Pharmacological mechanism of Liuwei Dihuang Decoction in treating Osteoporosis and Alzheimer’s disease based on Network Pharmacology

Objective:To predict the active components,targets of Liuwei Dihuang Decoction for the treatment of osteoporosis and Alzheimer’s disease with network pharmacology analysis.Methods:The components and targets of all the herbs of Liuwei Dihuang Decoction were obtained from ETCM database,Osteoporosis and Alzheimer’s disease targets were extracted from the GeneCards and DrugBank databases,selected based on STRING database for PPI network construction and build the network through the software of Cytoscape,Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses were carried out by R software.Results:181 active compounds and 762 disease-related from Liuwei Dihuang Decoction,there were 144 disease-related common targets obtained from Venn Diagram.IL6,TNF,PPARA,PPARG,SRC and other 11 targets are the node protein of the whole network.In the multisystem biological reaction process such as neurotransmitter,glucose and lipid metabolism,calcium and phosphorus metabolism.Conclusion:Liuwei Dihuang pill may play a co-therapeutic role in Osteoporosis and Alzheimer’s disease by participating in the multi-system biological reaction process such as neurotransmitter,glucose and lipid metabolism,calcium and phosphorus metabolism.

Active fraction combination from Liuwei Dihuang decoction improves adult hippocampal neurogenesis and neurogenic microenvironment in cranially irradiated mice

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.

Effects of Liuwei Dihuang decoction and its compatible prescriptions on the function of hypothalamus-pituitary-adrenal axis in senescence-accelerated mouse

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.

Effects of LW-AFC,a new formula derived from Liuwei Dihuang decoction,on intestinal microbiome in senescence-accelerated mouse prone 8 strain,a mouse model of Alzheimer disease

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.

Construction of NIM sub-network regulated by Liuwei Dihuang decoction and its characteristics

OBJECTIVE To construct the neuroendocrine immunomodulation(NIM) sub-network regulated by Liuwei Dihuang decoction(LW) and analyze its characteristics.METHODS We took the GSE57273 in GEO database and screened the differentially expressed genes(DEGs)(P<0.01) by the GEO2 R tool as gene expression signature of LW.The global PPI network was constructed in the context of whole PPI network through direct interaction algorithm and forest algorithm respectively.Then the enrichment and the topological characteristics of NIM signaling molecules were evaluated by permutation test.Finally,we abstracted the NIM sub-network by NIMNT,which combined the NIM molecular network and forest algorithm,and analyzed the topological characteristics of it by the Network Analyzer(release 2.7) plugin in Cytoscape v3.5.1.RESULTS We got 2468 DEGs in the gene expression signature of LW.After analyzing the global PPI network of LW got by two kinds of algorithms,we found that the NIM signaling molecules significantly enriched and located in important positions in the global PPI network.The NIM sub-network regulated by LW contained 1099 nodes and 1056 edges.We screened out 22 hub nodes(Degree>10).Among them,there were 19 NIM signaling molecules in which only ESR1 changed significantly and 3 non-DEGs(NFATC2,RARA,TP53).However,the down.stream of the hub nodes were significantly changes.CONCLUSION The results suggested that LW might mainly regulate the non-hub nodes to recovery of the network imbalance of the body in the state of disease.

Liuwei Dihuang Decoction improves cognitive impairments via regulating immune system in APP/PS1 transgenic mouse, a mouse model of Alzheimer disease

OBJECTIVE To investigate the effect and mechanisms of Liuwei Dihuang Decoction(LW) on cognition in PrP-hAβPPswe/PS1ΔE9(APP/PS1) transgenic mice.METHODS LW was adminis.trated with oral for 3 months.The locomotor activity test was performed to investigate the spontaneous motor activity of mice.The Morris water maze test and shuttle box test were performed to investigate the spatial learning and memory and active avoidance response respectively.The Αβ deposits and neuron loss in the hippocampus was detected by immunofluorescence staining and nissl staining respectively.The flow cytometry was employed to investigate the lymphocyte subsets of the mice.The 3 H-thymidine incorporation was performed to investigate the splenocytes proliferation.RESULTS The treatment of LW ameliorated the impairments of spatial learning and memory and active and passive avoidance in APP/PS1 mice.The administration of LW alleviated neuron loss in the brain,suppressed amyloid-β(Αβ) deposits in the hippocampus of APP/PS1 mice.The treatment of LW significantly increased ConAand LPS-induced proliferation of splenocytes,increased CD3+ T cells and CD19+ B cells in the spleen lymphocytes and reduced Gr1+ cells in APP/PS1 mice.CONCLUSION This data indicated the adminis.tration of LW ameliorated behavioral and pathological deterioration via regulating immune function.

