Therapeutic targets and signal transduction mechanisms of medicinal plant formula Gancao Xiexin decoction against ulcerative colitis:A network pharmacological study

Background:Ulcerative colitis(UC)is a chronic disease that often presents with abdominal pain,diarrhea,hematochezia,and significant morbidity.Gancao Xiexin decoction(GXD),a traditional Chinese medicine,has been applied for the clinical treatment of UC,while its action mechanisms are unclear.Methods:The active ingredients and their targets of GXD,and UC-related targets,were derived from public databases.Protein-protein interaction,Gene Ontology(GO),and the Kyoto Encyclopedia of Genes and Genomes(KEGG)were used to analyze the important active compounds,key targets,and signaling pathways.Then,molecular docking and animal experiments were performed to verify the findings.A total of 213 active compounds and 89 common targets of GXD for UC were obtained.Results:The hub gene network showed ALB,AKT1,IL6,TNF,VEGFA,TP53,CXCL8,MAPK1,PTGS2,and IL1βmay be potential targets of GXD against UC.GO and KEGG pathway enrichment analyses suggested that the action of GXD against UC was mainly related to response to oxygen levels,lipopolysaccharide,and molecule of bacterial origin,etc.,and achieved by advanced glycation endproducts/receptors for advanced glycation endproducts signaling pathway in diabetic complications,hypoxia-inducible factor(HIF)-1 signaling pathway,interleukin-17/HIF-1 signaling pathway,TNF signaling pathway,etc.Molecular docking results showed that the GXD had good potency of action with the hub target.In vivo experiments showed that GXD significantly alleviated the symptoms of UC and down-regulated the expression of inflammatory factors,nuclear factor-κB and signal transducer and activator of transcription 3.Conclusions:The anti-UC action of GXD is mainly attributed to its anti-oxidative stress,antiinflammatory,and immunomodulatory functions.

Anti-inflammatory Effect of Wumen Zhike Gancao Decoction on Rats with Lumbar Disc Herniation Associated with Lipid Metabolic Disorder

[Objectives] To study the anti-inflammatory effect of Wumen Zhike Gancao Decoction (ZKGC) on rats with lumbar disc herniation (LDH) associated with lipid metabolic disorder.[Methods] A rat model of LDH was established by implantation of the autologous nucleus pulposus from the coccygeal vertebra of each rat tail, and histopathology, immunohistochemistry and biochemistry assays were employed to evaluate the treatment effects of ZKGC. In addition, the metabolic characteristics of LDH and ZKGC treatment were investigated with a liquid-chromatography with time-of-flight mass spectrometer (LC/Q-TOF-MS)-based metabolomics study. Nucleus pulpous tissues from rat models were collected and analyzed by metabolomics.[Results] By metabolism network analysis, lipid metabolism was up-regulated in LDH rat models and the treatment with ZKGC significantly reversed the abnormal up-regulated lipid metabolism. Meanwhile, the treatment of ZKGC also regulated the markers of neuron autophagy and inflammatory response in serum.[Conclusions] These results indicated that a complex mechanism, including abnormal lipid metabolism, associates with the progress of LDH, and multiple pathways might be involved in ZKGC s therapeutic effects on LDH.

Network pharmacology study on the mechanism of Shaoyao Gancao decoction in treating cancer pain

Objective:This paper aims to explore the key targets and mechanism of action of Shaoyao Gancao Decoction in the treatment of cancer pain.Methods:TCMSP database was adopted to screen the active components and potential targets of Shaoyao Gancao Decoction.Genecards and OMIM databases were used to collect disease targets for cancer pain.Cytoscape software was used to construct the drug-component-target-disease network diagram.STRING database was used to draw PPI network.Finally,gene ontology(GO)enrichment analysis and KEGG pathway enrichment analysis were performed on key targets.Results:There were 98 potential targets for the treatment of cancer pain in Shaoyao Gancao Decoction.The protein interaction network suggested that IL-6,VEGFA,CASP3,EGFR and MAPK8 may be the core targets for the treatment of cancer pain in Shaoyao Gancao Decoction.GO enrichment analysis showed 127 cellular biological processes,and KEGG pathway enrichment analysis showed 116 related signaling pathways,including MPAK,AGE-RAGE,TNF,ErbB and so on.Conclusions:The treatment of cancer pain by Shaoyao Gancao Decoction may be multi-target,multi-channel and multi-level.This consequence may provide ideas and basis for further research.

