Objective:To evaluate the efficacy and symptom scores of early diabetic nephropathy(DKD)treated with modified Shenqi Dihuang Decoction.Methods:82 patients with early DKD who visited the hospital from February 2023 to ...Objective:To evaluate the efficacy and symptom scores of early diabetic nephropathy(DKD)treated with modified Shenqi Dihuang Decoction.Methods:82 patients with early DKD who visited the hospital from February 2023 to February 2025 were randomly divided into two groups by drawing.Group A received modified Shenqi Dihuang Decoction+SGLT2 inhibitor,while Group B received SGLT2 inhibitor only.The efficacy,symptom scores,blood glucose,and renal function were compared between the two groups.Results:The efficacy of Group A was higher than that of Group B in the treatment of early DKD(P<0.05).The DKD symptom scores of Group A were lower than those of Group B(P<0.05).The fasting blood glucose(FBG),2-hour postprandial blood glucose(PBG),and glycated hemoglobin(HbA1c)of Group A were better than those of Group B(P<0.05).The serum creatinine(SCr),blood urea nitrogen(BUN),and urinary albumin excretion rate(UAER)of Group A were also better than those of Group B.Conclusion:The combination of modified Shenqi Dihuang Decoction and SGLT2 inhibitor dapagliflozin has excellent efficacy in the treatment of early DKD,which can improve renal function,reduce DKD symptoms,and stabilize blood glucose levels.展开更多
Background:Diabetic kidney disease(DKD)is a major cause of end-stage renal disease,with limited effective treatment options currently available.Shenqi Dihuang Decoction(SQDH)has demonstrated clinical efficacy in manag...Background:Diabetic kidney disease(DKD)is a major cause of end-stage renal disease,with limited effective treatment options currently available.Shenqi Dihuang Decoction(SQDH)has demonstrated clinical efficacy in managing DKD;however,the metabolic mechanisms responsible for its therapeutic effects remain unclear.Methods:We established a DKD mouse model and treated the mice with SQDH to investigate its effects on renal function and tissue pathology.To explore the metabolic mechanisms,we conducted non-targeted metabolomics to identify differential metabolites in the renal tissues of DKD mice and the associated metabolic pathways affected by SQDH.Additionally,we performed RT-qPCR and Western blot analyses to assess the effects of SQDH on the expression of key genes and proteins within the targeted pathways.To further evaluate SQDH’s therapeutic effects,we measured oxidative stress markers and inflammatory factors,examining its antioxidant and anti-inflammatory properties in DKD.Results:SQDH treatment improved body weight and blood glucose levels in DKD mice.It also restored renal function,as indicated by improved 24h-UTP,serum creatinine,and blood urea nitrogen levels,and alleviated renal tissue pathology associated with DKD.Metabolomic analysis showed that SQDH primarily regulates glycerophospholipid metabolism,particularly by increasing phosphatidylcholine(PC)levels and decreasing lysophosphatidylcholine(LPC)levels.RT-qPCR and Western blot analyses revealed that SQDH upregulated LPCAT expression and downregulated PLA2G expression.Additionally,SQDH enhanced the activities of superoxide dismutase and glutathione peroxidase,reduced reactive oxygen species,4-hydroxy-2-nonenal,and malondialdehyde levels,and decreased the levels of inflammatory cytokines IL-1β,IL-6,and TNF-α.Conclusion:Our findings confirm that SQDH protects against DKD by regulating glycerophospholipid metabolism,restoring the balance of PC and LPC,inhibiting inflammatory responses,and reducing oxidative stress.展开更多
Objective:To evaluate the therapeutic effect of Shenqi Dihuang Decoction combined with calcium dobesilate on patients with diabetic nephropathy(DKD).Methods:90 patients with DKD who visited the hospital from March 202...Objective:To evaluate the therapeutic effect of Shenqi Dihuang Decoction combined with calcium dobesilate on patients with diabetic nephropathy(DKD).Methods:90 patients with DKD who visited the hospital from March 2024 to March 2025 were selected as samples and randomly divided into two groups.Group A was treated with Shenqi Dihuang Decoction combined with calcium dobesilate,while Group B was treated with calcium dobesilate alone.The efficacy,syndrome scores,blood glucose levels,and renal function indicators were compared between the two groups.Results:The efficacy of DKD treatment in Group A was higher than that in Group B(P<0.05).The syndrome scores in Group A were lower than those in Group B(P<0.05).The 2-hour postprandial blood glucose(PBG),fasting blood glucose(FBG),and glycated hemoglobin(HbA1c)levels in Group A were lower than those in Group B(P<0.05).The serum creatinine(SCr),urinary microalbumin,urinary albumin excretion rate(UAER),and β2-microglobulin(β2-MG)levels in Group A were also lower than those in Group B(P<0.05).Conclusion:The treatment of DKD with Shenqi Dihuang Decoction combined with calcium dobesilate can stabilize blood glucose levels,improve renal function,and reduce syndrome scores,which is highly effective and feasible.展开更多
OBJECTIVE： To investigate the anti-inflammatory, anti-oxidative stress, and adipokine-ameliorating effects of Liuwei Dihuang （LWDH）, a traditional Chinese herbal formula, in obese rats. METHODS： After 2 weeks of a...OBJECTIVE： To investigate the anti-inflammatory, anti-oxidative stress, and adipokine-ameliorating effects of Liuwei Dihuang （LWDH）, a traditional Chinese herbal formula, in obese rats. METHODS： After 2 weeks of acclimation with free access to regular rodent chow and water, obese-prone-caesarean-derived （OP-CD） rats were fed a modified AIN-93G diet containing 60% energy from fat. Treatment was performed twice daily by gavage feeding with 500, 1 500, or 3 500 mg/kg body weight LWDH suspended in water （n=12 rats per group）. Twelve obese-resistant-CD （OR-CD） rats were fed the atherogenic diet and gavaged with water, and served as the normal control. Blood biomarkers of inflammation, oxidative stress and adiponectin were measured post-sacrifice and used to determine the treatment effect of LWDH and assess the suitability of OR/OP-CD rats for studying these parameters. RESULTS： After 9 weeks of treatment, LWDH lowered serum C-reactive protein （CRP） and tumour necrosis factor-α （TNF-α） levels. Serum interleukin-6 （IL-6） levels showed a tendency towards reduction, but were not significantly different from the OP-CD control. Liver superoxide dismutase （SOD） activity was increased in response to all three doses of LWDH, while the levels of reduced （GSH） and oxidized glutathione （GSSG） and thiobarbituric acid reactive substances （TBARS） were unchanged. Serum adiponectin levels were increased in response to oral administration of LWDH at the dose of either 500 or 1 500 mg/kg body weight. In addition, comparisons between OR-CD and OP-CD rats revealed differential, and for some biomarkers, conflicting characteristics of high-fat diet-fed OP-CD rats in reference to obese human subjects in terms of inflammatory and oxidative stress biomarkers and circulating adiponectin levels. CONCLUSION： The results show, for the first time, the anti-inflammatory, anti-oxidative stress and adiponectin-ameliorating effects of LWDH in obese rats. The suitability of the OP-JOP-CD rat model as a research tool to study inflammation, oxidative stress, and adipokine production requires further investigation.展开更多
OBJECTIVE:To investigate if the Liuwei Dihuang pill(LWDHP)can inhibit metastasis to the liver and lungs in mice bearing triple-negative breast cancer(TNBC),and the molecular mechanism underpinning this action.METHODS:...OBJECTIVE:To investigate if the Liuwei Dihuang pill(LWDHP)can inhibit metastasis to the liver and lungs in mice bearing triple-negative breast cancer(TNBC),and the molecular mechanism underpinning this action.METHODS:Ninety-nine TNBC bearing-mice were distributed randomly to five groups:control(Con),paclitaxel(PTX),low-dose LWDHP(LLP,2.3 g·kg^-1·d^-1),middle-dose LWDHP(MLP,4.6 g·kg^-1·d^-1)and high-dose LWDHP(HLP,9.2 g·kg^-1·d^-1).The LWDHP were administered(p.o.)to the agonal stage.The morphology of BC cells was observed by hematoxylin&eosin staining.Expression of axin-2,β-catenin,T cell factor(TCF),cyclin-D1 and vascular endothelial growth factor(VEGF)was detected by western blotting or immunofluorescence.β-catenin/TCF-1 interaction was measured using a co-immunoprecipitation assay.RESULTS:After LWDHP treatment,metastasis of BC cells to the lungs and liver was inhibited,expression of axin-2 was increased,expression of TCF-1,β-catenin,cyclin-D1 and VEGF was decreased,andβ-catenin/TCF-1 interaction was disrupted.CONCLUSION:The LWDHP could inhibit metastasis of BC cells to the liver and lungs.The molecular mechanism underlying this action may be regulation of protein expression andβ-catenin/TCF-1 interactions in the Wnt pathway.展开更多
