Evaluation Of The Quality And Function Of The Plantaginis Semen And Its Application In The Plantago Asiatica Compound

Plantaginis Semen,commonly called Chenqianzi,is the dried seed of Plantago asiatica L.(PAS)or Plantago depressa Willd.(PDS),which is used to reducing fever and causing diuresis,antitussive and antipyretic propertieswith a long history.Modern pharmacological studies have shown that Plantaginis Semen has the effect of treating hypertension,hyperglycemia and lipid disorders,as well as treating constipation and enteritis.The main components of Plantaginis Semen are phenylethanoid glycosides,iridoids,terpenoids,flavonoids and polysaccharides.Although PAS and PDS are the same genus,the chemical composition and their efficacy showed some differences on the basis of our previous studies.Additionly the reasons for the differences have not been systematically studied.Plantago asiatica Compound(PAC)is firstly recorded in the book of 《Shengji zonglu 》 which consisting of Plantaginis Semen and Coptidis Rhizoma by 1:1.Plantaginis Semen and Coptis rhizome play an important role in hypoglycemic,antihypertensive and hypolipidemic effects,as wellknown,Chinese medicine compound has the characteristics of multi-pathway and multi-target comprehensive regulation.Therefore,whether of the PAC has potential advantages in the treatment of comprehensive metabolism diseases with the two drugs,and its pharmacodynamics and mechanism should be to investigate systematically.Which will lay the foundation for further research and development based on the prescription of new drugs.This thesis systematically evaluated the quality and function of the different basic varieties of the Plantaginis Semen by comprehensively applies the multi-disciplinary theories and techniques of traditional Chinese medicine,pharmacology,analytical chemistry,and to clarify the differences in chemical composition,hypoglycemic and antihypertensive effects between PAS and PDS;Systematic evaluation of the efficacy of the PAC using a model of hyperglycemia and hypertension was to screen and determin the effective dose,and the potential mechanisms were discussed according to two animal models from anti-inflammatory,regulatory RAAS system and vascular endothelium system.In this study,on the basis of the quality and function evaluation of PCA,the hypoglycemic,hypolipidemic and antihypertensive effects and mechanism of action of the prescription of the drug,it is expected to form a drug with prevention and early treatment of metabolic syndrome with independent intellectual property rights,and fill in the blank of clinical antihypertensive,hypoglycemic and lipid-lowering drugs.1 The quality and function evaluation of Plantaginis SemenIn this experiment,the quality and function evaluation of the PAS and PDS were focused on the chemical composition and pharmacological effects.At the chemical level,simultaneous quantification of the main active components such as geniposidic acid and acteoside,and plantagoamidinic acid A in PAS and PDS were carried out by using LC-MS,the results showed that the active components of geniposidic acid and acteoside in PAS were more than the PDS.In addition,the LC-MS fingerprints of PAS and PDS were developed,IS main components were identified.Geniposidic acid as the reference standard,the content of IS compentent was determined by the external standard.The results showed that the flavonoids in the PDS were significantly more than the PAS.At the pharmacodynamic level,two different models,including a highfat diet-induced obese diabetes model and an SHR model were used.The results showed that both PAS and PDS can significantly improve the symptoms of hyperglycemia and high lipid levels in the body due to obesity,but PAS is better than PDS.In the model of hypertension,there was no significant difference between of PAS and PDS.Therefore,according to the above results of chemical and pharmacological studies,PAS was selected as the best source for the Plantaginis Semen in PAC.2 Evaluation of the efficacy of hypoglycemic and hypotensive of PACIn order to screen the effective dose of PAC,the obesity-type hyperglycemia model and the hypertensive model induced by high-fat diet were used.Three doses of low,medium and high in PAC were screened by the effects of hypoglycemic,hypolipidemic and antihypertensive,and the effects on organs.Final determination of 2g crude drug / kg / d is the optimal dose.Furthermore,the obesity model induced by high-fat diet and the SHR model were used to evaluate and compare the effects of PACand its singledrug treatment on diabetes and hypertension.The results showed that PAC can significantly improve the symptoms of hyperglycemia,hypertension and hyperinsulinemia by treatment of PCA.It even has a good corrective effect on the hyperlipidemia produced in animals,improving body fat accumulation and hepatic steatosis.It also has potent therapeutic effect on the glucose tolerance and insulin resistance caused by obesity.PAC can significantly improve the damage of internal organs caused by high blood pressure such as cardiac hypertrophy,kidney damage and other symptoms.Plantaginis Semen and Coptidis Rhizoma play a complementary role in the treatment of these symptoms,and PAC has a greater advantage than the use of a single drug.2 Preliminary study on the mechanism of hypoglycemic and hypotensive of PACDisorders of body fat are one of the important causes of insulin resistance leading to diabetes.During the investigation of the mechanism of high fat diet-induced C57 obese mice treated by PAC,we found that the PAC effectively reversed the accumulation,degeneration and disorder of body fat,and had significantly improved the effects on free fatty acids,adipokines such as adiponectin,leptin and GLP-1.These might be one of the important pathways to treat obesity diabetes by treatment of PAC.Moreover,the occurrence of diabetes in the body can lead to the secretion of a large number of inflammatory factors which are closely related to the diabetes.The results revealed that the PAC significantly improve the body’s inflammatory factors such as CRP,TNF-α,IL-1β,IL-6.These might be another important pathway for improving diabetes by using PAC.In the discussion of the mechanism of treatment on hypertension by PAC,we combined the mass spectrometry and kit assays to examine the role of the drug in the RAAS system.The results indicated that the level of renin,angiotensin and aldosterone in serum was significantly improved by PAC.Furthermore,the body’s inflammation factors such as HO-1,s VCAM-1、ICAM-1 and COX-2 were also examined,the results showed that PAC had a good therapeutic effect on inflammatory factors caused by hypertension.Finally,it was found that PAC also had a good inhibitory effect on the overexpression of vascular endothelial function NOS,e NOS and ET-1,revealing a good ET inhibitor in PAC.And it had a good regulation of calcium channels on vascular smooth muscle.In summary,Comparison PAS with PDS in chemical composition and its pharmacological effects,PAS was better than PDS.Further,the system of hypoglycemia and antihypertensive effect evaluation was carried out of PAC.PAC could effectively improve the symptoms of obesity diabetes,hypertension model and STZ-induced islet injury,such as hyperglycemia,glucose tolerance and insulin,hypertension,organ damage,islet injury,etc.These effects may be caused by regulation of lipid disorders,reduction of expression of related inflammatory factors,regulation of the RAAS system,improvement of the endothelium,and regulation of ion channel regulation by smooth muscle cells.PAC had antihypertensive,hypoglycemic,lipidlowering and insulin-promoting effects.Among them,Plantaginis Semen mainly had antihypertensive effect,coptis rhizome played an important role in improving hyperlipidemia and hyperglycemia.The combination of Plantaginis Semen and coptis rhizome had interactions between components to improve the efficacy of the drug,which is characterized by the synergistic effect of hypoglycemic and lipid-lowering effects and the considerable efficacy of antihypertensive;and the safety is higher with the combination of the two.This thesis provides a theoretical basis for the development of innovative Chinese medicines with clear pharmacological substances and clear mechanisms,and also provides new research ideas and methods for the modern research of other Chinese herbal medicines.