Therapeutic Effect of Shaoyao Jiawei Gancao Decoction(芍药加味甘草汤)with Acupoint Application on Chronic Lumbar Muscle Strain and the Recovery of Lumbar Strength

Objective:To study the therapeutic effect of Shaoyao Jiawei Gancao Decoction(芍药加味甘草汤)with acupoint application on chronic lumbar muscle strain and the recovery of lumbar strength.Methods:From August 2018 to August 2019,100 patients with chronic lumbar muscle strain admitted to our hospital were selected and randomly divided into an acupoint application group and a combined group of 50 cases each.The acupoint application group was treated by acupoint application,and the combined group was treated with Shaoyao Jiawei Gancao Decoction(芍药加味甘草汤)based on acupoint application.The indexes scores,VAS scores,ADL scores,ODI scores,lumbar endurance,TCM syndrome scores and the treatment effects of the two groups before and after treatment were statistically analyzed,and TNF-αand TXB2 levels were detected.Results:After treatment,the scores of indexes,VAS,ODI,TCM syndrome,TNF-αand TXB2 in the combined group were lower than those in the acupoint application group,and the ADL score,lumbar endurance and treatment efficiency were higher than those in the acupoint application group,with a statistical difference(P<0.05).Conclusion:Shaoyao Jiawei Gancao Decoction(芍药加味甘草汤)with acupoint application can effectively reduce pain,improve lumbar function,restore lumbar strength,effectively relieve inflammation,with significant effects.

甘草抗炎活性物质基础及其作用机制研究进展

炎症是机体对于刺激所产生的一种防御反应,随着炎症的发展可能导致组织的变异和增生,进一步加剧疾病的进程。甘草作为“众药之王”“国之药老”,早在《神农本草经》中就记载其清热作用较强,能“主五脏六腑寒热邪气”。现代研究表明,甘草提取物对肾小球肾炎、结肠炎症状改善明显,甘草及其制剂在治疗肝炎、胃炎、支气管炎、心肌炎、强直性脊柱炎等炎症性疾病方面亦具有一定的独特优势和发展潜力。该文旨在通过对近期国内外甘草抗炎活性物质基础及其作用机制方面的相关文献进行收集和整理,探索甘草发挥抗炎作用的主要活性成分及靶点通路,以期为甘草抗炎作用的进一步研究及抗炎药物的研发提供思路和参考。

《方剂学》教材商榷5则

《方剂学》教材中存在一些值得商榷的问题,如安神药服药时间、麻黄杏仁甘草石膏汤证是否兼有外邪、四逆散证有无外邪的方义解释、牡蛎散是否治疗盗汗、大秦艽汤的分类归属等。这些问题不单涉及到教学,更影响临床应用,对此作一探讨,以有利于中医教学与临床。

芍药甘草汤通过JAK2/STAT3信号通路对神经病理性疼痛大鼠的镇痛及对免疫调节机制影响

目的探寻芍药甘草汤对神经病理性疼痛(NP)的改善作用及其机制。方法采用坐骨神经分支选择性损伤(SNI)法建立NP大鼠模型,模型制备成功后予以芍药甘草汤灌胃治疗14 d。治疗前后监测大鼠疼痛行为学指标变化,TUNEL染色检测脊髓背角细胞凋亡情况,免疫荧光组织化学法测定p-STAT3在脊髓中与Iba1的共定位情况,RT-PCR检测CD68、SOCS3、Arg-1的mRNA表达,ELISA检测白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)表达,Western blotting检测JAK2/STAT3通路蛋白表达。结果与假手术组比较,模型组大鼠机械缩足阈值(MWT)、热缩足潜伏期(TWL)明显降低(P<0.01),脊髓背角中凋亡细胞显著增加(P<0.05),IL-1β、1L-6和TNF-α的表达显著增加(P<0.01),JAK2、p-JAK2、STAT3、p-STAT3的表达显著增加(P<0.01),术后7、14 d的CD68、SOCS3 mRNA表达显著增加(P<0.01),Arg-1 mRNA表达显著降低(P<0.01)。与模型组比较,芍药甘草汤组大鼠治疗后MWT、TWL明显上升(P<0.01),脊髓背角中凋亡细胞减少,IL-1β、IL-6、TNF-α的水平显著减少(P<0.01),JAK2、p-JAK2、STAT3、p-STAT3蛋白表达水平明显降低(P<0.01),CD68、SOCS3 mRNA表达显著减少(P<0.01),Arg-1 mRNA表达水平显著增加(P<0.01)。结论芍药甘草汤可能通过调控JAK2/STAT3通路调控小胶质细胞极化状态进而发挥改善NP的作用。

