Network pharmacology and molecular docking analysis reveal insights into the molecular mechanism of Gualou Qumai Wan in clear cell renal cell carcinoma

Background:To initially clarify the potential therapeutic targets and pharmacological mechanism regarding Gualou Qumai Wan(GQW),a kind of traditional Chinese medicine(TCM),in clear cell renal cell carcinoma(ccRCC)by virtue of the network pharmacology analysis and molecular docking analysis.Methods:The screening of bioactive components and targets of GQW was based on the Traditional Chinese Medicine System Pharmacology(TCMSP)and the UniProt platform served for standardizing their targets.Online Mendelian Inheritance in Man(OMIM),PharmGkb,TTD,DrugBank and GeneCards databases were searched to collect the disease targets of ccRCC.Cytoscape assisted in constructing herb-compound-target(H-C-T)networks.The STRING database was searched for constructing the target protein-protein interaction(PPI)networks,while the R programming language served for analyzing GO functional terms and the KEGG pathways related to potential targets.Analyses of core genes related to survival and tumor microenvironment(TME)were conducted respectively based on the GEPIA2 database and TIMER 2.0 database.Human Protein Atlas(HPA)and The Cancer Genome Atlas(TCGA)helped to obtain core genes’protein expression as well as transcriptome expression level.Autodock Vina software validated the molecular docking regarding GQW components and pivotal targets.Results:The constructed H-C-T networks mainly had 33 compounds and 65 targets.A topological analysis of the PPI network identified that ESR1,AKT1,HIF1A,PTGS2,TP53 and VEGFA serve as core targets in the way GQW affects ccRCC.According to the GO and KEGG pathway enrichment analyses,the effects of GQW are mediated by genes related to hypoxia and oxidative stress as well as the Chemical carcinogenesis-receptor activation and PI3K-Akt signaling pathways.AKT1 shows a close relation to the recruitment of various immune cells and can remarkably affect disease prognosis according to reports.Molecular docking and molecular dynamics simulations showed that diosgenin has higher affinity with core targets.Conclusion:The study makes a comprehensive explanation of the biological activity,potential targets,as well as molecular mechanism regarding GQW against ccRCC,which promisingly assists in revealing the action mechanism of TCM formulae in disease treatment and the respective and scientific basis.

Comparing the mechanism of four classic Gualou-Xiebai prescriptions for cardiovascular diseases with phlegm and blood stasis syndrome based on molecular network modeling

Background:Four classical Traditional Chinese Medicine prescriptions,namely Gualou Xiebai Baijiu decoction,Gualou Xiebai Banxia decoction(GLXBBX),Zhishi Xiebai Guizhi decoction(ZSXBGZ)and Danlou prescription(DL),have been frequently used for treatment of phlegm and blood stasis syndrome(PBSS)-related cardiovascular diseases.However,its therapeutic mechanism has not been clearly elucidated.This study aimed to explore PBSS and its molecular mechanism,clarify and compare the mechanisms of four prescriptions in treating PBSS-related diseases.Method:In this study,we collected four prescriptions’compounds,predicted therapeutic targets,and enriched pathways which were based on network pharmacology.Then,we analysed the commen and different mechanisms by combing the network of components,targets and pathways.Finally,molecular docking was engaged to assess the binding potential of key compounds and hub targets.Results:We showed that four prescriptions’intersection genes(VEGFA,SRC,EGFR,etc.)were commonly enriched in PI3K-AKT signaling pathway,HIF-1 signaling pathway,etc.In addition,platelet activation and cAMP signaling pathway were singly enriched from the GLXBBX through unique compounds 12,13-epoxy-9-hydroxynonadeca-7,10-dienoic acid and Cyclo(L-tyrosyl-L-phenylalanyl).These bioactive compounds may exert GLXBBX’s unique pharmacological pathways via involving in mediating PPARA,PTGER3,etc.Sphingolipid signaling pathway was singly enriched from the ZSXBGZ through unique compounds tetramethoxyluteolin,ergosterol peroxide,etc.These bioactive compounds could mediate ADORA1,ADORA3 and TNFRSF1A to regulate ZSXBGZ’s unique pharmacological pathways.AMPK signaling pathway was singly enriched from the DL through unique compounds kaempferol,evofolinb,ethyl acid and aureusidin.These bioactive compounds were involved in mediating the main targets of AMPK signaling pathway,such as TNF,TNFRSF1A,etc.Conclusions:Our research demonstrated that GLXB-prescriptions involved in almost all pathological stages of PBSS-related cardiovascular diseases by modulating high-frequency shared pathways and targets mainly through key compounds(quercetin,mandenol,sitosteryl acetate and luteolin,etc.),for example,participate in the process of atherosclerosis,lipid metabolism,inflammation,immune response,thrombosis,inhibit inflammatory factors and platelet aggregation,regulate immune function,vascular function,oxidative stress.In addition to common pharmacological efficacies,there could also be specificities among GLXB prescriptions due to different compounds.For example,GLXBBX tends to regulate the function of vascular and endothelial barrier,prevent thrombosis.ZSXBGZ tends to regulate lipid metabolism and protect the heart from lipid accumulation.DL tends to maintain energy homeostasis and improve inflammation.

