枳实和白术及其配伍药对的现代研究

枳实、白术配伍具有行气消痞的功效,在临床上得到广泛的应用。通过查阅近几年来的相关文献,对枳实、白术及其配伍的化学成分、药理作用、药代动力学、临床应用等各方面文献进行了研究。目前,还没有该药对配伍后化学成分变化方面的报道,今后应该加强这方面的研究,为临床合理用药提供理论依据。     

枳实制白术的炮制工艺优选及HPLC特征图谱分析

目的:探讨枳实制白术的最佳炮制工艺,建立其HPLC特征图谱。方法:采用"脾虚泄泻"免疫力低下动物模型和大鼠饮水量来评价枳实制白术的健脾祛燥作用;通过对比不同配比枳实制白术饮片的健脾祛燥作用,筛选枳实与白术的最佳配比;采用正交试验,以辛弗林和白术内酯Ⅲ的含量为评价指标,优选枳实制白术的炮制工艺,并建立其特征图谱。结果:10%枳实制白术组的效果最佳。枳实制白术饮片炮制过程中,影响辛弗林及白术内酯Ⅲ的主次因素依次为烘制温度炒制温度炒制时间,最佳炮制工艺为取生白术饮片100 g,加入枳实汁50 mL(生药质量浓度0.2 g·mL~(-1)),浸泡24 h,不时翻动,直至汁尽药透,于110℃炒制6 min,取出,于40℃烘箱干燥。枳实制白术有5个共有峰,均能达到较好分离,该分析方法具有良好的精密度、重复性和稳定性,符合特征图谱相关要求。结论:药汁制是中药炮制的重要组成部分,枳实制白术的健脾祛燥作用充分体现了这一炮制特色——增效,纠正偏性。建立的HPLC特征图谱方法准确、可靠,为枳实制白术的质量控制提供了参考。     

枳术丸对胃排空肠推进作用的影响

本文采用改良的酚红含量测定法研究了枳实与白术不同比例组方，对胃排空肠推进作用的影响，实验结果显示，枳术丸对胃肠功能有良好的调节作用。表明枳木丸具有“治痞消食强胃”的作用。     

枳实、白术组方中药制剂治疗慢性便秘文献分析

目的:评价枳实、白术组方中药制剂治疗慢性便秘的有效性及安全性.方法:计算机检索中国生物医学文献服务系统、维普中文科技期刊全文数据库、万方数据资源、中国知网全文数据库,检索时间从建库到2013年9月.检索词包括便秘、传输、推动力、枳术、枳实白术.结果:检索到相关文献67篇,最终纳入10篇文献[9-18],包括1382例患者.其中1篇为CCT[10],其余均为RCTs,10篇均为中文文献,枳实、白术制剂痊愈率、总体有效率均优于对照组,复发率低于对照组,未发现明显不良反应.结论:枳实、白术组方中药制剂治疗慢性便秘安全有效,但缺乏高质量研究.     

甘草与白术配伍对IEC-6细胞p53,p21基因表达的影响

通过研究不同剂量甘草与白术配伍对DFMO模型小肠上皮细胞(IEC-6)增殖及p53,p21 mRNA和蛋白表达的影响,探讨甘草与白术配伍对细胞增殖影响的分子基础.采用流式细胞术分别检测药物对IEC-6细胞分裂速度及细胞周期的影响,qRT-PCR检测药物对IEC-6增殖相关基因p53,p21 mRNA的影响,Western blot检测药物对IEC-6细胞p53,p21蛋白表达的影响.白术颗粒可上调DFMO模型IEC-6细胞内p53,p21 mRNA和蛋白的表达水平;而甘草颗粒与白术颗粒不同比例配伍均能显著下调单独白术颗粒作用对DFMO模型IEC-6细胞p53,p21 mRNA和蛋白表达的影响,促进IEC-6细胞的增殖.对于DFMO模型IEC-6细胞,配伍用药甘草能调和白术对小肠上皮细胞的影响.     