AIM To investigate the inhibitory effect of Liuwei Dihuang Pill(LDP) on gastric tumorigenesis induced by N-methyl-N-nitrosourea(MNU) in diabetic mice.METHODS Four-week-old mice were divided into four groups: A, 12 db/...AIM To investigate the inhibitory effect of Liuwei Dihuang Pill(LDP) on gastric tumorigenesis induced by N-methyl-N-nitrosourea(MNU) in diabetic mice.METHODS Four-week-old mice were divided into four groups: A, 12 db/m mice treated with MNU and saline, as the non-diabetic control; B, 12 db/db mice treated with MNU and saline, as the diabetic control; C, 12 db/db mice treated with MNU and metformin, as the positive control; and D, 12 db/db mice treated with MNU and LDP. MNU was administrated for 20 wk to induce gastric carcinogenesis. LDP was administrated for 10 wk for improvement of insulin resistance. Body weight and food intake were measured every week. Blood samples were collected for assays of fasting blood glucose, insulin, insulin-like growth factor(IGF)-1, adiponectin and leptin. Stomach tissues were collected for histopathological analysis, immunohistochemical staining of Ki67, quantitative reverse transcriptionpolymerase chain reaction and western blotting. RESULTS The incidence of MNU-induced gastric dysplasia was significantly elevated in diabetic(db/db) mice relative to the control(db/m) mice. The incidence of gastricdysplasia was significantly reduced by LDP with suppression of cell proliferation, as demonstrated by a decrease in Ki67 staining. Hyperglycemia, hyperinsulinemia and serum IGF-1 were inhibited by LDP. Expression of IGF-1 and insulin receptor m RNAs was decreased, phosphorylation of IGF-1 receptor and AKT protein was reduced in the stomach tissues by LDP. In addition, adiponectin was increased and leptin was decreased in the serum by LDP. CONCLUSION LDP decreased risk of gastric dysplasia in type 2 diabetic mice by down-regulation of IGF and insulin activity and correction of adipokines disorders.展开更多
OBJECTIVE:To evaluate the efficacy of Liuwei Dihuang formula(六味地黄方,LWDHF)on endothelial cells,and to study the mechanism behind the action of modulating expression of estrogen receptors.METHODS:Hydrogen peroxide(...OBJECTIVE:To evaluate the efficacy of Liuwei Dihuang formula(六味地黄方,LWDHF)on endothelial cells,and to study the mechanism behind the action of modulating expression of estrogen receptors.METHODS:Hydrogen peroxide(H_(2)O_(2))was applied to induce the apoptosis of human umbilical vein endothelial cells(HUVECs).The concentration of nitric oxide(NO),endothelial nitric oxide synthase(eNOS)and inducible NOS(iNOS)were measured by assay kits.Western blot and real-time polymerase chain reaction(RT-PCR)were used to detect the expression of iNOS,eNOS,b-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),estrogen receptor(ER)αand ERβ.Also,small interfering RNA(siRNA)was involved to confirm whether the protective effects of LWDHF was medicated by ERs.In vivo,the female rats were ovariectomized to establish postmenopausal vascular injury model.Then the model rats were divided into three groups and treated with saline,estradiol and LWDHF respectively.The concentration of NO and NOS in serum were measured by assay kits,and the expression of Bax,Bcl-2,ERαand ERβwere detected by western blot and immunohistochemistry.RESULTS:In vitro study,LWDHF significantly protected HUVECs from H_(2)O_(2)-induced apoptosis,with the increase of Bcl-2 and the decrease of Bax.The treatment with LWDHF inhibited concentration of NO and iNOS,and upregulated the expression of eNOS,ERαand ERβ.In addition,ERαsiRNA could block the protective effects of LWDHF,while ERβsiRNA showed little influence.In vivo,the treatment with LWDHF suppressed the vascular injury and reduced the level of NO and NOS.LWDHF increased the expression of Bcl-2,ERαand ERβ,as well as inhibiting the Bax expression.CONCLUSION:LWDHF could improve endothelial function and protect HUVECs from apoptosis via increasing the expression of ERα.展开更多
The crude drug of Liuwei Dihuang was pulverized to nano particles to improve its bioavailability. The appropriate technique parameters were studied. Paeonol, typical marker of Liuwei Dihuang , was extracted with organ...The crude drug of Liuwei Dihuang was pulverized to nano particles to improve its bioavailability. The appropriate technique parameters were studied. Paeonol, typical marker of Liuwei Dihuang , was extracted with organic solveat in ultrasonic and its content was determined by HPLC. The appropriate techrdques parameters are as follows ： rotating speed control 1200 r/ min , grinding time control 50min and mass percent concentration control 3.8% . The experimental results show that the average particle diameter is 161.9 nm and the great majority of the plant cell wall is broken into pieces after nano pulverization. The extraction efficiency of paeonol is increased by 23.5% .展开更多
OBJECTIVE Cranial radiotherapy is clinically used in the treatment of brain tumors;however,the consequent cognitive and emotional dysfunctions seriously impair the life quality of patients.LW-AFC,an active fraction co...OBJECTIVE Cranial radiotherapy is clinically used in the treatment of brain tumors;however,the consequent cognitive and emotional dysfunctions seriously impair the life quality of patients.LW-AFC,an active fraction combination extracted from classical traditional Chinese medicine prescription Liuwei Dihuang decoction,can improve cognitive and emotional dysfunctions in many animal models;however,the protective effect of LW-AFC on cranial irradiation-induced cognitive and emotional dysfunctions has not been reported.Recent studies indicate that impairment of adult hippocampal neurogenesis(AHN)and alterations of the neurogenic microenvironment in the hippocampus constitute critical factors in cognitive and emotional dysfunctions following cranial irradiation.Here,our research further investigated the potential protective effects and mechanisms of LW-AFC on cranial irradiation-induced cognitive and emotional dysfunctions in mice.METHODS LW-AFC(1.6 g·kg^(-1))was intragastrically administered to mice for 14 d before cranial irradiation(7 Gyγ-ray).AHN was examined by quantifying the number of proliferative neural stem cells and immature neurons in the dorsal and ventral hippocampus.The contextual fear conditioning test,open field test,and tail suspension test were used to assess cognitive and emotional functions in mice.To detect the change of the neurogenic microenvironment,colorimetry and multiplex bead analysis were performed to measure the level of oxidative stress,neurotrophic and growth factors,and inflammation in the hippocampus.RESULTS LW-AFC exerted beneficial effects on the contextual fear memory,anxiety behavior,and depression behavior in irradiated mice.Moreover,LW-AFC increased the number of proliferative neural stem cells and immature neurons in the dorsal hippocampus,displaying a regional specificity of neurogenic response.For the neurogenic microenvironment,LW-AFC significantly increased the contents of superoxide dismutase,glutathione peroxidase,glutathione,and catalase and decreased the content of malondialdehyde in the hippocampus of irradiated mice,accompanied by the increase in brain-derived neurotrophic factor,insulin-like growth factor-1,and interleukin-4 content.Together,LW-AFC improved cognitive and emotional dysfunctions,promoted AHN preferentially in the dorsal hippocampus,and ameliorated disturbance in the neurogenic microenvironment in irradiated mice.CONCLUSION LW-AFC ameliorates cranial irradiation-induced cognitive and emotional dysfunctions,and the underlying mechanisms are mediated by promoting AHN in the dorsal hippocampus and improving the neurogenic microenvironment.LW-AFC might be a promising therapeutic agent to treat cognitive and emotional dysfunctions in patients receiving cranial radiotherapy.展开更多
Chronic intermittent hypoxia(CIH),a principal pathophysiological aspect of obstructive sleep apnea(OSA),is associated with cognitive deficits.Clinical evidence suggests that a combination of Shengmaisan and Liuwei Dih...Chronic intermittent hypoxia(CIH),a principal pathophysiological aspect of obstructive sleep apnea(OSA),is associated with cognitive deficits.Clinical evidence suggests that a combination of Shengmaisan and Liuwei Dihuang Decoctions(SMS-LD)can enhance cognitive function by nourishing yin and strengthening the kidneys.This study aimed to assess the efficacy and underlying mechanisms of SMS-LD in addressing cognitive impairments induced by CIH.We exposed C57BL/6N mice to CIH for five weeks(20%-5%O_(2),5 min/cycle,8 h/day)and administered SMS-LD intragastrically(15.0 or 30 g·kg^(-1)·day)30 min before each CIH session.Additionally,AG490,a JJanus kinase 2(JAK2)inhibitor,was administered via intracerebroventricular injection.Cognitive function was evaluated using the Morris water maze,while synaptic and mitochondrial structures were examined by transmission electron microscopy.Oxidative stress levels were determined using DHE staining,and the activation of the erythropoietin(ER)/ER receptor(EPOR)/JAK2 signaling pathway was analyzed through immunohistochemistry and Western blotting.To further investigate molecular mechanisms,HT22 cells were treated in vitro with either SMS-LD medicated serum alone or in combination with AG490 and then exposed to CIH for 48 h.Our results indicate that SMS-LD significantly mitigated CIH-induced cognitive impairments in mice.Specifically,SMS-LD treatment enhanced dendritic spine density,ameliorated mitochondrial dysfunction,reduced oxidative stress,and activated the EPO/EPOR/JAK2 signaling pathway.Conversely,AG490 negated SMS-LD’s neuroprotective and cognitive improvement effects under CIH conditions.These findings suggest that SMS-LD’s beneficial impact on cognitive impairment and synaptic and mitochondrial integrity under CIH conditions may predominantly be attributed to the activation of the EPO/EPOR/JAK2 signaling pathway.展开更多
