Protective Effects of Self-made Compound Taoren Danshen Decoction on Rats with Acute Liver Injury

[Objectives] To study the protective effects of self-made Compound Taoren Danshen Decoction( CTDD) on acute liver injury induced by D-galactosamine in rats,and to explore its mechanism. [Methods]An acute liver injury model was established by intraperitoneal injection of 500 mg/kg of D-galactosamine. The ALT,AST,MDA,SOD and GSH-Px in serum,as well as serum TNF-α,IL-1β and IL-6 levels were measured,and liver tissue lesions were observed under microscope. [Results] CTDD can significantly reduce ALT,AST and MDA levels,increase SOD,GSH-Px activity,and significantly reduce serum TNF-α,IL-1β and IL-6 levels,and improve liver tissue lesions.[Conclusions]CTDD has a protective effect on D-galactosamine-induced acute liver injury in rats,and its mechanism may be related to inhibition of oxidative stress and inflammatory reaction.

Analysis on the formation principle and present situation of nano phase state of multi-component self-assembly of traditional Chinese compound medicine decoction

Traditional Chinese medicine decoction is a complex polydispersed phase system containing real solution,colloid solution,emulsion and suspension.The compound decoction of traditional Chinese medicine has complex components,including saponins,alkaloids,polysaccharides,flavonoids,amino acids and so on,which can be self-assembled to form gels,fibers,micelles,vesicles and so on.The self-assembled nano-phase not only neutralizes the single drug and reduces the toxicity and side effects,but also has its own pharmacological effects,which complement each other to achieve synergistic effect,so as to achieve the role of drug supplement,which is of research significance.The formation principle,solubilization and synergism principle and characterization method of multi-component self-assembly of traditional Chinese medicine compound decoction are discussed in this paper.

Identification of prototype compounds and their metabolites in rats’ serum from Xuefu Zhuyu Decoction by UPLC-Q-TOF/MS

Objective: As a classic prescription in traditional Chinese medicine, Xuefu Zhuyu Decoction(XFZYD) has been widely used in the clinical treatment of cardiovascular and cerebrovascular diseases. In order to unveil the potentially effective compounds, a rapid ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS) method was established to identify prototype compounds and their metabolites from XFZYD in rats’ serum.Methods: The serum from rats after intragastric administration of XFZYD aqueous extract was analyzed by UPLC-Q-TOF/MS method. The prototype compounds and their metabolites were identified by comparison with the reference standards and tentatively characterized by comprehensively analyzing the retention time, MS data, characteristic MS fragmentation pattern and retrieving literatures.Results: A total of 175 compounds(24 prototype compounds and 151 metabolites) were identified and tentatively characterized. The metabolic pathways of prototype compounds in vivo were also summarized, including glucuronidation, hydrolyzation, sulfation, demethylation, and hydroxylation, and so on.Conclusion: In this study, a UPLC-Q-TOF/MS technique was developed to analyze prototype compounds and their metabolites from XFZYD in serum, which would provide the evidence for further studying the effective compounds of XFZYD.

STUDY ON THE TISSUE DISTRIBUTION OF COMPOUNDS AND METABOLITES OF THE MONGOLIAN MEDICINE DIGEDA-4 DECOCTION IN ACUTE LIVER INJURY INDUCED BY D-GaIN

The objective of this study was to study the distribution characteristics of Mongolian drug Digeda-4 decoction in rats with acute liver injury.The Mongolian drug Digeda-4decoction was administered intragastric in rats with acute liver injury induced by D-GalN.The removal of the Liver,spleen,lung,kidney and heart,10%tissue homogenate

Effect of compound Yindan decoction on alpha-naphthylisothiocyanate-Induced acute intrahepatic cholestasis in rats

