Effects of Radix Puerariae, Radix Rehmanniae and Their Compatibility on Blood Glucose and Blood Lipids in Mice

[Objectives]To explore the effects of the compatibility of Radix Puerariae and Radix Rehmanniae on blood glucose and blood lipids in diabetic mouses.[Methods]Diabetic mouse model was established.The body weight and fasting blood glucose of mice were measured after 7 and 14 d of administration,and the biochemical indicators of blood lipids(TC,HDL-C,and LDL-C)were detected after 14 d of administration.[Results]Compared with the Radix Puerariae group and Radix Rehmanniae group,the compatibility group(1:2)had the best hypoglycemic effect(P<0.05),and TC and LDL-C in the compatibility group(2:1)significantly decreased(P<0.05),while HDL-C in the compatibility group(1:1)significantly increased(P<0.05).[Conclusions]Radix Puerariae,Radix Rehmanniae and their combination can reduce the blood glucose of diabetic mice.The compatibility group(1:2)had a significant hypoglycemic effect(P<0.05),and LDL-C in the compatibility group(2:1)significantly declined,while HDL-C in the compatibility group(1:1)rose significantly.

Determination of Benzoylaconitine Compounds in the Decoctions of Aconiti Lateralis Radix Praeparata(Heishun Pieces),Trichosanthis Fructus and Their Combination

[Objectives]This study was conducted to determine the contents of benzoylmesaconine,benzoylaconitine and benzoylhypacoitine in the decoctions of Heishun pieces,Trichosanthis Fructus and their combination.[Methods]Heishun pieces,Trichosanthis Fructus and their combination were extracted for different time periods,and then grouped.HPLC was performed using an Agilent ZORBAX SB-C 18 chromatographic column(4.6 mm×250 mm,5μm)and acetonitrile-0.02 mol/L sodium dihydrogen phosphate as the mobile phase at a flow rate of 1 mL/min and a column temperature of 30℃,and the sample volume was 20μL.The detection wavelength was 230 nm.[Results]The total amounts of benzoylmesaconine,benzoylaconitine and benzoylhypacoitine in the single decoction group of Heishun pieces were all significantly different from those in the combined decoction group at corresponding time.[Conclusions]The total content of the benzoylaconitine type increased significantly after the combined decoction of Heishun pieces and Fructus Trichosanthis,which proves the scientificity of"eighteen incompatible medicaments,19 counteraction"in traditional Chinese medicine to some extent.

Deciphering the potential mechanism of Radix Rehmanniae Praeparata for treating cancer-related anemia based on network pharmacology and molecular docking technology

Background:Rehmanniae Radix Praeparata(RRP,Shu Dihuang in Cinese)is a traditional Chinese herb with multiple pharmacological effects and is commonly used to treat blood deficiency syndrome,such as cancer-related anemia(CRA),alone or in combination with other herbs.However,its main active ingredients and mechanisms of action in treating CRA remain unknown.This study aims to elucidate RRP’s potential mechanism and main active components in treating CRA by using network pharmacology and molecular docking technology system.Methods:The main components of RRP were obtained by the TCMSP database and literature search,and active components and potential targets were obtained by the SwissADME and SwissTargetPridiction databases.CRA targets were collected through GeneCards,DisGeNET,and DrugBank databases.Protein-protein interaction networks of potential targets were constructed via STRING 11.5 and analyzed visually with Cytoscape 3.9.1.The Metascape platform was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis,which were subsequently visualized with Cytoscape 3.9.1 or SangerBox platform.Moreover,Autodock Vina was used for the molecular docking of potential targets and main active ingredients that were visualized with PyMOL software.Results:In this study,31 main active ingredients of PPR were screened,and 155 related targets related to CRA were unearthed.Protein-protein interaction results showed that PPR’s core proteins for CRA intervention correlate to STAT3,SRC,MAPK3,MAPK1,PIK3R1,PIK3CA,and AKT.Multiple signaling pathways were closely related to the treatment of CRA intervened by PPR,including the PI3K-Akt signaling pathway,HIF-1 signaling pathway,JAK-STAT3 signaling pathway,TNF-αsignaling,cytokine signaling pathway and NF-kappB signaling pathway,which are closely involved in the proliferation and differentiation of hematopoietic stem cell and inflammatory response.Molecular docking results showed that these potential targets had good conformation with the core active components of RRP for treating CRA.Conclusion:This study revealed RRP’s main active components and potential molecular mechanisms in treating CRA,providing a reference for subsequent basic research.

