1.Clinical Observation on the Wenyang Huayin Prescription in the Treatment of Chronic Heart Failure in Elderly Patients with Fluid Retention due to Yang Deficiency
Jinchong YANG ; Chuansheng ZHANG ; Xiyan WANG ; Xiaona LIU ; Jin YU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(5):749-755
Objective To observe the clinical efficacy of Wenyang Huayin Prescription(cooked Aconiti Lateralis Radix Praeparata,Cinnamomi Ramulus,Codonopsis Radix,Atractylodis Macrocephalae Rhizoma,Poria,Descurainiae Semen Lepidii Semen,etc.)combined with conventional western medicine in the treatment of elderly patients with chronic heart failure(CHF).Methods A total of 120 elderly CHF patients with fluid retention due to yang deficiency syndrome who were treated in People's Hospital of Chenghai District from December 2021 to December 2022 were selected as the research objects.They were randomly divided into control group and observation group,with 60 cases in each group.The control group was given conventional western medicine treatment,and the observation group was treated with Wenyang Huayin Prescription on the basis of the treatment of the control group.The course of treatment was four weeks.The indexes of the two groups were observed before and after treatment:(1)TCM syndrome scores;(2)serum levels of N-terminal pro-B-type natriuretic peptide(NT-proBNP),high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6);(3)left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD);(4)6-minute walking distance.The clinical efficacy and safety of the two groups were compared.Results After treatment,(1)the scores of TCM syndromes in the two groups were significantly lower than those before treatment(P<0.05),and the scores in the observation group were significantly lower than those in the control group(P<0.05).(2)The levels of serum hs-CRP,TNF-α,IL-6 and NT-proBNP in the two groups were significantly lower than those before treatment(P<0.05),and the levels in the observation group were significantly lower than those in the control group(P<0.05).(3)The levels of LVEF in the two groups were significantly higher than those before treatment(P<0.05),and the levels of LVEDD were significantly lower than those before treatment(P<0.05).The level of LVEF in the observation group was significantly higher than that in the control group(P<0.05),and the level of LVEDD was significantly lower than that in the control group(P<0.05).(4)The 6-minute walking distance in the two groups was significantly increased when compared with that before treatment(P<0.05),and the increase in the observation group was significantly greater than that in the control group(P<0.05).(5)The total effective rate of the observation group(96.67%)was significantly higher than that of the control group(86.67%)(P<0.05);the total incidence of adverse reactions in the observation group(1.67%)was significantly lower than that in the control group(11.67%)(P<0.05).Conclusion Wenyang Huayin Prescription combined with conventional western medicine treatment can effectively reduce the TCM syndrome score of elderly CHF patients with fluid retention due to yang deficiency syndrome,improve clinical symptoms and cardiac function,and reduce the body's inflammatory response.The clinical efficacy is superior to that of western medicine alone,and the safety is relatively high.
2.Progress of Traditional Chinese Medicine in Regulating PI3K/Akt Signaling Pathway for the Treatment of Rheumatoid Arthritis
Weigang CHENG ; Haolin LI ; Juanjuan YANG ; Fangmei JIN ; Lili KAN ; Pengfei TAO ; Zhendong WANG ; Qian BAI ; Xiaojun SU ; Haidong WANG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(5):756-764
Rheumatoid arthritis(RA)is an autoimmune disease with the basic pathological manifestation of synovial inflammation.Symmetric poly-articular pain and swelling are the main symptoms in clinical practice,and even extra-articular manifestations and comorbidities such as interstitial fibrosis and coronary artery disease are triggered,which seriously affect the quality of life of patients.Traditional Chinese medicine(TCM)has achieved good clinical efficacy in the prevention and treatment of RA with the advantages of multi-pathway,multi-target,multi-component,and less toxic side effects,and plays an important role in the treatment of RA.Recently,many studies have demonstrated that Chinese medicine monomers and Chinese herbal compound can control inflammation,reduce angiogenesis,induce apoptosis of synovial fibroblasts,and inhibit their proliferation,invasion and migration by regulating the PI3K/Akt signaling pathway,so as to play a key role in the treatment of RA.For this reason,the article summarizes current knowledge regarding the PI3K/Akt signaling pathway and its role in RA,as well as summarizes the current research progress of TCM in the treatment of RA by regulating the PI3K/Akt signaling pathway.The aim of this review is to provide theoretical bases for the prevention and treatment of RA and the development of new drugs.