Objective To predict the molecular mechanism of Dihuang(Rehmanniae Radix)in the treatment of diabetic nephropathy(DN)complicated with depression based on network pharmacology.Methods The components of Dihuang(Rehmanni...Objective To predict the molecular mechanism of Dihuang(Rehmanniae Radix)in the treatment of diabetic nephropathy(DN)complicated with depression based on network pharmacology.Methods The components of Dihuang(Rehmanniae Radix)were identified from the Integrated Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP),Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and relevant literature.The component targets were detected by combining the SwissTargetPrediction and Pub Chem databases.Disease targets were collected from the Therapeutic Target Database(TTD),Dis Ge NET,and Ensembl databases with“diabetic nephropathy”and“depression”as keywords.The disease-component targets were mapped using Venny 2.1.0 to obtain potential targets.A protein-protein interaction(PPI)network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database and Cytoscape 3.7.2.The co-expression genes of the key targets were collected based on the COXPRESdb 7.3.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed for potential targets using R language.Target-component docking was verified and evaluated using Discovery Studio 4.5.Results According to the databases and literature reports,Dihuang(Rehmanniae Radix)contained 65 active components,and had 155 related targets for the treatment of DN complicated with depression.PPI screening showed that the key targets included serine/threonine protein kinase 1(AKT1),signal transducer and activator transcription 3(STAT3),interleukin 6(IL-6),mitogen-activated protein kinase 1(MAPK1),and vascular endothelial growth factor A(VEGFA),etc.GO enrichment analysis mainly involved biological processes,such as lipid metabolism,protein secretion regulation,cell homeostasis,and phosphatidylinositol 3 kinase activity.KEGG pathway enrichment analysis included the role of the AGE-RAGE signaling pathway in diabetic complements,insulin resistance(IR),neurotrophin signal path,Toll-like receptor signaling pathway,relaxin signaling pathway,epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs),etc.Molecular docking showed that the target had high affinity for stachyose,manninotriose,verbascose,nigerose,etc.Conclusion Based on network parmacology,this study preliminarily predict the effects of Dihuang(Rehmanniae Radix)in treating DN complicated with depression by regulating inflammation,glucose metabolism,nution nerve,etc.展开更多
Objective To explore the transitive regularity of holistic constituents from the crude slices of the medicinal raw materials(MCS)to the formula granules(FG),fufang decoction(FD),and finally,the concentrated pills(CP)o...Objective To explore the transitive regularity of holistic constituents from the crude slices of the medicinal raw materials(MCS)to the formula granules(FG),fufang decoction(FD),and finally,the concentrated pills(CP)of Liuwei Dihuang Fufang(六味地黄复方,LWDHF).Methods Samples for MCS,FG,FD,and CP of LWDHF were obtained,and a fingerprint data-base was established using high-performance liquid chromatography(HPLC),by separating the samples in an XB-C18 column and analyzing the transitive regularity of components us-ing the total quantum statistical moment(TQSM),including total quantum zero moment(AUCT),total quantum first moment(MRTT),total quantum second moment(VRTT),and its similarity approach.The AUCT,MRTT,and VRTT were calculated based on the representative HPLC chromatograms of FG,FD,and CP of LWDHF.Results AUCT of FG,FD,and CP of LWDHF was 71804,46553,and 144646μV·s,respectively;MRTT was 14.43,14.54,and 18.85 min,respectively;and VRTT was 106.98,112.84,and 269.12 min^(2),respectively.Comparing the similarity of FG/FD,FG/CP and FD/CP of LWDHF,the TQSM similarity values were 98.66%,76.62%,and 75.37%,respectively,whereas the tradi-tional similarity evaluation values were 98.68%,85.43%,and 85.60%,respectively.Conclusion The results perform little distinction in the total composition between FG and FD,whereas some distinction existed between FD and CP.Experimental evidence,therefore indicates that FG could be used as the alternative of MCS in clinical applications.展开更多
OBJECTIVE To investigate age-related functional change of hypothalamus-pituitary-adrenal(HPA)axis in senescence accelerated mouse(SAM)and the effects of Liuwei Dihuang decoction(LW)and its San-bu(three tonics)and San-...OBJECTIVE To investigate age-related functional change of hypothalamus-pituitary-adrenal(HPA)axis in senescence accelerated mouse(SAM)and the effects of Liuwei Dihuang decoction(LW)and its San-bu(three tonics)and San-xie(three eliminators)components on the function of HPA axis.METHODS Male SAM-resistance/1(SAMR1)and SAM-prone/8(SAMP8)at the ages of 6and 12 months old were used.SAMP8 were orally administered with LW,three tonics and three eliminators at the doses of 10,6.4and 3.6g·kg-1·d-1,respectively,for consecutive 60 d.Serum level of CORT was assayed with ELISA method.The levels of hypothalamic CRH and pituitary ACTH was determined with radioimmunoassay.RESULTS The levels of hypothalamic CRH,pituitary ACTH and serous CORT were much higher in 6 and 12 months old SAMP8 than those in age-matched SAMR1,which suggested the abnormal function of HPA axis in SAMP8.Oral administration of LW and three tonics significantly decreased the level of hypothalamic CRH of 6 and 12 months old SAMP8,and reduced the levels of pituitary ACTH and serous CORT of 6 month old SAMP8.Three eliminators significantly decreased the level of hypothalamic CRH of 6 months old SAMP8.The results indicated that oral administration of LW,three tonics and three eliminators improved the function of HPA axis of SAMP8.CONCLUSION The results showed the hyperactivity of HPA axis of SAMP8,and LW improved the hyperactivity of 6 month old SAMP8.Three tonics and three eliminators had similar effects as LW,which had better effect after compatibility.展开更多
OBJECTIVE To reveal the under mechanism of how Liuwei Dihuang(LWDH)inhibits the phenotypic con⁃version of VSMCs.METHODS 24 ApoE-/-mice were divided into 4 groups:sham group,model group,E2 group,and LWDH group.Six C57B...OBJECTIVE To reveal the under mechanism of how Liuwei Dihuang(LWDH)inhibits the phenotypic con⁃version of VSMCs.METHODS 24 ApoE-/-mice were divided into 4 groups:sham group,model group,E2 group,and LWDH group.Six C57BN/L6 mice were used as control group.The primary VSMCs were divided into control group,model group,E2 group,LWDH group,LWDH+MPP group,and LWDH+PHTPP group with or without control siRNA,ERαsiRNA,ERβsiRNA,and myocardin siRNA.Oil red staining was used to evaluate the lipid deposition in the cardiac aorta.Serum chemistry analysis to test serum TG,TC,LDL,and HDL.Immunofluorescence staining was used to testα-SMA,osteopontin and F-actin.Immunohistochemical staining was performed to check out the myocardin in the cardiac aorta.The mRNA levels ofα-SMA,osteopontin,ERα,ERβ,SRC3 and myocardin were detected by real time-PCR,and the protein expression levels of them were detected by Western blotting.Co-immunoprecipitation was proceeded to test the interaction between ERαand SRC3 and SRC3 and myocardin.Flow cytometry was used to check out the cell cycle.Wound healing assay and Transwell were managed to evaluate the migration capacity of VSMCs.RESULTS In vivo administration of LWDH suppressed atherosclerotic symptoms,decreases phenotypic marker of vascular endothelial cell,and increases phenotypic marker of VSMC in ovariectomized ApoE-/-female mice.Moreover,LWDH significantly increased the mRNA and protein expression levels of ERα,ERβ,SRC3 and myocardin in the cardiac aorta of ovariecto⁃mized ApoE-/-female mice.In vitro,LWDH altered cell cycle and reduced the elevated cyclinD protein expression migra⁃tion capacity and in the model VSMCs.In addition,LWDH inhibited phenotypic conversion and promoted the expression of ER,SRC3,and myocardin of the primary VSMC phenotypic conversion model.Inhibition of ERαalmost completely eliminated the impacts of LWDH onα-SMA and osteopontin.Furthermore,LWDH promoted the interaction between ERαand SRC3 and up-regulated the co-activation of SRC3 and myocardin.CONCLUSION LWDH could inhibit the pheno⁃typic conversion of VSMCs in vitro and in vivo by increasing the activity of myocardin through up-regulating the expres⁃sion of ERαand promoting the interaction between ERαand SRC3.Our research reveals the under mechanism of how LWDH inhibits the phenotypic conversion of VSMCs.展开更多
OBJECTIVE To investigate the effects of LW-AFC,a new formula derived fromLiuwei Dihuang decoction,on gut microbiota and the behavior of learning and memory of SAMP8 mice,a mouse model of Alzheimer Disease(AD),and iden...OBJECTIVE To investigate the effects of LW-AFC,a new formula derived fromLiuwei Dihuang decoction,on gut microbiota and the behavior of learning and memory of SAMP8 mice,a mouse model of Alzheimer Disease(AD),and identify the specific intestinal microbiota correlating with cognitive ability.METHODS Morris-water maze test,novel object recognition test and shuttle-box test were conducted to observe the ability of learning and memory.16S rRNA amplicon sequencing(Illumina,San Diego,CA,USA)was employed to investigate gut microbiota.RESULTS The treatment of LW-AFC improved cognitive impairments of SAMP8 mice,including spatial learning and memory ability,active avoidance response,and object recognition memory capability.Our data indicated that there were significantly 8 increased and 12 decreased operational taxonomic units(OTUs)in the gut microbiota of SAMP8 mice compared with senescence accelerated mouse resistant 1(SAMR1) strains,the control of SAMP8 mice.The treatment of LW-AFC altered 22(16 increased and 6 decreased)OTUs in SAMP8 mice and among them,15 OTUs could be reversed by LW-AFC treatment resulting in a microbial composition similar to that of SAMR1 mice.We further showed that there were7(3 negative and 4 positive correlation)OTUs significantly correlated with all the three types of cognitive abilities,at the order level,including Bacteroidales,Clostridiales,Desulfovibrionales,CW040,and two unclassified orders.LW-AFC had influences on bacterial taxa correlated with the abilities of learning and memory in SAMP8 mice and restored them to SAMR1 mice.CONCLUSION The effects of LW-AFC on improving cognitive impairments of SAMP8 mice might be via modulating intestinal microbiome and LW-AFC could be used as a potential anti-AD agent.展开更多