The dynamic changes and mechanisms of Rehmanniae radix processing based on Maillard reaction

Background:Traditional Chinese medicines are usually processed before they are used for clinical treatment.This is done in a way associated with the Maillard reaction.Methods:Based on the Maillard reaction,this paper analyzed the degree of processing of rehmannia root(Rehmanniae radix)relative to the dynamic variation rules of Maillard reaction index parameters,including pH,A420,amino acids,and 5-hydroxymethylfurfural.Furthermore,this study introduced thermal analysis techniques and pyrolysis kinetics to assess the influence of the correlation between processing raw rehmannia root and the Maillard reaction during carbonization.It then went through the whole process of transforming the raw material to end-product in order to explain the scientific connotation of processing it.Results:The results showed that each time rehmannia root was processed,its pH value and amino acid content decreased,while the A420 value and 5-HMF increased.Processing with wine shows a significant difference in these experimental indexes.The position and intensity of the maximum thermal weight loss rate peak of processed rehmannia root at different degrees of processing are different.Comprehensive quantitative 221±0.2°C for processed rehmannia root carbonization was the processing temperature limit.Moreover,the kinetic solution verified that the activation energy corresponding to the carbonization temperature was close to the maximum value of the activation energy of the whole carbonization process,and the optimal mechanism function was g(α)=((1−α)−1/3−1)2.Conclusion:The Maillard reaction occurred during the processing of rehmannia root mixed with carbonization.With each increase of the number of steaming and drying cycles involved in the processing,the level of Maillard reaction increased significantly.The wine-steaming method had a significant effect on the quality of the processed product.

Mechanisms of Dihuang(Rehmanniae Radix)in treating diabetic nephropathy complicated with depression based on network pharmacology

Objective To predict the molecular mechanism of Dihuang(Rehmanniae Radix)in the treatment of diabetic nephropathy(DN)complicated with depression based on network pharmacology.Methods The components of Dihuang(Rehmanniae Radix)were identified from the Integrated Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP),Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and relevant literature.The component targets were detected by combining the SwissTargetPrediction and Pub Chem databases.Disease targets were collected from the Therapeutic Target Database(TTD),Dis Ge NET,and Ensembl databases with“diabetic nephropathy”and“depression”as keywords.The disease-component targets were mapped using Venny 2.1.0 to obtain potential targets.A protein-protein interaction(PPI)network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database and Cytoscape 3.7.2.The co-expression genes of the key targets were collected based on the COXPRESdb 7.3.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed for potential targets using R language.Target-component docking was verified and evaluated using Discovery Studio 4.5.Results According to the databases and literature reports,Dihuang(Rehmanniae Radix)contained 65 active components,and had 155 related targets for the treatment of DN complicated with depression.PPI screening showed that the key targets included serine/threonine protein kinase 1(AKT1),signal transducer and activator transcription 3(STAT3),interleukin 6(IL-6),mitogen-activated protein kinase 1(MAPK1),and vascular endothelial growth factor A(VEGFA),etc.GO enrichment analysis mainly involved biological processes,such as lipid metabolism,protein secretion regulation,cell homeostasis,and phosphatidylinositol 3 kinase activity.KEGG pathway enrichment analysis included the role of the AGE-RAGE signaling pathway in diabetic complements,insulin resistance(IR),neurotrophin signal path,Toll-like receptor signaling pathway,relaxin signaling pathway,epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs),etc.Molecular docking showed that the target had high affinity for stachyose,manninotriose,verbascose,nigerose,etc.Conclusion Based on network parmacology,this study preliminarily predict the effects of Dihuang(Rehmanniae Radix)in treating DN complicated with depression by regulating inflammation,glucose metabolism,nution nerve,etc.

