The effect of Huanglian Jiedu Decoction on inflammatory factors and oxidative stress in patients with acute ischemic stroke

Objective:To study the clinical efficacy of Huanglian Jiedu decoction in treating acute ischemic stroke(AIS)and its effects on inflammatory factors and oxidative stress.Method:A total of 53 patients with AIS were recruited as the study subjects and randomly divided into a control group and a treatment group using a random number table method.The control group consisted of 26 patients and the treatment group consisted of 27 patients.The control group received conventional Western medicine treatment.The control group received routine Western medicine treatment,while the treatment group received Huanglian Jiedu decoction based on the control group,with 14 days as a course of treatment.The effects of Huanglian Jiedu decoction on neurological function and activities of daily living were evaluated using the National Institute of Health stroke scale(NIHSS)and activities of daily living(ADL)scores.The effects of Huanglian Jiedu decoction on inflammatory reactions and oxidative stress were evaluated by detecting interleukin-4(IL-4),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),transforming growth factorβ(TGF-β),total antioxidative capacity(T-AOC),malondialdehyde(MDA),superoxide dismutase(SOD),and catalase(CAT)levels.Results:After treatment with Huanglian Jiedu Decoction,the ALD scores of AIS patients in both groups increased,while the NISHH scores decreased,suggesting that Huanglian Jiedu Decoction has therapeutic effects on AIS patients.It also reduces the levels of serum IL-6,TNF-α,MDA in AIS patients and increases the levels of IL-4,TGF-β,CAT,SOD,T-AOC,suggesting that Huanglian Jiedu decoction can improve the anti-inflammatory and antioxidant abilities of AIS patients.Conclusion:Huanglian Jiedu decoction can help AIS patients recover their neurological function,increase their capacity for self-care in daily life,and strengthen the body’s anti-inflammatory and antioxidant defenses.

Effect of Huanglian Jiedu Decoction on the Behavior of Zebrafish with Alzheimer's Disease

[Objectives]To study the effect of Huanglian Jiedu Decoction on the behavior of zebrafish with Alzheimer's disease caused by AlCl 3.[Methods]Each portion of Huanglian Jiedu Decoction was prepared according to the proportion of Coptis chinensis∶Phellodendron chinense Rupr.∶Scutellaria baicalensis Georgi∶Gardenia jasminoides Ellis=63 g∶42 g∶42 g∶63 g.After that,each portion of Huanglian Jiedu Decoction was soaked in 6.3 L water for 30 min and boiled twice at 100℃.The extracts were combined twice and filtered,then concentrated to 308 g/L and put into refrigerator for later use.Before training,zebrafishes were put into T-maze to adapt for 2 d,and then behavioral training was carried out for 7 d.After video recording,the behavior of zebrafish was analyzed by Smart 3.0,and qualified zebrafishes were selected for follow-up experiments.Then 60 successfully trained zebrafishes were randomly divided into control group,model group,positive group,low-dose group,medium-dose group and high-dose group of Huanglian Jiedu Decoction.Except for the control group,all the other groups were exposed to 100μg/L AlCl 3 for 7 d.After that,video was recorded,and behavioral analysis was carried out with behavioral record and analysis software Smart 3.0.And then the zebrafishes in the other four groups except the model group were treated with Huperzine A(4μg/L)and Huanglian Jiedu Decoction(154,308,616 mg/L)for 6 d,respectively.After that,it was recorded and the behavior of each group was analyzed.[Results]There was a significant difference in the time spent in the left area and the percentage of time in the left area between the control group and the model group(P<0.001).The time spent in the left area and the percentage of time in the left area in the model group and positive group,low,medium and high dose groups of Huanglian Jiedu Decoction decreased significantly(P<0.05,P<0.01,P<0.001).The swimming distance in the left area and the percentage of swimming distance in the left area in the model group were significantly higher than those in the control group(P<0.001).There was a significant difference in swimming distance between model group and positive group,low,medium and high dose groups of Huanglian Jiedu Decoction(P<0.01,P<0.001).In the percentage of swimming distance in the left area,there was a significant difference between the model group and the low and high dose groups of Huanglian Jiedu Decoction(P<0.01,P<0.001).[Conclusions]Huanglian Jiedu Decoction can improve the behavior of zebrafish with Alzheimer's disease.

Huanglian decoction suppresses the growth of hepatocellular carcinoma cells by reducing CCNB1 expression

