Serotonin, or 5-hydroxytryptamine (5-HT), is a crucial neurotransmitter and plant growth regulator with potential applications for managing obesity and metabolic disorders. Gynostemma longipes is a dioecious plant with medicinal and nutritional value. This study investigates the chemical and molecular differences between female (FM-L) and male (M-L) G. longipes tender leaves, with a focus on 5-HT accumulation. Integrated transcriptomic and metabolomic analyses revealed 2759 differentially expressed genes and 300 differential metabolites between FM-L and M-L. A significantly higher concentration of 5-HT was consistently found in female plants. Kyoto encyclopedia of genes and genomes enrichment analysis indicated the tryptophan metabolism pathway as central to this disparity. Key genes in the 5-HT synthesis pathway (TDC, ASMT, and ALDH) were validated through qRT-PCR. In female plants, a significant inverse relationship was observed between gene expression and 5-HT end-product accumulation. This finding points to a complex feedback regulation mechanism within the tryptophan pathway.
Danshen-Honghua Herb Pair (DHHP) is a classic combination for treating cardiovascular diseases with significant clinical efficacy. However, it exhibits low oral bioavailability, suggesting gut microbiota metabolism may enhance its biological activity. This study investigated the pharmacological basis and mechanism of DHHP against myocardial ischemia through gut microbiota metabolites. We adopted an integrated strategy combining network pharmacology, molecular docking, and animal experiments. 15 metabolite-derived components and 85 potential antimyocardial ischemia targets were identified. GO and KEGG enrichment analyses revealed that these targets were mainly involved in apoptosis-related biological processes and multiple cardiovascular signaling pathways. Molecular docking indicated that Salvianolic acid B and its methylated derivative, Lithospermic acid and its methylated and decarboxylated derivatives, as well as Hydroxysafflor Yellow A and its dehydration product exhibited lower binding energies with key targets including AKT, GSK-3β, Bcl-2, Bax, and Caspase 3. These components showed potential anti-apoptotic activity accordingly. Animal experiments confirmed DHHP metabolites significantly upregulated p-AKT, p-GSK-3β, and Bcl-2 expression in myocardial tissue (p <0.01) while downregulating Bax and Cleaved-Caspase 3 (p <0.01). These results demonstrate that DHHP, via gut microbiota metabolism, exerts antimyocardial ischemia effects through the p-AKT-mediated Bcl-2/Bax/Caspase 3 pathway.
Acute lung injury (ALI) is a life-threatening respiratory disorder with high mortality. Forsythiae Fructus (FF), a traditional Chinese medicine widely used for respiratory diseases, shows therapeutic potential against ALI, yet its underlying mechanisms remain poorly understood from a multi-omics perspective. This study integrated network pharmacology, transcriptomics, and proteomics to elucidate the protective mechanisms of FF against ALI. The chemical profile of FF was characterized by UPLC-Q-TOF–MS/MS, and an LPS-induced ALI rat model was established for pharmacodynamic evaluation. The optimal dose group was selected for multi-omics analysis. A total of 95 compounds were identified, and integrated analysis revealed that 11 core components mediated anti-ALI effects by modulating 347 targets across 25 signaling pathways. Molecular docking and Western blot validation demonstrated that these targets are primarily associated with the PI3K-Akt/mTOR, MAPK/ERK/p-38, JAK-STAT, and PPARγ signaling pathways. This study provides a comprehensive multi-omics framework for understanding the mechanisms of FF against ALI.
Phillyrin (PHI) is one of the main active components in Forsythia suspensa (Thunb.) Vahl, belonging to the class of lignans, has anti-inflammatory, antioxidant, anti-tumor, antiviral, antibacterial, weight loss, and other pharmacological effects, involving a variety of potential signaling pathways, such as toll-like receptor (TLR), nuclear factor kappa B (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), nuclear factor erythroid 2-related factor 2 (Nrf2), and mechanisms related to polycyclic polyprenylated acylphloroglucinols (PPAP). The review search systematically and comprehensively CNKI, Wanfang, PubMed, Web of Science, and other databases, screened nearly 100 relevant literature in the past 5 years, and summarized and evaluated the information on PHI extraction and purification, pharmacological activity, potential mechanism, and structure-activity relationship. And further discusses the pharmacological effects of PHI and potential molecular mechanisms. The results of the review confirm that PHI has the potential to be developed into a therapeutic anti-inflammatory, anti-tumor, and other therapeutic agents, all of which provide a scientific basis and direct reference for the pharmacological research of PHI.