3.Research Progress on the Pharmacological Effects of Codonopsis Radix
Chongyang ZHANG ; Miao YU ; Rongchang CHEN ; Xiaobo SUN
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(5):765-770
Codonopsis Radix is a Codonopsis plant belonging to Campanulaceae family.It is widely used as a Chinese medicinal for invigorating qi in Chinese medicine clinics.The chemical compositions of Codonopsis Radix mainly contain flavonoids,alkaloids,sugars,saponins,steroids,amino acids,etc..It mainly exhibits the pharmacological effects such as enhancing the immune system function,improving gastrointestinal function,anti-inflammation,anti-tumor,improving the ability of learning and memory,regulating the cardio-cerebral vascular system,and slowing down the aging process,and so on.Based on a large number of literature studies on Codonopsis Radix at home and abroad in recent years,this paper summarizes its pharmacological effects.The aim of the review is to provide a certain theoretical basis and rationale for the research and application of Codonopsis Radix.
4.Exploration of the Mechanism of Huoxiang Zhengqi Dropping Pills Based on GC-TOF/MS Metabolo-mics Technology in Rats with Dampness Encumbering the Spleen and Stomach Type
Lixi LI ; Hailong LU ; Zhongjie ZOU ; Yuanyuan XIE ; Mengjuan GONG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(6):771-777
Objective To explore the mechanism of Huoxiang Zhengqi Dropping Pills in treating dampness encumbering the spleen and stomach type rats by metabolomics method based on gas chromatography-time of flight mass spectrometry(GC-TOF/MS).Methods Male SD rats were randomly divided into normal group,model group and Huoxiang Zhengqi Dropping Pills group(1 g·kg-1).The rat model of dampness encumbering the spleen and stomach was prepared by comprehensive physical modeling method combined with improper diet.Intragastric administration was performed once a day for 10 consecutive days.The macroscopic signs and behavioral indexes(body mass,body length,tail length,abdominal circumference index and spontaneous activities frequency)of rats were observed.GC-TOF/MS method was used to analyze the serum and urine metabolome of rats,identify potential biomarkers related to dampness encumbering the spleen and stomach,and analyze the metabolic pathway of Huoxiang Zhengqi Dropping Pills in rats with dampness encumbering the spleen and stomach.Results Compared with the normal group,the body mass,body length,tail length and spontaneous activities frequency of the rats in the model group were significantly reduced(P<0.05),and the abdominal circumference index was significantly increased(P<0.05).Compared with the model group,the body mass,body length and spontaneous activities frequency of the rats in the Huoxiang Zhengqi Dropping Pills group were significantly increased(P<0.05),and the abdominal circumference index was significantly decreased(P<0.05).A total of 38 and 44 potential biomarkers related to dampness encumbering the spleen and stomach were identified in rat serum and urine,respectively.Huoxiang Zhengqi Dropping Pills can effectively interfere with the serum and urine metabolic phenotypes of model rats,and can significantly reverse 17 and 13 potential biomarkers in serum and urine,involving a total of 7 metabolic pathways.Conclusion The intervention mechanism of Huoxiang Zhengqi Dropping Pills on rats with dampness encumbering the spleen and stomach syndrome may be related to the regulation of tryptophan metabolism,histidine metabolism,glutamate-glutamine metabolism,energy metabolism and intestinal flora.