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most prevalent cancers in human populations worldwide.Huanglian decoction is one of the most important Chinese medicine formulas,with the potential to treat cancer.AIM To investigate the role and mechanism of Huanglian decoction on HCC cells.METHODS To identify differentially expressed genes(DEGs),we downloaded gene expression profile data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma and Gene Expression Omnibus(GSE45436)databases.We obtained phytochemicals of the four herbs of Huanglian decoction from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.We also established a regulatory network of DEGs and drug target genes and subsequently analyzed key genes using bioinformatics approaches.Furthermore,we conducted in vitro experiments to explore the effect of Huanglian decoction and to verify the predictions.In particular,the CCNB1 gene was knocked down to verify the primary target of this decoction.Through the identification of the expression levels of key proteins,we determined the primary mechanism of Huanglian decoction in HCC.RESULTS Based on the results of the network pharmacological analysis,we revealed 5 bioactive compounds in Huanglian decoction that act on HCC.In addition,a protein-protein interaction network analysis of the target genes of these five compounds as well as expression and prognosis analyses were performed in tumors.CCNB1 was confirmed to be the primary gene that may be highly expressed in tumors and was significantly associated with a worse prognosis.We also noted that CCNB1 may serve as an independent prognostic indicator in HCC.Moreover,in vitro experiments demonstrated that Huanglian decoction significantly inhibited the growth,migration,and invasiveness of HCC cells and induced cell apoptosis and G2/M phase arrest.Further analysis showed that the decoction may inhibit the growth of HCC cells by downregulating the CCNB1 expression level.After Huanglian decoction treatment,the expression levels of Bax,caspase 3,caspase 9,p21 and p53 in HCC cells were increased,while the expression of CDK1 and CCNB1 was significantly decreased.The p53 signaling pathway was also found to play an important role in this process.CONCLUSION Huanglian decoction has a significant inhibitory effect on HCC cells.CCNB1 is a potential therapeutic target in HCC.Further analysis showed that Huanglian decoction can inhibit HCC cell growth by downregulating the expression of CCNB1 to activate the p53 signaling pathway.

Meta-analysis of the efficacy and safety of Huanglian Wendan Decoction alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance

Objective To evaluate the efficacy and safety of Huanglian Wendan Decoction(黄连温胆汤,HLWDD)alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance in recent 10 years.Methods The randomized controlled trials of HLWDD alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance from January 1,2012 to April 1,2022 were searched in China National Knowledge Infrastructure(CNKI),China Science and Technology Journal Database(VIP),Wanfang Database,China BioMedical Literature Database(CBM),PubMed,Web of Science,Embase,and Cochrane Library databases.After being screening,the included literature was analyzed to evaluate the effective rate,Pittsburgh Sleep Quality Index(PSQI)score,traditional Chinese medicine(TCM)syndrome score,and adverse reactions of HLWDD on insomnia caused by phlegm-heat internal disturbance.The subgroup analyzed the effect of HLWDD after different treatment courses,and compared the therapeutic effects of HLWDD alone and HLWDD combined with western medicine.Results Twenty-seven randomized controlled trials were finally included,with a total of 2395 patients.The results of the meta-analysis showed that the curative effect of HLWDD alone or combined with the western medicine group was better than that of the western medicine group[RR=1.14,95%CI(1.06,1.22),P=0.000].The PSQI score[SMD=-0.31,95%CI(-0.42,-0.20),P=0.000],TCM syndrome score[SMD=-0.40,95%CI(-0.67,-0.12),P=0.005],and adverse reaction rate[RR=0.21,95%CI(0.15,0.29),P=0.000]of HLWDD alone or combined with western medicine group were significantly reduced compared with the western medicine group.The subgroup’s analysis showed that the curative effect of HLWDD alone or combined with western medicine group of 4 weeks treatment course was better than that of the western medicine group[RR=1.14,95%CI(1.03,1.26),P<0.05].The TCM syndrome score of HLWDD alone or combined with the western medicine group of 4 weeks treatment course decreased more obviously than that of the western medicine group[SMD=-0.60,95%CI(-0.96,-0.25),P<0.05].There were no significant differences between HLWDD alone or combined with western medicine group and western medicine group with different treatment courses based on PSQI score and adverse reaction rate.Based on the effective rate,the comparison between the HLWDD alone group and the western medicine group[RR=1.09,95%CI(1.00,-1.20)P<0.05],and between the HLWDD combined with western medicine group and the western medicine group[RR=1.15,95%CI(1.03,1.29),P<0.05]was the same.PSQI score[SMD=-0.44,95%CI(-0.59,-0.30),P<0.05]and TCM syndrome score[SMD=-1.10,95%CI(-1.59,-0.61),P<0.05]of HLWDD combined with western medicine group were significantly lower than those of the western medicine group.There were no significant differences of adverse reaction rate between HLWDD alone group[RR=0.08,95%CI(0.04,0.17),P<0.05]and HLWDD combined with western medicine group[RR=0.36,95%CI(0.24,0.53),P<0.05].Conclusion HLWDD alone or combined with western medicine is an effective treatment for insomnia caused by phlegm-heat internal disturbance,which has a high effective rate,significantly reduced PSQI score and TCM syndrome score,and favorable safety.The best course of treatment is 4 weeks.

Cerebroprotective effect of Huanglian Jiedu decoction on amyloid protein precursor/presenilin-1 double transgenic mice

Huanglian Jiedu decoction （HLJDD） has been shown to improve cerebral blood flow, and reduce lipid peroxidation damage to the brain and its energy metabolism. The present study was designed to observe the cerebroprotective effect of HL.JDD on an Alzheimer＇s disease rodent model, presenilin-1/amyloid protein precursor double transgenic mice. HLJDD reduced serum interleukin-6 and interleukin-113 levels, decreased [3-amyloid precursor protein gene and senile plaque expression, resisted oxidation, and reduced free radical-induced injury, thereby improving the learning and memory of these mice. Moreover, HLJDD at 433 mg/kg per day exhibited better effects compared with that at 865 or 216 mg/kg per day, and donepezil hydrochloride at 30 mg/kg per day. Thus, these results suggest that HLJDD may have protective effects against Alzheimer＇s disease.