Radix Polygoni Multiflori Praeparata and Dioscorea Bulbifera Rhizome Decoctions Display Combined Effects Detected by a Three-Probe Drug Cocktail with Substrates of Rat Hepatic Cytochrome P450 Enzymes

Objectives: Radix Polygoni Multiflori Praeparata (RPMP) and Dioscorea Bulbifera Rhizomes (DBR) are used in Chinese herbal medicine and have been frequently reported for adverse reactions on liver. In this research, we aimed to evaluate in vivo effects of RPMP and DBR on rat cytochrome P450 enzymes (CYP1A2, CYP2E1 and CYP3A2) with their respective substrates as probes. Methods: Rats were orally administered RPMP, DBR and RPMP/DBR combination at 12, 10 and (12 + 10) g/kg, respectively, or saline as a control, once daily for 7 days. Thereafter, a cocktail containing 10 mg/kg caffeine, 20 mg/kg chlorzoxazone and 10 mg/kg dapsone was tail vein injected to rats. At defined time points, plasma drug concentrations were simultaneously evaluated by HPLC. Pharmacokinetic parameters simulated by DAS software were used to assess RPMP and/or DBR effects on cytochrome P450 enzymes activity. ANOVA and Dunnett’s test were used for data analysis. Results: Caffeine metabolism was enhanced in RPMP animals and reduced after pretreatment with DBR, but no effect was observed in RPMP/DBR combination group. Chlorzoxazone and dapsone metabolism was enhanced in both RPMP and DBR groups and consequently in combination group. The data suggested that RPMP independently induces rat CYP1A2, CYP2E1 and CYP3A2 activity, while DBR independently inhibits activity of rat CYP1A2 and induces that of CYP2E1 and CYP3A2. RPMP/DBR combination showed no significant benefit compared with the two drugs alone and even showed a neutralized effect in CYP1A2 activity. Conclusions: Caution is needed when RPMP and/or DBR are co-administered with drugs metabolized by human CYP1A2, CYP2E1 and CYP3A4.

Determination and Analysis of Flavonoid Contents in Different Batches of Dried Radix Rehmannia and Prepared Radix Rehmanniae

[Objectives] This study was conducted to understand Radix Rehmannia quality and provide reference for selection in application. [Methods] The contents of flavonoids in five batches of commercially available samples were determined by ultraviolet spectrophotometry, and the precision and reproducibility of the determination method were analyzed. [Results] The contents of flavonoids in different batches of Radix Rehmannia samples were not completely the same, but the differences were not large overall. The experiment results have good reliability. As a medicinal plant, the climate and soil conditions of the producing areas would have an impact on the quality of Radix Rehmannia. [Conclusions] The contents of flavonoids determined in Radix Rehmannia were relatively stable, the quality was basically the same, and the overall quality was good.

Research Progress in Toxicity and Toxicity-reducing and Efficacy-enhancing Compatibility of Radix Aconiti Lateralis Praeparata

Radix Aconiti Lateralis Praeparata contains alkaloids,flavonoids,polysaccharides,organic acids and organic alkalis,among which diester alkaloids are important effective ingredients,which can be used for treating heart failure,rheumatic heart disease,coronary heart disease,hypotension,shock and other diseases.However,it also contains the main ingredients that produce toxic effects and are highly toxic to the cardiovascular system,nervous system,digestive system,reproductive system,embryos,and livers and kidneys.In this study,we analyzed the toxicity-reducing and efficacy-enhancing effects of the compatibility of Radix Aconiti Lateralis Praeparata with with single herbs Glycyrrhiza uralensis Fisch.,Panax ginseng C.A.Meyer,Zingiber ojjicinale Rosc.and Rheum palmatum L.,aiming to provide references for further exploring the appropriate compatibility conditions of traditional Chinese medicine in the future and improving the safety of the clinical application of Radix Aconiti Lateralis Praeparata.