Anti-ischemic effect of Aurantii Fructus on contractile dysfunction of ischemic and reperfused rat heart

Aurantii Fructus (AF) is one of the most well-known traditional herbal medicines frequently used for the treatment of cardiovascular symptoms in Korea. The anti-ischemic effects of AF on ischemia-induced isolated rat heart were investigated through analyses of changes in perfusion pressure, aortic flow, coronary flow, and cardiac output. The subjects in this study were divided into two groups: an ischemia-induced group without any treatment, and an ischemia-induced group with AF treatment. There were no significant differences in perfusion pressure, aortic flow, coronary flow, and cardiac output between them before ischemia was induced. The supply of oxygen and buffer was stopped for 10 min to induce ischemia in isolated rat hearts, and AF was administered during ischemia induction. AF treatment significantly prevented decreases in perfusion pressure, aortic flow, coronary flow, and cardiac output under ischemic conditions (p < 0.01). These results suggest that AF has distinct anti-ischemic effects through recovery of contractile dysfunction in ischemic heart.     

中药调控肿瘤细胞自噬的研究进展

自噬是细胞自我吞食并通过溶酶体降解丧失功能的废旧细胞器和蛋白质等细胞内物质,以实现循环再利用、产生能量、对抗应激等现象.自噬可分为巨自噬、微自噬、分子伴侣介导的自噬3类.细胞自噬与肿瘤的增殖、凋亡、侵袭、转移和耐药性等密切相关.研究发现,中药能够增强肿瘤细胞自噬以诱导肿瘤细胞凋亡、抑制肿瘤细胞侵袭与转移、降低肿瘤耐药性...     

基于PI3K/AKT信号通路探究芍药甘草汤对神经根型颈椎病模型大鼠Bax和Bcl-2蛋白表达的影响

目的:探究芍药甘草汤对神经根型颈椎病(CSR)模型大鼠血清磷脂酰肌醇3-激酶(PI3K)/丝氧酸-苏氨酸蛋白激酶(AKT)的调控作用,分析芍药甘草汤对CSR大鼠Bax及Bcl-2的影响。方法:随机将90只SPF级Wistar大鼠分为空白组、模型组、对照组、芍药甘草汤治疗低、中、高剂量组六组,每组15只。除空白组外,其他组以颈部神经根腋下鱼线卡压法构建建立CSR模型大鼠,采用大鼠步态障碍行为学评分进行模型评价。造模后7 d进行干预治疗,空白组和模型组采用生理盐水灌胃,对照组采用3MA干预,芍药甘草汤低、中、高剂量治疗组分别按8、12、16 g/kg剂量进行灌胃,分别干预治疗7 d。末次给药24 h后处死大鼠,取脊髓及神经根组织,酶联免疫吸附法测定各组大鼠丝氨酸残基的底物Bax和Bcl-2的表达水平; HE染色检测各组大鼠脊髓组织病理表现; 蛋白免疫印迹法(Western blot)检测各组大鼠脊髓组织中PI3K/AKT通路蛋白的表达情况。结果:造模后14 d,除空白组外,各组大鼠步态积分增高,提示造模成功; 给药14 d后,模型组大鼠血清中Bax表达明显增高,Bcl-2表达下降,神经根组织中PI3K、p-AKT蛋白表达降低,差异有统计学意义(P<0.05)。与模型组比较,对照组和芍药甘草汤各治疗组CSR大鼠在治疗后神经根积分明显降低,而且组织中Bax表达降低,Bcl-2表达升高(P<0.05); 神经根组织中PI3K、p-AKT蛋白表达水平显著升高(P<0.05),且芍药甘草汤治疗组大鼠具有剂量依赖性(P<0.01)。结论:芍药甘草汤可有效调控CSR模型大鼠PI3K、p-AKT蛋白表达,其机制可能与芍药甘草汤能够激活CSR大鼠组织中Bax和Bcl-2等生物因子抗细胞凋亡相关。     