5.Study on the Protective Effect of Modified Buyang Huanwu Decoction and Shenqi Dihuang Decoction on Mice with Diabetic Kidney Disease by Regulating VEGF-C/VEGFR3 Pathway and Inhibiting Lymphangiogenesis
Jiaan HUANG ; Mengjuan ZHANG ; Fan YANG ; Yan LIU ; Yuehua WANG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(6):778-788
Objective To explore the protective effect and mechanism of modified Buyang Huanwu Decoction and Shenqi Dihuang Decoction on diabetic kidney disease(DKD)mice based on the regulation of VEGF-C/VEGFR3 pathway inhibiting lymphangiogenesis.Methods Twenty-four male db/db mice were randomly divided into model group,Chinese medicine group(modified Buyang Huanwu Decoction combined with Shenqi Dihuang Decoction,crude drug 24.44 g·kg-1)and western medicine group(Irbesartan,13.5 mg·kg-1),with eight mice in each group.Eight db/m mice were selected as control group.Intragastric administration was given once a day for 12 consecutive weeks.Fasting blood glucose(FBG),total cholesterol(TC),triglyceride(TG),urinary albumin/creatinine ratio(ACR)and kidney index were measured.The pathological changes of renal tissue were observed by HE and Masson staining.The expressions of fibronectin(FN),type I collagen(Col I),Vimentin,α-smooth muscle actin(α-SMA),transforming growth factor-β1(TGF-β1),vascular endothelial growth factor receptor 3(VEGFR3),vascular endothelial growth factor-C(VEGF-C),lymphatic endothelial hyaluronic acid receptor 1(LYVE-1),podoplanin(PDPN),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in renal tissue were detected by immunohistochemistry.The protein expressions of Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,VEGF-C,LYVE-1,TNF-α and IL-1β in renal tissue were detected by Western Blot.The mRNA expressions of FN,Col I,TGF-β1,VEGF-C,VEGFR3,TNF-α and IL-1β in renal tissue were detected by Real-time PCR.Results Compared with the control group,the levels of serum FBG,TG,TC,ACR and kidney index in the model group were significantly increased(P<0.05).Glomerular hypertrophy,mesangial matrix increased,basement membrane thickening,cystic cavity narrowing,renal tubular epithelial cell degeneration and necrosis,interstitial infiltration of a large number of inflammatory cells,renal tubular atrophy;the level of renal fibrosis was significantly increased(P<0.05).The protein expressions of FN,Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,LYVE-1,TNF-α,IL-1β in renal interstitium,the expression of VEGF-C protein in cytoplasm and the expression of VEGFR3 and PDPN protein around renal tubular capillaries were significantly up-regulated(P<0.05).The protein expressions of Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,VEGF-C,LYVE-1,TNF-α and IL-1β in renal tissue were significantly up-regulated(P<0.05).The mRNA expression levels of FN,Col I,TGF-β1,VEGF-C,VEGFR3,TNF-α and IL-1β in renal tissue were significantly increased(P<0.05).Compared with the model group,the levels of serum TG,TC and ACR in the Chinese medicine group were significantly decreased(P<0.05).Renal tissue injury was improved to varying degrees,renal inflammatory cell infiltration was reduced to a certain extent,and renal tissue fibrosis was significantly reduced(P<0.05).The protein expressions of FN,Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,LYVE-1,TNF-α,IL-1β in renal interstitium,the protein expression of VEGF-C in cytoplasm and the protein expressions of VEGFR3 and PDPN around renal tubular capillaries were significantly down-regulated(P<0.05).The protein expressions of Col I,Vimentin,α-SMA,TGF-β1,VEGFR3,VEGF-C,LYVE-1,TNF-α and IL-1β in renal tissue were significantly down-regulated(P<0.05).The mRNA expression levels of FN,Col I,TGF-β1,VEGF-C,VEGFR3,TNF-α and IL-1β in renal tissue were significantly decreased(P<0.05).Conclusion Modified Buyang Huanwu Decoction combined with Shenqi Dihuang Decoction can reduce the level of inflammation and fibrosis in renal tissue of DKD mice,and its mechanism may be related to the regulation of VEGF-C/VEGFR3 pathway to inhibit lymphangiogenesis.