Rehmanniae Radix Praeparata aqueous extract improves hepatic ischemia/reperfusion injury by restoring intracellular iron homeostasis

Hepatic ischemia/reperfusion injury(HIRI)is a common pathophysiological condition occurring during or after liver resection and transplantation,leading to hepatic viability impairment and functional deterioration.Recently,ferroptosis,a newly recognized form of programmed cell death,has been implicated in IRI.Rehmanniae Radix Praeparata(RRP),extensively used in Chinese herbal medicine for its hepatoprotective,anti-inflammatory,and antioxidant properties,presents a potential therapeutic approach.However,the mechanisms by which RRP mitigates HIRI,particularly through the regulation of ferroptosis,remain unclear.In this study,we developed a HIRI mouse model and monocrotaline(MCT)-and erastin-induced in vitro hepatocyte injury models.We conducted whole-genome transcriptome analysis to elucidate the protective effects and mechanisms of RRP on HIRI.The RRP aqueous extract was characterized by the presence of acteoside,rehmannioside D,and 5-hydroxymethylfurfural.Our results demonstrate that the RRP aqueous extract ameliorated oxidative stress,reduced intracellular iron accumulation,and attenuated HIRI-induced liver damage.Additionally,RRP significantly inhibited hepatocyte death by restoring intracellular iron homeostasis both in vivo and in vitro.Mechanistically,the RRP aqueous extract reduced intrahepatocellular iron accumulation by inhibiting ZIP14-mediated iron uptake,promoting hepcidin-and ferroportin-mediated iron efflux,and ameliorating mitochondrial iron aggregation through upregulation of Cisd1 expression.Moreover,siRNA-mediated inhibition of hamp synergistically enhanced the RRP aqueous extract's inhibitory effect on ferroptosis.In conclusion,our study elucidates the mechanisms by which RRP aqueous extracts alleviate HIRI,highlighting the restoration of iron metabolic balance.These findings position RRP as a promising candidate for clinical intervention in HIRI treatment.

陕产附子炮制前后急性毒性及强心作用研究

目的:考察陕产附子炮制前后的急性毒性和强心作用。方法:通过对生附子LD_(50)的测定和自制黑顺片最大耐受量实验比较生附子和自制黑顺片的急性毒性;通过复制慢性心衰大鼠模型,检测大鼠体质量、心脏指数、血流动力学指标,检测血清BNP及cTnI含量以及组织病理学检查比较其强心作用。结果:生附子的半数致死量(LD_(50))为9.45 g/kg,黑顺片的最大耐受量为27.39 g/kg,经炮制后毒性降低。与模型组相比,自制黑顺片组大鼠症状及体征均有改善,能够降低心脏指数、左心室指数降低和左心室舒张压(LVEDP),升高左心室收缩压(LVSP)、收缩期左心室内压上升最大变化速率(+dp/dt_(max))和舒张期左心室内压下降最大变化速率(-dp/dt_(max))(P<0.05,P<0.01);降低血清中脑钠肽(BNP)、心肌肌钙蛋白I(cTnI)含量(P<0.05);心肌纤维排列相对紧密,胞核清晰可见,但有一定断裂,其中有少量空泡存在,未发现炎性细胞浸润,各指标有明显差异。生附子组各指标有一定程度的改善,但差异无统计学意义(P>0.05)。结论:生附子经炮制后,毒性降低,起到减毒的作用;自制黑顺片较生附子强心作用有显著增强。