OBJECTIVE:To investigate the therapeutic mechanism of compound Yindan decoction (CYD) in a rat model of acute intrahepatic cholestatic (AIC).METHODS:A total of 108 adult male rats were randomly divided into control (n =18) and AIC groups (n =90).AIC was induced in rats using alpha-naphthylisothiocyanate (ANIT)(75 mg/kg,10 mL/kg in corn oil,p.o.).Then,90 AIC rats were randomly divided into five groups:a control group (n =18),a CYD high dose group (n =18),a CYD middle dose group (n =18),a CYD low dose group (n =18),and a ursodeoxycholicacid (UDCA) group (n =18).According to sampling time,each group was subdivided into three subgroups:24 h (n =6),48 h (n =6),and 72 h groups (n =6).The CYD-high,-middle and-low groups were orally administered 24.48,12.24,and 6.12 g.kg-1.d-1 modified CYD,respectively,while the model group was given 20 mL/kg of body weight of distilled water once a day.The UDCA group was given 67.5 mg.kg-1.d-1 UDCA once a day.Radioimmunity assay was used to detect the activity of alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),gamma-glutamyl transpeptidase (GGT) and the levels of total bilirubin (TBil) and indirectbiliruin (DBil) in rats.Reverse transcription quantitative polymerase chain reaction (qRT-PCR),Western blot analysis,and immunohistochemistry were used to detect multidrug resistance-associated protein 2 (MRP2) expression.In vitro,HepG2 hepatocellular carcinoma cells were treated with CYD medicated serum at a concentration of 15 mol/L.MRP2 and retinoid X receptor alpha (RXRα) expression was analyzed by qRT-PCR and Western blotting.RESULTS:Serum levels of ALT,AST,GGT,ALP,TBil,and DBil were significantly reduced in the CYD and positive drug groups compared with the control group (P < 0.05 and P < 0.01,respectively).Pathological changes in rat liver tissues at 72 h in the CYD-high and-medium dose groups and positive drug group were not significant compared with the control group.CYD and UDCA treatment ameliorated ANIT-induced biliary epithelial cell proliferation.Neutrophil infiltration was rare and little focal necrosis was observed in Iobules in the CYD-high and-medium dose groups and UDCA group at 72 h.Compared with the control group,the expression of MRP2 mRNA and MRP2 protein in the liver tissue of the CYD groups was significantly increased (P <0.05 and P < 0.01,respectively).MRP2 expression and RXRα nuclear receptor mRNA and protein levels in the CYD groups were significantly increased compared with the control and UDCA groups (P <0.01).CONCLUSION:CYD can alleviate cholestasis in ANIT-induced AIC rats,and the mechanism underlying this action might involve increases in ALT,AST,GGT,ALP,TBil,and DBil and upregulation of MRP2 and RXRα mRNA and protein levels.

Anticancer Effects of Zaoxiu Compound Decoction on H_22 Mice with Heps

Objective To investigate the anticancer effects of the Zaoxiu Compound Decoction(ZCD) on H22 mice with Heps and the influence on the construction of H22 cells. Methods With in vivo techniques, the antineoplastic drugs were given to hepatoma H22 model mice which were randomly divided into negative control(physiological saline), positive control(cyclophosphamide), high- and low-dose ZCD groups. After 10-d administration, the pathological examinations of tumor tissue, livers, and kidneys in mice were carried out and the inhibitory rate on tumor was calculated. Results The high-and low-dose ZCD had obvious inhibition on H22 cells. The pathological observation showed that high- and low-dose ZCD had a strong inhibitory effect on H22 cells as well as positive control, with few toxic effects to the livers and kidneys in mice. Conclusion ZCD has the anticancer effect and has no obvious toxic effects on the model mice.

Effect of compound Sophorae decoction in the treatment of ulcerative colitis by tissue extract metabolomics approach

OBJECTIVE: To investigate how compound Sophorae decoction(CSD) works on rats' models of ulcerative colitis(UC) induced by 2,4,6-trinitrobenzenesulfonic acid solution(TNBS) by metabolomics studies of colon, liver, and kidney tissue extracts.METHODS: Rats with UC induced by TNBS enema were used as models in this study. Metabolic profiles of the three tissues were analyzed and pathway analysis of biomarkers was performed after CSD administration and further integration of metabolic networks.RESULTS: Thirteen biomarkers were screened from colon, liver, and kidney tissue extracts, and the levels of these substances were up-or down-regulated in the model group, but their levels were reversed after CSD administration. These biomarkers were mainly related to Phenylalanine, tyrosine and tryptophan biosynthesis, Phenylalanine metabolism, Glutathione metabolism, Arachidonic acid metabolism, Nicotinate and nicotinamide metabolism,Alanine, aspartate and glutamate metabolism.CONCLUSION: CSD could significantly ameliorate the symptoms of UC by regulating multiple metabolic pathways.