The aplastic anemia mice model was established in this study.BALB/c mice shall be treated with whole body irradiation with 60 Co-γradiation(5.5Gy,1.1Gy/min×5 min).then within 4 h,DBA/2 mice were injected lymphoc...The aplastic anemia mice model was established in this study.BALB/c mice shall be treated with whole body irradiation with 60 Co-γradiation(5.5Gy,1.1Gy/min×5 min).then within 4 h,DBA/2 mice were injected lymphocyte suspension 1×106 cells/mouse through caudal vein.Grouping of testing animals:Normal control mice were healthy C57BL/6 mice without AA modeling.AA control group mice were exposed to radiation and cell transfusion and had no treatment with either CSA or XDD.CSA group mice received daily lavage with 0.027g/kg(0.1ml/10g)of CSA whereas XDD group mice received daily lavage with 19.5g/kg of XDD.The experimental result indicated CSA and XDD lavage mice had significantly higher platelet count andΔΨm than AA mice(P<0.05).Levels of Cyt C,PS and Ca2+were significantly lower in CSA and XDD groups compare with AA group.More specifically,compared to CSA group,XDD group also had lower level ofΔΨm and higher level of Cyt C and Ca2+(both P<0.05).Both CSA and XDD treatment reduced Bak and Bax levels significantly compared to AA mice.However,XDD treatment still showed higher expressions than CSA(P<0.05).CSA and XDD treatment increased the levels of Pro-apoptotic protein expressions(caspase-8,caspase-3,caspase-9).XDD showed less potent effect than CSA in increasing these protein expressions(all P<0.05).Therefore,we hypothesized XDD was possible to increase platelet number and prevent its apoptosis in immune-induced AA via the mitochondrial pathway.展开更多
Objective:A meta-analysis was used to systematically study the correlation between inflammatory response and diabetic nephropathy based on Shenqi Dihuang Decoction.Methods:The RCT literatures related to the efficacy a...Objective:A meta-analysis was used to systematically study the correlation between inflammatory response and diabetic nephropathy based on Shenqi Dihuang Decoction.Methods:The RCT literatures related to the efficacy and inflammatory response of Shenqi Dihuang Decoction in the treatment of diabetic nephropathy in Chinese and English databases were searched.The time limit was from the establishment of the database to February 2020.Literature screening and data extraction were performed according to the criteria for inclusion and exclusion.The evaluator's manual 5.1.0 was used to evaluate the risk of bias in the final included literature.Meta-analysis was performed using RevMan 5.3 software.Comparing western medicine treatment and Shenqi Dihuang decoction to inflammatory factors:interleukin-6(IL-6)Interleukin-8(IL-8),tumor necrosis factor-α(TNF-α),C-reactiveprotein(CRP),intercellular adhesion molecule-1(MCP-1),and monocyte chemotactic protein-1(ICAM-1)and efficacy indicators:the impact of urine microalbumin(mALB)and clinical efficacy.Results:A total of 11 related research reports were finally included,of which 9 evaluated IL-6[SMD=-1.09,95%CI(-1.57,-0.61),Z=4.43,P<0.00001];5 Item evaluated IL-8[SMD=-0.91,95%CI(-1.44,-0.37),Z=3.33,P=0.0009<0.05];7 items evaluated TNF-[SMD=-0.97,95%CI(-1.49,-0.45),Z=3.63,P=0.0003<0.05];9 items evaluated CRP[SMD=-1.40,95%CI(-1.89,-0.90),Z=5.49,P<0.00001];2 items evaluated MCP-1[SMD=-0.71,95%CI(-1.00,-0.43),Z=4.95,P<0.00001];1 item was ICAM-1 Evaluation was performed[SMD=-0.98,95%CI(-1.38,-0.58),Z=4.82,P<0.00001];6 items used mALB as the efficacy index[SMD=-1.85,95%CI(-2.65,-1.05),Z=4.52,P<0.00001];9 items evaluated the clinical efficacy,[OR=4.45,95%CI(2.96,6.69),Z=7.17,P<0.00001].Conclusion:Shenqi Dihuang Decoction was used in patients with diabetic nephropathy.Compared with the western medicine treatment group,the levels of IL-6,IL-8,TNF-α,CRP,MCP-1,ICAM-1and inflammatory factors were significantly reduced.The effect is significantly increased.It is suggested that Shenqi Dihuang Decoction has better anti-inflammatory response than diabetic nephropathy than western medicine alone.展开更多
BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explor...BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explore the effects of Zhibai dihuang pills and gonadotropin-releasing hormone analogue(GnRHa)on growth and ovarian function in girls with precocious puberty.METHODS The clinical data of 84 adolescent girls with precocious puberty and rapidly progressive puberty from February 2017 to August 2023 were retrospectively analyzed.Girls were divided into a control group and an observation group,with 42 cases in each group.The control group received diet intervention combined with GnRHa treatment,while the observation group received diet intervention combined with Zhibai dihuang pills+GnRHa treatment.Outcomes such as clinical efficacy,growth indicators,ovarian function,and adverse reactions were compared between the two groups.RESULTS The observation group showed superior clinical efficacy compared to the control group(P<0.05).Prior to the intervention,no significant differences were found in growth or ovarian function between the groups(P>0.05).Post-intervention,the observation group exhibited significantly lower rates in growth,height,and bone age,along with reduced levels of progesterone,testosterone,estradiol,prolactin,luteinizing hormone,and follicle-stimulating hormone compared to the control group(P<0.05).The incidence of adverse reactions was similar across both groups(P>0.05).CONCLUSION Combining Zhibai dihuang pills with GnRHa and dietary intervention effectively improves growth,enhances ovarian function,and minimizes adverse reactions in adolescent girls with precocious and rapidly progressive puberty.展开更多
Objective:It has been documented that ezrin/radixin/moesin(ERM)phosphorylation by the p38 mitogen-activated protein kinase(MAPK),Rho/ROCK,and protein kinase C(PKC)pathways leads to filamentous actin(F-actin)reorganiza...Objective:It has been documented that ezrin/radixin/moesin(ERM)phosphorylation by the p38 mitogen-activated protein kinase(MAPK),Rho/ROCK,and protein kinase C(PKC)pathways leads to filamentous actin(F-actin)reorganization and microvascular endothelial cell hyperpermeability.In this study,we investigated the effects of Xijiao Dihuang Decoction combined with Yinqiao Powder(XDY)on influenza virus(IV)-induced F-actin restructuring and ERM phosphorylation regulated by the Rho/Rho kinase 1(ROCK),p38 MAPK,and PKC signaling pathways in pulmonary microvascular endothelial cells(PMVECs).Methods:Serum containing XDY(XDY-CS;13.8 g/kg)was acquired using standard protocols for serum pharmacology.Primary PMVECs were obtained from male Wistar rats and cultured.After adsorption of IV A(multiplicity of infection,0.01)for 1 h,medium with 20%XDY-CS was added to the PMVECs.The distributions of F-actin and phosphorylated ERM were determined by confocal microscopy,and F-actin expression was measured by flow cytometry.The expression levels of ROCK1,phosphorylated myosin phosphatase target-subunit(p-MYPT),phosphorylated MAPK kinase,phosphorylated p38(p-p38),phosphorylated PKC(p-PKC),and phosphorylated ERM(p-ERM)were determined by western blotting.Results:F-actin reorganization in IV-infected PMVECs was reversed by XDY-CS treatment,which was accompanied by reduced p-ERM production.The p-ERM protein accumulated at plasma membrane of PMVECs infected with IV,which was also inhibited by XDY-CS treatment.展开更多
Objective:To study the effect of Baihe Dihuang Decoction in improving anxiety and its mechanism of action.Methods: Male mice were randomly divided into 5 groups: blank control group, Baihe Dihuang Decoction high, medi...Objective:To study the effect of Baihe Dihuang Decoction in improving anxiety and its mechanism of action.Methods: Male mice were randomly divided into 5 groups: blank control group, Baihe Dihuang Decoction high, medium, low-dose group and diazepam group. After continuous intragastric administration for 14 d, the behavioral test of the mouse elevated plus maze experiment and opening test was performed. The brain tissue GABA and Glu content was measured by immunosorbent assay (ELISA).Results: Compared with the blank control group, the middle and high doses of Baihe Dihuang Decoction could increase the time and frequency of movement of the mice in the open cross labyrinth in the open arm and increase the number of times that the mouse entered the central area in the opening test. The anti-anxiety effect also showed an increase in the brain tissue GABA content in mice, ignificantly decreased Glu contents in mice.Conclusion: Baihe Dihuang Decoction has some anxiolytic effect, and anti-anxiety effect may be related to increasing brain tissue GABA content, decreased Glu contents in mice.展开更多
文摘Objective:To evaluate the efficacy and symptom scores of early diabetic nephropathy(DKD)treated with modified Shenqi Dihuang Decoction.Methods:82 patients with early DKD who visited the hospital from February 2023 to February 2025 were randomly divided into two groups by drawing.Group A received modified Shenqi Dihuang Decoction+SGLT2 inhibitor,while Group B received SGLT2 inhibitor only.The efficacy,symptom scores,blood glucose,and renal function were compared between the two groups.Results:The efficacy of Group A was higher than that of Group B in the treatment of early DKD(P<0.05).The DKD symptom scores of Group A were lower than those of Group B(P<0.05).The fasting blood glucose(FBG),2-hour postprandial blood glucose(PBG),and glycated hemoglobin(HbA1c)of Group A were better than those of Group B(P<0.05).The serum creatinine(SCr),blood urea nitrogen(BUN),and urinary albumin excretion rate(UAER)of Group A were also better than those of Group B.Conclusion:The combination of modified Shenqi Dihuang Decoction and SGLT2 inhibitor dapagliflozin has excellent efficacy in the treatment of early DKD,which can improve renal function,reduce DKD symptoms,and stabilize blood glucose levels.