针药结合对糖尿病胃轻瘫小鼠胃窦Cajal间质细胞及SP、nNOS表达的影响

ObjectiveTo explore the effect of acupuncture combined with Chinese medicine on expression of interstitial cells of Cajal (ICC), substance P (SP) and nerve nitric oxide synthase (nNOS) in diabetic gastroparesis mice.MethodsEighty Kunming male mice were randomly divided into normal group (group A, 15 mice), diabetic gastroparesis model mice group (group B, 12 mice), acupuncture combined with Chinese medicine group (group C, 12 mice), Chinese medicine group (group D, 13 mice) and western medicine group (group E, 13 mice). The mice were intraperitoneally injected with steptozotocin and fed with high-fat diet-induced irregular except the normal group mice, that made mouse model of diabetic gastroparesis. And then, the ACM group were treated by acupuncture at the acupoints of Housanli (

ST 36) and Zhōngwăn (

CV 12) combined with Chinese medicine, the CM group were only treated by Chinese medicine; the WM group were treated by domperidone and vitamin B 6. Numbers and expression of ICC, SP and nNOS were detected by immunohistochemical methods.ResultsAfter treatment, compared with normal group, ICC and SP indexes of model group were significantly reduced. Compared with model group, all indexes in ACM and CM groups were improved significantly (P<0.05, P<0.01), but only the positive area and average optical density value in c-Kit and SP in WM group increased obviously (P<0.05). Compared with ACM group, no significant difference in c-Kit and SP of CM group were observed (P>0.05), but expression of nNOS were increased markedly (P<0.01). Besides, c-Kit and SP expressions of WM group were significantly induced was increased remarkably (P<0.01).ConclusionAcupuncture combined with Chinese medicine have much better therapeutic effects for diabetic gastroparesis mice, which may be due to repairing ICC damage, upregulating the expression of SP and lowering the expression of nNOS.     

中药祛痘1号软膜对金黄地鼠皮脂腺增生及其功能的影响

目的:观察金黄地鼠背部皮脂腺斑在使用中药祛痘1号软膜前后,其组织形态及增殖细胞核抗原(PCNA)、磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(Akt)表达的变化,研究该药对皮脂腺功能的影响,从而进一步探讨该药治疗痤疮的原理。方法:把32只雄性金黄地鼠随机分成四组,分别使用中药祛痘1号软膜、软膜基质、蒸馏水、维胺酯维E软膏外敷金黄地鼠背部皮脂腺斑块,1次/d,连续给药2周。干预前后观察指标:金黄地鼠皮脂腺斑大小变化; 金黄地鼠皮脂腺斑组织病理学变化; 各组皮脂腺组织PCNA、PI3K、Akt表达。结果:经干预后,中药软膜组的皮脂腺组织体积小于空白组和软膜基质组,且排列明显疏松,PCNA、PI3K、Akt表达下降,差异有统计学意义(P<0.05)。中药软膜组和阳性对照组观察指标相接近,差异无统计学意义(P>0.05)。结论:中药祛痘1号软膜可抑制金黄地鼠背部皮脂腺组织功能和皮脂腺斑的增生,其疗效比空白对照组好,接近于维胺酯维E软膏。     

Effects of San-Huang-Xie-Xin-tang,a traditional Chinese prescription for clearing away heat and toxin,on the pacemaker activities of interstitial cells of Cajal from the murine small intestine

Ethnopharmacological relevance

San-Huang-Xie-Xin-Tang (SHXXT) is a traditional Chinese medicinal formula composed of Coptidis rhizoma (Coptis chinesis Franch), Scutellariae radix (Scutellaria baicalensis Georgi), and Rhei rhizoma (Rheum officinale Baill) and is widely used in Eastern Asia, especially to ameliorate the symptoms of gastrointestinal (GI) disorders related to gastritis, gastric bleeding, peptic ulcers, and abnormal GI motility

Aim of the study

Interstitial cells of Cajal (ICCs) are pacemaker cells in the GI tract that generate rhythmic oscillations in membrane potentials known as slow waves. Because GI disorders, especially abnormal GI motility, are major lifelong problems, the authors investigated the effects of SHXXT on mouse small intestine ICCs, and sought to identify the receptors and the action mechanisms involved.

Materials and methods

Enzymatic digestions were used to dissociate ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record potentials generated by cultured ICCs.