基于UPLC特征图谱和含量测定的蜜远志标准汤剂质量评价研究

目的建立蜜远志标准汤剂特征图谱以及3种成分质量分数同时测定的UPLC方法,对不同来源蜜远志饮片制成的标准汤剂质量进行评价。方法采用UPLC法建立蜜远志标准汤剂的特征图谱以及细叶远志皂苷、远志酮Ⅲ和3,6′-二芥子酰基蔗糖质量分数测定的方法,并对16批标准汤剂进行测定,采用高分辨质谱对共有峰进行了指认,采用聚类分析及偏最小二乘法分析(PLS-DA)对共有峰进行了分析。结果蜜远志标准汤剂特征图谱标定了9个共有峰,通过高分辨质谱分别指认为:西伯利亚远志糖A5、西伯利亚远志糖A6、远志酮Ⅲ、3,6′-二芥子酰基蔗糖、黄花远志素A、细叶远志皂苷A、远志寡精H、远志寡糖A、1,2,3,7-四甲氧基呫吨酮,相似度结果显示16批样品的相似度均大于0.900。聚类分析及PLS-DA显示不同来源之间的样品可能存在质量差异。结论本研究建立的蜜远志标准汤剂特征图谱和质量分数测定方法简便、快速、准确,可为蜜远志相关制剂的质量评价提供参考。

熟地黄-山茱萸药对通过PI3K/AKT通路对Aβ25-35诱导的N2a细胞凋亡的影响

目的研究熟地黄-山茱萸药对通过磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)信号通路对β-淀粉样蛋白(Aβ25-35)诱导小鼠脑神经瘤细胞株(N2a)细胞凋亡的抑制作用。方法以Aβ25-35(20μmol/L)处理N2a细胞构建阿尔茨海默病(Alzheimer′s disease,AD)细胞模型,给予低、高浓度的熟地黄-山茱萸醇提物作用24 h。采用CCK8法测定细胞存活率,寻求最佳的Aβ25-35的诱导浓度;Hoechst 33342和Annexin V-FITC/PI染色检测细胞凋亡;比色法检测含半胱氨酸的天冬氨酸蛋白水解酶3(Caspase-3)活性;Western Blot法检测cleaved Caspase-3、p-PI3K、PI3K、p-AKT和AKT蛋白表达。结果与空白对照组比较,经过Aβ25-35处理后的N2a细胞凋亡率和Caspase-3蛋白表达及活性显著升高,p-PI3K/PI3K、p-AKT/AKT比值下降(P<0.05);给予低、高浓度的熟地黄-山茱萸醇提物作用24 h后,N2a细胞的凋亡率和Caspase-3蛋白表达及活性降低,p-PI3K/PI3K、p-AKT/AKT比值升高,与模型组比较差异有统计学意义(P<0.05);与低剂量组比,高剂量组N2a细胞的凋亡率和Caspase-3活性降低,p-AKT/AKT比值升高(P<0.05)。结论熟地黄-山茱萸醇提物可对Aβ25-35诱导的N2a细胞凋亡具有保护作用,其机制可能与促进PI3K/AKT信号通路有关。