基于整合药理学探讨“茯苓-甘草”协同配伍对肺腺癌的作用机制及验证研究

目的:基于网络药理学和生物信息学探讨“茯苓-甘草”协同配伍对肺腺癌的作用机制及靶点,并通过实验验证“茯苓-甘草”主要成分槲皮素对肺腺癌的抑制作用。方法:对肺腺癌相关基因进行差异分析,从TCMSP数据库下载“茯苓-甘草”有效成分及靶标,获取药物-疾病共同靶标,进行网络构建、富集分析、生存分析等。通过对“茯苓-甘草”主要成分与肺腺癌关键靶点进行分子对接,选出构效关系良好的有效成分进行后续实验验证。通过细胞增殖、划痕及侵袭实验检测药物对肺腺癌细胞的干预作用,实时荧光定量法检测药物对关键靶点的作用。结果:肺腺癌8 109个差异表达基因和102个药物靶基因取交集共获得32个共同基因,富集分析显示靶基因主要参与p53信号通路、细胞衰老等癌症相关通路,分子对接结果显示槲皮素具有良好的构效关系,因此选择槲皮素进行后续实验验证。有效成分槲皮素可以抑制肺腺癌A549及H1299细胞的增殖、迁移及侵袭能力,并且可以显著下调关键靶点含杆状病毒IAP重复序列蛋白5(BIRC5)、细胞周期蛋白B1(CCNB1)、检查点蛋白激酶1(CHEK1)的表达。结论“:茯苓-甘草”有效成分槲皮素可以有效抑制肺腺癌恶性表型,其机制可能与靶向调节关键基因BIRC5、CCNB1、CHEK1的表达有关。

甘草中三萜皂苷类成分抗肿瘤及联合抗肿瘤机制研究进展

甘草中三萜皂苷包括甘草酸、甘草次酸、乌拉尔甘草皂苷等,是甘草的主要活性成分之一。近年来,甘草三萜皂苷在抗肝癌、乳腺癌、肺癌等肿瘤及联合抗肿瘤方面的研究取得了一定进展。其可通过诱导肿瘤细胞凋亡、自噬、调控信息通路等机制抑制肿瘤细胞的增殖,在肿瘤的治疗上具有药用价值。

基于网络药理学探讨甘草泻心汤治疗白塞病的作用机制

目的:基于网络药理学方法分析甘草泻心汤治疗白塞病(BD)的潜在活性成分及其可能作用靶点和分子机制。方法:根据甘草泻心汤的药味组成,在中药系统药理学数据库,与分析平台(TCMSP)筛选各药材的有效活性成分及各成分相应的作用靶点;利用GeneCard、OMIM、PharmGkb及DrugBank数据库,以“Behcet's disease”为检索词收集BD相关靶点,同时将药物靶点及疾病靶点数据进行比对获得交集靶点,通过Cytoscape 3.8.2软件对药物-疾病靶点进行可视化网络分析;将药物-疾病靶点结果进行基因本体论(GO)、京都基因和基因组百科全书(KEGG)富集分析。结果:TCSMP数据库共检索到甘草泻心汤主要活性成分174个,包括槲皮素、山柰酚、汉黄芩素、黄芩素、β-胡萝卜素、刺槐素;甘草泻心汤潜在作用靶点247个,BD相关靶点1006个,甘草泻心汤有效成分靶点与BD相关靶点的交集靶点共60个。核心靶点为HMOX1、IFNG、CAT、EGF、VEGFA、PTGS2、CXCL8、TP53、IL1B、STAT3、SERPINE1、MPO、CCL2、SELE、ICAM1、VCAM1、MMP9、CASP3、NFKBIA、IL1A。GO富集分析共得到1697条条目,主要涉及对脂多糖的反应、对细菌来源的分子反应、外源性凋亡信号通路等生物过程。KEGG富集分析得到114个信号通路,主要包括糖尿病并发症AGE-RAGE信号通路、流体剪切应力与动脉粥样硬化、肿瘤坏死因子信号通路等。结论:甘草泻心汤可通过多靶点、多通路治疗BD,本研究为深入揭示其作用机制提供了生物信息学基础。