Study on Therapeutic Effect of Compound Decoction of Comcide in Treating Withdrawal Reaction of Heroin Dependent Rhesuses

Objective: To observe the therapeutic effect of compound decoction of Comcide (CDC), a traditional Chinese medicine (TCM) in treating the withdrawal reaction (WR) of heroin dependent rhesuses (HDR).Methods: To study therapeutic effects of CDC and methadone in treating WR of HDR models induced by administering of heroin. Through observing, comparing and evaluating the scores of all groups gained during the first 4 days when the WR was most severe.Results: CDC and methadone had the same therapeutic effects on WR of HDR. There were significant differences between the scores of CDC and methadone, and that of natural withdrawal,P < 0. 01; while there were insignificant difference between the scores of CDC and that of methadone,P > 0.05.Conclusion: CDC had the therapeutic effect in treating WR of HDR.

Gualou Guizhi decoction promotes neurological functional recovery and neurogenesis following focal cerebral ischemia/reperfusion

Recovery following stroke involves neurogenesis and axonal remodeling within the ischemic brain. Gualou Guizhi decoction （GLGZD） is a Chinese traditional medicine used for the treatment of post-stroke limb spasm. GLGZD has been reported to have neuroprotective effects in cerebral ischemic injury. However, the effects of GLGZD on neurogenesis and axonal remodeling following cerebral ischemia remain unknown. In this study, a rat model of focal cerebral ischemia/reperfusion was established by middle cerebral artery occlusion. Neurologi- cal function was assessed immediately after reperfusion using Longa＇s 5-point scoring system. The rats were randomly divided into vehicle and GLGZD groups. Rats in the sham group were given sham operation. The rats in the GLGZD group were intragastrically administered GLGZD, once daily, for 14 consecutive days. The rats in the vehicle and sham groups were intragastrically administered distilled water. Modified neurological severity score test, balance beam test and foot fault test were used to assess motor functional changes. Nissl staining was performed to evaluate histopathological changes in the brain. Immunofluorescence staining was used to examine cell proliferation using the marker 5-bromo-2＇-deoxyuridine （BrdU） as well as expression of the neural precursor marker doublecortin （DCX）, the astrocyte marker glial fibrillary acidic protein （GFAP） and the axon regeneration marker growth associated protein-43 （GAP-43）. GLGZD substan- tially mitigated pathological injury, increased the number of BrdU, DCX and GFAP-immunoreactive cells in the subventricular zone of the ischemic hemisphere, increased GAP-43 expression in the cortical peri-infarct region, and improved motor function. These findings suggest that GLGZD promotes neurological functional recovery by increasing cell proliferation, enhancing axonal regeneration, and in- creasing the numbers of neuronal precursors and astrocytes in the peri-infarct area.

Cerebral vasorelaxant material basis of Xiaoxuming decoction study with rat basilar artery