The components transitive regularity of three dosage forms of Liuwei Dihuang Fufang

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 min2,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.

Shengmaisan combined with Liuwei Dihuang Decoction alleviates chronic intermittent hypoxia-induced cognitive impairment by activating the EPO/EPOR/JAK2 signaling pathway

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.

Effects of Liuwei Dihuang Decoction(Yukmijihwang-tang)on Physical Fatigue by Regulating Neurotransmitters in Brain

Objective:To study the effect of Liuwei Dihuang Decoction(六味地黄汤)or Yukmijihwangtang(YJT)on endurance exercise by in vivo experiment.Methods:ICR mice were randomly divided into the control group(distilled water)and the YJT groups(1,10,100 mg/kg),5 animals per group.YJT and distilled water were orally administered.The anti-fatigue effect of YJT was evaluated by open fifiled test(OFT),forced swimming test(FST),and tail suspension test(TST).Results:In the OFT,YJT signifificantly increased the total movement distance in a dose-dependent manner.Additionally,treatment with YJT signifificantly decreased immobility time in the FST and the TST.Various neurotransmitters such as norepinephrine(NE),serotonin(5-HT),dopamine(DA)levels were increased by FST.Administration of YJT down-regulated the expression levels of NE,5-HT,5-hydroxyindole-acetic acid(5-HIAA),and DA in the brain stem and hypothalamus of mice.Moreover,protein expression of HSP70 in mice liver and heart muscles was signifificantly increased in the YJT groups.Conclusions:YJT could ameliorate fatigue and enhance exercise tolerance through suppressing of brain monoamines including NE,5-HT,5-HIAA,and DA in FST mice model.

Effect of Liuwei Dihuang Decoction (六味地黄汤) on LongTerm Potentiation in Hippocampal Dentate Gyrusin Rats

Objective: To investigate effect of Liuwei Dihuang decoction (LWDHD), a traditional Chinese medicinal prescription, on the formation of long term potentiation (LTP) in the hippocampal dentate gyrus in anesthetized rats. Methods: LTP experiments were conducted by using a bipolar stimulating electrode to stimulate perforant pathway and a monopolar electrode to record the evoked field potential in hippocampal dentate gyrus. In the present study, both suprathreshold and subthreshold tetanic stimulation to the perforant pathway were employed. Results: Single oral administration of LWDHD (per os, 5 g/kg and 10 g/kg respectively) has no effect on the basal spike amplitude. However, LWDHD (per os, 5 g/kg and 10 g/kg respectively) significantly intensified the spike amplitude induced by a subthreshold stimulation (60 Hz, 20 pulses) while it did not affect formation of LTP formation induced by suprathreshold tetanic stimulation (60 Hz, 30 pulses). Conclusion: The present results suggested that LWDHD given orally potentiate the synaptic plasticity and transmission in hippocampal dentate gyrus, which might account for the enhancing effect of LWDHD on learning and memory in senescence accelerated mice.