Lactation breast abscess treated with Gualou Xiaoyong decoction and painless lactation manipulation:A case report and review of literature

BACKGROUND Breast abscess during lactation is a severe complication of acute mastitis,which can lead to discomfort,high fever,breast fistula,sepsis,septic shock,breast damage,disease persistence and frequent hospitalization.Breast abscesses may also lead the mother to discontinue breastfeeding,thereby harming the infant’s health.The predominant pathogenic bacteria are Staphylococcus aureus,Staphylococcus epidermidis and Streptococcus.The incidence of breastfeeding abscesses in breastfeeding women ranges between 4.0%and 11.0%.In cases of breast abscess,the rate of cessation of lactation is 41.0%.In instances of breast fistula,the rate of cessation of lactation is very high(66.7%).Furthermore,50.0%of women with breast abscesses must be hospitalized and treated with intravenous antibiotics.Treatment includes antibiotics,abscess puncture and surgical incision and drainage.The patients suffer from stress,pain and easily induced breast scarring;the disease’s progression is prolonged and recurrent,interfering with infant feeding.Consequently,it is crucial to discover an adequate cure.CASE SUMMARY A 28-year-old woman with a breast abscess was treated with Gualou Xiaoyong decoction and painless breast opening manipulation 24 d after cesarean delivery.On the 2nd d of treatment,the patient’s breast mass was significantly reduced,the pain was significantly reduced,and the general asthenia was improved.All conscious symptoms disappeared after 3 d,breast abscesses faded after 12 d of treatment,inflammation images disappeared after 27 d,and normal lactation images were restored.CONCLUSION In treating breast abscesses during breastfeeding,the combination of Gualou Xiaoyong decoction and painless lactation provides a positive therapeutic impact.This disease’s treatment offers the advantages of a short course of treatment,no need to discontinue breastfeeding and the ability to rapidly mitigate symptoms,which can be used as a reference in clinical practice.

Gualou Guizhi decoction promotes neurological functional recovery and neurogenesis following focal cerebral ischemia/reperfusion