Effect of Huanglian Jiedu decoction on cogni⁃tive dysfunction of zebrafish with Alzheimer disease

OBJECTIVE To investigate the effects of Huanglian Jiedu decoction on cognitive dysfunction of zebrafish with Alzheimer disease.METHODS 126 g of coptis chinensis,84 g of phellorescent phellorescent chinensis,84 g of scutellaria chinensis and 126 g of gardenia chinensis were immersed in 10,8 and 8 times of water for 30 min,and then extracted at 100℃for 2,1.5 and 1.5 h,respectively.The three extracts were coarse filtered and concentrated into 308 g·L-1 and stored in refrigerator for later use.200 zebrafish were selected for behavioral train⁃ing in T-shaped tank for seven days.After that,the behavioral record analysis software Smart 3.0 was used to conduct behavioral analysis.Qualified zebrafish were selected as the blank group.Except for the blank group,zebrafish in the other 5 groups were exposed to AlCl3100μg·L-1 aquaculture water for modeling,and exposed for 6 d.The behavioral record analysis software Smart 3.0 was used to conduct behavioral analysis,and Select the successfully modeled zebraf⁃ish.After that,huperzine A(4μg·L-1)and Huan⁃glian Jiedu decoction of low,medium and high doses(154,308 and 616 mg·L-1)were adminis⁃tered respectively,and exposed for six days.Then,the behavior analysis was conducted again through the behavioral record analysis soft⁃ware Smart 3.0 to select qualified zebrafish.After the training,the brain and gut of zebrafish in each group were collected,and the expression changes of N-cadherin,p-P38/p38MAPK and p-Tau in the brain were detected by Western blot⁃ting and qPCR to show the effect of Huanglian Jiedu decoction on cognitive dysfunction of Zebrafish with Alzheimer disease.RESULTS Western blotting and qPCR results showed that the contents of N-cadherin increased(P<0.05),and the contents of p-P38/p38MAPK and p-Tau decreased(P<0.05)compared with the model group,indicating that Huanglian Jiadu decoction had an effect on the cognitive dysfunction of zebrafish with Alzheimer disease.CONCLU⁃SION Huanglian Jiedu decoction can alleviate cognitive dysfunction of zebrafish model with Alzheimer disease to a certain extent.

Mechanisms of Huanglian Jiedu Decoction in treating coronary heart disease and type 2 diabetes mellitus based on network pharmacology

Objective:To explore the common mechanism of Huanglian Jiedu Decoction in treating coronary heart disease and type 2 diabetes by network pharmacology.Methods:All chemical components and targets of the four drugs in Huanglian Jiedu Decoction were retrieved through TCMSP,and the genes were standardized through Uniprot database.Acquire disease targets related to coronary heart disease and diabetes in OMIM and GeneCards databases.The network diagram of"drug-component-target-disease"is constructed by using the software of cytopscape 3.7.2,the PPI network diagram of protein interaction is constructed by using STRING database,and the network diagram of"drug-disease"core target is constructed by using the software of cytopscape 3.7.2.DAVID's online database platform was used to analyze GO biological process and KEGG pathway enrichment of common targets of Huanglian Jiedu Decoction in treating coronary heart disease and type 2 diabetes.Results:103 active ingredients of Huanglian Jiedu Decoction were retrieved,including 140 acting targets,5342 coronary heart disease targets,114 diabetes targets,and 14 common intersection targets of drugs and diseases,involving AR,PPARG,TNF,IL6,CCL2,VEGFA,PON1,etc.The GO biological process analysis results in 98 biological processes,10 cell components and 10 molecular functions.Among them are positive regulation of gene expression,positive regulation of nitric oxide biosynthesis process,Extracellular space,cytokine activity,steroid hormone receptor activity and other biological processes;The enrichment analysis of KEGG pathway yielded 20 signal pathways(P≤0.05).It mainly involves Malaria,cancer in cancer,HIF-1 signaling pathway,TNF signaling pathway,NOD-like receptor signaling pathway,PI3K-Akt signaling pathway,etc.Conclusion:Huanglian Jiedu Decoction"treats different diseases at the same time"coronary heart disease and type 2 diabetes have the characteristics of multiple components,multiple targets and multiple pathways,which provide theoretical basis for Huanglian Jiedu Decoction to treat coronary heart disease and type 2 diabetes in clinic,but the key targets and pathways of Huanglian Jiedu Decoction to treat diseases still need further experimental verification.

Proteomics analysis of Huanglian Wendan decoction drug-containing serum on insulin resistance in 3T3-L1 cell

Objective:To explore possible mechanisms of Huanglian Wendan decoction drug-containing serum to improve insulin resistance.Method: 3T3-L1 fibroblasts were divided into control group, model group and TCM group. 3T3-L1 fibroblasts in model group and TCM group were induced to differentiation, and the 3T3-L1 adipocyte model of insulin resistance was constructed. The control group and model group were given normal serum stimulation, while the TCM group is treated with drug-containing serum. Finally, proceed bioinformatics analysis of the acquired differential expression protein by using TMT marking, liquid chromatography-mass (LC-MS) spectrometry, GO analysis and KEGG pathway analysis.Results:4982 proteins are identified in three groups of samples in this experiment, 4238 of them contain quantitative information. 210 up-regulate and 399 down-regulate proteins exist in model group and control group;221 up-regulate and 98 down-regulate ones are identified in TCM group and control group;310 up-regulate and 142 down-regulate proteins come to light with TCM group and control group. The result shows that the differentially expressed proteins were mainly distributed in s GO terms, such as DNA replication, nucleoplasm and protein binding of TCM group and control group. KEGG pathway enrichment analysis shows that, differentially expressed up-regulate proteins were enriched in 10 pathways, for instance DNA replication, cell cycle and mismatch repair, etc. Besides, differentially expressed down-regulate proteins were enriched in 25 pathways, enriched pathways are peroxisome, fatty acid degradation and metabolism process, etc.Conclusion: It is clear that Huanglian Wendan decoction drug-containing serum could improve insulin resistance by multi-targeting, multi-pathway synergy, and overall regulation.

