Mechanism of Huanglian Detoxification Soup Relieving Postherpetic Neuralgia by Enhancing IL-2 Levels in Rats

[Objectives]To explore the mechanism of Huanglian detoxification soup improving pain behavior by affecting serum IL-2 levels in postherpetic neuralgia(post herpes neuralgia,PHN)model rats.[Methods]20 PHN rats were randomly divided into model group(PHN group)and detoxification decoction group(n=10).In the group,10%Huanglian detoxification soup(0.4 mL/0.1 kg)was given once in the morning and evening for 14 d.The PHN group was filled with an equal volume of 0.9%sodium chloride solution.Tail vein serum inflammatory factor interleukin-2(IL-2),IL-βand IL-6 levels were measured using ELISA kits at 7 and 21 d.[Results]IL-2 increased at 14 and 21 d in IL group,while IL-βand IL-6 decreased compared with the PHN group(P<0.05).[Conclusions]Huanglian detoxification soup may raise IL-2 levels after VZV infection to promote the differentiation of cells of the immune system,so as to relieve the pain caused by IL-βand IL-6 inflammatory factors.

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.

Clinical Efficacy of Huanglian Ointment in the Treatment of Chronic Eczema

Objective:To investigate and analyze the clinical efficacy of Huanglian ointment in the treatment of chronic eczema.Methods:114 cases of chronic eczema patients admitted to the Department of Dermatology of our hospital from January 2023 to January 2024 were selected as the study subjects.They were divided into a study group(n=57)and a reference group(n=57)using the double-blind method.The study group was treated with dialyzed Huanglian ointment,while the reference group was treated with conventional treatment.Symptom scores,inflammatory levels,treatment effects,and immune indexes of the two groups were similar before treatment.Results:After treatment,the symptom scores of the study group were significantly lower than those in the reference group(P<0.05).Besides,the interleukin-2(IL-2),tumor necrosis factor-a(TNF-a),interferon-(IFN-),and other inflammatory indicators of the study group were significantly better than those of the reference group(P<0.05).The total efficacy of treatment in the study group was significantly higher than that in the reference group(P<0.05).Furthermore,after treatment,the immunity indexes such as CD3+,CD4+,and CD8+of the study group were significantly better than those of the reference group,(P<0.05).Conclusion:Huanglian ointment is extremely effective for treating chronic eczema so this treatment program should be popularized.

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.

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.

Effects of Huanglian Jiedu Decoction on Rat Gingivitis Induced by LPS

[Objectives] To evaluate the effects of Huanglian Jiedu Decoration( HLJD) on the treatment of rat gingivitis with excess internal heat through injecting lipopolysaccharide( LPS) in tooth-supporting tissues. [Methods]Gingival inflammation was established by LPS injection. Male SD rats were randomly divided into 7 groups: normal control group( no treatment group),solvent control group,model group( LPS injection),HLJD low dose group( 0. 25 g/kg),HLJD medium dose group( 0. 50 g/kg),HLJD high dose group( 1. 00 g/kg),and metronidazole and fenbufen capsule( MFC) group. Water intake and urine volume were observed through metabolic cage feeding; gingival tissue protein expressions were detected by LC-ESI-MS/MS method; oxidative stress-related molecules such as total superoxide dismutase( T-SOD) and hydrogen peroxidase catalase( CAT) were detected by the biochemical kit combined with a microplate reader; expressions of TSC related with energy metabolism-related signaling pathway were detected by western blotting. [Results]When rat gingivitis was injected by LPS,both water intake and urine volume were decreased,the levels of T-SOD and CAT were decreased,and the expressions of fructose-bisphosphate aldolase C,triosephosphate isomerase 1 and TSC2 were increased. Huanglian Jiedu Decoration can increase water intake and urine volume,increase the levels of T-SOD and CAT,reduce the expressions of fructose-bisphosphate aldolase C and triosephosphate isomerase 1,and inhibit the expression of energy metabolism-related pathway molecule TSC2. [Conclusions] Huanglian Jiedu Decoration can treat rat gingivitis through inhibiting energy metabolism and oxidative stress such as TSC signal pathway and glycolysis related molecules.

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.

Study of dual-directional regulatory effect of Banxia （Pinellia ternata） and Huanglian （Coptis chinensis） drug pair on gastrointestinal movement of mice