从芍药甘草汤方证与药量探讨胞轮振跳的治疗

胞轮振跳是临床中的难治性疾病,该病严重影响患者的情绪及生活质量。目前临床治疗手段有限,西医多以手术为主,且容易反复,创伤性较大。中医药治疗该病不良反应少且疗效稳固。芍药甘草汤主治肝脾阴虚证,而胞轮振跳的病机之一则为肝脾阴虚,这是与芍药甘草汤证的契合点。因此,根据异病同治原则,该方治疗此类疾病是辨病与辨证结合的临床思路的体现。通过文献考证古今度量衡质量的单位换算,芍药(白芍)与炙甘草的用量需达60 g以上方可获得良好临床疗效。本文总结了芍药甘草汤的临床使用经验,并结合文献从方义与药量角度论证其治疗胞轮振跳的可行性与合理性。

《伤寒论》甘草应用特点分析

目的:分析张机(字仲景)《伤寒论》中含甘草方剂的用药特点,为甘草的现代临床应用提供参考。方法:以《伤寒论》中含甘草的方剂为资料来源,使用Excel 2019、Clementine 12.0统计软件对纳入的药物进行频数、功效分类、性味归经、用量等的频次统计和关联规则分析。结果:在纳入的全部方剂中,累计出现频数最高的中药分别是甘草(70次,100.0%)、桂枝(36次,51.4%)、大枣(35次,50%)、生姜(32次,45.7%)、芍药(25次,35.7%),功效分类以补虚药(146次,52.3%)、解表药(81次,29.0%)最常见,药性主要集中在温(130次,46.6%)、平(86次,30.8%),药味以甘(169次,44.4%)、辛(122次,32.0%)最为常见,归经以脾经(219次,24.1%)、肺经(207次,22.7%)为主;甘草的用量以二两(45次,64.2%)为主,太阳病篇(56首,67.4%)使用含甘草的方剂最多;通过对含甘草的方剂进行关联规则分析,得到常用药物组合16种。结论:《伤寒论》中张机使用甘草以太阳病为主,常搭配补虚药、解表药,甘温补虚,辛温发散,多使用桂枝汤方义。

基于药材原产地芍药甘草汤质量评价体系研究

目的采用高效液相色谱法(HPLC)同时测定芍药甘草汤中没食子酸、芍药苷、甘草苷、甘草素和甘草酸5种指标成分的含量并建立芍药甘草汤指纹图谱,探究芍药甘草汤中间体关键质量属性,为其药材基源筛选和质量控制提供参考。方法制备来自不同产地不同批次的18批芍药甘草汤冻干粉作为中间体样品;采用Agilent ZORBAX Eclipse Plus C_(18)(4.6 mm×250 mm,5μm)色谱柱,以乙腈-0.2%磷酸水溶液为流动相,梯度洗脱,柱温35℃,流速0.8 mL/min,进样量10μL,对指标成分的含量和指纹图谱进行检测,评价多批次芍药甘草汤中间体质量属性差异,为其质量标准的建立提供参考。结果5种成分线性关系(R^(2)>0.999)、精密度(RSD≤0.89%,n=6)、重复性(RSD≤1.35%,n=6)、稳定性(RSD≤1.87%,72 h)均良好,加样回收率为(98.24±1.85)%~(104.88±1.38)%(n=6)。含量测定结果显示在不同批次芍药甘草汤中间体中仅没食子酸的含量波动范围较小(4.74~5.92 mg/g),芍药苷、甘草苷、甘草素和甘草酸在不同产地不同批次中的含量均有较大差异,含量范围分别为29.58~38.24、7.21~12.12、0.18~0.89、12.14~42.83 mg/g;建立芍药甘草汤指纹图谱,确定了14个共有峰,并对各峰进行药材归属,其中1、4、5、10号峰来自白芍,2、3、6、7、8、9、11、12、13、14号峰来自炙甘草,炙甘草对共有峰的贡献最大。其中13批芍药甘草汤中间体的HPLC指纹图谱与对照指纹图谱的相似度均大于0.98,第S4、S8、S16、S17、S18批次的相似度大于0.91,说明不同产地批次的药材质量差异较大。结论该方法准确可靠、灵敏度高,具有良好的重复性,可用于测定芍药甘草汤中5种成分的含量及建立芍药甘草汤的指纹图谱,可为经典名方芍药甘草汤的质量标准建立及评价提供依据。

