Astragaloside IV Ameliorates Inflammatory Damage in Mice with Acute Liver Failure

Acute liver failure is a life-threatening clinical syndrome with a high mortality rate. Currently, the research on Astragaloside IV in liver diseases primarily focuses on liver cancer, and there is limited understanding of its mechanism in acute liver failure’s innate immunity. Therefore, this study aims to investigate the potential protective effect of Astragaloside IV on acute liver failure and its impact on innate immune cells. The study employed D-GalN/LPS-induced acute liver failure mouse models and employed various techniques such as a range of molecular and analytical techniques. The experimental results demonstrated that treatment with Astragaloside IV significantly reduced the inflammatory response, alleviated liver injury, and improved the survival rate of mice with acute liver failure induced by D-GalN/LPS. Further investigations revealed that AS-IV played a beneficial role by regulating the proportion of CD11b+Ly6Chi monocytes and the secretion of inflammatory cytokines and anti-inflammatory metabolites. These findings suggest that the pharmacological mechanism of AS-IV may involve targeted regulation of CD11b+Ly6Chi monocytes in both peripheral blood and liver. The implications of this study’s results are twofold. Firstly, they provide a basis for the clinical application of AS-IV in treating liver failure, offering potential therapeutic benefits. Secondly, they serve as a reference for further development of safer and more effective modified compounds.

Protective effect of astragaloside IV on cardiac hypertrophy in rats and its mechanism

Objective:To investigate the effect of astragaloside IV on cardiac hypertrophy and its regulation on autophagy.Methods:Fifty male Sprague-Dawley rats were randomly divided into sham operation group and abdominal aortic coarctation group(AAC group).There were 10 rats in sham operation group and 40 rats in the AAC group.One week after the operation,there were 32 rats in AAC group,10 rats in sham group.AAC group was randomly divided into model group,low-dose astragaloside group,high-dose astragaloside group and rapamycin group,8 rats in each group.Rapamycin group was a positive autophagy contrast agent group.They were given the corresponding solvents once a day by gavage for six weeks.At the end of study,three rats were randomly selected from each group,left ventricular mass index(LVW/BW),cardiac mass index(HW/BW)and the content of hydroxyproline were measured.HE staining,masson staining and sirius red staining were used to observe the morphological changes of myocardium.The expression of LC3II,LC3I,Beclin1,AMPK and mTOR were detected by western blot.Results:Compared with the sham operation group,AAC group showed hypertrophy,LVW/BW,HW/BW,HYP and p-mTOR/mTOR were significantly increased(P<0.05),p-AMPK/AMPK,LC3II/LC3I,Beclin1 were significantly decreased(P<0.05).Compared with the model group,the low-dose astragaloside IV group showed the hypertrophy of cardiomyocytes was relatively light,LVW/BW and HW/BW were significantly decreased(P<0.05),there was no significant difference in HYP and p-mTOR/mTOR(P>0.05),LC3II/LC3I,Beclin1 and p-AMPK/AMPK were significantly increased(P<0.05).Compared with the model group,high-dose astragaloside IV group and rapamycin group showed reduced myocardial hypertrophy,LVW/BW,HW/BW,HYP and p-mTOR/mTOR were significantly decreased(P<0.05),LC3II/LC3I,Beclin1 and p-AMPK/AMPK were significantly increased(P<0.05).Compared with the low-dose astragaloside group,the high-dose astragaloside group showed reduced myocardial hypertrophy,there were significant differences in each index(P<0.05).Compared with rapamycin group,there was no obvious difference in morphology and structure of myocardial cells,LVW/BW,HYP and p-mTOR/mTOR were decreased(P<0.05),HW/BW and p-AMPK/AMPK had no significant difference(P>0.05),LC3II/LC3I and Beclin1 were increased in high-dose astragaloside group(P<0.05).Conclusion:As IV has protective effect on cardiac hypertrophy in a dose-dependent manner and its mechanism may be related to regulate autophagy.