The active ingredients of Huanglian Jiedu Decoction in treating COVID- 19 based on network pharmacology, molecular docking and molecular dynamics simulation

Objective:To explore the active ingredients of Huanglian Jiedu Decoction(HLJD)for the treatment of COVID-19 and to further verify the combination mode.Methods:The TCMSP database was used to search for HLJD active ingredients and targets.COVID-19 targets were collected from GeneCards,DisGeNET and OMIM databases.Material-active-ingredients-targets(gene)network and targets protein-protein interaction network were constructed using Cytoscape 3.8.0 and the STRING database.GO functional enrichment analysis and KEGG pathway enrichment analysis of core targets were performed using R software.Cytoscape 3.8.0 was used to build“compound-targets-pathways”to predict HLJD mechanisms,and active ingredients were used as ligands to molecularly dock with SARS-CoV-23CL hydrolase,Spike glycoprotein and ACE2.The binding energy was calculated by molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area method,and intermolecular interactions and the contribution of each residue to the binding free energy were analyzed.Results:Four medicinal materials,66 compounds and 219 targets were identified.It is found that the Protein-Protein Interaction core network contained 35 HLJD key targets proteins for COVID-19 treatment.705 GO functional enrichment entries(P<0.05)were produced;while KEGG pathway enrichment analysis identified 142 pathways(P<0.05)involving the Tumor Necrosis Factor signaling pathway and Interleukin-17 signaling pathway,etc.The binding energies of Kihadanin A,Palmidin A,Obacunone and Hispidone are much smaller than those of the currently reported clinical drugs with anti-SARS-CoV-2 drugs.The results of the binding energy indicate that van der Waals force is the main driving force for enzyme-substrate combination,whereas the electrostatic interaction and non-polar solvents contribute less.Conclusion:The“multi-component-multi-targets-multi-pathway”synergy of HLJD,which binds to SARSCoV-23CL hydrolase,Spike glycoprotein and ACE2,can act on targets Heat Shock Protein 90 Alpha Family Class A Member 1,Adrenoceptor Beta 2,Checkpoint Kinase 1,Peroxisome Proliferator-Activated Receptor Gamma and Mitogen-activated protein kinase 14 to regulate multiple signal pathways,and it may have a therapeutic effect on COVID-19.

Network pharmacology and molecular docking analysis on molecular targets and mechanism prediction of Huanglian Jiedu Decoction in the treatment of COVID-19

Objective To investigate and predict the molecular targets and mechanism of Huanglian Jiedu Decoction(黄连解毒汤,HLJDD)in the treatment of Corona Virus Disease 2019(COV-ID-19)through network pharmacology and molecular docking analysis.Methods The chemical constituents and action targets of HLJDD were retrieved on Tradi-tional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),SymMap v2,Encyclopedia of Traditional Chinese Medicine(ETCM),a High-throughput Ex-periment-and Reference-guided Database of Traditional Chinese Medicine(HERB),and Tra-ditional Chinese Medicine Integrated Database(TCMID).UniProt and GeneCards were used to query the target genes that corresponding to the active compounds,and then a compound-target network was constructed using Cytoscape 3.7.2.Gene Ontology(GO)database was used to annotate GO functions.Kyoto Encyclopedia of Genes and Genomes(KEGG)was used to predict the possible mechanisms of active compounds.The Database for Annotation,Visu-alization and Integrated Discovery(DAVID)was used to analysis the tissue enrichment.The main active compounds in HLJDD are molecularly docked with their corresponding related targets.Results Seventy-six compounds were screened and 458 corresponding targets in the network were obtained.Gene annotation showed that the targets were involved mainly in 1953 biolo-gical processes.884 signaling pathways was enriched,involving signaling by interleukins,cy-tokine signaling in immune system,generic transcription pathway,and RNA polymerase II transcription.The targets mainly distributed in the lung,liver,and placenta,involving a vari-ety of immune cells,such as T cells and B cells.The molecular docking results showed that core compounds such as wogonin,berberine,and baicalein had high affinity with tumor nec-rosis factor(TNF),insulin(INS),and tumor protein 53(TP53).Conclusion The active compounds in HLJDD may have a therapeutic effect on COVID-19 through regulating multiple signal pathways by targeting genes such as vascular endothelial growth factor A(VEGFA),INS,interleukin-6(IL-6),TNF,caspase-3,TP53,and mitogen-activ-ated protein kinase 3(MAPK3).