OBJECTIVE To investigate the cerebralvasorelaxant material basis of Xiaoxuming decoction.METHODS According to the Xiaoxuming decoction herb sources,we retrieved the chemical structure from the literatures and the Chinese Natural Product Database(http://pharmdata.ncmi.cn).By using microvessel tension system,we checked the vasorelaxanteffects of Xiaoxuming decoction anti-cerebral ischemia effective components group(XXMDECG)and the available composition compounds on pre-contracted basilar artery ring.RESULTS963 compoundsin the decoction,including 81Fangfeng,77 Mahuang,130 Shengjiang,31 Guizhi,91 Huangqin,127 Renshen,73 Chuanxiong,44 Shaoyao,39 Xingren,42 Fangji,62 Fuzi and 166 Gancao were collected.The five largest number classes of compounds in the decoction are volatile oil(32%),flavone(32%),alkaloid(13%),saponin(7%),polyphenol and organic acid(5%).XXMDECG at concentration from 1 to 400μg·mL-1can dilate the KCl(60 mmol·L-1)and ET-1(0.01μmol·L-1)pre-contracted rat basilar artery rings in a dose-dependent manner.There are 6 compounds with vasorelaxant ratio more than 50%at the concentration of 10μmol·L-1.CONCLUSION Xiaoxuming decoction contains abundant chemical structure.It has the material basis of multiple ingredients and multiple targets.The XXMDECG are able to dilate the rat basilar artery rings in a dose-dependent manner.The network interactions between varies of chemical compounds in Xiaoxuming decoction and the vasoconstriction associated targets result in the comprehensive regulation mechanisms of vascular function.

Network pharmacology analysis of the mechanisms of Banxia Xiexin Decoction against Ulcerative Colitis

Banxia Xiexin Decoction(BXXXD),a traditional herbal formula,has been used to treat ulcerative colitis(UC)clinically.In this study,chemical compounds and putative targets of BXXXD and UC related therapeutic targets were screened from multiple databases.The protein-protein interaction(PPI)was conducted using String database,and 31 candidate targets were screened from CytoNCA database.The Database for Annotation,Visualization and Integrated Discovery(DAVID)and Metascape database were used for Kyoto Encyclopedia of Genes and Genomes(KEGG)channel and Gene Ontology(GO)enrichment analysis respectively,and the enrichment analysis results were visualized by OmicShare platform.Meanwhile,the interaction network among Chinese herbs,active compounds,candidate targets and pathways was built by Cytoscape 3.7.2 software,and the potential compounds of BXXXD in the treatment of UC were screened.Finally,molecular docking technology was used to verify the putative key compounds.Combined with literature research,5 key compounds for the treatment of UC were identified,which are mainly involved in TNF signaling pathway,cancer signaling pathway,inflammatory bowel disease(IBD),Toll-like receptor signaling pathway,and NF-κB signaling pathway.This study provides a scientific basis for BXXXD as an effective alternative therapeutic agent for UC from a new perspective,and also provides a feasible method for basic chemical research and pharmacological research of BXXXD.

Network pharmacology and molecular docking analysis on molecular targets and mechanism prediction of Huanglian Jiedu Decoction in the treatment of COVID-19

Objective To investigate and predict the molecular targets and mechanism of Huanglian Jiedu Decoction(黄连解毒汤,HLJDD)in the treatment of Corona Virus Disease 2019(COV-ID-19)through network pharmacology and molecular docking analysis.Methods The chemical constituents and action targets of HLJDD were retrieved on Tradi-tional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),SymMap v2,Encyclopedia of Traditional Chinese Medicine(ETCM),a High-throughput Ex-periment-and Reference-guided Database of Traditional Chinese Medicine(HERB),and Tra-ditional Chinese Medicine Integrated Database(TCMID).UniProt and GeneCards were used to query the target genes that corresponding to the active compounds,and then a compound-target network was constructed using Cytoscape 3.7.2.Gene Ontology(GO)database was used to annotate GO functions.Kyoto Encyclopedia of Genes and Genomes(KEGG)was used to predict the possible mechanisms of active compounds.The Database for Annotation,Visu-alization and Integrated Discovery(DAVID)was used to analysis the tissue enrichment.The main active compounds in HLJDD are molecularly docked with their corresponding related targets.Results Seventy-six compounds were screened and 458 corresponding targets in the network were obtained.Gene annotation showed that the targets were involved mainly in 1953 biolo-gical processes.884 signaling pathways was enriched,involving signaling by interleukins,cy-tokine signaling in immune system,generic transcription pathway,and RNA polymerase II transcription.The targets mainly distributed in the lung,liver,and placenta,involving a vari-ety of immune cells,such as T cells and B cells.The molecular docking results showed that core compounds such as wogonin,berberine,and baicalein had high affinity with tumor nec-rosis factor(TNF),insulin(INS),and tumor protein 53(TP53).Conclusion The active compounds in HLJDD may have a therapeutic effect on COVID-19 through regulating multiple signal pathways by targeting genes such as vascular endothelial growth factor A(VEGFA),INS,interleukin-6(IL-6),TNF,caspase-3,TP53,and mitogen-activ-ated protein kinase 3(MAPK3).