6.Nuanxinkang Inhibits Endothelial-to-Mesenchymal Transition to Reduce Plaque Formation in Mice with Obstructive Sleep Apnea-Hypopnea Syndrome Comorbid with Atherosclerosis
Mingyang WANG ; Lingjun WANG ; Birong LIANG ; Zixin CHEN ; Yanhong CAO ; Yubing ZHANG ; Shuxian LI ; Jing LIU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(6):789-797
Objective To investigate the effect and mechanism of Nuanxinkang on plaque formation in obstructive sleep apnea-hypopnea syndrome(OSAHS)comorbid with atherosclerosis(AS)mice by inhibiting endothelial-to-mesenchymal transition(EndMT).Methods Male ApoE-/-mice were randomly divided into six groups:control group,model group,atorvastatin group(2.6 mg·kg-1)and Nuanxinkang low-,medium-and high-dose groups(crude drug 3.5,7.0,14.0 g·kg-1),with eight mice in each group.The mice were exposed to chronic intermittent hypoxia(CIH)environment during sleep for a long time,and fed with high-fat diet to replicate OSAHS comorbid with AS mouse model.Oil red O staining was used to observe the formation of plaque on aortic intima in mice.Masson trichrome staining was used to evaluate the collagen content of atherosclerotic plaques in the aortic root of mice.The expressions of endothelial cell marker CD31 and EndMT marker Vimentin in aortic plaque were detected by immunofluorescence.Blood lipid levels were determined by ELISA;the mRNA expression levels of EndMT markers α-SMA and Cdh2 in aortic tissue were detected by qPCR.Results Compared with the control group,the area of aortic atherosclerotic plaque in the model group was significantly increased(P<0.01),and the area of collagen deposition in the aortic root plaque was significantly increased(P<0.01).The number of CD31 positive cells in the plaque were significantly decreased(P<0.01),and the number of Vimentin positive cells were significantly increased(P<0.01).Serum TG,T-CHO and LDL-C levels were significantly increased(P<0.01),and HDL-C level was significantly decreased(P<0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue were significantly increased(P<0.01).Compared with the model group,the area of aortic atherosclerotic plaque in Nuanxinkang groups were significantly reduced(P<0.05,P<0.01),and the collagen deposition area of aortic root atherosclerotic plaque were significantly reduced(P<0.05,P<0.01).The number of CD31 positive expression cells in the plaque of Nuanxinkang high-dose group were significantly increased(P<0.05),and the number of Vimentin positive expression cells in the plaque of Nuanxinkang medium-and high-dose groups were significantly decreased(P<0.05,P<0.01).The serum TG level of mice in the high-dose group of Nuanxinkang was significantly decreased(P<0.01).The serum T-CHO and LDL-C levels of mice in each Nuanxinkang administration group were significantly decreased(P<0.05,P<0.01).The serum HDL-C levels of mice in the medium-and high-dose groups of Nuanxinkang were significantly increased(P<0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue of mice in each treatment group were significantly decreased(P<0.01).Conclusion Nuanxinkang can effectively reduce the plaque formation in OSAHS comorbid with atherosclerosis mice,which may be related to its inhibition of EndMT and reduction of collagen fiber formation.