Determination of the Content of Astragaloside IV in Yikangshu Granules by High Performance Liquid Chromatography

[Objectives]The research aimed to establish a high performance liquid chromatography method for the content determination of astragaloside IV in Yikangshu Granules.[Methods]Kromasil 5μm C18(2),100 A,250 mm×4.6 mm was used;the mobile phase was acetonitrile-water(32∶68);flow velocity was 1.0 mL/min;the temperature of evaporator and sprayer was 80 and 30℃;the column temperature was set at 30℃,and injection volume was 20μL.[Results]Astragaloside IV showed a good linear relationship in the range of 1.01-10.14μg with the peak area,and regression equation was lgY=1.7728lgX+1.597(r=0.9999).The limit of detection for astragaloside IV was 1.96 ng,and the average recovery rate was 95.31%.[Conclusions]This method is sensitive,accurate and reproducible,with good linearity,and it is suitable for the content determination of astragaloside IV in health food Yikangshu Granules.

Potential Role of Astragaloside IV in the Treatment of Fungal Keratitis

Fungal keratitis (FK) is a worldwide visual impairment disease. The pathogenesis of fungal keratitis involves fungi, corneal cells, inflammatory cell infiltration, collagen degradation, inflammatory cytokines and their interactions. Accumulated evidence indicated that Astragaloside IV (AS-IV) possesses a broad range of pharmacological properties, such as efficacy in anti-inflammation, alleviating fibrosis, and immunomodulatory effects. This paper summarizes new findings regarding AS-IV in immune and inflammatory diseases and analyzes the perspective application of Astragaloside IV in fungal keratitis.

Astragaloside IV prevents lipopolysaccharide-induced injury in H9C2 cardiomyocytes

This study aimed to investigate the protective effects of astragaloside IV(AS IV) on lipopolysaccharide(LPS)-induced injury in H9C2 cardiomyocytes. H9C2 Cardiomyocytes were cultured with LPS(10 μg·mL-1) for 4 h and treated with AS IV at 50, 100, and 150 μmol·L-1 for various durations. Cell viability was determined by MTT. The content of released TNF-α and IL-6 from cardiomyocytes were evaluated by enzyme-linked immunosorbent assay(ELISA). The levels of superoxidase dismutase(SOD), malondialdehyde(MDA), lactate dehydrogenase(LDH), and creatine phosphate kinase(CK) were measured by using commercial available kits. The mR NA and protein expression levels of NF-κB p65 were measured by RT-PCR and Western blotting, respectively. And the NF-κB p65 activity was measured by ELISA. Our results demonstrated that AS IV at 50, 100, and 150 μmol·L-1 markedly inhibited the release of TNF-α and IL-6 and decreased NF-κB expression, compared with the model group. Moreover, the improved SOD activity and decreased MDA, LDH and CK levels were detected after AS IV treatment. In summary, AS IV could increase the activities of antioxidant enzymes, inhibite lipid peroxidation, and down-regulate the inflammatory mediators involved in the inflammatory responses. These results demonstrated that AS IV could prevent LPS-induced injury in cardiomyocytes.

Astragaloside IV Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction in Rats via IKK/NF-κB Pathway