六味地黄汤对阿霉素肾病小鼠尿蛋白及肾小球p-p38 MAPK、α-actinin-4、synaptopodin的影响

目的探讨六味地黄汤对阿霉素肾病(adriamycin nephropaghy,ADRN)小鼠尿蛋白的干预作用及可能机制。方法30只SPF级雄性C57BL/6小鼠随机选取5只为空白组,余下小鼠以单次尾静脉注射阿霉素(0.01 g·kg^(-1))复制ADRN模型,2周后将造模成功的小鼠随机分为模型组、贝那普利组及低、中、高剂量六味地黄汤组,每组5只。空白组、模型组予等体积注射用水灌胃,贝那普利组予0.0013 g·kg^(-1)贝那普利灌胃,低、中、高剂量六味地黄汤组分别予9.75、19.5、39 g·kg^(-1)六味地黄汤灌胃,每日1次,连续8周。自动生化仪检测小鼠24 h尿蛋白定量、血清白蛋白、血清肌酐、血清钾;HE染色法、电镜观察小鼠肾脏病理改变及足突形态;免疫组织化学法、Western bolt检测小鼠肾脏磷酸化p38 MAPK(phosphorylated p38 MAPK,p-p38 MAPK)、α-辅肌动蛋白-4(α-actinin-4)、突触孔蛋白(synaptopodin)的表达;RT-PCR检测小鼠肾脏α-actinin-4、synaptopodin mRNA表达。结果与空白组比较,模型组小鼠体质量、24 h尿量、血清白蛋白降低,24 h尿蛋白定量升高(P<0.05);肾小球系膜细胞增生,部分系膜区扩大、肾小管蛋白管型,间质可见炎性细胞浸润,足突广泛融合;α-actinin-4蛋白及mRNA、p-p38 MAPK蛋白表达升高(P<0.05),synaptopodin蛋白及mRNA表达降低(P<0.05)。与模型组比较,各干预组病理改变及足突融合均得到不同程度改善,贝那普利组及中、高剂量六味地黄汤组24 h尿蛋白定量减少,高剂量六味地黄汤组p-p38 MAPK蛋白表达降低(P<0.05),低、中、高剂量六味地黄汤组synaptopodin蛋白及mRNA表达均升高(P<0.05)。贝那普利组及低、中、高剂量六味地黄汤组组间比较,各指标差异无统计学意义(P>0.05)。结论六味地黄汤可能通过抑制p38 MAPK通路活化和上调α-actinin-4、synaptopodin蛋白及mRNA表达,改善肾脏病理及足突融合,减轻足细胞损伤,减少ADRN小鼠尿蛋白。

六味地黄汤调控TGF-β及Smad家族蛋白表达对肾间质纤维化的影响研究

目的探究六味地黄汤抑制肾间质纤维化(renal interstitial fibrosis,RIF)的干预作用及机制。方法将30只SPF级SD大鼠随机均分为假手术组、模型组、阳性药物组、中药高剂量组和中药低剂量组,每组6只。除假手术组外,其余各组采用左侧输尿管结扎术制备RIF模型。造模结束后,假手术组和模型组予以蒸馏水灌胃,阳性药物组予以醋酸泼尼松片0.2 mg/kg灌胃,中药低、高剂量组分别予以六味地黄汤0.5、1 mg/kg灌胃,疗程为21 d。治疗结束后,采用HE染色法评估肾间质损伤,Masson染色法检测肾间质胶原蛋白沉积和纤维化,RT-PCR测定肾间质转化生长因子-β1(transforming growth factor-β1,TGF-β1)、针对半身不遂同源物2的重组母体(recombinant mothers against decapentaplegic homolog 2,Smad2)、Smad3、Smad7的mRNA表达,Western blot测定肾间质TGF-β1、Smad2、Smad3、Smad7的蛋白表达。结果与假手术组相比,模型组的病理呈现系膜增生、间质增宽、胶原蛋白大面积沉积和明显纤维化,且TGF-β1、Smad2、Smad3、Smad7的mRNA和蛋白表达均增加(P<0.05)。与模型组相比,阳性药物组和中药低、高剂量组的病理表现均减轻,且TGF-β1、Smad2、Smad3、Smad7的mRNA和蛋白表达均降低(P<0.05)。与中药低剂量组相比,阳性药物组和中药高剂量组的TGF-β1、Smad2、Smad3、Smad7的mRNA和蛋白表达均降低(P<0.05)。结论六味地黄汤能够减轻RIF大鼠的肾间质纤维化程度,且高剂量效果更佳,其机制可能与调控TGF-β及Smad家族蛋白表达有关。