Effect of Huanglian Jiedu Decoction on cardiac endoplasmic reticulum stress in spontaneously hypertensive rats

Huanglian Jiedu Decoction(HLJDD)is a quintessential prescription renowned for its heat-clearing and detoxifying properties.It is primarily prescribed to counteract the syndrome characterized by the excessive heat of the Sanjiao fire.Notably,the hyperactivity of liver fire is frequently linked with hypertension,where wind fire and wind toxicity emerge as pivotal pathogenic factors.This study aimed to investigate the impact of HLJDD on the endoplasmic reticulum in spontaneously hypertensive rats(SHR),further delving into the interplay between endoplasmic reticulum stress(ERS)and myocardial remodeling and damage.Fifty SHR rats were stratified randomly into five cohorts:model,low-dose HLJDD,medium-dose HLJDD,high-dose HLJDD,and captopril groups.For comparison,a set of Wistar-Kyoto(WKY)rats served as the baseline control group,with each group comprising 10 rats.While the model and control groups received equivalent volumes of normal saline via gavage,the other groups were administered the respective drug dosages through the same route daily for a span of 6 weeks.Upon the experiment’s conclusion,metrics such as the heart mass index(HWI)and left ventricular mass index(LVWI)were assessed.Cardiac tissue anomalies were identified using H&E staining,while ERS-related protein and mRNA expression levels were ascertained via Western blotting analysis and qPCR.Moreover,TUNEL staining was employed to detect cardiomyocyte apoptosis.The findings indicated that increasing HLJDD concentrations corresponded with escalated HWI and LVWI in rat hearts(P<0.05).There was a marked enhancement in myocardial structural integrity,accompanied by a notable reduction in collagen fibers.The mRNA and protein expressions of myocardial inositol-dependent enzyme 1α(IRE1α),X-box binding protein 1(XBP1),glycoregulatory protein 78(GRP78),and CCAAT enhancer binding protein homologous protein(CHOP)in the medium and high-dose groups saw significant declines(P<0.05).These effects mirrored those observed in the captopril group.The study underscored HLJDD’s efficacy in mitigating myocardial tissue damage in SHR.This therapeutic effect was potentially attributed to the downregulation of IRE1α,XBP1,GRP78,and CHOP,curbing excessive ERS,diminishing cardiomyocyte apoptosis,and thereby conferring cardioprotection.

黄连解毒汤通过抑制NLRP3炎性小体改善Tau/APP/PS1转基因AD小鼠神经元损伤的机制研究

目的 探讨黄连解毒汤对Tau/APP/PS1转基因阿尔茨海默病(Alzheimer's disease,AD)小鼠神经元损伤的影响及机制。方法 将Tau/APP/PS1转基因AD小鼠随机分成模型组和黄连解毒汤低、中、高剂量组,每组10只。选取10只相同月龄的雄性C57BL/6J小鼠作为对照组。药物干预4周后,ELISA法检测小鼠海马组织炎症因子及AD相关病理标志物可溶性淀粉酶前体蛋白α(soluble amyloid precursor protein α,s APPα)、β-淀粉样蛋白(amyloid β-protein,Aβ)40、Aβ42和磷酸化Tau蛋白(phosphorylated tau protein,p-Tau)的水平,免疫荧光双标法检测海马Nod样受体蛋白3(nod-like receptor protein 3,NLRP3)炎性小体和小胶质细胞特异性标志物离子钙结合衔接分子1(ionized calcium binding adapter molecule 1,Iba1)的表达,Western blot检测小鼠海马NLRP3炎性小体信号通路活化情况。结果 与对照组比较,模型组小鼠海马中NLRP3、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing CARD,ASC)、含半胱氨酸的天冬氨酸蛋白水解酶(cysteinyl aspartate specific proteinase,Caspase)-1和Iba1表达明显增加(P<0.05),炎症因子白细胞介素(interleukin,IL)-1β、IL-18、肿瘤坏死因子(tumor necrosis factor,TNF)-α水平上升(P<0.05),Aβ40、Aβ42和p-Tau水平及p-Tau/Tau值均升高(P<0.05),s APPα水平下降(P<0.05)。与模型组比较,不同剂量黄连解毒汤治疗组小鼠海马中s APPα水平上升(P<0.05),Aβ40、Aβ42及Tau蛋白磷酸化水平均明显下降(P<0.05),IL-1β、IL-18、TNF-α水平降低(P<0.05),NLRP3、ASC、Caspase-1和Iba1表达减少(P<0.05)。结论 黄连解毒汤可能通过下调AD小鼠海马NLRP3炎性小体信号通路活性,抑制小胶质细胞活化,降低Aβ、p-Tau等神经元毒性病理产物的水平,从而改善海马神经元损伤。

加味黄连温胆汤治疗代谢综合征的临床疗效及其对认知功能的影响

目的:研究加味黄连温胆汤治疗痰瘀互结型代谢综合征(MS)的临床疗效及其对认知功能的影响。方法:选取2022年6月—2023年3月就诊于黑龙江中医药大学附属第一医院心血管一科门诊的MS合并轻度认知功能障碍(MCI)病人70例,运用随机数字表法将其分为两组,对照组采用常规西药治疗,观察组在此基础上联合加味黄连温胆汤。治疗4周后,比较两组病人治疗前后中医证候积分、体质指数(BMI)、收缩压(SBP)、舒张压(DBP)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、空腹血糖(FPG)、血清胰岛素(FINS)及胰岛素抵抗指数(HOMA-IR)、蒙特利尔认知评估量表(MoCA)评分及不良反应发生情况。结果:治疗后两组病人中医证候积分、BMI、SBP、DBP、TG、TC、LDL、FPG、FINS及HOMA-IR水平均较治疗前降低,且观察组明显优于对照组,差异均有统计学意义(P<0.05)。治疗后两组MoCA评分及HDL水平均提高,且观察组优于对照组,差异均有统计学意义(P<0.05)。两组病人治疗中均未发生不良反应。结论:加味黄连温胆汤联合常规西药治疗可有效改善MS合并MCI病人的临床症状,调节糖脂代谢,改善认知功能,且无不良反应。