Recovery following stroke involves neurogenesis and axonal remodeling within the ischemic brain. Gualou Guizhi decoction （GLGZD） is a Chinese traditional medicine used for the treatment of post-stroke limb spasm. GLGZD has been reported to have neuroprotective effects in cerebral ischemic injury. However, the effects of GLGZD on neurogenesis and axonal remodeling following cerebral ischemia remain unknown. In this study, a rat model of focal cerebral ischemia/reperfusion was established by middle cerebral artery occlusion. Neurologi- cal function was assessed immediately after reperfusion using Longa＇s 5-point scoring system. The rats were randomly divided into vehicle and GLGZD groups. Rats in the sham group were given sham operation. The rats in the GLGZD group were intragastrically administered GLGZD, once daily, for 14 consecutive days. The rats in the vehicle and sham groups were intragastrically administered distilled water. Modified neurological severity score test, balance beam test and foot fault test were used to assess motor functional changes. Nissl staining was performed to evaluate histopathological changes in the brain. Immunofluorescence staining was used to examine cell proliferation using the marker 5-bromo-2＇-deoxyuridine （BrdU） as well as expression of the neural precursor marker doublecortin （DCX）, the astrocyte marker glial fibrillary acidic protein （GFAP） and the axon regeneration marker growth associated protein-43 （GAP-43）. GLGZD substan- tially mitigated pathological injury, increased the number of BrdU, DCX and GFAP-immunoreactive cells in the subventricular zone of the ischemic hemisphere, increased GAP-43 expression in the cortical peri-infarct region, and improved motor function. These findings suggest that GLGZD promotes neurological functional recovery by increasing cell proliferation, enhancing axonal regeneration, and in- creasing the numbers of neuronal precursors and astrocytes in the peri-infarct area.

Effect of Gualou Xiebai Banxia decoction combined with Danshen Decoction on clinical efficacy of unstable angina with phlegm and blood stasis syndrome

Objective:To observe the clinical efficacy and safety of Gualou Xiebai Banxia decoction combined with Danshen decoction on unstable angina(UA)with phlegm and blood stasis syndrome.Method:Eighty patients with UA were randomly divided into treatment group(40 cases)and control group(40 cases)by random number table.The control group was given conventional western medicine treatment,and the experimental group was given Gualou Xiebai Banxia decoction and Danshen decoction on the basis of the control group.Both groups were treated for 4 weeks.Before and after treatment,the angina attacks,dosage of nitroglycerin,traditional Chinese medicine syndrome score,quality of life score,blood lipid,coagulation index and clinical total efficacy were observed and recorded.Results:After 4 weeks of treatment,the attack times and duration of angina in the two groups were both decreased compared with those before treatment.And the treatment group was more significantly reduced than the control group,the difference was statistically significant(p<0.05);the consumption of nitroglycerin of the treatment group was 90.0%,which was better than 67.5%of the control group,the difference was statistically significant(p<0.05);the total effective rate of the treatment group was 90%,which was better than 65%of the control group,the difference was statistically significant(p<0.05);the traditional Chinese medicine(TCM)syndrome score of the experimental group was lower than that of the control group,the differences was significant(p<0.05).The improvement of low density lipoprotein(LDL-C),total cholesterol(TC)and prothrombin time(PT)in the experimental group was better than that in the control group(p<0.05).During the study,there were no obvious adverse reactions in both groups.Conclusion:Gualou Xiebai Banxia decoction combined with Danshen decoction can effectively relieve the attack of angina and the consumption of nitroglycerin,improve clinical symptoms,regulate blood lipid and blood flow state,and improve the quality of life of patients with UA,with good clinical efficacy and safety.

Research progress on synergetic effects of Fuzi(Radix Aconiti Lateralis Preparata)and Tubeimu(Rhizoma Bolbostemmatis)/Gualou(Trichosanthes kirilowii Maxim)

The compatibility of Chinese herbs is the focus and the difficulty in traditional Chinese medicine research,and it has an important guiding role for clinical medicine.Some scholars believe that the Fuzi(Radix Aconiti Lateralis Preparata,FZ)compatibility with Tubeimu(Rhizoma Bolbostemmatis,TBM)/Gualou(Trichosanthes kirilowii Maxim,GL)does not meet the Chinese medicine theory of“eighteen incompatibilities”.However,this combination has been used many times in many clinical medications.This study reviewed the research progress of pharmacological effects of FZ,and FZ compatibility with TBM/GL,in order to correctly understand and apply the“eighteen incompatibilities”drugs,and provide a reference for further exploration of the combined application in clinical treatment.