调补肺肾治疗慢性阻塞性肺疾病缓解期临床研究

目的探讨调补肺肾治疗慢性阻塞性肺疾病(COPD)缓解期的临床效果。方法选取2021年5月至2023年5月江西省胸科医院收治的94例COPD缓解期患者作为研究对象,按照随机数字表法分为对照组(47例)和观察组(47例)。对照组患者采用常规西医治疗,观察组患者加用调补肺肾治疗(六味地黄汤加减和揿针特定穴位治疗),两组均连续治疗12周。比较两组患者的临床疗效、肺功能、血气指标、呼吸困难程度、生活质量、中医证候积分及不良反应。结果观察组治疗总有效率高于对照组,差异有统计学意义(P<0.05);两组治疗前第1秒用力呼气容积(FEV_(1))、用力肺活量(FVC)、FEV_(1)/FVC、动脉二氧化碳分压(PaCO_(2))、动脉氧分压(PaO_(2))、中医证候积分、改良版英国医学研究委员会呼吸问卷(mMRC)、COPD评估测试问卷(CAT)评分比较,差异无统计学意义(P>0.05);两组治疗后FEV_(1)、FVC、FEV_(1)/FVC、PaO_(2)高于本组治疗前,PaCO_(2)、中医证候积分及mMRC、CAT评分低于本组治疗前,差异有统计学意义(P<0.05);观察组治疗后FEV_(1)、FVC、FEV_(1)/FVC、PaO_(2)高于对照组,PaCO_(2)、中医证候积分及mMRC、CAT评分低于对照组,差异有统计学意义(P<0.05);两组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论缓解期COPD患者应用调补肺肾治疗具有较高的价值,可改善通气及肺功能,缓解呼吸困难,提高生活质量,安全可靠,效果显著。

丹荷六味地黄汤对绝经后NAFLD患者脂代谢及心理状态评分的影响

目的:探讨丹荷六味地黄汤对绝经后非酒精性脂肪性肝病(NAFLD)患者脂代谢及心理状态评分的影响。方法:选取2021年12月至2022年12月河南中医药大学第一附属医院收治的绝经后NAFLD患者68例,按随机数字表法分为观察组和对照组,每组34例。观察组给予丹荷六味地黄汤,对照组给予维生素E软胶囊,2周为1个治疗周期,对比两组患者治疗6个周期后的肝功能、脂代谢、雌激素E2、脂肪变和肝纤维化评分、改良Kupperman评分、焦虑自评量表评分(SAS)、自评抑郁量表评分(SDS)及不良反应。结果:治疗6个周期后,观察组患者总有效率88.2%,高于对照组的65.6%(P<0.05)。观察组患者BMI、腰围减少,ALT、AST、GGT、TG、TC、HDL、LDL、游离脂肪酸、雌激素E2水平改善,肝硬度指数(CAP)、肝硬度值(LSM)、APRI值降低,改良Kupperman评分、SAS和SDS降低均优于对照组(P<0.05)。结论:丹荷六味地黄汤治疗绝经后NAFLD疗效确切,具有改善肝功能、脂代谢、雌激素水平,减少肝脂肪变和纤维化评分的作用,且对绝经后NAFLD患者的心理状态具有一定调节作用。

基于网络药理学及分子对接探讨六味地黄汤治疗原发性干燥综合征的作用机制

目的 探讨六味地黄汤治疗原发性干燥综合征(primary sjogren’s syndrome, pSS)的作用机制。方法 使用公共数据库平台TCMSP、GeneCards、DrugBank、PHARMGKB、OMIM和TTD对六味地黄汤组成药物的活性成分、作用靶点及PSS的疾病靶标进行检索,将药物成分靶点与疾病靶标取交集得到六味地黄汤治疗pSS的潜在靶点;使用STRING 11.5数据库获得六味地黄汤治疗PSS的蛋白互作网络(PPI),并通过Cytoscape 3.7.2软件分析得到核心靶点;通过基因本体(GO)富集分析、基因组百科全书(KEGG)通路富集分析筛选差异生物过程及靶点通路;使用Auto Dock 1.5.6及Pymol 2.2.0软件进行分子对接,验证核心靶点与活性成分之间的亲和力。结果 筛选得到六味地黄汤的药物活性成分74个,作用靶点184个,PSS疾病相关靶点1161个,药物-疾病交集靶点69个。数据分析显示,六味地黄汤的主要活性成分包括槲皮素、山柰酚、豆甾醇、海风藤酮和薯蓣皂苷元,六味地黄汤治疗pSS的8个核心靶点包括AKT1、CASP3、JUN、MMP9、NFKBIA、TP53、VEGFA。GO富集主要涉及脂多糖、氧化应激、活性氧代谢等生物过程。KEGG富集主要涉及抗炎、氧化应激等相关通路。分子对接结果显示,8个核心靶点与相应的活性成分的结合能均≤-5 kcal/mol,其中槲皮素与8个核心靶点均能较好地结合,可能是六味地黄汤干预pSS的主要有效成分。结论 六味地黄汤可能通过作用于AKT1、CASP3、JUN、MMP9、NFKBIA、TP53、VEGFA、IL-1β等关键靶点,通过“IL-17信号通路”“Th17细胞分化”“HIF-1信号通路”等发挥抗炎、免疫调节、抗氧化应激的作用,其中槲皮素可能是其发挥作用的主要有效成分。