基金supported by the Hebei Provincial Administration of Traditional Chinese Medicine 2022 Chinese medicine research program mandatory subject(2021.No.12)Hebei famous traditional Chinese medicine inheritance studio construction project(2024.No.37)Yunnan Fundamental Research Projects(grant No.202501AT070266).
文摘Background:Diabetic kidney disease(DKD)is a major cause of end-stage renal disease,with limited effective treatment options currently available.Shenqi Dihuang Decoction(SQDH)has demonstrated clinical efficacy in managing DKD;however,the metabolic mechanisms responsible for its therapeutic effects remain unclear.Methods:We established a DKD mouse model and treated the mice with SQDH to investigate its effects on renal function and tissue pathology.To explore the metabolic mechanisms,we conducted non-targeted metabolomics to identify differential metabolites in the renal tissues of DKD mice and the associated metabolic pathways affected by SQDH.Additionally,we performed RT-qPCR and Western blot analyses to assess the effects of SQDH on the expression of key genes and proteins within the targeted pathways.To further evaluate SQDH’s therapeutic effects,we measured oxidative stress markers and inflammatory factors,examining its antioxidant and anti-inflammatory properties in DKD.Results:SQDH treatment improved body weight and blood glucose levels in DKD mice.It also restored renal function,as indicated by improved 24h-UTP,serum creatinine,and blood urea nitrogen levels,and alleviated renal tissue pathology associated with DKD.Metabolomic analysis showed that SQDH primarily regulates glycerophospholipid metabolism,particularly by increasing phosphatidylcholine(PC)levels and decreasing lysophosphatidylcholine(LPC)levels.RT-qPCR and Western blot analyses revealed that SQDH upregulated LPCAT expression and downregulated PLA2G expression.Additionally,SQDH enhanced the activities of superoxide dismutase and glutathione peroxidase,reduced reactive oxygen species,4-hydroxy-2-nonenal,and malondialdehyde levels,and decreased the levels of inflammatory cytokines IL-1β,IL-6,and TNF-α.Conclusion:Our findings confirm that SQDH protects against DKD by regulating glycerophospholipid metabolism,restoring the balance of PC and LPC,inhibiting inflammatory responses,and reducing oxidative stress.
文摘Objective:To evaluate the therapeutic effect of Shenqi Dihuang Decoction combined with calcium dobesilate on patients with diabetic nephropathy(DKD).Methods:90 patients with DKD who visited the hospital from March 2024 to March 2025 were selected as samples and randomly divided into two groups.Group A was treated with Shenqi Dihuang Decoction combined with calcium dobesilate,while Group B was treated with calcium dobesilate alone.The efficacy,syndrome scores,blood glucose levels,and renal function indicators were compared between the two groups.Results:The efficacy of DKD treatment in Group A was higher than that in Group B(P<0.05).The syndrome scores in Group A were lower than those in Group B(P<0.05).The 2-hour postprandial blood glucose(PBG),fasting blood glucose(FBG),and glycated hemoglobin(HbA1c)levels in Group A were lower than those in Group B(P<0.05).The serum creatinine(SCr),urinary microalbumin,urinary albumin excretion rate(UAER),and β2-microglobulin(β2-MG)levels in Group A were also lower than those in Group B(P<0.05).Conclusion:The treatment of DKD with Shenqi Dihuang Decoction combined with calcium dobesilate can stabilize blood glucose levels,improve renal function,and reduce syndrome scores,which is highly effective and feasible.
基金supported by funding from the Canadian Institutes of Health Research(CIHR)-China-Canada Joint Health Research Initiative(CCI-92219)
文摘OBJECTIVE： To investigate the anti-inflammatory, anti-oxidative stress, and adipokine-ameliorating effects of Liuwei Dihuang （LWDH）, a traditional Chinese herbal formula, in obese rats. METHODS： After 2 weeks of acclimation with free access to regular rodent chow and water, obese-prone-caesarean-derived （OP-CD） rats were fed a modified AIN-93G diet containing 60% energy from fat. Treatment was performed twice daily by gavage feeding with 500, 1 500, or 3 500 mg/kg body weight LWDH suspended in water （n=12 rats per group）. Twelve obese-resistant-CD （OR-CD） rats were fed the atherogenic diet and gavaged with water, and served as the normal control. Blood biomarkers of inflammation, oxidative stress and adiponectin were measured post-sacrifice and used to determine the treatment effect of LWDH and assess the suitability of OR/OP-CD rats for studying these parameters. RESULTS： After 9 weeks of treatment, LWDH lowered serum C-reactive protein （CRP） and tumour necrosis factor-α （TNF-α） levels. Serum interleukin-6 （IL-6） levels showed a tendency towards reduction, but were not significantly different from the OP-CD control. Liver superoxide dismutase （SOD） activity was increased in response to all three doses of LWDH, while the levels of reduced （GSH） and oxidized glutathione （GSSG） and thiobarbituric acid reactive substances （TBARS） were unchanged. Serum adiponectin levels were increased in response to oral administration of LWDH at the dose of either 500 or 1 500 mg/kg body weight. In addition, comparisons between OR-CD and OP-CD rats revealed differential, and for some biomarkers, conflicting characteristics of high-fat diet-fed OP-CD rats in reference to obese human subjects in terms of inflammatory and oxidative stress biomarkers and circulating adiponectin levels. CONCLUSION： The results show, for the first time, the anti-inflammatory, anti-oxidative stress and adiponectin-ameliorating effects of LWDH in obese rats. The suitability of the OP-JOP-CD rat model as a research tool to study inflammation, oxidative stress, and adipokine production requires further investigation.
基金Supported by the Chinese National Natural Science Foundation(No.81160531)Jiangxi Natural Science Foundation(No.20161BAB205223,20192ACBL21032)Scientific Research Fund of Jiangxi Provincial Education Department(No.GJJ180648)
文摘OBJECTIVE:To investigate if the Liuwei Dihuang pill(LWDHP)can inhibit metastasis to the liver and lungs in mice bearing triple-negative breast cancer(TNBC),and the molecular mechanism underpinning this action.METHODS:Ninety-nine TNBC bearing-mice were distributed randomly to five groups:control(Con),paclitaxel(PTX),low-dose LWDHP(LLP,2.3 g·kg^-1·d^-1),middle-dose LWDHP(MLP,4.6 g·kg^-1·d^-1)and high-dose LWDHP(HLP,9.2 g·kg^-1·d^-1).The LWDHP were administered(p.o.)to the agonal stage.The morphology of BC cells was observed by hematoxylin&eosin staining.Expression of axin-2,β-catenin,T cell factor(TCF),cyclin-D1 and vascular endothelial growth factor(VEGF)was detected by western blotting or immunofluorescence.β-catenin/TCF-1 interaction was measured using a co-immunoprecipitation assay.RESULTS:After LWDHP treatment,metastasis of BC cells to the lungs and liver was inhibited,expression of axin-2 was increased,expression of TCF-1,β-catenin,cyclin-D1 and VEGF was decreased,andβ-catenin/TCF-1 interaction was disrupted.CONCLUSION:The LWDHP could inhibit metastasis of BC cells to the liver and lungs.The molecular mechanism underlying this action may be regulation of protein expression andβ-catenin/TCF-1 interactions in the Wnt pathway.