A Systematic Review and Meta-Analysis on Gualou Niubang Decoction for Acute Mastitis

Objective:To systematically evaluate the clinical efficacy of Gualou Niubang decoction in the treatment of acute mastitis.Methods:Randomized controlled trials of Gualou Niubang decoction in the treatment of acute mastitis included in PubMed,Springer,Embase,Cochrane Library,CNKI,Wanfang,Weipu,and China Biomedical Literature Database from January 2016 to present.The Cochrane risk bias assessment tool was used to evaluate the risk of bias.Used Revman 5.3 software for Meta analysis.Results:There are 8 articles that meet the inclusion criteria,comprising 919 subjects,the test group were 462,cases and control group were 457 cases.The results of statistical analysis showed that the clinical efficacy of the experimental group was significantly higher than which of the control group,[RR=1.19,95%CI(1.07,1.33),P=0.002],the difference was statistically significant.Among the secondary outcome indicators,compared to the control group,Gualou Niubang decoction can effectively relieve the main symptoms of acute mastitis[MD=-1.96,95%CI(-2.27,-1.65),P<0.0001].Gualou Niubang decoction combined with antibiotics can shorten the length of hospital stay[MD=-5.23,95%CI(-6.02,-4.44),P<0.00001]and reduce white blood cell count[MD=-2.40,95%CI(-4.71,-0.08),P=0.04]are better than antibiotics.Conclusion:The use of Gualou Niubang decoction to treat acute mastitis can not only improve clinical efficacy,but also effectively relieve clinical symptoms,shorten hospital stay and reduce white blood cell count.

Research Progress of Gualou Xiebai in the Treatment of Coronary Heart Disease

Gualou Xiebai is a basic prescription for the treatment of angina pectoris in Synopsis of the Golden Chamber.This article is a summary of the theoretical research and clinical application of Gualou Xiebai,in hope to promote the use of Gualou Xiebai in clinical practice.

Elucidation of the Mechanism of Gualou-Xiebai-Banxia Decoction for the Treatment of Unstable Angina Based on Network Pharmacology and Molecular Docking

Objective: The aim of this study was to identify the potential pharmacological mechanisms of Gualou-Xiebai-Banxia decoction(GLXBBX) against unstable angina(UA). Materials and Methods: The active compounds of GLXBBX were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and their targets were predicted using the Swiss Target Prediction database. The targets associated with UA were obtained from the Online Mendelian Inheritance in Man, Gene Cards, and Therapeutic Target Database. Individual targets associated with UA and GLXBBX were cross-checked to identify the targets of GLXBBX involved in the treatment of UA. A protein–protein interaction network was built using the STRING online database. Cytoscape 3.7.2 software was used to screen out hub genes. Additional gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the cluster Profiler package in R. Results: A total of 28 bioactive compounds and 320 protein targets of GLXBBX associated with UA were screened out. Enrichment analysis indicated that the therapeutic effect of GLXBBX may be mediated through the PI3K/AKT, MAPK, and HIF-1 signaling pathways. Molecular docking suggested that the active compounds including Vitamin E, cavidine, and baicalein can bind to their protein receptors. Conclusions: This research confirmed the multifactorial effects of GLXBBX in the treatment of UA and laid the foundation for the experimental research on GLXBBX.