熟地黄对雌性中枢性性早熟大鼠下丘脑-垂体-IGF-1轴影响的实验研究

目的 探讨熟地黄对雌性中枢性性早熟(CPP)大鼠的治疗作用,并阐明其可能的作用机制。方法 将48只SPF级雌性28日龄SD大鼠随机分为正常组、模型组、阳性对照(亮丙瑞林100μg/kg)组和熟地黄低、中、高剂量(0.8、1.6、3.2 g/kg)组,每组8只。采用N-甲基-DL-天冬氨酸(NMA)法建立CPP大鼠模型,造模期间同时给予亮丙瑞林或不同剂量熟地黄干预,每天1次;记录大鼠阴道开口时间及首个动情间期时间;HE染色检测大鼠子宫内膜厚度及卵巢黄体个数;ELISA检测大鼠血清中促黄体生成激素(LH)、卵泡刺激素(FSH)、雌二醇(E2)水平;Western blot检测大鼠下丘脑中性腺激素释放激素(GnRH)、胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)及生长激素(GH)蛋白表达水平。结果 与正常组比较,模型组大鼠阴道开口及首个动情间期时间明显提前(均P<0.05);子宫壁厚度和卵巢黄体数显著增加,同时血清中LH、FSH、E2水平以及下丘脑组织中GnRH、IGF-1、IGFBP-3、GH蛋白表达水平显著升高(均P<0.05)。与模型组比较,阳性对照组及熟地黄各剂量组大鼠阴道开口时间及首个动情间期时间明显较长(均P<0.05);子宫壁厚度和卵巢黄体数显著减少,同时血清中LH、FSH、E2水平以及下丘脑组织中GnRH、IGF-1、IGFBP-3、GH蛋白表达水平显著降低(均P<0.05)。结论 熟地黄可降低CPP大鼠机体生长激素水平,抑制性早熟表现,其机制可能与延缓下丘脑-垂体-IGF-1轴启动有关。

扶阳学派运用附子之经验

基于“阳主阴从”观,扶阳学派集百年之经验,将大剂量附子灵活应用于各类急危重症和疑难杂症,取得了显著的临床疗效。文章通过阐述四川江油道地药材附子的辨证运用要点、配伍方法、剂量把握等方面的内容,并结合临床医案,对扶阳学派运用附子的用药经验进行了回顾性总结,旨在为其临床推广和应用提供可借鉴的依据。

熟地黄中促神经干细胞增殖活性的成分研究

目的 探究熟地黄中促进体外培养的神经干细胞(NSCs)增殖的活性成分。方法 采用系统溶剂萃取法及柱色谱法分离熟地黄各部位,CCK-8法测定熟地黄不同化学分离部位及活性部位所获化合物对NSCs增殖活性的影响。结果 熟地黄水提醇沉后水部位经大孔树脂、硅胶、聚酰胺分离后所得FrC5部分具有显著的促进NSCs增殖的活性(P<0.05)。FrC5部分按照溶解性不同分为FrC5-1和FrC5-2,FrC5-1部位相较于其他组别作用较强且与对照组相比差异有统计学意义(P<0.05),与对照组相比对NSCs的增殖率为75.85%。进一步分离得到2个化合物,根据MS、NMR数据及参考文献鉴定得出活性化合物为毛蕊花糖苷和异毛蕊花糖苷。毛蕊花糖苷对NSCs的增殖率为65.04%,异毛蕊花糖苷对NSCs的增殖率为35.86%。结论 毛蕊花糖苷和异毛蕊花糖苷可能是熟地黄中促进NSCs增殖的主要活性成分。

地黄的临床应用及其用量探究

通过搜集古代名医及现代医家临床应用中药地黄的不同经验及用量,总结出汤剂中地黄用量约10~440 g;常用剂量约10~30 g;散剂用量约0.305~12.39375 g。如治疗急慢性肾小球肾炎、硬皮病、肌无力、脑萎缩、老年性白血病、多囊卵巢综合征、骨纤维发育异常等疾病,可使用熟地黄益精填髓,生地黄清热凉血解毒,常配伍当归、淫羊藿、生晒参、山茱萸、菟丝子、鹿角胶等,剂量为15~30 g;再生障碍性贫血、状疱疹及后遗神经痛、慢性乙肝、肝硬化、糖尿病及其并发症等疾病,可使用生地黄清热凉血解毒,常配伍牡丹皮、赤芍、水牛角、玄参、枸杞、当归等,剂量为10~30 g;治疗类风湿关节炎、阿尔茨海默病、崩漏等疾病,可使用熟地黄补肾扶正,生地黄滋阴养血,常配伍淫羊藿、海风藤、乌梢蛇、山茱萸、生晒参等,剂量为10~30 g;治疗崩漏时常取其滋补肾精、充养冲任、凉血止血之功,常配伍菟丝子、女贞子、枸杞子,剂量为10~30 g。