黄连解毒汤加减联合Onlay植骨术治疗重度牙周炎的临床效果

目的:探讨黄连解毒汤加减联合Onlay植骨术治疗重度牙周炎的临床效果。方法:选择2021年9月—2023年5月于遂宁市中心医院口腔分院就诊的重度牙周炎患者92例,采用随机数字表法分成常规组和中药组,每组46例。常规组采用Onlay植骨术治疗,中药组在常规组的基础上采用黄连解毒汤加减治疗。观察两组患者的中医证候积分、牙龈出血指数(BI)、牙周袋深度(PD)、附着丧失(CAL)、菌斑指数(PLI)水平、白介素-23(IL-23)、白介素-1β(IL-1β)、基质金属蛋白酶-8(MMP-8)、基质金属蛋白酶抑制剂-1(TIMP-1)、牙槽嵴骨量、临床疗效及不良反应发生情况。结果:治疗前,两组患者中医证候积分比较,差异无统计学意义(P>0.05);两组患者PD、BI、PLI、CAL水平比较,差异无统计学意义(P>0.05);两组患者IL-23、IL-1β、MMP-8及TIMP-1水平比较,差异无统计学意义(P>0.05);两组患者牙槽嵴骨量比较,差异无统计学意义(P>0.05)。治疗后,中药组患者BI、PD、CAL、PLI水平、中医证候积分与IL-23、IL-1β及MMP-8水平均低于常规组(P<0.01);中药组TIMP-1水平与牙槽嵴骨量高于常规组(P<0.01);中药组患者治疗总有效率高于常规组(P<0.05);不良反应总发生率两组差异无统计学意义(P>0.05)。结论:黄连解毒汤加减联合Onlay植骨术治疗能够改善患者牙周情况及龈沟液生化指标,降低中医证候积分,提高患者牙槽嵴骨量与临床疗效,安全性较高。

基于TLR4/NF-κB/NLRP3信号通路探讨黄连解毒汤对冠状动脉性心脏病小鼠心肌保护作用

目的 研究基于Toll样受体4(TLR4)/核转录因子-κB(NF-κB)/NOD样受体蛋白3(NLRP3)信号通路探讨黄连解毒汤对冠状动脉粥样硬化性心脏病(CHD)小鼠心肌保护作用。方法 50只6周的雄性SD小鼠中取10只作正常对照组,其余小鼠给予高脂饮食建立CHD模型。采用随机数字表法将40只模型小鼠分为模型组、黄连解毒汤低、中、高剂量组,每组各10只。黄连解毒汤低、中、高剂量组每日分别以10、20、40 g/kg剂量进行灌胃,每日1次,持续6周;正常组、模型组每日给予等量蒸馏水灌胃。干预后采用生化法检测各组总胆固醇、甘油三酯、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)水平,酶联免疫吸附试验检测超氧化物歧化酶(SOD)、丙二醛、内皮素水平;采用苏木精-伊红染色法观察小鼠心肌细胞病理形态,蛋白质印迹法检测心肌组织中TLR4、NF-κB、NLRP3的表达。比较各组小鼠血脂、心肌组织中抗氧化相关指标和TLR4、NF-κB、NLRP3的表达。结果 模型组、黄连解毒汤低、中、高剂量组血脂水平均高于对照组,差异均有统计学意义(P<0.05);黄连解毒汤低剂量组与模型组血脂水平比较,差异无统计学意义(P>0.05);黄连解毒汤中、高剂量组总胆固醇、甘油三酯、LDL水平均低于模型组,HDL水平高于模型组,差异均有统计学意义(P<0.05)。模型组、黄连解毒汤低、中、高剂量组心肌组织中SOD水平均低于对照组,丙二醛、内皮素水平均高于对照组,差异均有统计学意义(P<0.05);黄连解毒汤低、中、高剂量组SOD水平均高于模型组,丙二醛、内皮素水平均低于模型组,差异均有统计学意义(P<0.05)。对照组心肌纤维排列整齐,横纹清晰且细胞完整,无细胞肿胀、炎症浸润等;模型组心肌纤维排列紊乱,结构发生异常,有严重细胞肿胀、炎症浸润;黄连解毒汤低、中、高剂量组未见心肌纤维断裂,黄连解毒汤中、高剂量组细胞肿胀和炎症浸润情况优于黄连解毒汤低剂量组,黄连解毒汤高剂量组优于黄连解毒汤中剂量组。模型组、黄连解毒汤中、高剂量组TLR4、NF-κB、NLRP3蛋白表达量均高于对照组,差异均有统计学意义(P<0.05);黄连解毒汤低、中、高剂量组TLR4、NF-κB、NLRP3蛋白表达量均低于模型组,差异均有统计学意义(P<0.05)。且黄连解毒汤各剂量组中以上指标变化呈剂量依赖性。结论 黄连解毒汤能降低CHD小鼠血脂水平,保护心肌细胞,其能够通过下调组织TLR4、NF-κB、NLRP3蛋白表达以调节血脂水平并改善心肌功能,且黄连解毒汤的效果随着剂量的增加而增强。