六味地黄汤加减对血液透析肝肾阴虚型血小板减少症患者微炎症状态、血管通路功能及血清GPⅡb、PMPs和PAIg的影响

目的:观察六味地黄汤加减对血液透析肝肾阴虚型血小板减少症患者微炎症状态、血管通路功能及血清血小板膜糖蛋白(GPⅡb)、血小板微颗粒(PMPs)和血小板相关免疫球蛋白(PAIg)水平的影响。方法:选择2020年4月至2023年4月该院收治的血液透析肝肾阴虚型血小板减少症患者120例,根据随机数字表法分为观察组及对照组。对照组60例患者给予常规西医治疗,观察组60例患者在对照组的基础上给予六味地黄汤加减治疗。治疗前后检测两组患者Th17/Treg细胞比例、PAIg、GPⅡb、PMPs、高迁移率族蛋白B1(HMGB1)、血小板活化因子(PAF)、白细胞介素10(IL-10)、血栓调节蛋白(TM)、血小板生成素(TPO)、P-选择素(CD62P)、脂蛋白相关磷脂酶A2(Lp-PLA2)和血小板计数(PLT)水平,并计算血小板压积(PCT)、血红蛋白、总胆红素水平,比较两组患者的临床疗效及不良反应发生情况。结果:本研究无脱落病例。治疗后,观察组患者的Th17/Treg、HMGB1、Lp-PLA2、PAF、CD62P、TM、GPⅡb、PMPs、PAIg、TPO、白细胞总数和总胆红素水平较对照组明显降低,IL-10、PLT、PCT和血红蛋白水平较对照组明显升高,差异均有统计学意义(P<0.05)。观察组患者的总有效率为96.67%(58/60),较对照组的86.67%(52/60)明显更高,差异有统计学意义(P<0.05)。治疗期间,两组患者均无明显不良反应产生。结论:六味地黄汤加减治疗血液透析肝肾阴虚型血小板减少症患者,可调节患者机体免疫,改善微炎症状态及血管通路功能,降低GPⅡb、PMPs和PAIg水平,改善血小板水平,调节白细胞总数、总胆红素和血红蛋白水平,提高临床疗效,安全性高。

早期糖尿病肾病的证型分布及其治疗的理论研究

糖尿病肾病(diabetic nephropathy, DN)是糖尿病较常见的微血管并发症,常引起终末期肾病,最终演变为肾衰竭,危及生命。出自《小儿药证直诀》的六味地黄汤,具有滋阴补肾之功效,古典医籍记载及现代医学均已证实此方对糖尿病具有较好的疗效。补阳还五汤出自《医林改错》,补气活血通络,故常用来治疗气虚血瘀证。该文收集查阅相关医家文献资料,统计分析得出DN发生率最高的证型为气阴两虚兼血瘀证。文章从中医理论、西医机制研究等方面,阐述六味地黄汤合补阳还五汤治疗早期DN的理论研究,以期为临床应用提供参考。