文摘AIM To investigate the inhibitory effect of Liuwei Dihuang Pill(LDP) on gastric tumorigenesis induced by N-methyl-N-nitrosourea(MNU) in diabetic mice.METHODS Four-week-old mice were divided into four groups: A, 12 db/m mice treated with MNU and saline, as the non-diabetic control; B, 12 db/db mice treated with MNU and saline, as the diabetic control; C, 12 db/db mice treated with MNU and metformin, as the positive control; and D, 12 db/db mice treated with MNU and LDP. MNU was administrated for 20 wk to induce gastric carcinogenesis. LDP was administrated for 10 wk for improvement of insulin resistance. Body weight and food intake were measured every week. Blood samples were collected for assays of fasting blood glucose, insulin, insulin-like growth factor(IGF)-1, adiponectin and leptin. Stomach tissues were collected for histopathological analysis, immunohistochemical staining of Ki67, quantitative reverse transcriptionpolymerase chain reaction and western blotting. RESULTS The incidence of MNU-induced gastric dysplasia was significantly elevated in diabetic(db/db) mice relative to the control(db/m) mice. The incidence of gastricdysplasia was significantly reduced by LDP with suppression of cell proliferation, as demonstrated by a decrease in Ki67 staining. Hyperglycemia, hyperinsulinemia and serum IGF-1 were inhibited by LDP. Expression of IGF-1 and insulin receptor m RNAs was decreased, phosphorylation of IGF-1 receptor and AKT protein was reduced in the stomach tissues by LDP. In addition, adiponectin was increased and leptin was decreased in the serum by LDP. CONCLUSION LDP decreased risk of gastric dysplasia in type 2 diabetic mice by down-regulation of IGF and insulin activity and correction of adipokines disorders.
基金Supported by the National Natural Science Foundation of China(No.8177319081774029)+2 种基金Qing Lan Project of Colleges and Universities in Jiangsu,the Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica(No.JKLPSE201809)the Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions(No.JKLPSE201605)Jiangsu Provincial Special Program of Medical Science(No.BE2017610)。
文摘OBJECTIVE:To evaluate the efficacy of Liuwei Dihuang formula(六味地黄方,LWDHF)on endothelial cells,and to study the mechanism behind the action of modulating expression of estrogen receptors.METHODS:Hydrogen peroxide(H_(2)O_(2))was applied to induce the apoptosis of human umbilical vein endothelial cells(HUVECs).The concentration of nitric oxide(NO),endothelial nitric oxide synthase(eNOS)and inducible NOS(iNOS)were measured by assay kits.Western blot and real-time polymerase chain reaction(RT-PCR)were used to detect the expression of iNOS,eNOS,b-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),estrogen receptor(ER)αand ERβ.Also,small interfering RNA(siRNA)was involved to confirm whether the protective effects of LWDHF was medicated by ERs.In vivo,the female rats were ovariectomized to establish postmenopausal vascular injury model.Then the model rats were divided into three groups and treated with saline,estradiol and LWDHF respectively.The concentration of NO and NOS in serum were measured by assay kits,and the expression of Bax,Bcl-2,ERαand ERβwere detected by western blot and immunohistochemistry.RESULTS:In vitro study,LWDHF significantly protected HUVECs from H_(2)O_(2)-induced apoptosis,with the increase of Bcl-2 and the decrease of Bax.The treatment with LWDHF inhibited concentration of NO and iNOS,and upregulated the expression of eNOS,ERαand ERβ.In addition,ERαsiRNA could block the protective effects of LWDHF,while ERβsiRNA showed little influence.In vivo,the treatment with LWDHF suppressed the vascular injury and reduced the level of NO and NOS.LWDHF increased the expression of Bcl-2,ERαand ERβ,as well as inhibiting the Bax expression.CONCLUSION:LWDHF could improve endothelial function and protect HUVECs from apoptosis via increasing the expression of ERα.
文摘The crude drug of Liuwei Dihuang was pulverized to nano particles to improve its bioavailability. The appropriate technique parameters were studied. Paeonol, typical marker of Liuwei Dihuang , was extracted with organic solveat in ultrasonic and its content was determined by HPLC. The appropriate techrdques parameters are as follows ： rotating speed control 1200 r/ min , grinding time control 50min and mass percent concentration control 3.8% . The experimental results show that the average particle diameter is 161.9 nm and the great majority of the plant cell wall is broken into pieces after nano pulverization. The extraction efficiency of paeonol is increased by 23.5% .
文摘OBJECTIVE Cranial radiotherapy is clinically used in the treatment of brain tumors;however,the consequent cognitive and emotional dysfunctions seriously impair the life quality of patients.LW-AFC,an active fraction combination extracted from classical traditional Chinese medicine prescription Liuwei Dihuang decoction,can improve cognitive and emotional dysfunctions in many animal models;however,the protective effect of LW-AFC on cranial irradiation-induced cognitive and emotional dysfunctions has not been reported.Recent studies indicate that impairment of adult hippocampal neurogenesis(AHN)and alterations of the neurogenic microenvironment in the hippocampus constitute critical factors in cognitive and emotional dysfunctions following cranial irradiation.Here,our research further investigated the potential protective effects and mechanisms of LW-AFC on cranial irradiation-induced cognitive and emotional dysfunctions in mice.METHODS LW-AFC(1.6 g·kg^(-1))was intragastrically administered to mice for 14 d before cranial irradiation(7 Gyγ-ray).AHN was examined by quantifying the number of proliferative neural stem cells and immature neurons in the dorsal and ventral hippocampus.The contextual fear conditioning test,open field test,and tail suspension test were used to assess cognitive and emotional functions in mice.To detect the change of the neurogenic microenvironment,colorimetry and multiplex bead analysis were performed to measure the level of oxidative stress,neurotrophic and growth factors,and inflammation in the hippocampus.RESULTS LW-AFC exerted beneficial effects on the contextual fear memory,anxiety behavior,and depression behavior in irradiated mice.Moreover,LW-AFC increased the number of proliferative neural stem cells and immature neurons in the dorsal hippocampus,displaying a regional specificity of neurogenic response.For the neurogenic microenvironment,LW-AFC significantly increased the contents of superoxide dismutase,glutathione peroxidase,glutathione,and catalase and decreased the content of malondialdehyde in the hippocampus of irradiated mice,accompanied by the increase in brain-derived neurotrophic factor,insulin-like growth factor-1,and interleukin-4 content.Together,LW-AFC improved cognitive and emotional dysfunctions,promoted AHN preferentially in the dorsal hippocampus,and ameliorated disturbance in the neurogenic microenvironment in irradiated mice.CONCLUSION LW-AFC ameliorates cranial irradiation-induced cognitive and emotional dysfunctions,and the underlying mechanisms are mediated by promoting AHN in the dorsal hippocampus and improving the neurogenic microenvironment.LW-AFC might be a promising therapeutic agent to treat cognitive and emotional dysfunctions in patients receiving cranial radiotherapy.
基金This work was supported by the National Natural Science Foundation of China(No.82274617)the Hebei Natural Science Foundation(Nos.H2022423352,H2022423370)+2 种基金the Fundamental Research Funds for the Provisional Universities of Hebei University of Chinese Medicine(No.YXTD2021005)Yanzhao Medical Research Project of Hebei University of Chinese Medicine(No.YZZY2022004)the Graduate Innovation Fund of Hebei University of Chinese Medicine(No.XCXZZSS2021005)。
文摘Chronic intermittent hypoxia(CIH),a principal pathophysiological aspect of obstructive sleep apnea(OSA),is associated with cognitive deficits.Clinical evidence suggests that a combination of Shengmaisan and Liuwei Dihuang Decoctions(SMS-LD)can enhance cognitive function by nourishing yin and strengthening the kidneys.This study aimed to assess the efficacy and underlying mechanisms of SMS-LD in addressing cognitive impairments induced by CIH.We exposed C57BL/6N mice to CIH for five weeks(20%-5%O_(2),5 min/cycle,8 h/day)and administered SMS-LD intragastrically(15.0 or 30 g·kg^(-1)·day)30 min before each CIH session.Additionally,AG490,a JJanus kinase 2(JAK2)inhibitor,was administered via intracerebroventricular injection.Cognitive function was evaluated using the Morris water maze,while synaptic and mitochondrial structures were examined by transmission electron microscopy.Oxidative stress levels were determined using DHE staining,and the activation of the erythropoietin(ER)/ER receptor(EPOR)/JAK2 signaling pathway was analyzed through immunohistochemistry and Western blotting.To further investigate molecular mechanisms,HT22 cells were treated in vitro with either SMS-LD medicated serum alone or in combination with AG490 and then exposed to CIH for 48 h.Our results indicate that SMS-LD significantly mitigated CIH-induced cognitive impairments in mice.Specifically,SMS-LD treatment enhanced dendritic spine density,ameliorated mitochondrial dysfunction,reduced oxidative stress,and activated the EPO/EPOR/JAK2 signaling pathway.Conversely,AG490 negated SMS-LD’s neuroprotective and cognitive improvement effects under CIH conditions.These findings suggest that SMS-LD’s beneficial impact on cognitive impairment and synaptic and mitochondrial integrity under CIH conditions may predominantly be attributed to the activation of the EPO/EPOR/JAK2 signaling pathway.