超声龈下刮治联合黄连解毒汤加味含漱治疗慢性牙周炎临床研究

目的:观察超声龈下刮治联合黄连解毒汤加味含漱治疗慢性牙周炎热毒炽盛证的临床疗效。方法:选取104例慢性牙周炎热毒炽盛证患者,按随机数字表法分成对照组和观察组各52例。对照组剔除2例,最终纳入研究观察组52例、对照组50例。2组均进行龈上洁治、抛光,7 d后进行超声龈下刮治。对照组给予0.9%氯化钠溶液含漱,观察组给予黄连解毒汤加味含漱。比较2组临床疗效、牙周指数[牙周探诊深度(PD)、牙龈指数(GI)、牙龈出血指数(BI)、菌斑指数(PLI)]、龈沟液中炎症因子[白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)]水平及龈沟液中氧化应激指标[丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、一氧化氮(NO)]水平。结果:治疗1个月后,观察组临床疗效总有效率98.08%,高于对照组84.00%(P<0.05)。2组PD、GI、BI、PLI均较治疗前降低(P<0.05),观察组上述4项牙周指数均低于对照组(P<0.05)。2组龈沟液中IL-1β、TNF-α水平均较治疗前降低(P<0.05),观察组龈沟液中IL-1β、TNF-α水平均低于对照组(P<0.05)。2组龈沟液中MDA、NO水平均较治疗前降低(P<0.05),龈沟液中SOD、GSH-Px水平均较治疗前升高(P<0.05);观察组龈沟液中MDA、NO水平均低于对照组(P<0.05),龈沟液中SOD、GSH-Px水平均高于对照组(P<0.05)。结论:超声龈下刮治联合黄连解毒汤加味含漱治疗慢性牙周炎热毒炽盛证,可有效改善牙周症状,作用机制可能与抑制牙周组织炎症及改善牙周组织氧化应激反应有关。

黄连解毒汤对ApoE^(-/-)小鼠动脉粥样硬化炎症及主动脉斑块稳定性作用的机制研究

目的观察黄连解毒汤对ApoE^(-/-)小鼠主动脉粥样硬化炎症及斑块稳定性的影响,探讨黄连解毒汤治疗主动脉斑块稳定性的作用机制。方法将36只ApoE^(-/-)小鼠随机分为空白组,模型组,黄连解毒汤低、中、高剂量组,阿托伐他汀组,每组6只。模型组及给药组ApoE^(-/-)小鼠给予高脂饮食构建主动脉粥样硬化模型8周后,黄连解毒汤低、中、高剂量组小鼠分别按10、20、40 g/(kg·d)剂量给予黄连解毒汤;阿托伐他汀组小鼠按10 mg/(kg·d)剂量给予阿托伐他汀;空白组、模型组给予等量的蒸馏水。每日灌胃1次,共8周。第16周末采集标本,采用苏木精—伊红染色观察各组小鼠主动脉内膜的组织形态;半自动生化分析仪检测各组小鼠血清总胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)、低密度脂蛋白—胆固醇(low density lipoprotein-cholesterol,LDL-C)及高密度脂蛋白—胆固醇(high density lipoprotein-cholesterol,HDL-C)水平;采用ELISA法检测各组白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-10(interleukin-10,IL-10)含量;组织学特殊病理染色技术测定斑块内巨噬细胞含量、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)细胞含量、斑块内胶原纤维含量及斑块内脂质含量,从而计算斑块不稳定指数(vulnerability index,VI)。结果黄连解毒汤能明显改善小鼠主动脉管壁的病理变化。与空白组比较,模型组小鼠血清TC、TG、LDL-C水平均显著上升(P<0.05),HDL-C水平显著下降(P<0.05);IL-1β、IL-6、TNF-α含量均显著增加(P<0.05),IL-10含量显著减少(P<0.05);VI显著增加(P<0.05)。与模型组比较,黄连解毒汤中、高剂量组小鼠血清TG、TC、LDL-C水平均显著下降(P<0.05),HDL-C水平显著上升(P<0.05);IL-1β、IL-6、TNF-α含量均显著减少(P<0.05),IL-10含量显著增加(P<0.05);各给药组小鼠主动脉内膜斑块VI均显著减少(P<0.05)。黄连解毒汤高剂量组改善上述指标的效果与阿托伐他汀组相当(P>0.05)。结论黄连解毒汤对动脉粥样硬化ApoE^(-/-)小鼠主动脉血管内炎症反应及斑块稳定性具有一定的改善作用,且呈剂量依赖性,其机制可能与降低血脂水平、缓解炎症损伤有关。

从胆论治失眠研究概况

现今社会,失眠的发病率正逐年递增,已成为临床上的常见病、多发病,严重危害了人们的身心健康,因此如何有效地防治失眠备受医学界关注。中医药治疗失眠,从整体观念出发,辨证分型,个体化治疗,用药安全,疗效稳定,相较西药颇受患者推崇。文章结合中医理论,从胆为少阳之枢、胆主决断、喜静谧、十一脏取决于胆、胆与三焦的关系等理论出发,突出胆腑在睡眠中的关键作用。参考历代相关文献记载,将胆病不寐分为胆寒证、胆火证、胆郁痰扰证、胆虚证4个证型进行辨证。并结合现代药理实验研究,将黄连温胆汤作用于失眠的相关机制进行归纳,认为其多与抑制失眠患者的炎症介质血清水平、方药成分中含有类黄酮化合物两方面关系密切。其方药多被现代医家所应用,临床疗效突出,颇受推崇。故作者认为从胆腑论治失眠不失为一种佳法,使“阴平阳秘,精神乃治”,以期更好地指导临床实践。