Fraxinus species, with a long history of medicinal use, are diverse in type. All species that feature terminal inflorescences and exhibit a blue-purple fluorescence reaction under sunlight are considered to have medicinal value. However, only four species-Fraxinus rhynchophylla, Fraxinus chinensis, Fraxinus szaboana, and Fraxinus stylosa-are officially recognized in the Chinese Pharmacopoeia. Despite this, there is currently a lack of comprehensive reports on the research related to Fraxinus, preventing a deeper understanding of its full medicinal potential. A total of 326 chemical constituents have been identified across these species, including coumarins, secoiridoids, phenolic glycosides, lignans, flavonoids, terpenoids, and volatile compounds. These species have demonstrated various pharmacological activities, such as antibacterial, anti-inflammatory, antioxidant, anticancer, neuroprotective, and anti-hyperuricemic effects. This article provides a systematic review of the phytochemistry and pharmacological effects of Fraxinus, aiming to address gaps in the existing literature, highlight the biological mechanisms of its activity, and offer a foundation for the development and application of Fraxinus in drug research. Given the significance of Fraxinus, future research should take a more comprehensive and holistic approach.
Amber and subfossil resins are subjects of interdisciplinary research across multiple fields. However, due to their diverse origins and complex compositions, different disciplines vary in their definitions and functional interpretations. In traditional Chinese medicine(TCM), amber has been utilized as a medicinal material since ancient time, with extensive historical documentation. However, its classification, provenance, and nomenclature remain ambiguous, and authentic medicinal amber artifacts are exceedingly rare. This study employed Fourier-transform infrared spectroscopy(FTIR) to characterize amber and subfossil resins from various geological sources and commercially "medicinal amber". Additionally, historical literature and market surveys were analyzed to explore their provenance, composition, and functional attributes. The results indicate that amber and subfossil resins from different sources and with different compositions exhibit distinct fingerprint characteristics in the FTIR spectral range of 1 800-700 cm~(-1). "Medicinal amber" available in the market primarily consists of subfossil or modern resins, significantly differing in composition and structure from geological amber. This study highlights the importance of interdisciplinary research on amber identification and resource management. It is essential to establish a systematic database of amber and subfossil resin characteristics and integrate modern analytical techniques to enhance research on their composition, pharmacological mechanisms, and potential therapeutic effects, thereby promoting the standardized utilization of amber resources and advancing the modernization of TCM.
Introduction: Gynostemma longipes a species within the genus Gynostemma of the Cucurbitaceae family, serves as the source of the traditional Chinese medicine known as Heba Gynostemma. Notably, there are significant differences in the chemical composition between its male and female specimens, which influence both the quality and efficacy. Objective This study conducted a systematic analysis of the differences in chemical constituents between male and female G. longipes plants, as well as among different plant parts, including roots, stems, and leaves. Methods This study utilized both female and male specimens of G. longipes sourced from the primary production region as research materials. Advanced multivariate statistical techniques, including ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS), principal component analysis (PCA), and orthogonal partial least squares discriminant analysis (OPLS-DA), were employed for the analytical processes. Results In this study, a total of 2,196 metabolites were identified and categorized into 13 distinct groups. The primary active components among these were flavonoids, constituting 19.36% with 192 types, terpenoids at 16.67% with 362 types, and alkaloids at 11.39% with 61 types. Principal Component Analysis (PCA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) revealed that samples from identical parts of male and female plants exhibited strong clustering, with the first principal component (PC1) accounting for 55.4% to 84.78% of the variance. The OPLS-DA model demonstrated an excellent fit (R²Y = 1) and high predictive capability (Q² = 0.971–0.998), with no evidence of overfitting. Conclusion This study elucidated the variations in chemical constituents between male and female specimens, as well as among different parts of G. longipes , and identified the differential compounds. These findings offer an empirical foundation for the quality assessment of the medicinal material and the selection of superior varieties.
