Study On The Dissolution Mechanism Of Berberine In Gegen Qinlian Decoction Based On Quantum Mechanics And Molecular Dynamics

Research background Zhang Zhongjing's"Treatise on Febrile Diseases"in the genus Pueraria lobata first sautéed Pueraria and then various medicines.Berberine is the main active ingredient of Radix Coptidis which is a derivative of isoquinoline and its hydrochloride is commonly used.It has the characteristics of wide antibacterial spectrum low toxicity and side effects but its poor water solubility is an important factor restricting its use.Therefore it is a top priority in this field to explore the dissolution mechanism of berberine.The genus Pueraria is a rhizome that contains a lot of starch.Amylum is a commonly used pharmaceutical excipient.After gelatinization the hydrogen bonds between the ordered and disordered?crystalline and amorphous?starch molecules in the starch granules are broken and the starch granules expand to the original.50 to 100 times the volume dispersed in water.This may have an effect on the dissolution of berberine.Objective To study the dissolution mechanism of berberine in Gegen Qinlian Decoction to explore the properties of berberine and various sites that may interact with water to investigate the changes of pueraria and decoction and to carry out amylose and berberine molecules.Interaction molecular dynamics simulation.Method?1?Quantum mechanical calculation of the interaction between berberine and water molecules.Using Gaussian software to simulate the binding site of berberine which may interact with water by DET-B3LYP/6-31G?d?method optimize berberine hydration dimerization The geometric and electronic structures of the body are analyzed for their geometry charge distribution and transfer natural bond orbitals binding energy and thermodynamic properties.?2?Determination of the solubility of berberine hydrochloride and the amount of starch decoction.The double-wavelength spectrophotometry was used to determine the amount of starch in the roots of Pueraria lobata.Determination of the effect of starch on the amount of active ingredients in Coptis chinensis by ultraviolet spectrophotometry.The acidity and alkalinity of Pueraria lobata were compared under different decoction methods.Beryllium solubility effects.The morphology of starch and gelatinized starch was observed by transmission electron microscopy.?3?Molecular dynamics simulation of the interaction between amylose molecules and berberine using Mattheran Studio 8.0 to simulate the structure and properties of amylose and amylose fragments respectively to simulate amylose fragments and small The interaction between the purine base monomers is analyzed for their properties such as structure and interaction energy.Result?1?Successfully optimized the structure of berberine water and dimer?I^XI?and compared the properties of each water binding site.The contact point?CH...O?has the shortest distance to dimer VI and the distance is0.237 5nm.The maximum binding energy and stabilization energy are-28.10 kJ·mol^-11 and 6.527 kJ·mol^-11 respectively.?2?As the decoction time of Pueraria lobata increased the concentration of amylose was increased from 0.4256?0.008 mg·mL^-11 to4.246?0.079 mg·mL^-1.The content of the active ingredient?as berberine hydrochloride?in the berberine decoction is 1.960?0.073 mg·mL^-1.The active ingredient content of the decoction added with 0.2g of starch is2.857?0.062 mg·mL^-1.The pH value of Gegen Qinlian Decoction varied from 5.41 to 5.81 under different decoction methods.The 4h solubility of berberine hydrochloride was 3.005?0.005 mg·mL^-11 the solubility of berberine hydrochloride added with starch was 3.047?0.008 mg·mL^-11 and the solubility of berberine hydrochloride added with gelatinized starch was3.836?0.027 mg·mL^-1.The starch granules are polyhedral with rounded edges and a dispersed distribution.The gelatinized starch granules are in an amorphous shape the particle morphology is almost completely destroyed and there is obvious adhesion between the starch granules and the distribution is also more compact and the distribution is similar to the reticular structure.?3?At the morphological structure of amylose fragments at different temperatures the optimized molecular morphology has different degrees of stretching compared with the normal temperature?298.15K?high temperature?373.15K?amylose fragments simulated and optimized molecules Stretch more.For the blend system the morphologically373.15K amylose fragment the berberine molecule is embedded in the hydrophobic cavity at one end of the amylose.In terms of energy the non-bond energy hydrogen bond energy and van der Waals force of the amylose fragment and berberine blended system after gelatinization at high temperature?373.15K?were higher than normal temperature?298.15K?.Conclusion:The most active site in the binding site of berberine to water is C18-H19 and the most stable structure in the formed dimer is dimer VI;the amount of amylose decoction in puerarin increases with increasing boiling time.There was no significant change in the amount of amylopectin decoction and there was obvious adhesion between the gelatinized starch granules and the distribution was similar to the reticular structure.With the increase of the amount of added starch the amount of the active ingredient?as compared with berberine hydrochloride?in Coptis is increasing.The addition of gelatinized starch has a significant increase in the dissolution of berberine hydrochloride.There is no significant difference between the ungelatinized starch and the un-added starch group.The gelatinized starch promotes the dissolution of berberine hydrochloride;in terms of morphology and energy phase Compared with the amylose fragment at room temperature?298.15K?the amylose fragment after gelatinization at high temperature?373.15K?is relatively tightly bound to berberine and has strong binding and adsorption capacity for berberine.