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.

Evaluating the effect and mechanism of Yiqi Huayu Jiedu decoction combined with FLOT regimen neoadjuvant chemotherapy for the patients with locally advanced gastric cancer:protocol for a prospective,double-arm,randomized controlled clinical trial

Background:Neoadjuvant chemotherapy plays a vital role in the treatment of advanced gastric cancer(GC),however,optimizing its effectiveness remains an important research focus.Traditional Chinese medicine(TCM),a promising adjunctive therapy,has shown enhanced clinical outcomes when combined with postoperative adjuvant chemotherapy.Therefore,this study is designed to evaluate the clinical efficacy of Yiqi Huayu Jiedu decoction combined with neoadjuvant chemotherapy FLOT in the treatment of advanced GC.Methods:This study is a prospective,double-arm,randomized controlled trial.It involves a total of 260 patients diagnosed with advanced GC,who will be randomly assigned to two groups-a TCM treatment group and a control group,each comprising 130 patients.All patients will receive standard FLOT chemotherapy,and patients in the TCM treatment group will additionally receive TCM treatment with Yiqi Huayu Jiedu decoction.After four cycles of chemotherapy,GC D2 radical surgery will be performed.The primary objective is to evaluate the postoperative pathological response rate of the tumor.The secondary objectives include evaluating the perioperative nutritional status,the efficacy of TCM syndrome,and adverse events associated with both chemotherapy and surgery.Discussion:Currently,no trials have investigated the impact of TCM in combination with neoadjuvant chemotherapy on the preoperative treatment in patients with advanced GC.Accordingly,it is imperative to conduct this prospective study to evaluate the clinical efficacy and safety of this regimen,meanwhile providing high-level clinical evidence for TCM combined with neoadjuvant chemotherapy and introducing an innovative regimen for preoperative comprehensive treatment of GC.

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.

Identifying medication regularity of traditional Chinese medicine and potential pharmacological mechanism of Jiedu Sangen decoction in colorectal cancer treatment by data mining and network pharmacology

Objective:Colorectal cancer(CRC)is one of the most common malignancies in the world,and traditional Chinese medicine(TCM)is widely used in its treatment in China.However,the medication rules of TCM for CRC treatment remain unclear.Therefore,data mining combined with network pharmacology was utilized to establish treatment principles and rules.Methods:The CRC cases treated at Zhejiang Provincial Hospital of Chinese Medicine from January 1,2016 to October 31,2021 were analyzed using data mining methods.UPLC-Q/TOF-MS analysis was performed to identify the chemical composition of Jiedu Sangen decoction(JSD).Network pharmacology was used to reveal the therapeutic mechanism of JSD.Results:A total of 312 cases 2,998 prescriptions that met the inclusion criteria used 343 kinds of traditional Chinese medicines.The nature of the herbs used in treatment was mainly warm and mild.The taste was mainly sweet,bitter,and pungent.The meridian tropisms were mainly the spleen meridian,followed by lung and stomach meridians.Tonifying and replenishing herbs were the most frequently used in treatment.High-frequency herbs were classified into 11 categories by cluster analysis,and 42 association rules were obtained by association rule analysis.Combined with complex network analysis,3 core prescriptions for clinical CRC treatment were obtained.Jiedu Sangen decoction contains 64 chemical ingredients,out of which 31 active ingredients were identified,including polydatin,caffeic acid,and glutamic acid,along with 130 potential targets such as AKT1,SRC,and MAPK1.Jiedu Sangen decoction may play a role in regulating inflammation,immunity,metabolism,and hormones in the development of CRC via pathways such as the relaxin signaling pathway,IL-17 signaling pathway,prolactin signaling pathway,and T cell receptor signaling pathway.Conclusions:This study summarizes the treatment and medication principles for clinical CRC treatment,promoting the inheritance and development of the traditional Chinese medical experience.