Objective To evaluate the protective effects of Astragaloside IV(AST)in a rat model of myocardial injury induced by cecal ligation and puncture(CLP).Methods The model of sepsis-induced cardiac dysfunction was induced by CLP.Using a random number table,50 specific pathogen free grade of Sprague Dawley rats were randomized into 5 groups:the sham group(sham),the model group(CLP,18 h/72 h)and AST group(18 h/72 h).Except the sham group,the rats in other groups received CLP surgery to induce sepsis.CLP groups received intragastric administration with normal saline after CLP.AST groups received intragastric administration with AST solution(40 mg/kg)once a day.The levels of inflammatory mediators and oxidative stress markers in the serum of the septic rats were determined via enzyme-linked immunosorbent assay(ELISA)at different time point,such as interleukin 6(IL-6),IL-10,high mobility group box-1 protein B1(HMGB-1),superoxide dismutase(SOD),and malondialdehyde(MDA).Cardiac function was determined by echocardiography.Moreover,changes in myocardial pathology were evaluated using hematoxylin and eosin staining.The levels of lactate dehydrogenase(LDH)and creatine kinase-MB(CK-MB)were analysed to determine the status of CLP-induced myocardium.In addition,the apotosis of myocardial cells was analysed by terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL).The protein levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X(Bax),IκB kinaseα(IKKα),nuclear factor kappa B p65(NF-κB p65)were detected by Western blot analysis.Moreover,survival rate was investigated.Results AST improved the survival rate of CLP-induced rats by up to 33.3%(P<0.05).The cardioprotective effect of AST was observed by increased ejection fraction,fractional shortening and left ventricular internal diameter in diastole respectively(P<0.01 or P<0.05).Subsequently,AST attenuated CLP-induced myocardial apoptosis and the ratio of Bcl-2/Bax in the myocardium,as well as the histological alterations of myocardium(P<0.01 or P<0.05);the generation of inflammatory cytokines(IL-6,IL-10,HMGB-1)and oxidative stress markers(SOD,MDA)in the serum was significantly alleviated(P<0.01 or P<0.05).On the other hand,AST markedly suppressed CLP-induced accumulation of IKK-αand NF-κB p65 subunit phosphorylation(P<0.01 or P<0.05).Conclusions AST plays a significant protective role in sepsis-induced cardiac dysfunction and survival outcome.The possible mechanism of cardioprotection is dependent on the activation of the IKK/NF-κB pathway in cardiomyocytes.

Effect of astragaloside IV and salvianolic acid B on antioxidant stress and vascular endothelial protection in the treatment of atherosclerosis based on metabonomics

Vascular endothelial cells and oxidation reduction system play an important role in the pathogenesis of atherosclerosis(AS).If these conditions are disordered,it will inevitably lead to plaque formation and even rupture.Astragaloside IV(AsIV)and salvianolic acid B(Sal B)are the main active ingredients of Astragalus membranaceus and Salvia miltiorrhiza,respectively,and found to ameliorate vascular endothelial dysfunction and protect against oxidative stress in recent studies.However,it is still unknown if the combination of AsIV and Sal B(AsIV+Sal B)can inhibit the development of plaque through amplifying the protective effect of vascular endothelial cells and anti-oxidative stress effect.To clarify the role of AsIV+Sal B in AS,we observed the efficacy of each group(Control,Model,AsIV,Sal B,and AsIV+Sal B)by biomolecular assays,such as observing the pathological morphology of the aorta by oil red O staining,evaluating the level of oxidative stress and endothelial cells in the serum by the Elisa test,and analyzing the changes of all small molecule metabolites in liver tissue by UPLC-QTOF-MS.Results showed that AsIV,Sal B and AsIV+Sal B decreased the deposition of lipid in the arterial wall,so as to exert the effect of anti-oxidant stress and vascular endothelial protection,where the inhibitory effect of AsIV+Sal B was the most obvious.Metabonomics analysis showed that Sal B regulated the metabolic pathways of arginine and proline.AsIV regulated glycerol metabolism and saturated fatty acid biosynthesis metabolism.AsIV+Sal B is mainly related to the regulation of the citrate cycle(TCA cycle),alanine,aspartic acid,and glutamate metabolism,cysteine,and methionine metabolism.Succinic acid and methionine are synergistic metabolites that exert an enhancing effect when AsIV and Sal B were used in combination.In conclusion,we demonstrated that AsIV acompanied with Sal B can be successfully used for anti-oxidative stress and vascular endothelial protection of AS,and succinic acid and methionine are the synergistic metabolites.