Results

SHXXT produced membrane depolarization in current-clamp mode, and Y25130 (a 5-HT₃ receptor antagonist) and RS39604 (a 5-HT₄ receptor antagonist) blocked SHXXT-induced membrane depolarizations, whereas SB269970 (a 5-HT₇ receptor antagonist) did not. However, during external Ca²⁺ free conditions or in the presence of thapsigargin, SHXXT did not exhibit membrane depolarization. Furthermore, the application of flufenamic acid (a nonselective cation channel (NSCC) blocker) or DIDS (a chloride channel blocker) abolished pacemaker potential generation and blocked SHXXT-induced membrane depolarizations. In addition, SHXXT-induced membrane depolarizations, which are dependent on G-protein, in ICCs were blocked by PD 98059 (a p42/44 mitogen-activated protein kinase (MAPK) inhibitor), SB203580 (a p38 MAPK inhibitor), and by a c-jun NH2-terminal kinase (JNK) II inhibitor. Regarding the components of SHXXT, Coptidis rhizome and Rhei rhizoma modulated ICC pacemaking activity, whereas Scutellariae radix did not.

Conclusion

SHXXT modulates pacemaker potentials via 5-HT₃ and 5-HT₄ receptor-mediated pathways, external Ca²⁺ influx, and Ca²⁺ release from internal stores. Furthermore, NSCCs and Cl- channels play important roles in the regulation of pacemaking activity in a MAPK dependent manner in ICCs. The regulation of pacemaking activity by SHXXT may be due to the activity of Coptidis rhizome and Rhei rhizome. The study shows SHXXT can modulate the pacemaking activity of ICCs in the GI tract, and thus, suggests SHXXT has potential pharmacological relevance for the treatment of GI motility disorders.     

基于网络药理学研究黄连-黄柏药对治疗溃疡性结肠炎的作用机制

目的:运用网络药理学技术研究黄连-黄柏药对治疗溃疡性结肠炎的主要活性成分,预测活性成分的作用靶点、建立"药对-活性成分-疾病-作用靶点"网络,探讨黄连-黄柏药对治疗溃疡性结肠炎的潜在作用机制.方法:运用中药系统药理学数据库与分析平台(TCMSP)筛选黄连-黄柏药对的化学成分,借助人类基因数据库获取溃疡性结肠炎的相关靶点...     

Elucidation of the hepatoprotective effect and mechanism of Melastoma dodecandrum Lour. based on network pharmacology and experimental validationOA

Objective: To systematically explore the effect and mechanism of melastomatis dodecandri herba(Melastoma dodecandrum Lour.) in the treatment of hepatitis based on network pharmacology.Method: We evaluated the hepatoprotective effects of M. dodecandrum in concanavalin A(Con A)-induced hepatitis in mice by assessing survival rate, histological analysis, serum transaminases, and related cytokines. Then the mechanism of action was predicted by a network pharmacology-based strategy. Based on the resu...     

PI3K/Akt信号通路影响食管癌细胞生长的机制及中药干预作用研究进展

食管癌是我国肿瘤发病死亡率较高的恶性肿瘤之一,国家癌症中心2019年发布的中国最新癌症报告中显示,2015年食管癌患病人口达到了24. 6万人,死亡人数高达18. 8万人。如何有效的治疗食管癌,提高患者的生存率也是当今医学领域中亟待解决的首要问题之一。磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)信号通路是调节机体内细胞存活、分化及凋亡的重要信号通路之一,在各种癌症的发生及作用机制中起到了重要的作用。近年来的研究表明,PI3K/Akt信号通路的激活是调节食管癌细胞的增殖、凋亡、周期阻滞、迁移与侵袭的重要因素。长期的临床观察发现中药治疗食管癌作用平稳、毒副作用小,尤其在改善肿瘤患者的生活质量,延长患者生存期等方面作用独特、效果显著。用中药干预该信号通路以探索其对食管癌的作用机制是目前中药治疗食管癌的研究热点。本文对2009—2019年CNKI,Pubmed数据库中PI3K/Akt信号通路,食管癌,miRNA为关键词进行检索,共检索文献226篇,整理、归纳与中药,食管癌,miRNA,PI3K/Akt信号通路相关文献61篇。综述了PI3K/Akt信号通路在食管癌中的作用机制,miRNA与PI3K/Akt信号通路与食管癌发生发展的关系以及中药如何通过调控PI3K/Akt信号通路中相关蛋白的表达而抑制细胞增殖、影响细胞生长周期、诱导细胞凋亡、诱导细胞自噬、抑制肿瘤的侵袭和转移、抑制血管生成等,最终对食管癌起到一定的改善作用。对中医药治疗食管癌提供理论基础以及科学依据。     