瓜蒌薤白半夏汤对冠心病心绞痛患者PCI术后心肌损伤标志物水平的影响

目的探讨瓜蒌薤白半夏汤对冠状动脉粥样硬化性心脏病(冠心病)心绞痛患者经皮冠状动脉介入治疗(PCI)术后心肌损伤标志物水平的影响。方法选取2022年1月~2023年2月于保定市第一中心医院心内科行PCI的冠心病心绞痛患者98例,随机分为观察组和对照组,每组各49例。对照组术后给予常规西药治疗,观察组在对照组的基础上加用瓜蒌薤白半夏汤。比较两组患者临床疗效、中医证候积分、心肌损伤标志物[肌酸激酶同工酶(CK-MB)、肌钙蛋白T(cTnT)、肌红蛋白(MB)]、生活质量[西雅图心绞痛量表(SAQ)评定]和不良反应率。结果治疗4周后,观察组患者临床疗效高于对照组(P>0.05);两组患者中医证候积分均低于同组治疗前(P<0.05),且观察组低于对照组(P<0.05)。治疗4周后,两组患者CK-MB、cTnT、MB水平均低于同组治疗前(P<0.05),且观察组低于对照组(P<0.05)。治疗4周后,两组患者SAQ各项评分均高于同组治疗前(P<0.05),且观察组高于对照组(P<0.05)。两组患者不良反应率比较无统计学差异(P>0.05)。结论瓜蒌薤白半夏汤可改善冠心病心绞痛患者PCI术后的临床症状,具有减轻心肌损伤、保护心肌的作用。

基于《金匮要略》探讨经方治疗糖尿病肾病

文章探析《金匮要略》方栝蒌瞿麦丸、金匮肾气丸、五苓散对糖尿病肾病的疗效,阅读古书籍以及相关文献资料,总结分析三则经方对糖尿病肾病的疗效及成果。栝蒌瞿麦丸、金匮肾气丸与五苓散治疗糖尿病肾病效果显著,在临床上有很大的应用价值。

Mechanistic study of lipid metabolism disorders in diabetic kidney disease treated with GLQMP based on network pharmacology,molecular docking and in vitro experiments

Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.

加味瓜蒌瞿麦汤联合米非司酮治疗子宫肌瘤患者的疗效及对其性激素水平的影响

目的探讨加味瓜蒌瞿麦汤联合米非司酮治疗子宫肌瘤患者的疗效及对其性激素水平的影响。方法选取2020年2月—2022年3月期间于河南省南阳市第二人民医院就诊的痰湿瘀结证子宫肌瘤患者120例,按随机数字表法分为对照组和研究组,每组各60例。对照组单纯给予米非司酮治疗,研究组在对照组治疗的基础上联合加味瓜蒌瞿麦汤治疗,两组患者均于月经干净开始服药,经期停药,均治疗3个月。观察比较两组患者临床疗效及不良反应发生率,治疗前后月经质量、子宫肌瘤体积及子宫体积,并检测两组患者血清性激素[雌二醇(Estradial,E_(2))、促卵泡生长激素(Folliclestimulating hormone,FSH)、孕酮(Progesterone,P)、促黄体生成素(Luteinizing hormone,LH)]水平。结果治疗后研究组临床总有效率95.00%(57/60)明显高于对照组80.00%(48/60),差异有统计学意义(P<0.05)。治疗后两组患者视觉模拟量表(Visual analog scale,VAS)评分及月经失血图(Pictorial blood loss assessment chart,PBAC)评分均较治疗前降低,差异有统计学意义(P<0.05);且研究组VAS、PBAC评分均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者子宫肌瘤、子宫体积均较治疗前降低,差异有统计学意义(P<0.05);且研究组子宫肌瘤、子宫体积均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者血清性激素LH、P、E_(2)及FSH水平均较治疗前降低,差异有统计学意义(P<0.05);且研究组血清性激素LH、P、E_(2)及FSH水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗期间,研究组不良反应发生率10.00%(6/60)与对照组6.67%(4/60)比较,差异无统计学意义(P>0.05)。结论加味瓜蒌瞿麦汤与米非司酮联用能进一步提高子宫肌瘤的疗效,改善月经质量,缩小肌瘤体积,调节性激素水平,具有良好的安全性。