Background: The Danshen-Honghua herb pair (DHHP) is a common modern Chinese medicine pair for activating blood circulation and resolving blood stasis. It has been used for centuries to treat cardiovascular and cerebrovascular diseases and is often found in some herbal compounds for treating cardiovascular diseases. The aim of this study was to explore the effects of DHHP on the intestinal flora of rats with acute myocardial ischemia and its microbial transformation in vitro. Methods: In this study, we investigated the protective effect of DHHP on isoproterenol-induced acute myocardial ischemia in rats based on metagenomic sequencing technology, and further characterized the in vitro metabolic transformation products of DHHP, so as to investigate its anti-myocardial ischemic efficacy material basis. Results: Pharmacodynamic results demonstrated that DHHP significantly ameliorated pathological changes and improved abnormal cardiac enzyme levels in acute myocardial ischemia rats. In addition, metagenomic analysis showed the efficacy of DHHP in ameliorating the isoproterenol-induced modifications of the intestinal flora in rats. Specifically, DHHP promoted the growth of the intestinal potential probiotics such as Lactobacillus while suppressing the pathogenic bacteria, including Escherichia and Streptococcus. The in vitro metabolism results showed that the DHHP's active components underwent primarily phase I metabolism through hydroxylation, decarboxylation, and dehydration inversions in the isolated intestinal flora of acute myocardial ischemia rats and in phase II through sulfation esterification and methylation reactions. Conclusion: The results suggest that there may be a bidirectional regulatory effect between DHHP and intestinal flora, which is important to explain the pharmacological mechanism of DHHP.
目的 采用系统预试法对缘毛太行花的化学成分进行预实验,初步探索缘毛太行花的化学成分类别.方法 采用乙醇、三氯甲烷、甲醇等不同溶剂对缘毛太行花进行提取,提取液A中分别加入氢氧化钠溶液,乙酸钾溶液、三氯化铁溶液、浓硫酸没食子酸溶液、碘化铋钾试剂、碘-碘化钾试剂、盐酸-镁粉:提取液B分别加入浓硫酸,浓硫酸-乙酸酐溶液观察有无阳性反应的发生;在试管反应的基础上采用薄层色谱鉴别及高效液相色谱法对其中的三萜类成分进一步进行定性鉴别.结果 缘毛太行花的提取液加氢氧化钠溶液变为红色、加乙酸钾溶液变为橙黄色、加三氯化铁溶液为墨绿色、加入浓硫酸-没食子酸溶液无明显变化、加入浓硫酸有绿色荧光、加浓硫酸-乙酸酐产生黄-蓝的颜色变化、加入碘化铋钾生成橘红色沉淀、加入碘-碘化钾溶液生成红棕色无定形沉淀;薄层色谱鉴别样品和对照品在同一处显示相同颜色的斑点;高效液相色谱法显示样品和对照品在相同保留时间出峰.结论 初步确定缘毛太行花中包含酚羟基类官能团的特征以及蒽醌类、三萜类及生物碱类等多种化学成分,为缘毛太行花的研究奠定基础.
Background Bupleuri Radix (Chaihu) is a famous traditional Chinese medicine derived from Bupleurum, Apiaceae. The origin of cultivated Chaihu germplasm in China is unclear, which has led to unstable Chaihu quality. In this study, we reconstructed the phylogeny of the main Chaihu germplasm species in China and identified potential molecular markers to authenticate its origin. Methods Three Bupleurum species (eight individuals), B. bicaule, B. chinense, and B. scorzonerifolium, were selected for genome skimming. Published genomes from B. falcatum and B. marginatum var. stenophyllum were used for comparative analysis. Results Sequences of the complete plastid genomes were conserved with 113 identical genes ranging from 155,540 to 155,866 bp in length. Phylogenetic reconstruction based on complete plastid genomes resolved intrageneric relationships of the five Bupleurum species with high support. Conflicts between the plastid and nuclear phylogenies were observed, which were mainly ascribed to introgressive hybridization. Comparative analysis showed that noncoding regions of the plastomes had most of the variable sequences. Eight regions (atpF-atpH, petN-psbM, rps16-psbK, petA-psbJ, ndhC-trnV/UAC and ycf1) had high divergence values in Bupleurum species and could be promising DNA barcodes for Chaihu authentication. A total of seven polymorphic cpSSRs and 438 polymorphic nSSRs were detected across the five Chaihu germplasms. Three photosynthesis-related genes were under positive selection, of which accD reflected the adaptation fingerprint of B. chinense to different ecological habitats. Our study provides valuable genetic information for phylogenetic investigation, germplasm authentication, and molecular breeding of Chaihu species.
RATIONALE:Gleditsiae spina (GS) is an important herb used in traditional and folk medicinal systems of East Asian countries for its various medicinal properties. In China, it has been traditionally used through the centuries for its anticancer, detoxication, detumescence, apocenosis, and antiparasitic effects. Although some of its ingredients have been isolated and identified, most active constituents remain unknown. Past research mostly exploited nuclear magnetic resonance for the identification of compounds, which is suitable for monomers only. Moreover, the extraction and isolation procedures for obtaining purified molecules are time consuming. Therefore, establishing an efficient approach will assist in rapid discovery of the potential active ingredients of GS. The present study aimed to identify the chemical constituents in GS by a data analysis strategy using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry.METHODS:First, the theoretical formula of the candidate compound was calculated using the accurate mass of the precursor/adduct ions. Second, the compounds were classified by the diagnostic ions from the MS/MS data. Third, characteristic ion filtering was used to identify the structures. Finally, the diverse skeletons and substitutions were further identified through the neutral loss in the GS.RESULTS:A total of 277 compounds were identified in GS, comprising 169 flavonoids, 70 lignans, and 38 other compounds. At least 43 potential new compounds were represented.CONCLUSIONS:This experiment devised an efficient and systematic method for detecting complex compounds and provided a foundation for future research into bioactive ingredients and quality control of GS.