Molecular Mechanism of Induction on Apoptosis of Human Esophageal Cancer HCE-4 Cells by Active Components from Astragalus membranaceus

[Objectives] To investigate the pharmacologic effects of active components from A. membranaceus on human esophageal cancer HCE-4 cells and its apoptosis mechanism. [Methods] The viabilities of HCE-4 cells were measured by MTT assay. The induction of active components from A. membranaceus on apoptosis of HCE-4 cells was detected by Annexin V-FITC/PI double staining. The apoptotic-related protein expression levels were determined by Western blotting. [Results] Formononetin and astragaloside IV suppressed the proliferation of HCE-4 cells in a dose-dependent manner. The Annexin V-FITC/PI double staining results showed that formononetin and astragaloside IV could induce HCE-4 cells apoptosis in a time-dependent manner. The Western blotting results showed that formononetin and astragaloside IV could significantly down-regulate p-AKT,pro-caspase-3,and increase cle-caspase-3 protein expression in HCE-4 cells. [Conclusions]Active components from A. membranaceus such as formononetin and astragaloside IV significantly inhibited the proliferation of human esophageal cancer HCE-4 cells by inducing mitochondrial dependent apoptosis via AKT signaling pathway.

Astragaloside IV Alleviates Acute Liver Failure Induced by D-GalN/LPS by Upregulating Autophagy and Reducing Inflammation

Acute liver failure(ALF)is a life-threatening condition that manifests in an extremely serious manner and progresses rapidly.The following study investigated the protective effect of astragaloside IV(AS-IV),a traditional Chinese drug,on ALF,and its underlying mechanisms,focusing on autophagy and inflammation regulation.Mice were randomly divided into a saline group,a D-galactosamine and lipopolysac-charide(D-GalN/LPS)group and an AS-IV group.Biochemical analysis,immunohistochemistry,cytometric bead array,high-throughput quantitative PCR,flow cytometry and Western analysis were used to assess inflammation and liver damage 5 hours after D-GalN/LPS ex-posure.Astragaloside IV treatment reduced mortality by alleviating D-GalN/LPS–induced hepatic damage and decreasing inflammation(decreasing Ly6c+monocyte levels,reducing inflammatory cytokines and increasing anti-inflammatory factors)as well as upregulating au-tophagy.Furthermore,PCR array was used to detect expression of autophagy-related genes,which demonstrated a Log2 fold change in gene expression between the AS-IV and D-GalN/LPS groups ranging from 1.19 to-3.53,with Tnfsf10 showing the largest alteration be-tween the two groups.These data suggest that AS-IV may alleviate ALF by upregulating autophagy and reducing inflammation,and it may therefore be an interesting drug for alleviating ALF.

Effects of Astragaloside Ⅳ Derivative on Heart Failure in Rats

Objective Astragaloside Ⅳ derivative(ASId) is one of Astragaloside Ⅳ(ASI) derivatives with higher water-solubility and may have more druggability than ASI.The present study aims at observing the effects of ASId on cardiovascular parameters in chronic heart failure in rats.Methods Using echocardiographic and haemodynamic measurements,the effects of ASId on congestive heart failure(CHF) induced by ligation of the left coronary artery in rats were investigated.Results ASId iv 0.5,1.0,and 2.0 mg/(kg·d) attenuated the decline of ejection fraction.The peak derivatives of the left ventricle(LV) pressure(dp/dt) in ASId treated groups were significantly increased.Both LV volumes in diastole and in systole were decreased significantly after ASId treatment,accompanied with a trend towards normalization of relative wall thickness at end-systole.ASId 0.5,1.0,and 2.0 mg/(kg·d) attenuated the increase of LV systolic and diastolic wall stress.ASId treatment also inhibited compensatory hypertrophy of depressed heart.Conclusion ASId could improve cardiac functions and inhibite compensatory hypertrophy and LV remodelling,which suggests the possibility of ASId as a new therapeutic drug for the treatment of CHF.