基金National Natural Science Foundation of China(81960714)Jiangxi University of Chinese Medicine Graduate Innovation Project(JZYC21S52)。
文摘Objective To predict the molecular mechanism of Dihuang(Rehmanniae Radix)in the treatment of diabetic nephropathy(DN)complicated with depression based on network pharmacology.Methods The components of Dihuang(Rehmanniae Radix)were identified from the Integrated Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP),Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and relevant literature.The component targets were detected by combining the SwissTargetPrediction and Pub Chem databases.Disease targets were collected from the Therapeutic Target Database(TTD),Dis Ge NET,and Ensembl databases with“diabetic nephropathy”and“depression”as keywords.The disease-component targets were mapped using Venny 2.1.0 to obtain potential targets.A protein-protein interaction(PPI)network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database and Cytoscape 3.7.2.The co-expression genes of the key targets were collected based on the COXPRESdb 7.3.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed for potential targets using R language.Target-component docking was verified and evaluated using Discovery Studio 4.5.Results According to the databases and literature reports,Dihuang(Rehmanniae Radix)contained 65 active components,and had 155 related targets for the treatment of DN complicated with depression.PPI screening showed that the key targets included serine/threonine protein kinase 1(AKT1),signal transducer and activator transcription 3(STAT3),interleukin 6(IL-6),mitogen-activated protein kinase 1(MAPK1),and vascular endothelial growth factor A(VEGFA),etc.GO enrichment analysis mainly involved biological processes,such as lipid metabolism,protein secretion regulation,cell homeostasis,and phosphatidylinositol 3 kinase activity.KEGG pathway enrichment analysis included the role of the AGE-RAGE signaling pathway in diabetic complements,insulin resistance(IR),neurotrophin signal path,Toll-like receptor signaling pathway,relaxin signaling pathway,epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs),etc.Molecular docking showed that the target had high affinity for stachyose,manninotriose,verbascose,nigerose,etc.Conclusion Based on network parmacology,this study preliminarily predict the effects of Dihuang(Rehmanniae Radix)in treating DN complicated with depression by regulating inflammation,glucose metabolism,nution nerve,etc.
基金Hunan Provincial Natural Science Foundation of China(2019JJ40220 and 2021JJ30514)Hunan Provincial Administration of Traditional Chinese Medicine(2021204and 2021073)+1 种基金Scientific Research Fund of Hunan Provincial Education Department(2021204 and 2021073)Pharmaceutical Open Fund of Domestic First-class Disciplines(Cultivation)of Hunan Province(2018YX11)。
文摘Objective To explore the transitive regularity of holistic constituents from the crude slices of the medicinal raw materials(MCS)to the formula granules(FG),fufang decoction(FD),and finally,the concentrated pills(CP)of Liuwei Dihuang Fufang(六味地黄复方,LWDHF).Methods Samples for MCS,FG,FD,and CP of LWDHF were obtained,and a fingerprint data-base was established using high-performance liquid chromatography(HPLC),by separating the samples in an XB-C18 column and analyzing the transitive regularity of components us-ing the total quantum statistical moment(TQSM),including total quantum zero moment(AUCT),total quantum first moment(MRTT),total quantum second moment(VRTT),and its similarity approach.The AUCT,MRTT,and VRTT were calculated based on the representative HPLC chromatograms of FG,FD,and CP of LWDHF.Results AUCT of FG,FD,and CP of LWDHF was 71804,46553,and 144646μV·s,respectively;MRTT was 14.43,14.54,and 18.85 min,respectively;and VRTT was 106.98,112.84,and 269.12 min^(2),respectively.Comparing the similarity of FG/FD,FG/CP and FD/CP of LWDHF,the TQSM similarity values were 98.66%,76.62%,and 75.37%,respectively,whereas the tradi-tional similarity evaluation values were 98.68%,85.43%,and 85.60%,respectively.Conclusion The results perform little distinction in the total composition between FG and FD,whereas some distinction existed between FD and CP.Experimental evidence,therefore indicates that FG could be used as the alternative of MCS in clinical applications.
基金The project supported by the Key Program of Natural Science Foundation of China(90709012)National Natural Science Foundation of China(30701073)
文摘OBJECTIVE To investigate age-related functional change of hypothalamus-pituitary-adrenal(HPA)axis in senescence accelerated mouse(SAM)and the effects of Liuwei Dihuang decoction(LW)and its San-bu(three tonics)and San-xie(three eliminators)components on the function of HPA axis.METHODS Male SAM-resistance/1(SAMR1)and SAM-prone/8(SAMP8)at the ages of 6and 12 months old were used.SAMP8 were orally administered with LW,three tonics and three eliminators at the doses of 10,6.4and 3.6g·kg-1·d-1,respectively,for consecutive 60 d.Serum level of CORT was assayed with ELISA method.The levels of hypothalamic CRH and pituitary ACTH was determined with radioimmunoassay.RESULTS The levels of hypothalamic CRH,pituitary ACTH and serous CORT were much higher in 6 and 12 months old SAMP8 than those in age-matched SAMR1,which suggested the abnormal function of HPA axis in SAMP8.Oral administration of LW and three tonics significantly decreased the level of hypothalamic CRH of 6 and 12 months old SAMP8,and reduced the levels of pituitary ACTH and serous CORT of 6 month old SAMP8.Three eliminators significantly decreased the level of hypothalamic CRH of 6 months old SAMP8.The results indicated that oral administration of LW,three tonics and three eliminators improved the function of HPA axis of SAMP8.CONCLUSION The results showed the hyperactivity of HPA axis of SAMP8,and LW improved the hyperactivity of 6 month old SAMP8.Three tonics and three eliminators had similar effects as LW,which had better effect after compatibility.
基金National Natural Science Foundation of China(8177319081774029)Jiangsu Provincial Science and Technology Department Social Development Fund(BE2011846)
文摘OBJECTIVE To reveal the under mechanism of how Liuwei Dihuang(LWDH)inhibits the phenotypic con⁃version of VSMCs.METHODS 24 ApoE-/-mice were divided into 4 groups:sham group,model group,E2 group,and LWDH group.Six C57BN/L6 mice were used as control group.The primary VSMCs were divided into control group,model group,E2 group,LWDH group,LWDH+MPP group,and LWDH+PHTPP group with or without control siRNA,ERαsiRNA,ERβsiRNA,and myocardin siRNA.Oil red staining was used to evaluate the lipid deposition in the cardiac aorta.Serum chemistry analysis to test serum TG,TC,LDL,and HDL.Immunofluorescence staining was used to testα-SMA,osteopontin and F-actin.Immunohistochemical staining was performed to check out the myocardin in the cardiac aorta.The mRNA levels ofα-SMA,osteopontin,ERα,ERβ,SRC3 and myocardin were detected by real time-PCR,and the protein expression levels of them were detected by Western blotting.Co-immunoprecipitation was proceeded to test the interaction between ERαand SRC3 and SRC3 and myocardin.Flow cytometry was used to check out the cell cycle.Wound healing assay and Transwell were managed to evaluate the migration capacity of VSMCs.RESULTS In vivo administration of LWDH suppressed atherosclerotic symptoms,decreases phenotypic marker of vascular endothelial cell,and increases phenotypic marker of VSMC in ovariectomized ApoE-/-female mice.Moreover,LWDH significantly increased the mRNA and protein expression levels of ERα,ERβ,SRC3 and myocardin in the cardiac aorta of ovariecto⁃mized ApoE-/-female mice.In vitro,LWDH altered cell cycle and reduced the elevated cyclinD protein expression migra⁃tion capacity and in the model VSMCs.In addition,LWDH inhibited phenotypic conversion and promoted the expression of ER,SRC3,and myocardin of the primary VSMC phenotypic conversion model.Inhibition of ERαalmost completely eliminated the impacts of LWDH onα-SMA and osteopontin.Furthermore,LWDH promoted the interaction between ERαand SRC3 and up-regulated the co-activation of SRC3 and myocardin.CONCLUSION LWDH could inhibit the pheno⁃typic conversion of VSMCs in vitro and in vivo by increasing the activity of myocardin through up-regulating the expres⁃sion of ERαand promoting the interaction between ERαand SRC3.Our research reveals the under mechanism of how LWDH inhibits the phenotypic conversion of VSMCs.
