigantol or syringic acid Decreased or increased, the binding gradually can decrease. The PH and temperature has little impact for a combination of both.6. The ADMET result of gigantol and syringic acid show that the absorption and the aqueous solubility are very good.the blood brain barrier of the gigantol is Low and the syringic acid is high. There is inhibit of gigantol to CYP2D6 and there is no inhibit of syringic acid to CYP2D6. Gigantol has some hepatotoxicity and syringic acid has no hepatotoxicity. Gigantol and syringic acid are not bound to plasma proteins, for the free type with drug activity. Conculsion:1.The results showed a good inhibitory activity of gigantol and Syringin acid to AR and iNOS.2. Dendrobium docking results showed that the gigantol, syringic acid and AR, the gigantoland iNOS have a more stable combination which lay the foundation for theinhibition of gigantol, syringic acid to AR and iNOS. Dynamics simulation results showed that the RMSD calculation trajectory is stable of gigantol, syringic acid and AR. CSI-MS show better binding between the gigantol, syringic acid and AR. The PH and temperature have no significant effect on its combination.3. The ADMET simulation shows a good medicine of syringic acid. Gigantol has some hepatotoxicity.This Study is to develop anti-diabetic cataract use eye drops,without going throughdigestive system, so there is no effect of the druggability of gigantol.