Effects of Yangyin Jiedu Decoction on Acute Oral Mucositis Caused by Radiation

[Objectives] The aim was to observe the clinical effect of Yangyin Jiedu Decoction for acute oral mucositis caused by radiotherapy for nasopharyngeal carcinoma( NPC). [Methods]Total 64 patients with non-keratinizing squamous cell carcinoma of nasopharynx were divided evenly and randomly into two groups,treatment group and control group. In the treatment group,the patients began to take Yangyin Jiedu Decoction one week before radiotherapy; while in the control group,the patients were treated with mixed solution of dexamethasone,lidocaine,recombinant human granulocyte colony stimulating factor and vitamin B12. From the beginning to the end of radiotherapy,the curative effect in the two groups was observed and compared. In addition,the levels of serum CRP,TGF-β1 and IL-6 were measured to detect the inflammatory response. [Results] The incidence of acute oral mucositis in the treatment group was significantly lower than that in the control group( P <0. 05). The effective rate was 96. 88% in the treatment group and 67. 74% in the control group. The levels of serum CRP,TGF-β1 and IL-6 in the treatment group were also lower than those in the control group. [Conclusions]Yangyin Jiedu Decoction has a good effect on prevention and treatment of acute radioactive oral mucositis and it is worthy of clinical application.

Expression of phosphatase and tensin homolog deleted on chromosome ten in liver of athymic mice with hepatocellular carcinoma and the effect of Fuzheng Jiedu Decoction

AIM: To explore the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in liver of athymic mice with hepatocellular carcinoma (HCC) and the effect of Fuzheng Jiedu Decoction (FJD). METHODS: Forty eight male BALB/c athymic mice models were built by Bel-7402 with an indirect method. After 24 h of postoperation, the 48 athymic mice were distributed randomly into 4 groups: A, B, C, D, each group had 12 athymic mice. Group A were were treated by intragastric administration with FT207 (Tegafur) for 4 wk. Group B, C and D were treated by intragastric administration with FJD (complex prescription of Chinese crude drug) that had been delegated into 3 kinds of density as the low, middle, and high for 4 wk. At last, athymic mice were put to death, live time, volume of tumors, exponent of tumors and the tumor metastasis in livers were observed; and PTEN was detected in hepatic tissue, latero-cancer tissue and cancer tissue by immunohistochemistry.RESULTS: Four weeks later, the total survival rate in treatment group (A + B + C) was 50% and higher than the control group (0%) treated by FT207, (P < 0.01). The survival rate in group A, B, C was higher than in group D, and except group A with D, there was significant differentces (Fisher's Exact Test P = 0.05 or 0.01). And no differences were observed between the treatment groups and the control group in volume of tumors and exponent of tumors (P > 0.05). Tumor metastasis in livers of the treatment group was less than the controls (Fisher's Exact Test, P = 0.021). The result of immunohistochemistry showed that the intensity of PTEN in latero-cancer tissue was the highest, and then the hepatic tissue, the lowest was cancer tissue (Kruskal-Wallis test, χ2 = 60.67, P = 0.000). It also showed that the intensity of PTEN in treatment groups (A, B, C) was higher than the control group (D) (F = 5.90, P = 0.002 in hepatic tissue and F = 15.99, P = 0.000 in latero-cancer tissue and χ2 = 26.08, P = 0.000 in cancer tissue), and group B is the highest in the treatment groups (P < 0.05, r = 0.01. respectively). However, there was no significant statistic difference between group A and group C (P > 0.05).CONCLUSION: FJD can prolong the survival time and decrease tumor metastasis in livers of these experimental mice. Mechanisms of FJD healing HCC may partially be explained by enhancing the expression of PTEN in liver.

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.

Effects of Wenglian Jiedu decoction on expression of serum IL-18, TNF-α and MUC2 in colon tissue of ulcerative colitis rats

Objective:To study the effect of Wenglian jiedu decoction on the expression of serum interleukin-18(IL-18),tumor necrosis factor-α(TNF--α)and colonic mucin-2(MUC2)in rats with ulcerative colitis of turbid toxin type,and to explore its mechanism.Methods:60 Wistar male rats were randomly divided into model group,Wenglian jiedu decoction low,middle and high dose groups,mesalazine group and blank group.Except for the blank group,the rat model of ulcerative colitis was established by trinitrobenzenesulfonic acid(TNBS)/ethanol compound method.The general condition,body weight,fecal properties and occult blood of rats were observed 2 weeks after administration.The disease activity index(Diseaseactivityindex,DAI)was scored,the content of MUC2 protein was detected by immunohistochemical method,and the contents of IL-18 and TNF-αin serum were detected by enzyme-linked immunosorbent assay(Elisa).Results:compared with the blank group,the DAI score increased,the contents of IL-18 and TNF-αincreased significantly,and the content of MUC2 protein decreased in the model group.Compared with the model group,the DAI score,the content of IL-18 and TNF-αdecreased and the content of MUC2 protein increased in each treatment group.Compared with the mesalazine group,the DAI score and the contents of IL-18 and TNF-αin the high and middle dose groups had no significant difference.Compared with the low dose group,the DAI score in the mesalazine group and the high and middle dose group decreased,and the contents of IL-18 and TNF-αdecreased.Conclusion:Wenglian jiedu decoction can regulate the immune system of intestinal epithelium by regulating the levels of serum IL-18 and TNF-αand increasing the expression of MUC2 protein,so as to achieve the purpose of repairing intestinal mucosa.