7.Study on the Effect and Mechanism of Di'ao Xinxuekang Combined with Simvastatin on Atherosclero-sis Mice
Wei LI ; Luyao LI ; Liping QU ; Honglin LIU ; Mengting LAI ; Ziqian WANG ; Wenjun ZOU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(6):798-804
Objective To investigate the effect and mechanism of Di'ao Xinxuekang(hereinafter referred to as Xinxuekang)combined with Simvastatin on atherosclerosis(AS)mice.Methods Eight C57BL/6J mice were used as control group,and 32 ApoE-/-mice were randomly divided into model group,Xinxuekang group(160 mg·kg-1),Simvastatin group(1.3 mg·kg-1)and combined treatment group(Xinxuekang 160 mg·kg-1+Simvastatin 1.3 mg·kg-1),with eight mice in each group.The control group was fed with conventional diet,and the other four groups were fed with high-fat diet.At the same time,each administration group was given intragastric administration according to the above dose,and the volume of intragastric administration was 10 mL·kg-1,once a day for 18 weeks.After administration,the levels of serum total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)were detected.Oil red O staining was used to observe the formation of aortic plaque and liver lipid accumulation in mice.Serum PCSK9 level was detected by ELISA.The mRNA and protein expression levels of LDLR,HNF1α and SREBP2 in liver tissues were detected by qRT-PCR and Western Blot.Results(1)Compared with the control group,the levels of serum TC,TG and LDL-C in the model group were significantly increased(P<0.01),and the level of HDL-C was significantly decreased(P<0.01).The percentage of aortic root plaque area,the percentage of total aortic plaque area and the percentage of liver lipid droplet area were significantly increased(P<0.01).The mRNA and protein expression levels of LDLR in liver tissue were significantly decreased(P<0.01),and the serum PCSK9 level was significantly increased(P<0.01).The mRNA and protein expression levels of HNF1α and SREBP2 in liver tissues were significantly increased(P<0.05,P<0.01).(2)Compared with the model group,the levels of serum TC,TG and LDL-C in the Xinxuekang group and the combined treatment group were significantly decreased(P<0.05,P<0.01),and the level of HDL-C was significantly increased(P<0.05).The level of serum LDL-C in Simvastatin group was significantly decreased(P<0.01).The percentage of aortic root plaque area and the percentage of total aortic plaque area in the Xinxuekang group and the combined treatment group were significantly decreased(P<0.05,P<0.01),and the percentage of liver lipid droplet area in each administration group was significantly decreased(P<0.01).The protein expression level of LDLR in liver tissue of mice in Xinxuekang group and combined treatment group was significantly increased(P<0.05),the serum PCSK9 level was significantly decreased(P<0.05,P<0.01),and the mRNA and protein expression levels of HNF1 α and SREBP2 in liver tissue were significantly decreased(P<0.05,P<0.01).(3)Compared with the Simvastatin group,the serum HDL-C level in the combined treatment group was significantly increased(P<0.05).The percentage of aortic root plaque area and the percentage of liver lipid droplet area were significantly decreased(P<0.05,P<0.01).The protein expression level of LDLR in liver tissue was significantly increased(P<0.01),and the serum PCSK9 level was significantly decreased(P<0.01).The expression levels of HNF1α protein and SREBP2 mRNA in liver tissues were significantly decreased(P<0.05,P<0.01).Conclusion Xinxuekang may play a synergistic effect on lipid-lowering and anti-AS effects of Simvastatin by inhibiting the expressions of SREBP2 and HNF1α and regulating the PCSK9/LDLR signaling pathway.
8.Effects and Mechanism Study of Kudinoside D on Proliferation,Apoptosis and Autophagy of Human HCC-1806 Breast Cancer Cells
Yongxu JIANG ; Mingcong DING ; Zeyi ZHAO ; Jiajun XIAO
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(6):805-813
Objective To investigate the effect and mechanism of kudinoside D(KD-D)on proliferation,apoptosis and autophagy of human HCC-1806 breast cancer cells.Methods Human HCC-1806 breast cancer cells were treated with different concentrations of KD-D,and the cell viability was detected by CCK-8 method.EdU method was used to detect cell proliferation ability;the ability of cell clone formation was detected by crystal violet staining.Apoptosis was detected by flow cytometry(Annexin V-FITC/PI).Mitochondrial membrane potential was detected by JC-1 staining.The protein expressions of Cleaved Caspase-3,LC3 and P62 were detected by immunofluorescence.The protein expressions of Cleaved Caspase-3,Pan-AKT,Phosp-AKT and LC3Ⅱ were detected by Western Blot.Autophagy double-labeled mRFP-EGFP-LC3 adenovirus infection assay was