瓜蒌大黄汤对重症肺炎大鼠模型肺肠组织损伤的作用

目的观察瓜蒌大黄汤对重症肺炎大鼠模型肺肠组织损伤的作用。方法制备重症肺炎模型SD大鼠60只,随机分为盐水灌肠组、中药灌肠组,观察两组大鼠24、48、72 h 3个时间点的情况。再取10只健康SD大鼠作为空白组和10只重症肺炎模型大鼠作为模型组,造模成功后立即处死大鼠,采血并取肺、结肠组织。盐水灌肠组及中药灌肠组分别于造模成功后6、18、30、42、54、66 h进行盐水或中药灌肠,分别在24、48、72 h时处死大鼠,采血并取肺、结肠组织。HE染色观察肺肠组织病理损伤情况并评分;ELISA检测血清表面活性蛋白-A(SP-A)、降钙素原(PCT)、C反应蛋白(CRP);Western blotting、免疫荧光方法检测肺、肠组织中SP-A、肿瘤坏死因子-α(TNF-α)的表达。结果病理评分示:盐水灌肠组的肠组织病理评分高于各时间段中药灌肠组(P<0.05);盐水灌肠组的肺组织病理评分与中药灌肠组比较无统计学差异(P>0.05)。ELISA结果示:与空白组比较,模型组CRP、PCT、SP-A均升高(P<0.05);与模型组比较,盐水灌肠组血清CRP、PCT、SP-A各时间段呈升高趋势(P<0.05),中药灌肠组血清CRP、PCT变化不明显(P>0.05),SP-A在48 h至72 h升高(P<0.05);West⁃ern blotting和免疫荧光示:中药灌肠组肺、肠组织SP-A在各时间段呈升高趋势;盐水灌肠组肺、肠组织SP-A变化不明显。Western blotting结果示:与空白组比较,模型组肺、肠组织中TNF-α表达升高(P<0.05);与模型组比较,中药灌肠组肺组织TNF-α在72 h下降,而肠组织TNF-α在48、72 h表达下降(P<0.05);盐水灌肠组肺、肠组织TNF-α在48 h和72 h表达升高(P<0.05)。结论瓜蒌大黄汤灌肠可通过上调重症肺炎大鼠肺、肠组织SP-A的表达,下调TNF-α的表达,减轻炎性因子对肺、肠组织的损伤。

瓜蒌瞿麦丸探微

瓜蒌瞿麦丸出自《金匮要略》,因其违反了“十八反”,故医家在临床应用不多。根据条文可知,其主治病证为上燥下寒所致的小便不利。治疗以润上温下为主,方药配伍以寒燥温凉,淡渗补利同施,上中下三焦共治,以达到清上、温下、建中之效。诸药研末,和蜜为丸,以小便利,腹中温为愈。临床上多用于泌尿系统疾患、糖尿病肾病及糖尿病等疾病。

基于TGF-β通路探讨瓜蒌薤白汤对肺纤维化的作用机制

目的探索瓜蒌薤白汤对肺纤维化的作用机制。方法将SPF级SD大鼠分为空白组(Control)、模型组(Mod⁃el)、吡非尼酮组(Pirfenidone 0.15 g·kg^(-1))、瓜蒌薤白汤低剂量组(GLXB-L 2.4 g·kg^(-1))、瓜蒌薤白汤高剂量组(GLXB-H 4.8 g·kg^(-1))。除空白组外,其余各组大鼠采用一次性向气管内滴注博来霉素复制特发性肺纤维化模型。造模第2天,开始灌胃给予各组大鼠相应药物,连续14、28 d。末次给药后,取材。酶联免疫吸附测定法(enzyme-linked immunosorbent assay,ELISA)检测血清和肺泡灌洗液白细胞介素-4(interleukin-4,IL-4)、IL-6、IL-8水平;Masson染色检测大鼠肺组织中胶原纤维和肌纤维;免疫荧光法检测大鼠肺组织TGF-β、α-SMA蛋白表达;实时荧光定量PCR(quantitative real-time PCR,RT-PCR)检测大鼠肺脏TNF-αmRNA、IL-4 mRNA、IL-6 mRNA表达。结果博来霉素致大鼠肺纤维化模型制备成功,瓜蒌薤白汤可降低肺纤维化模型大鼠血清和肺泡灌洗液IL-4、IL-6、IL-8水平,下调肺组织TGF-β、α-SMA蛋白表达,降低TNF-αmRNA、IL-4 mRNA、IL-6 mRNA表达水平,缓解肺组织纤维化病变,且以瓜蒌薤白汤高剂量组效果明显。结论瓜蒌薤白汤可以通过抑制TGF-β信号通路,干预气道炎症反应,减少胶原沉积,从而干预肺纤维化进程。