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.

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.

基于血清代谢组学探讨养筋解毒汤对糖尿病周围神经病变大鼠的作用机制

目的 基于血清代谢组学研究养筋解毒汤治疗糖尿病周围神经病变(Diabetic peripheral neuropathy,DPN)大鼠的作用机制。方法 将24只SPF级雄性SD大鼠按随机数字表法分为对照组、模型组、养筋解毒汤组,每组各8只,除对照组外,其余各组给予大鼠高脂高糖饲料饲喂8周,之后腹腔注射链脲佐菌制备DPN模型,采用体质量、体长、BMI指数和空腹GLU水平验证模型,模型成功后继续高脂高糖饲料饲喂8周后给予相应药物灌胃给药,2次/d,连续8周。采用空腹GLU水平评价疗效,采集大鼠血液分离血清利用非靶向代谢组学技术,通过主成分分析(PCA)、正交偏最小二乘法判别分析(OPLS-DA),结合t检验、变量重要性投影及差异倍数值筛选差异代谢物及可能的代谢通路。结果 经养筋解毒汤干预后与模型组比较,DPN大鼠血糖水平明显降低(P<0.01)。差异代谢物脯氨酸-亮氨酸(Pro-leu)、脯氨酸-异亮氨酸(Pro-Ile)、亮氨酸-酪氨酸(Leu-Tyr)等148种代谢物水平发生变化,同时对类固醇激素生物合成、精氨酸和脯氨酸代谢、甘氨酸、丝氨酸和苏氨酸代谢等代谢通路产生影响。结论 养筋解毒汤对DPN大鼠具有一定的治疗疗效,其机制可能与调节氨基酸及皮质激素代谢等有关。

化浊解毒消痈方治疗溃疡性结肠炎机制的网络药理学研究

目的基于网络药理学对化浊解毒消痈方治疗溃疡性结肠炎(UC)的分子机制进行研究。方法通过TCMSP数据库筛选化浊解毒消痈方中药的活性成分和作用靶点,然后采用GeneCards数据库筛选疾病作用相关基因,运用Cytoscape3.7.2软件构建“药物-成分-靶点”网络图,通过String数据库进行蛋白质-蛋白质相互作用网络,筛选化浊解毒消痈方治疗UC的核心靶点,再利用Cytoscape的ClueGO插件进行基因本体及KEGG信号通路富集分析,并通过动物实验进行验证。结果化浊解毒消痈方治疗UC共有81个活性成分和20个关键蛋白靶点,包括前列腺素过氧化物合酶2(PTGS2)、前列腺素过氧化物合酶1(PTGS1)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、半胱氨酸蛋白酶9(CASP9)、过氧化物酶体增殖物激活受体γ(PPARG)、B细胞淋巴瘤2(BCL2)、细胞促凋亡蛋白(Bax)、半胱氨酸蛋白酶3(Caspase-3)等;GO分析和KEGG通路分析结果表明,化浊解毒消痈方治疗UC主要涉及膜微结构域、膜区、囊泡腔、核染色质等,生物学过程包括细胞对脂多糖的反应、凋亡信号通路的调节、氧化应激、细胞对抗生素的反应等,分子功能涉及细胞因子活性、核受体活性、受体配体活性、蛋白激酶调节剂活性、蛋白质丝氨酸/苏氨酸激酶活性等;主要富集于IL-17、PI3K-Akt、TNF信号通路等,主要通过调节炎症因子、免疫反应、细胞凋亡、抗病毒感染、抗癌等发挥作用。动物实验表明:模型组中小鼠血清IL-6、肿瘤坏死因子-α(TNF-α)升高,结肠组织中Bcl-2、Caspase-3蛋白表达升高;经过化浊解毒消痈方干预后,小鼠血清IL-6、TNF-α以及结肠组织Bcl-2、Caspase-3蛋白均表达下降。结论通过网络药理学研究化浊解毒消痈方治疗UC的潜在作用机制,揭示其多成分、多靶点、多途径的复杂作用过程,初步推测并验证了化浊解毒消痈方治疗UC的主要靶蛋白与通路,为临床应用提供了理论依据。

