Study Of The Mechanism Of Action Of Ginseng Decoction In Synopsis Of Golden Chamber Against AS Based On The Autophagic Effect Of TRPV1 On Arterial Vascular Smooth Muscle

Synopsis of the Golden Chamber(abbreviated as Panax ginseng decoction)is a classical prescription for the treatment of thoracic paralysis and consists of three or two herbs each,ginseng,liquorice,dried ginger,and Baizhu,while this prescription focuses on the deficiency of invigorating the chest Yang,destroying the clotting Yin with Xinsan,and can Fuzheng it to remo Ginseng Decoction ve evil.This formula enriches the cure method of chest paralysis by treating deficiency cold chest paralysis through Wenzhong Huiyang.Ginseng decoction is clinically used for the treatment of cardiovascular system diseases such as coronary heart disease,arrhythmia,and chronic heart failure.Some studies have shown that ginseng decoction can reduce blood lipid levels and improve myocardial ischemia and hemorheology,among others.And modern studies have shown that the main components of ginseng,dried ginger and liquorice,which are the main medicines in Ginseng Decoction,can directly alleviate atherosclerosis(AS).In addition,current studies have shown the anti as effects of transient receptor potential vanilloid type 1(TRPV1)channels,but no relevant studies have been reported on the treatment of as by increasing autophagy levels in vascular smooth muscle from TRPV1.And some studies have confirmed ginseng and dried ginger in Panax ginseng decoction,which are TRPV1 agonists,so elucidating whether Panax ginseng decoction exerts therapeutic effects on as through TRPV1 will potentially provide new directions and ideas for the prevention and treatment of atherosclerotic diseases.Therefore,in this study,based on a previous study,ApoE-/-mice were fed an 8-week high-fat diet to prepare as mouse model,which was administrated by gavage and observed whether ginseng decoction formula improved adenylate activated protein(AMPK)-mediated autophagy to treat as via TRPV1,thus further revealing the mechanism of action of Ginseng Decoction to treat as and providing an experimental basis for elucidating the scientific connotation of the formula’s efficacy.OBJECTIVE:To explore the mechanism of action of Ginseng Tang in the treatment of AS based on the autophagic effect of TRPV1 on arterial vascular smooth muscle.METHODS:Fourteen SPF-grade 8-week-old male C57BL/6J mice were used as normal blank control group and 70 8-week-old ApoE-/-mice were used as model group.Atherosclerosis(AS)mouse model was prepared by feeding high-fat chow for 8 weeks in the model group,and then randomly divided into model group,Ginseng Tang formula low,medium and high dose(2.715 g/kg/d,5.43 g/kg/d,10.68 g/kg/d)group and simvastatin(0.02 g/kg/d)group,which were administered continuously for 8 weeks.after 8 weeks,serum was taken and assay kits were used to Serum total cholesterol,triglyceride,LDL cholesterol and HDL cholesterol levels were measured to observe the changes of lipid levels in mice;aorta was taken,and hematoxylin-eosin staining(HE)was used to observe the overall pathology of the aortic root,and oil red O staining was used to detect the lipid deposition within the aortic plaque and calculate the percentage of the aortic root area to the lumen area;the Western blot technique was used to detect the expression of TRPV1,AMPK,phosphorylated adenylate-activated protein kinase(p-AMPK),and autophagy effector protein 1(Beclin-l),microtubule light chain protein Ⅰ(LC3Ⅰ),and microtubule light chain protein Ⅱ(LC3Ⅱ)in mouse aortic tissues;immunofluorescence(IF)technique was used to detect the expression of TRPV1 in each group of The average fluorescence intensity of TRPV1 in the aortic root of mice was detected by immunofluorescence(IF)technique.RESULTS:The lipid-lowering effect of Ginseng Tang in Synopsis of Golden Chamber was significant in reducing total cholesterol(TC),triglyceride(TG)and low-density lipoprotein cholesterol(LDL-C)levels in AS model mice,and both the low and medium dose groups of this formula showed significant advantages(P<0.01);in terms of reducing plaque area,the simvastatin group and the low,medium and high dose groups of Ginseng Tang were able to significantly reduce aortic root plaque area(P<0.05),among which the effect of ginseng soup high-dose group reduced plaque most significantly(P<0.01);in terms of mechanism of action,the relative expression of TRPV1,p-AMPK/AMPK,Beclinl,LC3Ⅱ/LC3Ⅰ was significantly reduced in the model group mice compared with the normal group(P<0.01,P<0.01,P<0.05),and the differences were all statistically significant.Compared with the model group,the relative expressions of TRPV1,p-AMPK/AMPK,Beclinl,LC3Ⅱ/LC3Ⅰ were significantly increased in both the middle and high dose groups of Ginseng Tang in Synopsis of Golden Chamber(P<0.05),among which TRPV1 and Beclinl increased more significantly in the middle dose group(P<0.01),and the differences were all statistically significant.Immunofluorescence results also confirmed this,the expression of TRPV1 mean fluorescence intensity was significantly increased in the model group(P<0.05),and the mean fluorescence intensity of TRPV1 was increased in the simvastatin group and the low and medium dose groups of Ginseng Tang compared with the model group,but the differences were not statistically significant.The high dose group of Ginseng Tang could increase the mean fluorescence intensity of TRPV1 significantly compared with the model group(P<0.05),and the difference was statistically significant.CONCLUSION:The anti-AS effect of Ginseng Decoction may be achieved by regulating the rise of TRPV1 expression,which in turn restores the level of autophagy mediated by AMPK.