基于网络药理学与分子对接探讨瓜蒌薤白半夏汤治疗心绞痛的作用机制

目的:通过网络药理学及分子对接技术探索瓜蒌薤白半夏汤治疗心绞痛的作用机制。方法:使用TCMSP数据库收集瓜蒌薤白半夏汤的有效成分,通过Uniprot数据库匹配有效成分的基因名称。在GeneCards数据库、DrugBank数据库、OMIM数据库、TTD数据库以及DisGeNET数据库中获取疾病相关靶点,绘制韦恩图,找到药物和疾病的共有靶点。在Cytoscape 3.7.1中构建“药物-有效成分-靶点网络”。使用STRING数据库对共有靶点进行蛋白质-蛋白质相互作用网络分析。通过Metascape数据库进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)信号通路富集分析。分子对接所需的配体与受体文件从PubMed数据库和PDB数据库下载,借助CB-DOCK进行分子对接验证。结果:瓜蒌薤白半夏汤治疗心绞痛的有效成分可能为黄芩素、柚皮素和槲皮素,涉及的核心靶点有丝氨酸/苏氨酸蛋白激酶1 (Akt Serine/Threonine Kinase 1,AKT1)、肿瘤蛋白p53(Tumor Protein p53,TP53)、肿瘤坏死因子(Tumor Necrosis Factor, TNF)、白细胞介素-6 (Interleukin-6,IL-6),主要涉及的信号通路有癌症通路、脂质和动脉粥样硬化、糖尿病并发症中的晚期糖基化终末产物-糖基化终末产物受体信号通路、磷脂酰肌醇3激酶-蛋白激酶B信号通路等。分子对接结果显示各成分与靶点的对接结果良好。结论:本研究通过网络药理学与分子对接技术初步揭示了瓜蒌薤白半夏汤治疗心绞痛的潜在化合物与作用机制,为进一步探索治疗心绞痛的潜在药物提供了新思路。

瓜蒌薤白汤正丁醇部位对Ⅱ型心肾综合征大鼠内质网应激的调控作用

目的:观察瓜蒌薤白汤(Gualou Xiebai Decoction,GXD)正丁醇部位对Ⅱ型心肾综合征大鼠内质网应激的影响,探讨瓜蒌薤白汤对心脏和肾脏的保护作用。方法:32只SPF级健康雄性Wistar大鼠随机分为假手术组、模型组和瓜蒌薤白汤高、低剂量组。除假手术组外,其余各组采用结扎左冠状动脉前降支的方法复制Ⅱ型心肾综合征大鼠模型,灌胃给予相应药物10周后,ELISA法检测血清中NT-proBNP、Cys-C的含量;取心脏、肾脏组织,HE染色观察心脏、肾脏的细胞形态学变化,Masson染色检测组织胶原沉积和纤维化程度;透射电镜观察内质网超微结构;RT-PCR检测心、肾组织Ⅰ、Ⅲ型胶原含量;Western blot检测内质网相关蛋白ATF-6、GRP78、XBP-1s、ATF-4、p-eIF2α、CHOP的表达。结果:与假手术组比较,模型组大鼠血清中NT-proBNP、Cys-C的水平明显升高(P<0.01),瓜蒌薤白汤高、低剂量组较模型组明显降低(P<0.01)。与模型组比较,瓜蒌薤白汤组能显著改善由慢性心衰引起的大鼠心脏、肾脏组织病理学改变;透射电镜观察发现,模型组大鼠内质网肿胀、断裂,核糖体脱落,瓜蒌薤白汤组心脏、肾脏内质网基本恢复正常。RT-PCR结果表明,模型组心脏、肾脏中Ⅰ、Ⅲ型胶原mRNA表达明显高于假手术组,瓜蒌薤白汤高、低剂量组明显低于模型组(P<0.01);瓜蒌薤白汤组内质网相关蛋白ATF-6、GRP78-、XBP-1s、ATF-4、p-eIF2α、CHOP的表达显著低于模型组(P<0.01)。结论:瓜蒌薤白汤对Ⅱ型心肾综合征大鼠心脏、肾脏具有明显的保护作用,且该作用可能与抑制内质网应激有关。