二地鳖甲煎汤联合六味地黄软胶囊治疗勃起功能障碍肾阴虚证患者的临床疗效分析

目的 探究应用二地鳖甲煎汤联合六味地黄软胶囊治疗勃起功能障碍(ED)肾阴虚证患者的临床疗效。方法 80例勃起功能障碍肾阴虚证患者,采用计算机随机分为观察组和对照组,每组40例。观察组患者应用二地鳖甲煎汤联合六味地黄软胶囊治疗,对照组患者口服安慰剂颗粒。比较两组患者治疗前后的勃起功能国际问卷(IIEF-5)评分、主要症状以及次要症状积分、血清性激素指标[促黄体生成素(LH)、催乳素(PRL)、睾酮(T)、卵泡刺激素(FSH)、雌二醇(E2)]。结果 治疗8周后,观察组IIEF-5评分为(20.96±4.12)分,对照组为(15.30±3.48)分,与对照组相比,观察组IIEF-5评分显著提升(P<0.05)。治疗8周后,观察组主要症状以及次要症状积分分别为(2.16±0.63)、(7.96±1.45)分,对照组分别为(3.26±0.45)、(10.36±3.58)分,与对照组相比,观察组主要症状以及次要症状积分显著下降(P<0.05)。治疗8周后,观察组FSH、LH、T、E2、PRL水平分别为(2.22±0.54)mIU/ml、(1.06±0.26)mIU/ml、(25.86±4.65)ng/dl、(38.65±4.54)ng/L、(11.04±3.47)ng/ml,对照组分别为(4.81±1.11)mIU/ml、(2.85±0.44)mIU/ml、(20.99±4.19)ng/dl、(58.79±6.16)ng/L、(11.18±3.18)ng/ml,与对照组相比,观察组FSH、LH、E2水平显著下降, T水平显著提升(P<0.05);两组患者的PRL水平相比无明显差异(P>0.05)。结论 应用二地鳖甲煎汤联合六味地黄软胶囊治疗勃起功能障碍肾阴虚证患者效果显著,可明显改善患者的勃起情况、主要症状以及次要症状、血清性激素指标,值得应用。

肾虚论治加外治法治疗颈椎病的临床疗效观察

目的:探究肾虚论治加外治法治疗颈椎病的临床疗效。方法:选取2021年8月—2023年9月收治的80例颈椎病病人为研究对象,按随机数字表法将其分为观察组、对照组,每组40例。所有病人行常规护理,观察组在此基础上采用肾虚论治联合外治法治疗,对照组仅采用外治法,两组均干预2个疗程。比较两组病人临床疗效及干预前后疼痛评分、颈部功能障碍评分、中医证候积分。结果:观察组治疗总有效率为95.00%,高于对照组的77.50%(P<0.05);观察组干预后疼痛及颈部功能障碍评分均低于对照组(P<0.05);观察组病人的中医证候积分均低于对照组(P<0.05)。结论:中医辨证论治探索肾虚论治加外治法在颈椎病病人中应用效果显著,能有效缓解病人临床症状,减轻颈部疼痛程度及功能障碍,对促进颈椎功能恢复具有重要作用,利于改善预后。

中西医结合治疗肾虚血瘀型腰椎间盘突出症临床观察

目的:观察六味地黄汤加味联合甲钴胺片和右酮洛芬胶囊治疗肾虚血瘀型腰椎间盘突出症的临床疗效。方法:选取符合纳入标准的腰椎间盘突出症患者60例,采用随机数字表法将其分为两组各30例。对照组予甲钴胺片联合右酮洛芬胶囊,治疗组在对照组基础上加用六味地黄汤加味。2周为1个疗程,治疗2个疗程。比较两组患者治疗前后视觉模拟量表(VAS)评分、日本骨科协会评估治疗分数(JOA)评分、Oswestry功能障碍指数问卷表(ODI)评分。结果:治疗组总有效率为90.00%,高于对照组的66.67%(P<0.05);治疗后,治疗组VAS、JOA、ODI评分均明显改善(P<0.05),且改善程度优于对照组(P<0.05);治疗组复发率为7.40%,低于对照组的25.00%,两组比较差异有统计学意义(P<0.05)。结论:六味地黄汤加味联合甲钴胺片和右酮洛芬胶囊治疗肾虚血瘀型腰椎间盘突出症效果较好,可缓解患者腰部疼痛症状,改善其生活质量。