Effect of Guizhi Gancao Longgu Muli Tang on sleep disturbances in menopausal women

OBJECTIVE: To evaluate the effect of Guizhi Gancao Longgu Muli Tang(GGLMT), a decoction prepared with herbal medicine of Traditional Chinese Medicine, on sleep disturbances in women with menopause.METHODS: Totally 162 participants were recruited for the treatment of sleep difficulty from February,2012 to December, 2014. Decoction of 200 mL was taken by every participant twice daily in half an hour after lunch and dinner during two weeks.Sleep quality was assessed by Pittsburg sleep quali-ty index(PSQI) and menopausal symptoms and quality of life were evaluated by the menopause rating scale(MRS) and the Chinese version of World Health Organization quality of life-BREF at the final fellow-up in the fourth weekend after beginning.RESULTS: The average scores of PSQI had reduced from(13.82 ± 4.97) to(8.14 ± 3.19), 95% CI(- 4.87,- 3.05) after 2-week GGLMT treatment in the fourth week. GGLMT improved symptoms in patients with more severe conditions(MRS ≥ 16).Three adverse drug reaction, mouth ulcer, constipation, and folliculitis, might be related with GGLMT and disappeared after withdrawals of the treatment.CONCLUSION: For menopausal women suffering from chronic sleep disturbances, our findings suggest that two weeks treatment of GGLMT was safe and effective.

Mechanism of cAMP-PKA Signaling Pathway Mediated by Shaoyao Gancao Decoction(芍药甘草汤)on Regulation of Aquaporin 5 and Muscarinic Receptor 3 Levels in Sjogren’s Syndrome

Objective:To investigate the mechanism of c AMP-PKA signaling pathway mediated by Chinese medicine formula Shaoyao Gancao Decoction(芍药甘草汤,SGD)on the regulation of aquaporin 5(AQP5)and muscarinic receptor 3(M3 R)levels in Sjogren’s syndrome(SS).Methods:Of the 30 mice,5 were randomly selected as control,and others were used for creating SS model.After successful modeling,mice were randomly divided into 5 groups(n=5 per group)and intragastrical y administered with saline(8 m L/kg),pilocarpine(1.4 mg/kg),or low,medium and high doses SGD(0.14,0.21,0.35 g/kg Radix paeoniae with 0.01 g/kg Radix glycyrrhizae,respectively)for 6 weeks.Human labial gland acinar cel s were treated with pilocarpine or varying doses of SGD with saline as the placebo.Hematoxylin and eosin staining was used to observe the histopathological changes of the submandibular glands of mice.The serum levels of anti-SS antigen A(SS-A),anti-SS antigen B(SS-B),M3 R,andα-fodrin in submandibular glands of mice were measured by enzyme-linked immunosorbent assay.Immunofluorescence staining was used to observe the spatial localization of AQP5 and M3 R in acinar cells.Reverse transcriptase polymerase chain reaction and Western blot were used to detect the expressions of PKA,c AMP,Epac1,AQP5,M3 R,nuclear factor kappa-B(NF-κB),and tumor necrosis factor(TNF)-αin submandibular gland tissues and cel s of each group.Results:Compared to normal mice,body weight,5-min salivary secretion,30-min secretion of tears and breakup time of tear film of model mice decreased at 1–6 weeks after immunization(al P<0.05),whereas water intake increased(al P<0.05).In the model group,glands of the submandibular glands showed atrophy,accompanied by acini of different sizes,decreased numbers and loose arrangement,with catheter dilatation and different degrees of lymphocyte infiltration.Conditions of mice in SGD groups were improved.The positive expression of AQP5 and M3 R were higher in the acinar cel s treated with al doses SGD compared to the normal group;serum levels of SS-A,SS-B,andα-fodrin were lower,and that of M3 R was higher in al doses SGD treated animals than the model or pilocarpine treated ones(al P<0.05).Compared to the model and pilocarpine groups,the m RNA and protein levels of NF-κB and TNF-αwere lower in mice or cel s treated with medium or high-dose SGD(al P<0.05),while those of PKA,Epac1,AQP5 and M3 R were higher(al P<0.05).Conclusion:SGD can improve symptoms of SS by regulating the c AMP-PKA signaling pathway and increasing AQP5 and M3 R levels.