瓜蒌薤白白酒汤调节肠道菌群及其代谢物改善小鼠动脉粥样硬化的实验研究

目的探索瓜蒌薤白白酒汤通过调节肠道菌群(gut microbiota,GM)及其代产物从而改善小鼠动脉粥样硬化(atherosclerosis,AS)的作用机制。方法将32只雄性ApoE^(-/-)小鼠随机分为空白(Blank)组、模型(Model)组、阿托伐他汀(Ato)组、瓜蒌薤白白酒汤(GXB)组,每组8只。除Blank组以外的3组小鼠建立AS模型后按组别灌胃给药。用油红O染色检测主动脉斑块面积,HE染色观察主动脉组织病理变化。采用16S rRNA基因测序技术分析小鼠GM。检测小鼠GM代谢物氧化三甲胺(TMAO)、短链脂肪酸(SCFA)以及血清中TG、TC、LDL⁃C、HDL⁃C和NO水平。结果与Blank组比较,Model组、Ato组AS斑块面积均增多(P<0.01、P<0.001);Model组血清TG、TC、LDL⁃C水平升高(P<0.001),HDL⁃C、NO水平降低(P<0.01、P<0.001)。与Model组比较,Ato组、GXB组斑块面积减少(P<0.001);Ato组、GXB组中血清TG、TC、LDL⁃C水平降低(P<0.001),NO水平升高(P<0.01);GXB组HDL⁃C水平升高(P<0.05)。与Ato组比较,GXB组斑块面积减少(P<0.05),NO水平升高(P<0.01)。16S rRNA所得特征序列有6345个。α多样性分析提示GXB能降低AS小鼠GM的丰富度(P<0.001)并提升其均匀度(P<0.05)。β多样性分析提示GXB组的菌群群落结构与Blank组较为相似。各组菌群丰度在门水平、属水平上均存在差异。门水平上,小鼠AS造模后Proteobacteria的丰度上升(P<0.01),GXB干预后能使其丰度下降(P<0.01)的同时提升Verrucomicrobiota的丰度(P<0.05)。属水平上,GXB干预后能有效提升Akkermansia的丰度水平(P<0.05)。与Model组比较,GXB组中SCFA水平显著升高(P<0.01),TMAO水平显著降低(P<0.01)。结论本研究发现,瓜蒌薤白白酒汤可以调节GM及其代谢物SCFA、TMAO来改善AS,Akkermansia可能是GXB通过GM改善AS的关键菌属。

《金匮要略》柔痉的再辨析

由于历史背景的原因,仲景论治柔痉多从外感风寒入手,认为柔痉多由外感风寒过汗误治化热而来,瓜蒌桂枝汤为治疗柔痉一病的专方。而后世医家受温病学启发认为柔痉亦可由津液亏虚外感风热而发,瓜蒌桂枝汤非治疗柔痉之良方。通过分析原文与各家注释,旁参《伤寒论》中相关条文对《金匮要略》中柔痉的相关内容再次进行辨析,认为《金匮要略》中所论述的柔痉既可起于风寒误治,亦可源于津液亏虚直接外感风热,但其基本病机均为热盛津伤。而瓜蒌桂枝汤为治疗柔痉的主方,应当根据临床实际辨证用之。