炒白芍-炙甘草配伍前后化学成分与抗炎作用相关性研究

目的明确炒白芍-炙甘草配伍对化学成分的影响及其与抗炎作用的相关性。方法采用HPLCDAD建立同时测定炒白芍-炙甘草中芍药苷、芍药内酯苷、苯甲酰芍药苷、氧化芍药苷、甘草酸、甘草苷多成分含量的分析方法;建立佐剂性关节炎大鼠模型,给药组分别灌胃炒白芍、炙甘草、炒白芍-炙甘草药液2周,ELISA检测大鼠血清炎症因子白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、前列腺素E_(2)(PGE_(2))含量;采用析因设计、双变量相关分析、多元线性回归方法研究配伍对化学成分的影响及其与抗炎药效的相关性。结果建立HPLC-DAD分析方法,炒白芍-炙甘草配伍后氧化芍药苷、芍药内酯苷、苯甲酰芍药苷含量增加(P<0.05);与模型组比较,各给药组大鼠血清IL-1β、TNF-α、PGE_(2)含量降低(P<0.01),且配伍组血清IL-1β、TNF-α、PGE_(2)含量低于炒白芍组、炙甘草组(P<0.05,P<0.01);析因设计结果显示炒白芍-炙甘草配伍存在交互效应,双变量相关分析结果显示氧化芍药苷、芍药内酯苷、芍药苷、甘草苷、苯甲酰芍药苷、甘草酸含量分别与IL-1β、TNF-α、PGE_(2)含量呈负相关,多元线性回归结果显示甘草苷、甘草酸与IL-1β、TNF-α、PGE_(2)含量呈负相关。结论本研究建立的炒白芍-炙甘草多成分含量分析方法简便快捷、专属性强、准确可靠,可用于其质量评价与控制。炒白芍-炙甘草配伍可抑制炎症因子IL-1β、TNF-α、PGE_(2)表达,且化学成分含量与抗炎作用具有相关性。

基于网络药理学和分子对接探讨熟地黄—黄精治疗阿尔茨海默病的作用机制

目的 整合网络药理学、分子对接技术探究熟地黄—黄精治疗阿尔茨海默病(Alzheimer’s disease, AD)的作用机制。方法 在中药系统药理数据库(Traditional Chinese Medicine System Pharmacology, TCMSP)数据库中收集熟地黄、黄精化学成分和潜在作用靶点,在在线人类孟德尔遗传(online mendelian inheritance in man, OMIM)、治疗靶点(therapeutic target database, TTD)、GeneCards、Drug Bank数据库收集AD疾病靶点基因,运用Cytoscape3.9.1构建“中药—成分—靶点”网络;将熟地黄、黄精与AD的交集靶点基因上传至STRING数据库中分析核心靶点基因;将交集靶点上传至DAVID数据库中进行GO和KEGG富集分析,并通过分子对接检测核心化学成分和核心靶点基因的结合能力。结果 在熟地黄、黄精中共筛选出13个化学成分,其中薯蓣皂苷、3′-甲氧基黄豆苷、豆甾醇、黄芩苷、β-谷甾醇为核心化学成分;AD相关靶点共筛选出2471个,熟地黄、黄精与AD的交集靶点共有68个;PPI分析显示,蛋白激酶B(protein kinase B,Akt1)、前列腺素G/H合成酶2(prostaglandin G/H synthase 2,PTGS2)、凋亡相关蛋白Caspase-3等为核心交集靶点基因;GO分析显示,生物过程主要涉及对含氧化合物、对化学物质的反应等,细胞组成主要涉及神经元投射、神经元部分、躯体树突间室等,分子功能主要涉及酶结合、G蛋白偶联胺受体活性、相同蛋白质结合等;KEGG分析结果显示,核心靶点基因涉及的通路主要为内分泌抵抗、麻疹、雌激素信号通路、凋亡、流体剪切应力与动脉粥样硬化等;分子对接结果显示,核心化学成分黄芩苷、β-谷甾醇、3′-甲氧基黄豆苷与核心靶点结合效能高。结论 熟地黄、黄精防治AD的成分主要为黄芩苷、β-谷甾醇、3′-甲氧基黄豆苷等,这些成分可通过调节10个核心靶点基因发挥防治AD的作用,其机制可能与凋亡、雌激素通路等5个途径有关。

