Allotetraploidization event of Coptis chinensis shared by all Ranunculales

Coptis chinensis Franch.,also named Chinese goldthread is a member of Ranunculaceae in the order Ranunculales and represents an important lineage of early eudicots with traditional medicinal value.In our study,by using syntenic analysis combined with phylogenomic analysis of C.chinensis and four other representative genomes from basal and core eudicots,we confirmed that the WGD event in C.chinensis was shared by Aquilegia coerulea and Papaver somniferum L.and quickly occurred after Ranunculales diverged from other eudicots,likely a Ranunculales common tetraploidization(RCT).The synonymous nucleotide substitutions at synonymous sites distribution of syntenic blocks across these genomes showed that the evolutionary rate of the P.somniferum genome is faster than that of the C.chinensis genome by approximately 13.7%,possibly due to Papaveraceaes having an additional special tetraploidization event(PST).After Ks correction,the RCT dated to 115—130 million years ago(MYA),which was close to the divergence of Ranunculaceaes and Papaveraceaes approximately115.45—130.51 MYA.Moreover,we identified homologous genes related to polyploidization and speciation and constructed multiple sequence alignments with different reference genomes.Notably,the event-related subgenomes in the basal genomes all showed genomic fractionation bias,suggesting a likely allopolyploid nature of the RCT,PST and T-Alpha and T-Beta events in Tetracentron sinense.In addition,we detected that the sixteen P450 subfamilies were markedly expanded in the genomes of Ranunculales,and most of them were related to the RCT and PST events.We constructed a new platform for Early Eudicot Comparative Genomic Research(http://www.cgrpoee.top/index.html)to store more information.In summary,our findings support the WGD of C.chinensis shared by Ranunculales,which is likely an allotetraploidization event.This present effort offered new insights into the evolution of key polyploidization events and the genes related to secondary metabolites during the diversification of early eudicots.

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.

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.

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.

Optimization of Compound Coptis Ointment Extraction through the Integration of Pharmacodynamic Indices and Orthogonal Test

[Objectives]To determine the optimal reflux extraction process conditions for Compound Coptis Ointment.[Methods]The study employed the orthogonal experimental design method and drug-sensitive disc agar diffusion method to evaluate the extraction rate,berberine hydrochloride content,and bacteriostatic ring diameter of the extract as comprehensive indices,and optimized the extraction process conditions of Compound Coptis Ointment using ethanol reflux.[Results]Based on the results of comprehensive indices,the optimal reflux extraction conditions for Compound Coptis Ointment were determined to be soaking in 1.5 times the amount of 70%ethanol for 2 h,followed by two extractions with 6 times the amount of 70%ethanol for 1 h each time.Three verification tests were conducted under the optimal process conditions.The yield of the extract was 28.32%±0.53%,the content of berberine hydrochloride was 4.68%±0.45%,and the diameter of the bacteriostatic ring was(2.5±0.2)cm.[Conclusions]The extract had higher drug content and exhibited better antibacterial effects.The optimized extraction process is simple,stable,and reliable,and can be effectively used to optimize the extraction process of Compound Coptis Ointment.

Effects of Different Alkaloids in Coptis chinensis on Inhibiting TGEV Proliferation

[Objectives]To study the effects of different alkaloids in Coptis chinensis on inhibiting the proliferation of Transmissible gastroenteritis virus(TGEV).[Methods]The components and content of the main alkaloids in the extract of C.chinensis were analyzed.The main alkaloids were selected as drugs to inhibit the proliferation of TGEV.The maximum non-toxic concentration of Columbamine,Jatrorrhizine,Epiberberine,Coptisine,Palmatine,and Berberine was screened.The protective rate of each drug on TGEV-infected ST cells was determined,and the transcriptional inhibitory effect of the drug on TGEV N gene was detected by fluorescent quantitative PCR.[Results]The extract of C.chinensis mainly contains 6 alkaloids:Columbamine,Jatrorrhizine,Epiberberine,Coptisine,Palmatine,and Berberine,accounting for 2.03%,8.88%,9.21%,15.07%,14.63%,and 50.18%,respectively.In the range of the safe concentration,Jatrorrhizine,Palmatine,and Coptisine had better protective effects on ST cells infected with TGEV;compared with the Columbamine group,the cell protection rate was significantly different(P<0.05);compared with the Berberine group,the difference was extremely significant(P<0.01).The Coptisine and Palmatine groups had significant inhibitory effects on the transcription of TGEV N gene,and the difference was extremely significant compared with the virus group(P<0.05).[Conclusions]Jatrorrhizine and Palmatine in C.chinensis are the main components to inhibit the proliferation of TGEV.

