Study On The Pharmacokinetics And Qualitative Changes Of Phellodendron Chinense Before And After Processing

Purpose:The cortex of Phellodendron chinense（Chinese name:Huang-Bo,HB）were first recorded in Shen Nong Ben Cao Jing.It tastes bitter and cold,in kidneys and bladder channel tropism.The history of HB have been used for clearing heat and purging fire more than 20 hundred years in clinic.Generations of physicians attaches great importance to the processing in the clinical application of HB,the earliest record of HB’s processed products was in Ge Hong Zhou Hou Bei Ji Fang of Jin Dynasty.The traditional processing method of HB inciuding cleaning,cutting,processed into carbonized,processed with honey,rice-wine,salt-water,milk,etc,but it mainly processed with rice-wine,salt-water,and honey.The cortex of Phellodendron chinense processed with rice-wine can reduce its bitter and cold.The cortex of Phellodendron chinense processed with salt-water can enhance its bitter and cold.The cortex of Phellodendron chinense processed with honey can promote the effect in middle energizer.,From the current cortex of Phellodendron research,this theory is mostly at the level of theoretical expression and lacks modern research verification.In addition,combined with the previous research results in our laboratory,the berberine has undergone a qualitative change during the processing.the new production is the berberrubine.The structure of berberine and berberrubine are similar.They are belong to the original berberine-type alkaloid.Does berberubine have a similar or better pharmacodynamic effect than berberine?So the following experiments were carried out on this subject.The effects of the above-mentioned problems were explored through the study on the pharmacodynamic effects of the indicator components and the new components of the raw Phellodendron,the wine processed Phellodendron,the salt processed Phellodendron,and the salt processed Phellodendron.So we can further reveal the processing principle and analysis of the processed Phellodendron.This study suported the scientific connotation of traditional Chinese medicine pharmaceutical theory.Materials and methods:Materials:Phellodendri Chinensis Cortex collected from Ya’an City,Yingjing country,Sichuan Province.Methods:1.Study on processing technology and the pharmacological actions of Phellodendri Chinensis Cortex processed with honey.（1）With the orthogonal design L₉（3⁴）the Phellodendri Chinensis Cortex processed with honey technology was optimized.The investigation factors were the contents of the Berberine hydrochloride and Phellodendrine chloride,honey amounts,frying temperature and frying time.（2）The oral oxidative damage model was established by using 1 mmoL/L hydrogen peroxide.The SOD activity and the NO and MDA content of the cells after the action of oxidative damage of oral cells was compared by water extraction and 70%ethanol extraction and extraction with different polar solvents.2.Pharmacokinetics study of different processed products of Phellodendri（1）The rats were given the raw Phellodendron,the wine processed Phellodendron,the salt processed Phellodendron,and the salt processed Phellodendron.UPLC-QqQ-MS method was used to determine the content of berberine,phellodendron,magnoliline,phellodendron and corkone in plasma.The content was compared and analyzed.（2）The rats were given the raw Phellodendron,the wine processed Phellodendron,the salt processed Phellodendron,and the salt processed Phellodendron.UPLC-QqQ-MS method was used to determine the content of berberine,phellodendron,magnoliline,phellodendron andcorkone in heart,liver,spleen,lung,kidney,large intestine,small intestine,stomach.The content was compared and analyzed.3.Study on the pharmacodynamic effects of the quality components before and after the processing of Phellodendron chinense（1）A mouse model of ulcerative colitis was prepared by freely drinking an aqueous solution containing DSS.The anti-colitis and oxidative stress responses of berberine and berberine were compared by the monomeric components of berberine and berberine.（2）The effects of berberine,berberine,jatrorrhizine and phellodendron on the proliferation activity of HT-29 cells at different concentrations were determined by CCK-8method.The effects of the above alkaloids on the levels of Survivin,Caspase-3,BCL-2,FHIT and PDCD4 in HT-29 cells were examined,and the anti-colon cancer effects of the above alkaloids were compared.（3）LPS was used to induce inflammatory response in bovine lymphocytes,and the effects of berberine and berberine on the expression of ERK/JNK protein in inflammatory response were detected by WB assay.Results:1.Study on the Processing Technology and Pharmacodynamic Effect of Honey-made Cork（1）The best processing technology for cork candied fruit is:use 30 Kg of honey per 100Kg of cedar pieces,（honey:water=1:1）,and the honey water completely penetrates into the inside of the piece of tissue,at 120°C¹30°C Stir for 4 min（2）Compared with the blank group,SOD activity and NO content in Phellodendri chinensis Cortex processed with honey group increased significantly（P<0.05）,the content of MDA decreased significantly（P<0.05）,compared with model group,SOD activity and NO content in Phellodendri chinensis Cortex processed with honey group decreased significantly（P<0.05）,the content of MDA increased significantly（P<0.05）,there were no significant differences in the Phellodendron chinense group.2.Study on pharmacokinetics of different processed products of Cork（1）Honey-made cork significantly reduced the t1/2 value of berberine and increased the CLz/F value.Compared with the raw products,the cedar significantly reduced the AUC0-t and AUC0-∞values??of berberine and increased the Vz/F and CLz/F values.Cork significantly increased the Cmax,AUC0-∞and t1/2 values??of cedarone by salt,and decreased the CLz/F value.The chlorophyll significantly increased the t1/2 and Vz/F values??of the paeoli lactone.Cork significantly increased the Cmax,AUC0-t and AUC0-∞values??after salt production.The Cmax and AUC0-t values??of magnolia are significantly increased after the salt of Phellodendron chinense.（2）Berberine,phellodendron,magnolia,paeolactone,and cedarone are distributed in tissues.3.Study on the pharmacodynamic effects of the quality components before and after the processing of Phellodendron chinense（1）Both berberine and berberine can significantly increase the activity of SOD and significantly reduce the production of MDA.Berberine and berberine inhibit the expression of TNF-αand IL-1βin colon tissue.（2）After berberine and berberine act on the cells,the cytoplasm of the cells appears turbid,the cell body shrinks,becomes round and wrinkled,the cell adhesion decreases,and more cells fall off the bottle wall,and cell growth is inhibited..The drug concentration was negatively correlated with the expression of Survivin protein,Caspase-3 protein,BCL-2protein,PDCD4 and FHIT.（3）Both berberine and berberine can reduce the phosphorylation level of ERK/JNK protein,thereby reducing the expression level of ERK/JNK protein.Conclusion:1.Study on the Processing Technology and Pharmacodynamic Effect of Honey-made CorkThrough the research on the processing technology of honey-made cork,it is found that the best processing technology of honey-made cork is reasonable and feasible,and honey-made cork can significantly reduce the oxidative damage of oral fibroblasts,and has a certain therapeutic effect on oral ulcers.2.Study on pharmacokinetics of different processed products of Cork（1）Wine-made cork can increase the distribution of berberine in tissues,and salt-based cork can increase the bioavailability of cork lactone,corkone and magnolia in cork.（2）The stomach and small intestine are the main absorption sites of berberine,corkaline,magnoliline,corkactone and corkone in the body.It can provide a reference for explaining the principle of salt,wine and honey.3.Study on the pharmacodynamic effects of the quality components before and after the processing of Phellodendron chinense（1）Berberine and berberine have an effect of treating ulcerative colitis and oxidative stress damage.（2）Berberine and berberine have anti-colon cancer effects.（3）Both berberine and berberine can produce anti-inflammatory effects by reducing the expression level of P-ERK/JNK protein.