基于指纹图谱和多成分含量测定的护肝解毒汤标准煎液量值传递研究

目的:建立护肝解毒汤标准煎液的指纹图谱及多指标成分含量测定方法,为其标准煎液及制剂的质量评价研究提供参考。方法:采用HPLC法结合中药色谱指纹图谱相似度评价系统,对15批护肝解毒汤标准煎液进行指纹图谱、相似度分析及共有峰的指认,并建立煎液中5种指标性成分的同时检测方法,计算各成分的转移率。结果:15批标准煎液指纹图谱相似度>0.90,有22个共有峰,对照品比对出绿原酸、葛根素、芍药苷、甘草素、落新妇苷、黄藤苷、盐酸小檗碱、五味子醇甲、黄柏酮、梣酮10个成分,15批标准煎液中绿原酸、葛根素、落新妇苷、盐酸小檗碱、五味子醇甲的转移率分别为48.26%~63.80%、20.30%~31.50%、28.24%~39.11%、2.89%~5.60%、13.51%~21.85%。结论:采用指纹图谱、出膏率及指标性成分含量测定相结合的模式,对护肝解毒汤标准煎液的量值传递过程进行分析,可初步拟定护肝解毒汤标准煎液的质量标准,为其后续新药开发及相关制剂的质量控制提供依据。

健脾渗湿解毒汤治疗湿浊中阻型高尿酸血症的临床效果

目的探讨健脾渗湿解毒汤治疗湿浊中阻型高尿酸血症的临床效果。方法选取2021年2月至2022年12月于海南省中医院内分泌科门诊或病房诊治的高尿酸血症患者106例,按随机数字表法分研究组(54例)和对照组(52例)。研究组服用健脾渗湿解毒汤,对照组口服苯溴马隆片(50 mg/次,1次/d)。两组均治疗3个月。观察两组治疗前后血尿酸(UA)、胆固醇、甘油三酯(TG)、低密度脂蛋白(LDL-C)、空腹血糖(FPG)、中医证候积分及安全性分析。结果治疗后,两组尿酸低于治疗前,差异有统计学意义(P<0.05);两组尿酸比较,差异无统计学意义(P>0.05)。治疗后,研究组FPG、TC低于治疗前,且低于对照组,差异有统计学意义(P<0.05)。治疗后,两组TG、LDL-C、肌酐、谷草转氨酶、谷丙转氨酶与治疗前比较,差异无统计学意义(P>0.05);两组TG、LDL-C比较,差异无统计学意义(P>0.05)。治疗后,两组症候总积分低于治疗前,且研究组低于对照组,差异有统计学意义(P<0.05)。研究组不良反应发生率与复发率低于对照组,差异无统计学意义(P>0.05)。结论健脾渗湿解毒汤治疗湿浊中阻型高尿酸血症,能显著改善患者的中医临床症候,较好地降低尿酸水平,且安全性较高,具有较高的临床应用价值。

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。

陈氏清肝解毒汤治疗肝经郁热型带状疱疹临床观察

目的:观察陈氏清肝解毒汤治疗肝经郁热型带状疱疹的临床效果。方法:选择上海市中医医院治未病科2020年1月~2022年12月带状疱疹患者75例进行研究,随机将其分为两组,其中对照组(n=37)接受盐酸伐昔洛韦片+甲钴胺片+炉甘石洗剂治疗,治疗组(n=38)加用陈氏清肝解毒汤,均实施为期10d治疗。观察两组10d治疗结束后的临床治疗效果;对比治疗前后的症状量化评分;对比治疗前,治疗后3d, 7d, 10d疼痛情况(VAS)评分;对比水疱停止增加时间、病灶结痂时间和脱痂时间;对比治疗前后血清水痘-带状疱疹病毒IgM抗体(VZV-IgM);对比不良反应情况;对比治疗后3个月带状疱疹后遗神经痛(PHN)的发生率。结果:治疗组10d治疗结束后临床疗效总有效率为90.32%,且高于对照组80.00%(P<0.05);10d药物治疗完成后,治疗组症状量化评分低于对照组(P<0.05);治疗后7d, 10d,治疗组疼痛低于优于对照组(P<0.05);与对照组相比,治疗组患者经药物治疗后水疱未增多、病灶结痂及脱痂时间均较低(P<0.05)。10d药物治疗完成后,治疗组患者VZV-IgM低于对照组(P<0.05);两组不良反应发生率相同(P>0.05)。治疗组治疗后3个月PHN发生率低于对照组(P<0.05)。结论:陈氏清肝解毒汤加入西药治疗后,不仅能有效改善肝经郁热型带状疱疹患者临床疗效,同时对病程缩短、疼痛减轻及减少PHN发生均有积极作用。