石菖蒲-熟地黄对认知功能障碍模型大鼠的网络药理学作用机制及实验研究

目的:探究石菖蒲-熟地黄对认知功能障碍模型大鼠学习记忆力的影响及作用机制,并进行实验验证。方法:在中药系统药理学数据库与分析平台(TCMSP)、人类基因数据库(GeneCards)、在线人类孟德尔遗传数据库(OMIM)中获取石菖蒲-熟地黄药对治疗认知功能障碍的潜在作用靶点,并构建蛋白质-蛋白质相互作用(PPI)网络,在生物学信息注释库(DAVID)分析平台中对共同靶点进行基因本体(GO)和京都基因和基因组百科全书(KEGG)通路富集分析。基于网络药理学预测结果,用动物实验进行验证。采用双侧脑室注射脂多糖(LPS)的方法模拟中枢神经炎症损伤引起的认知障碍模型,连续灌胃给药8周,假手术组予以注射等量生理盐水。Morris水迷宫观察各组大鼠空间学习记忆力的变化情况;酶联免疫吸附试验(ELISA)检测大鼠血清肿瘤坏死因子-α(TNF-α)含量;蛋白质印迹法(Western Blotting)检测Toll样受体4/核因子κB(TLR4/NF-κB)通路相关蛋白含量。结果:从石菖蒲-熟地黄药对中筛选到26个有效成分,疾病相关靶点64个,涉及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、TNF信号通路、白细胞介素17(IL-17)信号通路、Toll样受体通路、NF-κB信号通路等5条主要信号通路。动物实验结果显示,石菖蒲-熟地黄中、高剂量组大鼠逃避潜伏期明显缩短(P<0.05),在目标象限停留时间明显延长(P<0.05),TNF-α的表达水平明显降低(P<0.05);石菖蒲-熟地黄低、中、高剂量组能显著降低TLR4、p-NF-κB p65/NF-κB p65、IL-6的表达(P<0.05)。结论:石菖蒲-熟地黄可能通过TLR4/NF-κB通路减少炎症介质释放,抑制神经炎症来干预认知功能障碍的发生发展,为该药对抗认知功能障碍有效成分的开发和运用提供了方向。

何首乌及其中成药制剂导致的中草药相关肝损伤的回顾性研究

目的:观察何首乌、润燥止痒胶囊和百乐眠胶囊引起的中草药相关肝损伤(HILI)在接受中医药治疗人群中的可能发生率,探索其危险因素。方法:以2020年1月至2022年6月在上海中医药大学附属曙光医院门诊接受中医药治疗时曾运用何首乌、润燥止痒胶囊、百乐眠胶囊的患者为研究对象,分析HILI发生的可能性。结果:运用何首乌导致HILI的可能发生率为2.64‰,运用润燥止痒胶囊导致HILI的可能发生率为2.40‰,运用百乐眠胶囊导致HILI的可能发生率为2.06‰。甲状腺疾病是影响服用百乐眠胶囊患者HILI发生的危险因素(P<0.001)。结论:何首乌及其中成药制剂导致的中草药相关肝损伤发生率较低,应当正确评价中草药相关肝损伤,安全合理应用中药。