used to detect cell autophagy flow.Results Compared with the control group,HCC-1806 cells were treated with 12.5,25,50,100,200,400 μmol·L-1 KD-D for 24 and 48 hours.With the increase of drug concentration and treatment time,the cell activity was significantly decreased(P<0.001),the intracellular absorbance value was significantly decreased(P<0.001),and the cell proliferation was inhibited.The cell clone formation counts in 60 and 80 μmol·L-1 KD-D groups were significantly decreased(P<0.001).The proportion of early and late apoptosis in 50,100,150 μmol·L-1 KD-D groups were significantly increased(P<0.05,P<0.001).The proportion of red fluorescence in 40,60 and 80 μmol·L-1 KD-D groups were significantly decreased(P<0.001),the proportion of green fluorescence was significantly increased(P<0.01,P<0.001),and the mitochondrial membrane potential of HCC-1806 cells decreased.The protein expression of Cleaved Caspase-3 in 60,80,100 μmol·L-1 KD-D group were significantly up-regulated(P<0.001),and the protein expressions of Pan-AKT and Phosp-AKT in 60 μmol·L-1 KD-D group were significantly up-regulated(P<0.001).In the 60 μmol·L-1 KD-D group,the number of LC3 protein fluorescent dots was significantly increased(P<0.001),the average fluorescence intensity of P62 protein was significantly decreased(P<0.001),the expression of LC3Ⅱ protein was significantly up-regulated(P<0.001),the number of autophagosomes and autolysosomes were significantly increased(P<0.01,P<0.001),and the autophagic flow was activated.Compared with 60 μmol·L-1 KD-D group,the expression of Cleaved Caspase-3 and Pan-AKT protein in KD-D+AKT inhibitor(Afuresertib)group was significantly down-regulated(P<0.01,P<0.001),and the expression of Phosp-AKT protein was significantly up-regulated(P<0.001).Conclusion KD-D can inhibit the proliferation of human breast cancer HCC-1806 cells and induce apoptosis and autophagy.The apoptosis of HCC-1806 cells induced by KD-D may be related to the activation of AKT signal and the expression of Cleaved Caspase-3.
9.The Mechanism of Protective Effect of Jianpi Yichang Powder on Intestinal Mucosa of Rats with Ulcerative Colitis Based on Autophagy
Qin LIU ; Sainan ZHOU ; Jiemin LIU ; Xiaoyuan LIN
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(6):814-821
Objective To explore the mechanism of protective effect of Jianpi Yichang Powder on intestinal mucosa by observing its effect on the expression of autophagy-related molecules in colon of ulcerative colitis(UC)model rats.Methods SD rats were randomly divided into normal group,model group,Jianpi Yichang Powder group and sulfasalazine group.UC rat model was established by 2,4,6-trinitrobenzene sulfonic acid/ethanol solution.After the model was successfully reproduced,the rats were given drugs orally once a day for 14 days.The general condition of rats was observed and the disease activity index(DAI)score was calculated.The pathological morphology of colonic tissue in all groups was observed by hematoxylin eosin(HE)staining.Autophagy of colonic epithelial cells was examined by transmission electron microscope.The expressions of myosin-like BCL2 interacting protein(Beclin1)and microtubule-associated protein 1 light chain 3(LC3)in colonic tissue were detected by immunofluorescence staining and Western Blot.The mRNA expressions of autophagy protein 5(Atg5),autophagy protein 7(Atg7)and ubiquitin-binding protein 62(p62)were detected by real-time quantitative polymerase chain reaction(Real-time PCR).Results Compared with the normal group,the general situation of the model group was worse,and the DAI score increased significantly(P<0.000 1).There was obvious epithelial cell damage in colonic tissue,and the number of autophagosomes decreased obviously under electron microscope.The expressions of Beclin1 and LC3-Ⅱ/LC3-Ⅰ protein as well as Atg5 and Atg7 mRNA in colonic tissue decreased significantly(P<0.000 1),while the expression of p62 mRNA increased significantly(P<0.000 1).Compared with the model group,the general condition of rats in Jianpi Yichang Powder group had recovered significantly,and the DAI score decreased significantly(P<0.000 1).Pathological damage of colonic tissue has been improved in different degrees,and the number of autophagosomes increased significantly under electron microscope.The expressions of Beclin1 and LC3-Ⅱ/LC3-Ⅰ protein as well as Atg5 and Atg7 mRNA in colonic tissue were significantly increased(P<0.01,P<0.001,P<0.000 1),while the expression of p62 mRNA was significantly decreased(P<0.01).Conclusion Jianpi Yichang Powder can protect UC colon mucosa from injury by up-regulating the expression of autophagy-related molecules including Beclin1,LC3,Atg5 and Atg7,down-regulating the expression of p62 and enhancing autophagy.