目的 通过网络药理学和动物实验探究丹参红花药对治疗心肌缺血的潜在作用和机制.方法 检索中药系统药理学数据库与分析平台(TCMSP)和文献手动补充确定丹参-红花的活性成分及治疗心肌缺血靶点.以"心肌缺血"及"急性心肌缺血"为关键词,在CTD、DisGeNET、GeneCards和OMIM数据库中检索疾病的潜在靶点.利用Venny 2.1.0将筛选得到的有效化学成分靶点与疾病靶点进行交集,确定丹参-红花药对治疗心肌缺血的作用靶点.将交集靶点信息上传至STRINGv11.0,构建活性成分-靶点网络及蛋白质相互作用网络(PPI).通过DAVID数据库对丹参-红花治疗心肌缺血的靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路的富集分析.40只SD雄性大鼠,根据体质量随机分成4组,每组10只,即对照组、模型组、复方丹参滴丸(73mgkg-1·d-1)组、丹参-红花(生药量16 g·kg-1-d-1)组.对照组和模型组大鼠每天ig等量0.9%氯化钠溶液,给药组ig相应剂量的药物,每天1次,共7d.于第6天,除对照组外,其余各组给药1h后sc异丙肾上腺素(ISO,85mgkg-1),连续2 d造模.HE染色观察各组大鼠心肌组织病理变化;蛋白免疫印迹法检测各组大鼠心肌组织磷酸化哺乳动物雷帕霉素靶蛋白(p-mTOR)、磷酸化转录激活蛋白3(p-STAT3)、缺氧诱导因子1α(HIF-1α)、血管内皮生长因子A(VEGFA)、血小板衍生生长因子A(PDGFA)和碱性成纤维细胞生长因子(bFGF)蛋白表达水平.结果 网络药理学筛选得到丹参-红花药对治疗心肌缺血的活性成分91个,靶点246个.PPI网络结果显示主要靶点包括STAT3、MAPK1、JUN、RELA、MAPK3、AKT1、SRC、APP、TNF、PIK3CA、CXCL8、KNG1、IL6、VEGFA、MAPK14、HSP90AA1、MAPK8、EGFR、FOS和IL2等.主要靶点相关的通路涉及血管生成(如HIF-1信号通路和VEGF信号通路)、炎症反应(如NF-κB信号通路和TNF信号通路)和细胞凋亡(如细胞凋亡信号通路和p53信号通路)等.动物实验HE染色结果表明,对照组大鼠心肌细胞正常;模型组大鼠心肌纤维肿胀且有断裂,心肌细胞增宽,局部有明显水肿、渗出、炎性细胞浸润;复方丹参滴丸组与模型组大鼠比较,心肌纤维排列略微紊乱且较窄,病理改变程度有所减轻.丹参-红花组大鼠的心肌纤维排列整齐,细胞形态结构完整,心肌纤维肿胀轻,无毛细血管扩张,接近正常心肌形态.蛋白质免疫印迹检测结果表明,与对照组比较,模型组大鼠心肌组织中HIF-1α、VEGFA、PDGFA和bFGF的蛋白表达水平显著升高(P<0.05,0.01),p-mTOR和p-STAT3的蛋白表达水平显著下降(P<0.05,0.01).与模型组比较,丹参-红花显著上调了p-mTOR、p-STAT3、HIF-1α、VEGFA、PDGFA和bFGF的蛋白表达水平(P<0.05、0.01).结论 丹参红花可能通过上调与血管生成密切相关的蛋白水平来促进急性心肌缺血模型大鼠缺血心肌组织的血管生成,从而改善其缺血性损伤.