基金supported by National Science and Technology Major Project(2013ZX09508104,2012ZX09301003-002-001)
文摘OBJECTIVE To investigate the effects of LW-AFC,a new formula derived fromLiuwei Dihuang decoction,on gut microbiota and the behavior of learning and memory of SAMP8 mice,a mouse model of Alzheimer Disease(AD),and identify the specific intestinal microbiota correlating with cognitive ability.METHODS Morris-water maze test,novel object recognition test and shuttle-box test were conducted to observe the ability of learning and memory.16S rRNA amplicon sequencing(Illumina,San Diego,CA,USA)was employed to investigate gut microbiota.RESULTS The treatment of LW-AFC improved cognitive impairments of SAMP8 mice,including spatial learning and memory ability,active avoidance response,and object recognition memory capability.Our data indicated that there were significantly 8 increased and 12 decreased operational taxonomic units(OTUs)in the gut microbiota of SAMP8 mice compared with senescence accelerated mouse resistant 1(SAMR1) strains,the control of SAMP8 mice.The treatment of LW-AFC altered 22(16 increased and 6 decreased)OTUs in SAMP8 mice and among them,15 OTUs could be reversed by LW-AFC treatment resulting in a microbial composition similar to that of SAMR1 mice.We further showed that there were7(3 negative and 4 positive correlation)OTUs significantly correlated with all the three types of cognitive abilities,at the order level,including Bacteroidales,Clostridiales,Desulfovibrionales,CW040,and two unclassified orders.LW-AFC had influences on bacterial taxa correlated with the abilities of learning and memory in SAMP8 mice and restored them to SAMR1 mice.CONCLUSION The effects of LW-AFC on improving cognitive impairments of SAMP8 mice might be via modulating intestinal microbiome and LW-AFC could be used as a potential anti-AD agent.
文摘The aplastic anemia mice model was established in this study.BALB/c mice shall be treated with whole body irradiation with 60 Co-γradiation(5.5Gy,1.1Gy/min×5 min).then within 4 h,DBA/2 mice were injected lymphocyte suspension 1×106 cells/mouse through caudal vein.Grouping of testing animals:Normal control mice were healthy C57BL/6 mice without AA modeling.AA control group mice were exposed to radiation and cell transfusion and had no treatment with either CSA or XDD.CSA group mice received daily lavage with 0.027g/kg(0.1ml/10g)of CSA whereas XDD group mice received daily lavage with 19.5g/kg of XDD.The experimental result indicated CSA and XDD lavage mice had significantly higher platelet count andΔΨm than AA mice(P<0.05).Levels of Cyt C,PS and Ca2+were significantly lower in CSA and XDD groups compare with AA group.More specifically,compared to CSA group,XDD group also had lower level ofΔΨm and higher level of Cyt C and Ca2+(both P<0.05).Both CSA and XDD treatment reduced Bak and Bax levels significantly compared to AA mice.However,XDD treatment still showed higher expressions than CSA(P<0.05).CSA and XDD treatment increased the levels of Pro-apoptotic protein expressions(caspase-8,caspase-3,caspase-9).XDD showed less potent effect than CSA in increasing these protein expressions(all P<0.05).Therefore,we hypothesized XDD was possible to increase platelet number and prevent its apoptosis in immune-induced AA via the mitochondrial pathway.
基金Research project of TCM of Jiangxi provincial health and family planning commission(No.2018A004)
文摘Objective:A meta-analysis was used to systematically study the correlation between inflammatory response and diabetic nephropathy based on Shenqi Dihuang Decoction.Methods:The RCT literatures related to the efficacy and inflammatory response of Shenqi Dihuang Decoction in the treatment of diabetic nephropathy in Chinese and English databases were searched.The time limit was from the establishment of the database to February 2020.Literature screening and data extraction were performed according to the criteria for inclusion and exclusion.The evaluator's manual 5.1.0 was used to evaluate the risk of bias in the final included literature.Meta-analysis was performed using RevMan 5.3 software.Comparing western medicine treatment and Shenqi Dihuang decoction to inflammatory factors:interleukin-6(IL-6)Interleukin-8(IL-8),tumor necrosis factor-α(TNF-α),C-reactiveprotein(CRP),intercellular adhesion molecule-1(MCP-1),and monocyte chemotactic protein-1(ICAM-1)and efficacy indicators:the impact of urine microalbumin(mALB)and clinical efficacy.Results:A total of 11 related research reports were finally included,of which 9 evaluated IL-6[SMD=-1.09,95%CI(-1.57,-0.61),Z=4.43,P<0.00001];5 Item evaluated IL-8[SMD=-0.91,95%CI(-1.44,-0.37),Z=3.33,P=0.0009<0.05];7 items evaluated TNF-[SMD=-0.97,95%CI(-1.49,-0.45),Z=3.63,P=0.0003<0.05];9 items evaluated CRP[SMD=-1.40,95%CI(-1.89,-0.90),Z=5.49,P<0.00001];2 items evaluated MCP-1[SMD=-0.71,95%CI(-1.00,-0.43),Z=4.95,P<0.00001];1 item was ICAM-1 Evaluation was performed[SMD=-0.98,95%CI(-1.38,-0.58),Z=4.82,P<0.00001];6 items used mALB as the efficacy index[SMD=-1.85,95%CI(-2.65,-1.05),Z=4.52,P<0.00001];9 items evaluated the clinical efficacy,[OR=4.45,95%CI(2.96,6.69),Z=7.17,P<0.00001].Conclusion:Shenqi Dihuang Decoction was used in patients with diabetic nephropathy.Compared with the western medicine treatment group,the levels of IL-6,IL-8,TNF-α,CRP,MCP-1,ICAM-1and inflammatory factors were significantly reduced.The effect is significantly increased.It is suggested that Shenqi Dihuang Decoction has better anti-inflammatory response than diabetic nephropathy than western medicine alone.
文摘BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explore the effects of Zhibai dihuang pills and gonadotropin-releasing hormone analogue(GnRHa)on growth and ovarian function in girls with precocious puberty.METHODS The clinical data of 84 adolescent girls with precocious puberty and rapidly progressive puberty from February 2017 to August 2023 were retrospectively analyzed.Girls were divided into a control group and an observation group,with 42 cases in each group.The control group received diet intervention combined with GnRHa treatment,while the observation group received diet intervention combined with Zhibai dihuang pills+GnRHa treatment.Outcomes such as clinical efficacy,growth indicators,ovarian function,and adverse reactions were compared between the two groups.RESULTS The observation group showed superior clinical efficacy compared to the control group(P<0.05).Prior to the intervention,no significant differences were found in growth or ovarian function between the groups(P>0.05).Post-intervention,the observation group exhibited significantly lower rates in growth,height,and bone age,along with reduced levels of progesterone,testosterone,estradiol,prolactin,luteinizing hormone,and follicle-stimulating hormone compared to the control group(P<0.05).The incidence of adverse reactions was similar across both groups(P>0.05).CONCLUSION Combining Zhibai dihuang pills with GnRHa and dietary intervention effectively improves growth,enhances ovarian function,and minimizes adverse reactions in adolescent girls with precocious and rapidly progressive puberty.
基金This work was supported by funding from the National Natural Science Foundation of China(Grant Nos.81473520 and 81102697).
文摘Objective:It has been documented that ezrin/radixin/moesin(ERM)phosphorylation by the p38 mitogen-activated protein kinase(MAPK),Rho/ROCK,and protein kinase C(PKC)pathways leads to filamentous actin(F-actin)reorganization and microvascular endothelial cell hyperpermeability.In this study,we investigated the effects of Xijiao Dihuang Decoction combined with Yinqiao Powder(XDY)on influenza virus(IV)-induced F-actin restructuring and ERM phosphorylation regulated by the Rho/Rho kinase 1(ROCK),p38 MAPK,and PKC signaling pathways in pulmonary microvascular endothelial cells(PMVECs).Methods:Serum containing XDY(XDY-CS;13.8 g/kg)was acquired using standard protocols for serum pharmacology.Primary PMVECs were obtained from male Wistar rats and cultured.After adsorption of IV A(multiplicity of infection,0.01)for 1 h,medium with 20%XDY-CS was added to the PMVECs.The distributions of F-actin and phosphorylated ERM were determined by confocal microscopy,and F-actin expression was measured by flow cytometry.The expression levels of ROCK1,phosphorylated myosin phosphatase target-subunit(p-MYPT),phosphorylated MAPK kinase,phosphorylated p38(p-p38),phosphorylated PKC(p-PKC),and phosphorylated ERM(p-ERM)were determined by western blotting.Results:F-actin reorganization in IV-infected PMVECs was reversed by XDY-CS treatment,which was accompanied by reduced p-ERM production.The p-ERM protein accumulated at plasma membrane of PMVECs infected with IV,which was also inhibited by XDY-CS treatment.
文摘Objective:To study the effect of Baihe Dihuang Decoction in improving anxiety and its mechanism of action.Methods: Male mice were randomly divided into 5 groups: blank control group, Baihe Dihuang Decoction high, medium, low-dose group and diazepam group. After continuous intragastric administration for 14 d, the behavioral test of the mouse elevated plus maze experiment and opening test was performed. The brain tissue GABA and Glu content was measured by immunosorbent assay (ELISA).Results: Compared with the blank control group, the middle and high doses of Baihe Dihuang Decoction could increase the time and frequency of movement of the mice in the open cross labyrinth in the open arm and increase the number of times that the mouse entered the central area in the opening test. The anti-anxiety effect also showed an increase in the brain tissue GABA content in mice, ignificantly decreased Glu contents in mice.Conclusion: Baihe Dihuang Decoction has some anxiolytic effect, and anti-anxiety effect may be related to increasing brain tissue GABA content, decreased Glu contents in mice.