10.The Effect and Mechanism of Three Compounds in Lagotis brachystachya Maxim on Chronic Alcoholic Liver Injury Combined with Gouty Arthritis in Rats
Jixiao ZHU ; Lin ZHOU ; Chuling ZHANG ; Wenwen XIONG ; Hongyu CHENG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(6):822-831
Objective To study the effects of monomers in Lagotis brachystachya Maxim including quercetin,echinacoside,and apigenin on the p38MAPK/JNK,TLR4/MyD88/NF-κB,and NLRP3 signaling through establishing a rat model of chronic alcoholic liver injury combined with gouty arthritis,and to explore the mechanism of the above-mentioned monomers in the treatment of chronic alcoholic liver injury combined with gouty arthritis.Methods Eighty rats were randomly divided into normal group,model group,bifendate group(100 mg·kg-1),colchicine group(0.3 mg·kg-1),and different dose groups of quercetin(50,25 mg·kg-1),echinacoside(50,25 mg·kg-1),and apigenin(50,25 mg·kg-1).The rats were administered at a dose of 10 mL·kg-1 per day in the morning and administered with 56-degree Red Star Erguotou at a dose of 4 mL·kg-1 in the afternoon,with gradual increasement of 2 mL·kg-1 per week until a final dose of 10 mL·kg-1.The rats were continuously fed by gavage for 8 weeks.Gouty arthritis model was induced at the 53th day of alcohol-based feeding.Toe volume was measured at difference time.At the end of the 8th week,blood was collected after the last administration.Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP)levels,total cholesterol(TC)and triglycerides(TG)were measured.Enzyme-Linked Immunosorbent Assay(ELISA)was used to detect interleukin-1β(IL-1β)in rat serum.Western Blot was used to detect the expression of p38 mitogen-activated protein kinase(p38MAPK),phosphorylated p38MAPK(p-p38MAPK),c-Jun N-terminal kinase(JNK),phosphorylated JNK(p-JNK),Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),nuclear factor-κB(NF-κB),phosphorylated NF-κB(p-NF-κB),and NOD-like receptor protein domain containing 3(NLRP3)in liver and synovial tissues.Results Compared with the normal group,the toe swelling degree in the model group was significantly increased at difference time(P<0.05,P<0.01).The levels of ALT,AST,ALP,TC,TG,and IL-1β in serum were significantly increased(P<0.01).The protein expression levels of p-p38MAPK,p-JNK,MyD88,p-NF-κB,TLR4,and NLRP3 in liver and synovial tissues were all increased to varying degrees(P<0.01).Compared with the model group,the toe swelling degree in all treatment groups significantly decreased after 24 hours(P<0.01).The levels of ALT and TC in the bifendate group and different dose groups of monomers decreased to varying degrees(P<0.05,P<0.01).Except for the low dose group of echinacoside,the levels of AST and ALP in other treatment groups decreased to varying degrees(P<0.01).Except for the high dose group of quercetin,the levels of TG in other treatment groups decreased to varying degrees(P<0.01).The protein expression levels of p-p38MAPK,p-JNK,MyD88,p-NF-κB,TLR4,and NLRP3 in liver and synovial tissues of rats in all treatment groups were down-regulated(P<0.05,P<0.01).Conclusion The monomers in Lagotis brachystachya Maxim show certain therapeutic effects of treating different diseases with same treatment on the rat model of chronic alcoholic liver injury combined with gouty arthritis,and their therapeutic effects may be mediated through p38MAPK/JNK,TLR4/MyD88/NF-κB,and NLRP3 signaling pathways.

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