黄连生物碱对TGEV诱导的ST细胞炎症反应的调节作用

分别用质量浓度为100、50、25μg/m L的黄连生物碱(ACC)处理猪传染性胃肠炎病毒(TGEV)感染的猪睾丸细胞(ST),采用噻唑蓝(MTT)法检测细胞的活力;采用硝酸还原酶法检测NO含量;采用比色法检测总一氧化氮合成酶(TNOS)和诱导型一氧化氮合成酶(i NOS)活性;采用荧光定量PCR检测TNF-α、IL-1β、IL-6、IL-10等炎症基因的表达。结果表明:100、50μg/mL的ACC可极显著提高TGEV感染的ST细胞的存活率,25μg/mL的ACC可显著提高TGEV感染的ST细胞存活率;TGEV感染后ST细胞NO含量急剧升高,100、50μg/mL的ACC可极显著降低ST细胞TNOS和i NOS活性,25μg/mL ACC可显著降低TNOS和i NOS活性;ACC可极显著下调ST细胞TNF-α、IL-1β、IL-6、IL-10m RNA的表达水平。表明黄连生物碱可以降低TGEV诱导的ST细胞的炎症反应,缓解病毒对细胞的损伤。

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。

复合木霉制剂防治黄连根腐病及其机理研究

为评价复合木霉制剂对黄连根腐病的防治效果,并揭示其防病机理,为黄连根腐病专用微生物农药的研发奠定基础,本试验将深绿木霉Trichoderma atroviride、长枝木霉T.longibrachiatum、钩状木霉T.hamatum、拟康宁木霉T.koningiopsis等4种木霉配制的复合制剂和尖镰孢Fusarium oxysporum以不同的方式分别施用于黄连,统计根腐病发生情况,检测黄连根部防御酶活性,用高通量测序分析根际土壤真菌群落结构。结果表明,复合木霉制剂对尖镰孢导致的根腐病具有明显预防效果;复合木霉制剂和尖镰孢分别接种黄连可提高SOD、POD、CAT、PAL、PPO等防御性酶活性,产生诱导抗性;而它们先后接种黄连可产生强化效应,从另一个途径提高植株抗病性。复合木霉制剂和尖镰孢都会降低真菌的数量、多样性,和某些真菌的相对丰度,而复合木霉制剂的抑菌作用更强烈,尤其能明显抑制尖镰孢、Ilyonectria sp.等病原真菌的生长,且能改善土壤真菌群落结构。木霉和尖镰孢都能在土壤中较长期定殖。可见,复合木霉制剂可以预防尖镰孢导致的黄连根腐病,防病机理包括诱导黄连植株产生抗性,接种后再遭受病原菌侵染产生的强化效应,优化土壤真菌群落结构,抑制土壤中病原菌等,且有效期较长。因此复合木霉制剂具有开发为微生物农药防治黄连根腐病的潜力。

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。

黄连的化学成分及药理作用研究进展

黄连是我国传统大宗中药,最早在《神农本草经》中被列为上品,到现在为止有两千多年的入药史。黄连是毛茛科多年生草本植物,是多种药方的构成基础。黄连物质基础繁多、药理作用复杂,且随着现代研究的不断深入,黄连新的化学成分不断被发掘,为进一步探索黄连的生产及功能价值,进而促进黄连的应用和开发。本文从黄连的生物学特性、化学成分、药理作用以及药用价值开发方面进行综述,发现黄连化学成分主要为生物碱、黄酮类、木脂素、酸性化合物、多糖类、甾体类及人体所必需的氨基酸、微量元素等,可通过不同的途径和作用靶点起到抑菌、降血糖、抗炎、抗氧化、抑制癌细胞增殖、缓解心肌缺血等药理作用。因此,应对黄连的化学成分进行系统性分离提取和生物活性测定,以及对相关机制加以研究。