扶正解毒汤对结直肠癌患者的作用效果

目的研究扶正解毒汤对结直肠癌患者的作用效果。方法选取2020年1月至2022年10月河南中医药大学第三附属医院收治的96例结直肠癌患者,根据简单随机分组法分为化疗组(48例)和扶正解毒组(48例)。化疗组接受FOLFOX4化疗方案治疗,扶正解毒组在化疗组的基础上接受扶正解毒汤治疗,两组均治疗18周。统计两组治疗18周后的临床疗效,比较两组治疗前和治疗18周后中医证候积分、功能状态、肿瘤标志物、磷脂酰肌醇3酶-丝苏氨酸蛋白激酶(PI3K-Akt)信号通路、肠道菌群、生活质量。结果治疗18周后,扶正解毒组疾病控制率及总缓解率(68.75%、54.17%)高于化疗组(47.92%、31.25%)(P<0.05)。治疗18周后扶正解毒组主症、次症评分与治疗前比较降低,且低于化疗组(P<0.05);与治疗前比较,两组功能状态评分、乳酸杆菌、双歧杆菌数量及未来展望评分升高,且扶正解毒组高于化疗组(P<0.05);与治疗前比较两组血清癌胚抗原、糖类抗原199、外周血PI3K mRNA、Akt mRNA水平、肠球菌、大肠杆菌数量及排尿便问题、体重下降评分降低,且扶正解毒组低于化疗组(P<0.05)。结论扶正解毒汤联合FOLFOX4化疗方案可改善结直肠癌患者中医证候、功能状态,降低肿瘤标志物水平,调节PI3K-Akt信号通路、肠道菌群,提高患者生活质量,具有较好的治疗效果。

基于ERK/p38 MAPK信号通路探究解毒活血汤治疗Ⅲ型前列腺炎的作用机制

目的探究解毒活血汤调控ERK/p38 MAPK信号通路治疗Ⅲ型前列腺炎的作用机制。方法采用去势手术+苯甲酸雌二醇(EB)诱导慢性前列腺炎大鼠模型。36只SD大鼠随机分为空白组(生理盐水,4 mL·kg^(-1))、模型组(生理盐水,4 mL·kg^(-1))、阳性药物对照组(前列康片混悬液,4 mL·kg^(-1))、解毒活血汤低(4 mL·kg^(-1))、中(8mL·kg^(-1))、高剂量组(12 mL·kg^(-1)),每组6只,所有实验动物连续给药30 d。苏木精-伊红(HE)染色观察各组大鼠组织病理学变化;免疫组化法、RT-PCR、Western Blot技术检测相关炎症因子及蛋白表达水平。结果与正常对照组相比,慢性前列腺炎大鼠前列腺组织增生及水肿明显、炎症浸润增加,而阳性药物对照组及解毒活血汤各剂量组大鼠前列腺组织病变减轻或消失、炎症浸润减少,且与解毒活血汤剂量成正比;免疫组化表示模型组p38、P-p38、STAT3、P-STAT3表达较高,阳性药物对照组、不同剂量解毒活血汤组的p38、P-p38、STAT3、P-STAT3表达呈下降趋势,且均低于模型组。RT-PCR结果显示阳性药物对照组及解毒活血汤低、中、高剂量组均能降低大鼠前列腺组织中TNF-α、IL-2、IL-6的表达水平;Western Blot检测提示大鼠疾病发生进展过程中p38、P-p38、P-ERK1/2、STAT3、P-STAT3呈高表达状态,解毒活血汤能够降低其表达,从而降低相关炎症因子的过度激活。结论解毒活血汤能够抑制ERK/p38 MAPK信号通路的过度激活,从而降低IL-2、IL-6、TNF-α等炎症因子的表达,以改善前列腺组织炎症反应。