黄连温胆汤联合西格列汀治疗老年T2DM的效果及对患者炎症水平的影响

目的探究黄连温胆汤联合西格列汀治疗老年2型糖尿病(T2DM)效果及对患者炎症水平的影响。方法回顾性分析2020年5月至2023年5月鹿邑县人民医院收治的108例老年T2DM患者的临床资料,按照治疗方案不同分为对照组52例和研究组56例。对照组患者予以常规生活方式干预联合西格列汀治疗,研究组患者在对照组治疗的基础上加用黄连温胆汤,两组患者均连续治疗8周。治疗8周后,比较两组患者的治疗效果,以及治疗前后的糖脂代谢相关指标[空腹血糖(FPG)、餐后2 h血糖(2 h PG)、低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)]、胰岛素相关指标[胰岛素敏感指数(ISI)、胰岛β细胞功能指数(HOMA-β)、胰岛素抵抗指数(HOMA-IR)]、炎症因子水平[肿瘤坏死因子(TNF-α)、白细胞介素(IL)-6、IL-10]和血清核因子-κB(NF-κB)m RNA和Toll样受体4(TLR4)m RNA表达水平,同时比较两组患者治疗期间的药物不良反应情况。结果研究组患者的治疗总有效率为85.71%,明显高于对照组的67.31%,差异有统计学意义(P<0.05);治疗前,两组患者的糖脂代谢相关指标比较差异无统计学意义(P>0.05),治疗8周后,两组患者的糖脂代谢相关指标较治疗前均降低,且研究组患者的FPG、2 h PG、LDL-C、TC分别为(5.89±1.32)mmoL/L、(10.21±2.30)mmoL/L、(2.83±0.57)mmoL/L、(4.62±0.61)mmoL/L,明显低于对照组的(7.22±1.44)mmoL/L、(12.32±2.25)mmoL/L、(3.22±0.49)mmoL/L、(5.01±0.47)mmoL/L,差异均有统计学意义(P<0.05);治疗前,两组患者的ISI、HOMA-β及HOMA-IR水平比较差异均无统计学意义(P>0.05),治疗8周后,两组患者的ISI、HOMA-β水平较治疗前均升高,而HOMA-IR较治疗前均降低,且研究组患者的ISI、HOMA-β水平明显高于对照组,HOMA-IR水平明显低于对照组,差异均有统计学意义(P<0.05);治疗前,两组患者的TNF-α、IL-6、IL-10及NF-κB m RNA及TLR4 m RNA表达水平比较差异均无统计学意义(P>0.05),治疗8周后,两组患者的TNF-α、IL-6及NF-κB mRNA及TLR4 mRNA表达水平较治疗前均降低,而IL-10水平较治疗前均升高,且研究组患者的TNF-α、IL-6及NF-κB mRNA及TLR4 mRNA表达水平明显低于对照组,IL-10水平明显高于对照组,差异均有统计学意义(P<0.05);治疗期间对照组患者药物不良反应发生率为7.69%,略高于研究组的7.14%,但差异无统计学意义(P>0.05)。结论黄连温胆汤联合西格列汀治疗老年T2DM的效果显著,能有效改善患者糖脂代谢水平及胰岛素抵抗情况,减轻患者炎症反应,其作用机制可能与调控机体TLR4/NF-κB通路表达有关。

黄连解毒汤调控肠道菌群介导的色氨酸代谢干预帕金森病作用机制研究

目的 基于16S rRNA技术及非靶向代谢组学技术,分析黄连解毒汤对帕金森模型小鼠肠道菌群及代谢产物的影响,探究黄连解毒汤干预帕金森病(PD)的作用机制。方法 通过皮下注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP,20 mg·kg^(-1)·d^(-1))联合丙磺舒(200 mg·kg^(-1)·d^(-1))腹腔注射诱导帕金森小鼠模型,给予黄连解毒汤干预后,测定小鼠的体质量、行为学指标;采用HPLC-QTRAP-MS/MS技术检测小鼠纹状体神经递质的水平;采用ELISA法检测小鼠纹状体炎性因子的水平;采用16S rRNA技术分析小鼠肠道菌群的变化;采用UHPLC-Q-TOF-MS检测小鼠粪便、纹状体内源性代谢物水平,结合主成分分析(PCA)及正交偏最小二乘判别分析(OPLS-DA)筛选潜在的差异代谢物,导入MetaboAnalyst 5.0预测与PD有关的代谢途径。结果 黄连解毒汤显著改善帕金森小鼠的运动症状及神经炎症(P<0.01),调节小鼠神经递质水平(P<0.01),并纠正帕金森模型小鼠的肠道菌群紊乱,表现为肠道微生物多样性增加、菌群轮廓的恢复等。黄连解毒汤治疗后显著增加帕金森模型小鼠肠道中普雷沃氏菌、阿克曼菌等的丰度,下调梭状菌的丰度,并主要通过对帕金森模型小鼠粪便、纹状体中色氨酸代谢通路进行调节,恢复异常代谢产物水平。结论 黄连解毒汤显著改善帕金森模型小鼠的病理损伤,调节紊乱的肠道菌群及色氨酸代谢通路可能是黄连解毒汤干预PD的潜在机制。