白藜芦醇对U251人脑胶质瘤细胞生长的抑制及相关机制的研究

目的:研究白藜芦醇(Res)对U251人脑胶质瘤细胞生长的抑制及相关作用机制.方法:将不同浓度Res作用于U251细胞系,MTT法检测Res对U251细胞生长增值的抑制作用,流式细胞仪(FCM)检测Res.对细胞凋亡的影响,免疫组织化学法检测Res处理前后Bcl-2,Bcl-XL,CyclinD1,STAT3的表达及Westem blot(蛋白印迹法)法检测Bcl-2,Bcl-XL,cyclinD1,Caspase-3,Bax,STAT3的表达.结果:经Res处理后的U251细胞,MTT结果显示细胞增殖现象被抑制,并呈时间-剂量依赖性;FCM显示随着Res作用时间的延长,细胞晚期凋亡数增加;免疫组织化学法显示Bcl-2,Bcl-XL,CyclinD1,STAT3的表达下降;Westem-blot检测显示Bcl-2,Bcl-XL,CyclinD1,STAT3表达下降,而Caspase-3和Bax的表达上调.结论:Res诱导U251细胞凋亡的分子机制可能是通过下调Bcl-2,Bcl-XL蛋白的表达,而上调Bax与Caspase-3蛋白的表达,并随着Res剂量与作用时间的延长这种趋势在加强.     

Metabonomic study on the anti-osteoporosis effect of Rhizoma Drynariae and its action mechanism using ultra-performance liquid chromatography-tandem mass spectrometry

Ethnopharmacological relevance

Rhizoma Drynariae (RD) is an effectively traditional Chinese medicine which is usually used in treating osteoporosis, bone fracture, streptomycin ototoxicity and hyperlipemia. Up to now, studies on pharmacological mechanism of RD mostly focus on cell and gene level, little is known about its metabonomics study. The aim of this study is to establish the rats plasma metabonomic profiles of control, model and treatment group, then to investigate the anti-osteoporosis effect of RD and its action mechanism.

Method

A total of 21 Wistar rats was divided into three groups: control group, model group and treatment group. The model and treatment rats were injected prednisolone for 12 weeks, at the same time the treatment rats were orally administered RD extract at a therapeutic dose (10 g/kg, expressed as the weight of raw material) once daily throughout the experimental period, control group and model group were orally gavaged approximately volume normal saline solution. After 12 weeks, all plasma samples of three groups were collected and their metabolic profiling changes were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The resulting dataset was analyzed by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). The identification of all potential biomarkers was performed using reference standard by comparing their mass spectra, MS/MS fragmentation and retention time. Furthermore, clinical biochemistry and biomechanics study were also carried out to ensure the success of the osteoporosis model and to investigate the anti-osteoporosis effect of RD.

Results

Obvious separation trend between control and model group was found in PCA score plot, the anti-osteoporosis effect of RD can be indicated in PLS-DA score plot among these three groups. Six potential metabolite biomarkers, Lysophosphatidylcholines (C16:0 LPC, C18:0 LPC, C18:1 LPC and C18:2 LPC), tryptophane and phenylalanine, which were proved to be related with osteoporosis, were identified in the rats plasma. Compared with control group, level of all biomarkers increased significantly in model group, while that was much closer to normal in treatment group.

Conclusion

The anti-osteoporosis effect of RD has been reliably confirmed by the metabonomics method. The osteoporosis might be prevented by RD via intervening antioxidant-oxidation balance, tryptophane metabolism and phenylalanine metabolism in vivo in rats.     