草酸艾司西酞普兰联合复方解郁汤治疗青少年抑郁症的临床疗效分析

目的 探讨草酸艾司西酞普兰联合复方解郁汤治疗青少年抑郁症的临床疗效。方法 选择该院2021年12月—2022年12月期间精神科收治青少年抑郁症患者86例,按照随机数字表法分试验组(43例)和对照组(43例)。所有患者均予以认知行为疗法治疗,对照组予以草酸艾司西酞普兰片,试验组在对照组的基础上联用复方解郁汤治疗。两组均以4周为1个疗程,共治疗2个疗程。对比两组治疗前后脑源性神经营养因子水平、血清炎症因子水平、单胺类神经递质水平、抑郁情况评分、睡眠质量评分、自杀态度评分,观察并评估两组治疗效果及治疗期间不良反应。结果 与治疗前比,治疗后两组BDNF水平较高,IL-1β、IL-6、TNF-α水平降低;与对照组比,治疗后试验组BDNF水平较高,IL-1β、IL-6、TNF-α水平较低(P<0.05)。与治疗前比,治疗后两组NE、5-HT、DA水平升高;与对照组比,治疗后试验组NE、5-HT、DA水平较高(P<0.05)。与治疗前比,治疗后两组HAMA及PSQI评分降低;与对照组比,治疗后试验组HAMA及PSQI评分较低(P<0.05)。试验组临床总有效率较对照组高,差异有统计学意义(P<0.05)。与治疗前比,治疗后两组自杀意念QSA评分较高;与对照组比,治疗后试验组自杀意念QSA评分较高(P<0.05)。两组均未出现严重不良反应,比较差异无统计学意义(P>0.05)。结论 草酸艾司西酞普兰联合复方解郁汤对青少年抑郁症患者的治疗效果显著,能上调脑源性神经营养因子及单胺类神经递质水平,降低血清炎症因子水平,改善睡眠质量及自杀意念,不良反应较少,是一种安全有效的治疗方案。

藿朴夏苓汤合桑菊饮加减治疗感染后咳嗽临床观察

目的 观察藿朴夏苓汤合桑菊饮加减治疗感染后咳嗽(湿热型邪郁肺卫证)的临床疗效及安全性。方法 采用随机数字表法将患者120例分为对照组与观察组各60例。对照组予以口服复方甲氧那明胶囊,观察组予以霍朴夏苓汤合桑菊饮加减,治疗7 d后,观察两组患者治疗前后的咳嗽症状积分、中医证候积分、生活质量评分、临床疗效、不良反应。结果 两组患者治疗后的咳嗽症状评分、中医证候积分均较前显著下降(P <0.05),观察组下降更为明显(P <0.05)。两组生活质量评分均较治疗前提高(P <0.05),观察组显著高于对照组(P <0.05);观察组的总有效率为93.33%,高于对照组的78.33%(P> 0.05),两组不良反应差异无统计学意义(P> 0.05)。结论 藿朴夏苓汤合桑菊饮加减可以有效提高感染后咳嗽(湿热型邪郁肺卫证)患者的临床疗效,且无明显不良反应。