Pretreatment of Shaoyao Gancao Decoction(芍药甘草汤)Alters Pharmacokinetics of Intravenous Paclitaxel in Rats

Objective：To investigate the effect of Shaoyao Gancao Decoction（芍药甘草汤,SGD）on the pharmacokinetics of intravenously administered paclitaxel in rats.Methods：Paclitaxel was intravenously administered to rats（3 mg/kg）with or without the concomitant administration of SGD（752 mg/kg,a single day or 14 consecutive days pretreatment）.The paclitaxel in the serum was quantified using a simple and rapid ultra performance liquid chromatography（UPLC）method for the pharmacokinetic study.The pharmacokinetic parameters were calculated via a non-compartment model using the computer program DAS 2.0.Results：The pharmacokinetic parameters of paclitaxel were significantly altered in response to 14 consecutive days of pretreatment with SGD.The area under the curve（AUC0-t,from 4 820±197 to 4 205±186 ng·m L-1·h-1）and AUC0-∞（from 5 237±280 to 4 514±210 ng·m L-1·h-1）significantly decreased in response to the 14-day pretreatment with SGD.The values of V dss（L/kg）were 10.74±1.08 and 9.35±0.49,those of CL（L/kg）were0.67±0.03 and 0.57±0.03 and the t1/2（h）values were 11.17±0.84 and 11.32±0.93,respectively,for the14-day SGD pretreatment and intravenous paclitaxel alone.The AUC0-t and AUC0-∞values decreased by13%and 14%（P〈0.01）,respectively.The area under the curve decreased significantly（P〈0.01）,and the total clearance increased by 1.2-fold（P〈0.01）,after 14 consecutive days of pretreatment with SGD.A single-day pretreatment with SGD did not significantly affect the pharmacokinetic parameters of paclitaxel.Conclusions：SGD administration for 14 consecutive days increased the metabolism of paclitaxel,while a 1-day pretreatment had little effect.The results would contribute important information to the study on interaction between Chinese medicines and chemotherapy and also help to utilize SGD better in the adjunctive therapy of cancer patients.

甘草泻心汤加减联合美沙拉嗪对溃疡性结肠炎肠道功能屏障及色氨酸代谢的影响分析

目的探讨甘草泻心汤加减联合美沙拉嗪对溃疡性结肠炎(Ulcerative colitis, UC)患者肠道功能屏障及色氨酸代谢的影响。方法选择医院于2019年4月—2021年4月就诊的UC患者142例,依据随机数字表法随机分为观察组(71例)与对照组(71例)。对照组患者给予美沙拉嗪治疗,观察组在对照组基础上结合甘草泻心汤加减治疗。两组治疗疗程12周。比较两组治疗12周临床疗效,治疗前与治疗12周肠道黏膜病变严重程度(改良Mayo评分和Geboes指数)、肠道屏障功能[内毒素、二胺氧化酶(Diamine oxidase, DAO)和D-乳酸]、色氨酸代谢[犬尿氨酸(Kynurenine, Kyn)、犬尿喹啉酸(Kynurenic acid, KynA)和喹啉酸(QuinA)]及药物不良反应。结果观察组UC患者治疗总有效率(91.55%,65/71)高于对照组(74.65%,53/71)(P<0.05)。两组治疗12周UC患者改良Mayo评分和Geboes指数较治疗前降低(P<0.05);观察组治疗12周UC患者改良Mayo评分和Geboes指数低于对照组(P<0.05)。两组治疗12周UC患者内毒素、DAO和D-乳酸水平较治疗前降低(P<0.05);观察组治疗12周UC患者内毒素、DAO和D-乳酸水平低于对照组(P<0.05)。两组治疗12周UC患者QuinA/Kyn较治疗前降低,而KynA/QuinA和KynA/Kyn较治疗前升高(P<0.05);观察组治疗12周UC患者QuinA/Kyn低于对照组,而KynA/QuinA和KynA/Kyn高于对照组(P<0.05)。两组治疗12周UC患者IBDQ评分较治疗前增加(P<0.05);观察组治疗12周UC患者IBDQ评分高于对照组(P<0.05)。两组患者用药期间均未发生明显不良反应。结论甘草泻心汤加减联合美沙拉嗪对UC患者疗效良好,可减轻患者肠道黏膜病变严重程度,改善患者肠道屏障功能和色氨酸代谢。