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。

黄连解毒散治疗牛附红细胞体病的效果研究

[目的]通过使用黄连解毒散治疗牛附红细胞体病,探究更合理的治疗方案。[方法]选取呼伦贝尔某养殖场患有牛附红细胞体病的肉牛20例,随机分为4组,分别为高剂量黄连解毒散组(A)、中剂量黄连解毒散组(B)、低剂量黄连解毒散组(C)、西药对照组(D),A、B、C组分别给予80、60、40 g/d剂量的黄连解毒散,D组为100g/d剂量的土霉素。分别于给药第5天、给药第10天、停药后第5天进行记录,并分析治愈率、复发率以及预后生产性能变化情况。[结果]给药第5天,D组治愈率最高,为60%;而给药第10天,B组治愈率优于D组且疗程结束时治愈率最高,为100%。C组复发率为25%、D组复发率为20%、A、B组复发率为0;给药后5d,B组效果最好。[结论]中剂量黄连解毒散组虽然相对于西药治疗发挥作用较慢,但具有最佳的治疗效果,且复发率低、预后良好,推荐60 g/d剂量为临床常用治疗剂量。

基于网络药理学与分子对接探讨黄连解毒汤治疗白念珠菌感染的作用机制

目的运用网络药理学与分子对接探讨黄连解毒汤治疗白念珠菌感染的作用机制,为临床应用和基础研究提供理论依据。方法运用TCMSP和BATMAN-TCM数据库检索黄连解毒汤的有效成分及作用靶点,通过GeneCards、OMIM、PharmGkb、TTD、DrugBank数据库收集疾病相关靶点。运用Cytoscape 3.8.0软件构建“活性成分-靶点”网络,借助STRING平台构建交集蛋白互作网络,并使用Cytoscape对网络进行拓扑分析,获取核心靶点,通过R语言进行GO富集分析和KEGG通路富集分析,最后将主要活性成分与核心靶点进行分子对接验证。结果黄连解毒汤治疗白念珠菌感染的活性成分有槲皮素、山柰酚、汉黄芩素、黄芩新素等,核心靶点为HIF1A、MMP9、AKT1、FN1、PTGS2、IFNG、IL1B、STAT1、CASP8。富集得到IL-17信号通路、Th17细胞分化、Toll样受体信号通路等,主要通过调节炎症反应和细胞免疫等生物过程发挥治疗作用。分子对接结果表明,主要活性成分与核心靶点具有较强的结合能。结论黄连解毒汤能通过多成分-多靶点-多途径共同治疗白念珠菌感染,为临床应用及基础研究提供理论基础和参考依据。

黄连及其配伍在消渴病中的应用

黄连味苦性寒,善泄善燥,是消渴病治疗中应用颇广的传统中药之一。现代研究表明黄连的主要成分小檗碱可通过多条细胞信号通路发挥作用,提高糖尿病患者胰岛β细胞抗氧化应激能力,改善胰岛功能,提高胰岛素敏感性,降低患者血糖及糖化血红蛋白水平,并且可减少血管内皮损伤,降低糖尿病血管并发症的风险。黄连单药使用即可对消渴病起到良好的治疗效果,与木香、葛根、人参、天花粉、黄芩、知母等相伍成药对,既可增强临床效果,又可防其苦寒败胃。黄连复方葛根芩连汤、大黄黄连泻心汤、黄连解毒汤、半夏泻心汤、黄连温胆汤、小陷胸汤则可通过多靶点、多途径、多环节发挥作用,达到降糖减脂、改善患者临床症状的效果。总之黄连及其配伍可通过抑制糖异生、调节肠道菌群结构、改善胰岛功能、降低胰岛素抵抗等多重途径,标本兼治,实现降糖降脂、延缓糖尿病进展之功效。对黄连单药及其药对、复方在消渴病治疗中的应用作以叙述,以期为消渴病的临床治疗提供思路。