清化复肝汤联合复方甘草酸苷注射液治疗急性早幼粒细胞白血病化疗后肝损伤患者的效果

目的:观察清化复肝汤联合复方甘草酸苷注射液治疗急性早幼粒细胞白血病(APL)化疗后肝损伤患者的效果。方法:选取2021年1月至2022年1月该院收治的152例化疗后出现肝损伤的APL患者进行前瞻性研究,按照随机数字表法将其分为对照组和研究组各76例,两组均采用维A酸联合亚砷酸化疗,对照组采用复方甘草酸苷注射液进行保肝治疗,研究组在对照组基础上联合清化复肝汤治疗。比较两组临床疗效,治疗前后血清炎性因子[超敏C反应蛋白(hs-CRP)、白细胞介素-6(IL-6)]水平、肝功能指标[丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)]水平、细胞免疫指标(CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))水平,以及不良反应发生率。结果:研究组治疗总有效率为98.68%(75/76),高于对照组的86.84%(66/76),差异有统计学意义(P<0.05);治疗后,研究组血清hs-CRP、IL-6、AST、ALT、CD8^(+)水平均低于对照组,CD4^(+)、CD4^(+)/CD8^(+)水平均高于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:清化复肝汤联合复方甘草酸苷注射液治疗APL化疗后肝损伤患者效果显著,可降低ATL、AST、hs-CRP、IL-6水平,改善细胞免疫指标水平,效果优于单用复方甘草酸苷注射液。

中药复方基于Wnt/β-catenin信号通路调控糖尿病肾病研究进展

糖尿病肾病是糖尿病最常见的微血管并发症之一,也是造成终末期肾病的主要原因。Wnt/β-catenin信号通路与糖尿病肾病肾小管间质纤维化密切相关,主要通过足细胞、肾小球系膜细胞、肾小管上皮细胞等来改善糖尿病肾病。中药复方基于调控Wnt/β-catenin信号通路来改善肾脏病变及纤维化,保护肾脏功能,进而延缓病程进展,在治疗中发挥激活自噬、减少炎症反应及减弱氧化应激等作用。目前,关于中药复方基于Wnt/β-catenin信号通路的研究仍存在以下不足之处:(1)在中药复方的研究中,能够得出中药复方可通过Wnt/β-catenin信号通路发挥作用,但由于中药复方成份复杂多样,大多数仅仅发现相关性,而没有分析其具体的活性成分;(2)Wnt/β-catenin信号通路的相关研究并未深入探索该信号通路在肾纤维化中的作用机制;(3)目前关于中医药的大部分实验为动物体内实验,缺乏体外细胞的相关实验探究。今后,需加强对中药复方活性成分的研究,并开展更多的体外细胞实验,进行深层次的作用机制及靶点研究。

大柴胡汤加减联合复方嗜酸乳杆菌片治疗功能性便秘患者临床疗效观察

目的探讨大柴胡汤加减联合复方嗜酸乳杆菌片治疗功能性便秘(FC)患者的临床疗效。方法根据随机数字表法将河南中医药大学第三附属医院2020年5月—2022年4月门诊治疗的70例FC患者随机分为两组,对照组(35例)服用复方嗜酸乳杆菌片治疗,治疗组联合大柴胡汤加减治疗。对比两组临床疗效、临床症状和便秘评分、胃肠道生活质量指数(GIQLI)、胃肠激素[P物质(SP)、胃动素(MTL)、胃泌素(GAS)]水平及不良反应。结果治疗组临床有效率(97.14%)高于对照组(80.00%)(P<0.05)。与治疗前相比,治疗后两组临床症状评分和便秘评分降低,胃肠激素水平和生活质量评分升高(P<0.05);与对照组相比,治疗组上述指标均优于对照组(P<0.05)。对照组与治疗组不良反应发生率(8.57%vs 5.71%)无统计学差异(P>0.05)。结论大柴胡汤加减联合复方嗜酸乳杆菌片治疗FC安全有效,且可减轻患者便秘症状,调节胃肠激素水平,提高生活质量。

参术健脾增食汤对小儿厌食症患者的临床疗效

目的考察参术健脾增食汤对小儿厌食症患者的临床疗效。方法176例患者随机分为对照组和观察组,每组88例,对照组给予复方胃蛋白酶颗粒,观察组在对照组基础上加用参术健脾增食汤,疗程21 d。检测临床疗效、中医证候评分、小儿生长和营养状况指标(身高、体质量、BMI、进食量、血红蛋白、CD4^(+)、CD8^(+))、食欲调节因子(瘦素、血管活性肽、胃动素、胃泌素、促人生长激素释放肽)、不良反应发生率、复发率变化。结果观察组总有效率高于对照组(P<0.05),复发率更低(P<0.05)。治疗后,2组中医证候评分、CD8^(+)降低(P<0.05),身高、体质量、BMI、进食量、血红蛋白、CD4^(+)、食欲调节因子升高(P<0.05),以观察组更明显(P<0.05)。2组不良反应发生率比较,差异无统计学意义(P<0.05)。结论参术健脾增食汤可安全有效地缓解小儿厌食症患者临床症状,改善食欲及营养状态,降低复发率。