芍药甘草颗粒对斑秃样小鼠毛发生长、行为学及下丘脑-垂体-肾上腺轴的影响

目的探讨芍药甘草颗粒对斑秃样小鼠毛发生长、行为学及下丘脑-垂体-肾上腺轴的影响。方法C3H/HeJ小鼠42只,随机分为空白对照组、模型组、芍药甘草颗粒高、中、低剂量组、促肾上腺皮质激素释放激素1型受体拮抗剂组、复方甘草酸苷片组,每组6只,分别予以不同药物干预。进行照片和毛发镜拍摄、体重称量、行为学测定,以及促肾上腺皮质激素释放激素、促肾上腺皮质激素、皮质醇、糖皮质激素受体、脑源性神经营养因子检测。结果与模型组比较,高剂量芍药甘草颗粒可加速斑秃样小鼠毛发再生及体重增长(P<0.05),增加旷场实验运动总路程及中央区运动路程占总路程百分比(P<0.05),减少强迫游泳实验及悬尾实验不动时间(P<0.05),降低外周血促肾上腺皮质激素释放激素、促肾上腺皮质激素、皮质醇水平(P<0.05),增加海马体糖皮质激素受体及脑源性神经营养因子表达(P<0.05)。结论芍药甘草颗粒能促进斑秃样小鼠毛发生长、改善其行为学表现,其作用的发挥可能与下调促肾上腺皮质激素释放激素、促肾上腺皮质激素、皮质醇水平,上调糖皮质激素受体、脑源性神经营养因子表达,抑制下丘脑-垂体-肾上腺轴过度活化相关。

基于网络药理学的银花甘草汤治疗放射性肺炎的机制

目的:探讨银花甘草汤治疗放射性肺炎的有效成分及其靶点的作用机制。方法:利用TCMSP数据库筛选出银花甘草汤的有效成分及相关靶点蛋白,Uniport数据库对靶点蛋白进行基因标准化处理,结合Genecard数据库中放射性肺炎的疾病靶点进行映射,将筛选得到的中药活性成分和映射得到的作用靶点导入Cytoscape软件中进行活性成分-靶点网络图的构建,并运用Enrich数据库进行GO生物学过程及KEGG信号通路富集分析。结果:获得银花甘草汤有效成分115个,映射得到59个治疗放射性肺炎的靶点,富集到相关生物学过程13个、信号通路61条,山萘酚、木樨草素、β-胡萝卜素、槲皮素等13化合物可能是银花甘草汤治疗放射性肺炎的重要有效成分,PTGS2、NOS2、AKT1、PRARG、MAPK14等5个核心作用靶点是其可能的作用靶点,这些靶点与MAP激酶活性、蛋白丝氨酸/苏氨酸/酪氨酸激酶活性、丝裂原活化蛋白激酶结合、氧化还原酶活性等13条生物过程有关,通过血管内皮生长因子(VEGF)信号通路、小细胞肺癌、C型凝集素受体信号通路、TNF信号通路等61条信号通路进行调节。结论:银花甘草汤对放射性肺炎具有一定的治疗效果,其机制可能通过调节PTGS2、NOS2、AKT1、PRARG、MAPK14等靶点,调控VEGF信号通路、小细胞肺癌、C型凝集素受体信号通路、TNF信号通路等多种途径有关。

基于网络药理学的甘草附子汤治疗类风湿关节炎的作用机制

目的通过网络药理学探讨甘草附子汤治疗类风湿关节炎(RA)的作用机制。方法采用网络药理学方法,构建药物-靶点-疾病网络,进行富集分析,研究药物对靶点的作用、靶点的功能与疾病的相关关系,探讨甘草附子汤治疗RA涉及靶点和主要成分。结果从中药系统药理学数据库与分析平台(TCMSP)中筛选出有效成分127个,得到49个甘草附子汤治疗RA潜在靶点,建立“药物-靶点-疾病”网络,得到135节点,473条边。筛选出Degree值较高的槲皮素、山柰酚、柚皮素等10个活性成分,以及白细胞介素(IL)-6、表皮生长因子受体(EGFR)、IL-1β、TP53、过氧化物酶体增生激活受体(PPARG)等30个Degree值较高的靶点。结论甘草附子汤治疗RA主要与脂多糖反应、血管调节和血管反应、脂质与动脉粥样硬化、糖尿病晚期糖基化终末产物-晚期糖基化终末产物受体(AGE-RAGE)信号通路和辅助性T细胞(Th17)细胞分化等信号通路有关,为扩大甘草附子汤的临床应用提供理论依据。