化痰行瘀通腑汤保留灌肠治疗慢性阻塞性肺疾病急性加重期临床疗效及对肺功能和炎症因子的影响

目的 观察化痰行瘀通腑汤保留灌肠治疗慢性阻塞性肺疾病急性加重期(AECOPD)临床疗效及对患者肺功能、白细胞介素6(IL-6)、白三烯B4(LTB4)、C反应蛋白(CRP)、肿瘤坏死因子α(TNF-α)的影响。方法 将160例AECOPD患者按照随机数字表法分为2组。对照组80例予西医常规治疗;观察组80例在对照组治疗基础上加用化痰行瘀通腑汤保留灌肠治疗。2组均治疗2周后统计临床疗效,并观察2组治疗前后肺功能肺活量(VC)、第1s用力呼气容积(FEV1)、第1s用力呼气容积占用力肺活量百分比(FEV1/FVC)、最大呼气中段流速(MMEF),动脉血氧分压[p(O2)]、二氧化碳分压[p(CO2)]、氧饱和度(SaO2),以及检测IL-6、LTB4、CRP、TNF-α水平。结果 观察组总有效率87.5%,对照组总有效率75.0%,观察组临床疗效优于对照组(P<0.05)。治疗后2组VC、FEV1、FEV1/FVC、MMEF均升高(P<0.05),且观察组高于对照组(P<0.05)。治疗后2组p(O2)、p(CO2)、SaO2均改善(P<0.05),且观察组改善优于对照组(P<0.05)。治疗后2组IL-6、LTB4、CRP、TNF-α水平均下降(P<0.05),且观察组低于对照组(P<0.05)。结论 化痰行瘀通腑汤保留灌肠治疗AECOPD临床疗效显著,并可明显改善肺功能及缺氧情况,减轻炎性反应。     

丹参、人参、连翘、麦冬对肺纤维化模型大鼠肺组织中BMP-4表达的影响

目的:观察丹参、人参、连翘、麦冬对博来霉素诱导的肺纤维化模型大鼠肺组织中BMP-4表达的影响,探讨这四种药物抗纤维化的作用机制。方法:将168只健康Wistar雄性大鼠随机分成空白对照组、模型组、人参组、丹参组、连翘组、麦冬组、吡啡尼酮组,每组24只。除空白对照组外,其他各组大鼠均通过气管内注射博来霉素(5 mg/kg)建立肺纤维化模型,空白对照组大鼠气管内注射等量生理盐水。造模后第4天,人参组、丹参组、连翘组、麦冬组、吡非尼酮组大鼠分别给予相应药物灌胃,空白对照组、模型组每日予等量生理盐水灌胃。分别于给药后第7天、第14天、第28天随机处死每组的8只大鼠,取大鼠左肺下叶组织作切片,观察肺组织病理学变化,并以酶联免疫分析法检测各组大鼠BMP-4水平。结果:除空白对照组外,其他各组大鼠均有不同程度的肺泡炎症及肺纤维化表现,说明造模成功。与各给药组比较,模型组大鼠肺纤维化程度最明显;给药后第7天、第14天、第28天,人参组、丹参组、连翘组、麦冬组、吡啡尼酮组大鼠肺泡炎症及肺纤维化表现较模型组减轻。建模后模型组大鼠BMP-4水平降低,与空白对照组比较,差异有统计学意义(P0.01);连翘组、麦冬组、吡非尼酮组大鼠给药后第7天、第14天、第28天的BMP-4水平均高于空白对照组,差异有统计学意义(P0.01);丹参组、人参组大鼠给药后第14天、第28天的BMP-4水平与空白对照组比较,差异无统计学意义(P 0.05)。结论:丹参、人参、连翘、麦冬均能降低肺纤维化大鼠的肺纤维化程度,其中连翘、麦冬可能通过提高BMP-4水平发挥抗肺纤维化作用。     

中药抗肝癌细胞增殖和诱导细胞凋亡的信号通路研究进展

从信号转导通路方面综述中药抗肝癌细胞增殖和诱导细胞凋亡的研究进展。中药和中药提取物可通过调控肝癌相关信号通路,如MAPK信号转导通路、PI3K/AKT信号转导通路、JAK-STAT通路、Caspase途径、Wnt信号通路等,改变肝癌细胞特性发挥抑制肝癌细胞增殖和诱导细胞凋亡的效果。