复方玉液汤通过调控PI3K/Akt信号通路抑制糖尿病大鼠心肌细胞凋亡和炎症反应

目的运用网络药理学技术分析复方玉液汤防治糖尿病心肌病(DCM)的作用机制,并通过动物实验进行验证。方法利用TCMSP数据库检索复方玉液汤所含6种中药(黄芪、山药、知母、葛根、五味子、天花粉)中的化学成分,根据口服生物利用度(OB)和药物相似性(DL)筛选出活性化学成分以及与DCM相关的靶点;利用Drugbank、Gene Cards、OMIM和PharmGKb数据库获取与DCM相关靶点;STRING数据库对核心靶点进行PPI网络的构建和分析;Metascape进行核心靶点的GO和KEGG富集分析;利用Cytoscape3.9.1构建“中药-关键成分-核心靶点-关键通路”网络,并对核心靶点对接的关键成分进行分子对接。建立糖尿病心肌病Wistar大鼠动物模型,将大鼠分为正常组、模型组、玉液汤低剂量组(YYT-低组,0.29 g/kg)、玉液汤高剂量组(YYT-高组,1.15 g/kg),15只/组,药物剂量为生药含量。给药8周后观察各组大鼠的心脏组织病理切片,检测各组大鼠心脏电生理变化、血清中的LDH、CK、CK-MB含量变化以及心脏组织中PI3K、P-PI3K、Akt、P-AKT、BAX、IL-6、TNF-α蛋白的表达情况。结果筛选后得到复方玉液汤中61个活性化合物,1057个靶点;3682个DCM相关疾病靶点,共同靶点551个。根据筛选获得的核心靶点富集得到的核心通路发现,凋亡和炎症及相关PI3K/Akt信号通路可能是治疗DCM的关键信号通路;分子对接结果显示,金色酰胺醇酯、山柰酚等活性成分与AKT1和PIK3R1的结合活性较好。利用动物实验对筛选的靶点及通路进行验证,结果显示,与DCM模型组大鼠比较,复方玉液汤能改善模型大鼠心肌组织细胞紊乱及炎性浸润的病理特征,降低模型大鼠血清中LDH、CK、CK-MB水平及模型大鼠心脏组织中BAX、IL-6、TNF-α的蛋白含量并升高P-PI3K和P-AKT的蛋白含量(P<0.05)。结论复方玉液汤防治DCM是多成分、多靶点和多信号通路共同作用的结果。复方中主要活性成分金色酰胺醇酯、山柰酚等通过调控PI3K/Akt信号通路,抑制DCM发病过程中心肌细胞凋亡及炎症反应,发挥对DCM的保护作用。

复方葛根汤调控IL-6/STAT3和铁死亡通路抑制在体结肠癌发展

目的 探究复方葛根汤在体抗结肠癌的分子机制。方法 建立HCT116细胞荷瘤小鼠模型,每日以1.0 g·kg^(-1)的剂量灌胃给予复方葛根汤或等体积生理盐水,每3日测量一次体重和瘤体大小,连续给药23 d;Western blot检测铁死亡通路、IL-6通路和细胞迁移相关蛋白。结果 与对照组相比,复方葛根汤显著抑制HCT116细胞衍生瘤体增长,显著上调铁死亡相关蛋白ACSL4、PTGS2,而明显下调SLC7A11、GPX4,还显著下调IL-6、p-STAT3/STAT3比及其下游蛋白MMP2、TWIST和MMP7水平。结论 复方葛根汤能显著抑制体内结肠癌发展,其机制可能为通过抑制IL-6/STAT3和诱导铁死亡通路。