Astragaloside Ⅳ for Heart Failure: Preclinical Evidence and Possible Mechanisms, A Systematic Review and Meta-Analysis

Objective:To explore the cardioprotective effects of astragaloside Ⅳ(AS-Ⅳ) in heart failure(HF).Methods:PubMed,Excerpta Medica Database(EMBASE),Cochrane Library,Web of Science,Wanfang Database,Chinese Bio-medical Literature and Retrieval System(SinoMed),China Science and Technology Journal Database(VIP),and China National Knowledge Infrastructure(CNKI) were searched from inception to November 1,2021for animal experiments to explore AS-Ⅳ in treating HF in rats or mice. The left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventricular end-diastolic dimension(LVEDD),left ventricular endsystolic dimension(LVESD),left ventricular weight-to-body weight(LVW/BW) and B-type brain natriuretic peptide(BNP) were recorded.The qualities of included studies were assessed by the risk of bias according to the Cochrane handbook.Meta-analysis was performed using Stata 13.0.Results:Twenty-one articles involving 558 animals were considered.Compared with the control group,AS-Ⅳ improved cardiac function,specifically by increasing LVEF(mean difference(MD)=6.97,95% confidence interval(CI)=5.92 to 8.03,P<0.05;fixed effects model) and LVFS(MD=7.01,95% CI=5.84 to 8.81,P<0.05;fixed effects model),and decreasing LVEDD(MD=-4.24,95% CI=-4.74to-3.76,P<0.05;random effects model) and LVESD(MD-4.18,95% CI=-5.26 to-3.10,P<0.05;fixed effects model).In addition,the BNP and LVW/BW levels were decreased in the AS-Ⅳ treatment group(MD=-9.18,95%CI=-14.13 to-4.22,P<0.05;random effects model;MD=-1.91,95% CI=-2.42 to-1.39,P<0.05;random effects model).Conclusions:AS-Ⅳ is a promising therapeutic agent for HF.However,this conclusion needs to be clinically validated in the future.

A New Triterpenoid Saponin from Aidi Injection

Objective To investigate the chemical constituents from Aidi Injection.Methods The chemical constituents were isolated by chromatography on Sephadex LH-20 gel columns and reverse phase semi-preparative HPLC repeatedly.Their structures were identified by spectroscopic analysis(NMR and MS).Results Twenty-two compounds were isolated and identified to be 3-O-3′,4′-diacetyl-β-D-xylopyranosyl-6-O-β-D-glucopyranosyl- cycloastragenol(1),astragaloside IV(2),astragaloside II(3),astragaloside I(4),isoastragaloside I(5), acetylastragaloside I(6),ginsenosid Re(7),ginsenoside Rf(8),ginsenoside Rg1(9),ginsenoside Rb3(10), notoginsenoside R4(11),ginsenoside Rb1(12),ginsenoside Rc(13),ginsenoside Rb2(14),ginsenoside Rd(15), lucyoside H(16),3-O-β-D-glucopyranosyl(1→4)-β-D-glucopyranosyl(1→3)-α-L-rhamnopyranosyl(1→2)-α-L- arabinopyranosyl oleanolic acid 28-O-α-L-rhamnopyranosyl(1→4)-β-D-glucopyranosyl(1→6)-β-D-glucopyranoside (17),3-O-β-D-glucopyranosyl(1→3)-α-L-rhamnopyranosyl[β-D-glucopyranosyl-(1→4)]-(1→2)-α-L-arabinopyranosyl oleanolic acid 28-O-α-L-arabinopyranosyl(1→4)-β-D-glucopyranosyl(1→6)-β-D-glucopyranoside(18),syringin (19),elentheroside E(20),4-(1,2,3-trihydroxypropyl)-2,6-dimethoxyphenyl-1-O-β-D-glucopyranoside(21),and coniferin(22).Conclusion Compounds 1-6 are originated from Astragalus membranceus,compounds 7-18 are originated from Panax ginseng,and compounds 19-22 are originated from Acanthopanax senticosus by LC-MS analysis.Compound 1 is a new compound.