摘要目的：观察半夏-黄连药对对功能性消化不良小鼠胃肠运动的调节作用.方法：采用三种不同配比的半夏-黄连药液（1：1,3：1,4：1）予昆明种雄性小鼠灌胃.10天后用阿托品腹腔注射法复制胃肠运动抑制模型,新斯的明腹腔注射法复制胃肠运动亢进模型,并且检测其小肠推进率.此外,使用与第一个实验相同的建模方法,对半夏-黄连3：1配比组设立高、中、低三种剂量浓度（4.68g/L,2.34g/L和1.17g/L）.运用酶联免疫吸附试验检测小肠组织内胃肠激素如胃泌素、血管活性肠肽和生长抑素的含量.结果：在新斯的明诱导的胃肠运动亢进模型中,3种不同配比的半夏-黄连药液（1：1,3：1,4：1）均能显著降低小鼠的小肠推进率（P=0.003,P=0.012,P=0.021）;在阿托品诱导的胃肠运动抑制模型组中,仅3：1配比的半夏-黄连药液能显著增加模型小鼠的小肠推进率.在新斯的明诱导的胃肠运动亢进模型中,半夏-黄连药液低剂量组、中剂量组和高剂量组的胃泌素水平均低于模型组（P=0.001,P=0.004,P=0.003）.半夏-黄连药液中剂量组和高剂量组的血管活性肠肽水平均高于模型组（P=0.004,P=0.002）.半夏-黄连药液中剂量组的生长抑素水平高于模型组（P=0.002）;在阿托品诱导的胃肠运动抑制模型中,半夏-黄连药液中剂量组和高剂量组的胃泌素水平均高于模型组（P=0.007,P=0.021）.半夏-黄连药液低剂量组,中剂量组和高剂量组的血管活性肠肽水平均高于模型组（P=0.001,P=0.001,P=0.001）.半夏-黄连药液中剂量组的生长抑素水平低于模型组（P=0.001和P=0.006）.结论：半夏-黄连可以通过影响小肠组织内的胃泌素、血管活性肠肽和生长抑素的水平来双向调节由阿托品及新斯诱导的小鼠功能性消化不良.

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。

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。

Comparative study of the protective effect between Jiawei huanglian jiedu decoction and Huanglian jiedu decoction in septic rats

Background Sepsis is a complex pathophysiologic process, which is the leading cause of death in the world. Many studies have revealed that Chinese medicine has shown tremendous advantages on the treatment of sepsis. Our study aims to explore the effect of Huanglian jiedu decoction and Jiawei huanglian jiedu decoction on organ function in septic rats. Methods SD rats were randomly divided into 7 groups, sham-group, cecal ligation and puncture group （CLP, 18h/72h）, Jiawei huanglian jiedu decoction group （JW, 18h/72h）, Huanglian jiedu decoc-tion group （W, 18h/72h）. Except the Sham group, the rats in other groups received cecal ligation and puncture method to induce sepsis. CLP groups were intragastric administration with normal saline after CLP. Huanglian jiedu decoction and Jiawei huanglian jiedu decoction groups were intragastric administration with Huanglian jie-du decoction and Jiawei huanglian jiedu decoction in the same time points. Glutamic-pyruvic transaminase （ALT）, glutamic oxalacetic transaminase （AST）, total bilirubin （TBIL）, creatinine（Cr）, urea, creatine kinase-MB （CK-MB）, lactate dehydrogenase （LDH） were detected by biochemical analyzer. Brain natriuretic peptide （BNP）, surfactant protein A （SP-A）, chemotactic factor for monocyte-1 （MCP-1）, D-lactic acid （D-LAC）, complement 5a, mobility group box-1 protein B 1 （HMGB-1）, interleukin 6 （IL-6） were analyzed by enzyme-linked immunosor-bent assay （ELISA）. Total lung capacity （TLC） and function residual capacity （FRC） were measured by buxco re-search system. The wet to dry weight ratio （W/D） was tested. Moreover, changes in tissue pathology were evaluat-ed using hematoxylin and eosin （H＆E） staining and electron microscope. Results The level of AST/ALT in se-rum was decreased after treatment with Huanglian jiedu decoction and Jiawei huanglian jiedu decoction. More-over, the level of TLC and FRC was significantly increased, and the level of SP-A, W/D was significantly de-creased. In addition, the level of CK-MB, IL-6, HMGB-1 and MCP-1 in serum was decreased. Inflammation fac-tors were positively correlated with lung function, and the cardiac function was positively correlated with the or-gan function, the differences were statistically significant. In addition, the histological alterations of myocardium, lung and intestine were attenuated after treatment with Huanglian jiedu decoction and Jiawei huanglian jiedu de-coction. Conclusion Huanglian jiedu decoction and Jiawei huanglian jiedu decoction can inhibit the inflamma-tory infiltration of septic rats and improve organ function.

小檗碱调节糖脂代谢作用机制研究进展

随着生活质量的提高,糖脂代谢紊乱导致的疾病如糖尿病、高脂血症、肥胖症、胰岛素抵抗、脂肪肝等的发生率逐年上升。中药黄连在治疗糖脂代谢紊乱相关疾病方面有着显著疗效。小檗碱为黄连中含量最高、代表性最强的活性成分,属异喹啉类生物碱,能通过保护胰岛β细胞,改善胰岛素抵抗、调节胰岛素分泌、促进胰高血糖素样肽1(GLP-1)分泌、调节肠道菌群调节糖代谢,通过减少脂质沉积、促进脂质清除等调节脂代谢,还可通过AMPK通路、肠道菌群等共同调节糖脂代谢。其来源广泛、作用安全,在防治糖脂代谢紊乱导致的相关疾病中有着多通路、多效应的优势。该文归纳总结国内外相关文献,对小檗碱调节糖脂代谢作用机制进行综述,以期为中医药改善糖脂代谢紊乱提供一定的思路和理论依据。