Abstract Syringa oblata is a flowering tree endemic to China, which has high medicinal and economic value. Comparative genomic analysis is necessary to elucidate the variation and phylogenetic relationships among Syringa species. An Illumina NovaSeq 6000 sequencing platform was used to sequence the whole genome of Syringa oblata plastomes in this study, and sequence assembly, annotation and characterization were performed by bioinformatics analysis, and a phylogenetic tree using Maximum Likelihood (ML) was constructed. A total of 155,668 bp was contained in the genome, which comprised two inverted repeats (IR) of 25,733 bp each, separated by a small single copy (SSC) region of 17,926 bp and a large single copy (LSC) region of 86 bp. There is a total GC content of 37.9% in the chloroplast genome, while the GC content in each region of SSC, LSC, and IR is 36.0%, 32.1%, and 43.2%. The genome contains 132 genes, including 88 protein-coding genes (CDS), 36 tRNA genes and 8 rRNA. There are seven protein-coding genes in the IR region, seven tRNA genes, and four rRNA genes. There was the most abundance of leucine and the least abundance of tryptophan among all amino acids. We detected 36 simple sequence repeats (SSRs) in the repeat structure analysis which included 32 mononucleotides (p1), 1 dinucleotide (p2), 1 trinucleotide (p3), 1 tetranucleotides (p4), and 1 complex nucleotide were explored, in the S. oblata chloroplast genome. In addition, we identified 50 long repeats, comprising 21 forward repeats, 28 palindromic repeats, and 1 complementary repeat. A phylogenetic analysis suggested that S. oblata (MW464119) is closely related to Syringa vulgaris (MG255768). It is anticipated that our results will be useful to further species identification, population genetic analysis, and biological research on Syringa oblata in the future.
In recent years, more and more evidence has shown that the disorder of gut microbiota (GM) is closely correlated with myocardial ischemia (MI). Even though the Danshen and Honghua herb pair (DHHP) is widely used in treating cardiovascular disease in China and exhibits obvious clinical efficacy on MI, the anti-MI mechanism of DHHP remains and needs to be explored in depth. Thus, in this study, we investigated whether the amelioration effect and molecular mechanism of DHHP on MI were related to regulating GM through pharmacodynamics evaluation and metagenomic sequencing. Histopathological testing results showed that DHHP treatment could alleviate the pathological changes of myocardial tissue in the acute MI (AMI) rats induced by isoproterenol (ISO), especially structural disorder, irregular distribution, and enlargement of the myocardial space. These pathological changes were all alleviated to some extent by DHHP treatment. Biochemical analysis results suggested that compared with the control group, the serum levels of AST, CTn-I, CK-MB, and TNF-alpha in model group rats were notably decreased, and the CAT and SOD levels in serum were markedly increased. These abnormal trends were significantly reversed by DHHP treatment. Furthermore, metagenomic sequencing analysis results indicated that DHHP could improve disorders in the composition and function of GM in AMI rats, mainly reflected in increasing diversity and richness, and obviously enhancing the abundance of Bacteroides fluxus, B. uniformis, B. stercoris, Roseburia hominis, Schaedlerella arabinosiphila, and R. intestinalis, and reducing the abundance of Enterococcus avium and E. canintestini, which were associated with purine metabolism, tyrosine metabolism, cyanoamino acid metabolism, and glutathione metabolism. In conclusion, DHHP may attenuate ISO-induced MI by regulating the structure, composition, and function of GM, thus contributing to further our understanding of the anti-MI mechanisms of DHHP and providing new therapeutic ideas and diagnostic targets for the clinical studies of MI. Danshen and Honghua herb pair could improve the disorder of the composition and function of intestinal flora in rats with myocardial ischemic injury.
伴随培养目标、行业需求和学科发展以及课程改革的深入开展,"中药分析"方面的教材数量和种类上由少到多,教材内容逐步丰富.笔者回顾"中药分析"课程的发展,通过调研、思考、比较、分析,对"中药分析"教材研究从时代背景、编写遵旨、教材体系、教材功能与特点及教材使用情况等方面进行综述.
目的 观察丹参-红花药对(简称药对)对急性心肌缺血模型大鼠心肌损伤的保护作用,并对其机制进行了初探.方法 将SD大鼠随机分为空白组、模型组、药对组和药对+2-甲氧基雌二醇组,大鼠sc盐酸异丙肾上腺素(Iso)建模,连续2 d,于造模12 h后,ig给予相应药物,空白组和模型组给予等体积纯净水,连续给药7 d;于末次给药后1 h,麻醉大鼠,收集血液和心肌组织,用于生化、病理和凋亡检测.结果 药对可显著抑制Iso 诱导的心肌缺血模型大鼠心肌细胞的凋亡,降低心肌损伤标志物的升高,改善心肌的病理损伤.结论 药对可能是通过调节参与细胞凋亡的HIF-1α通路实现对大鼠心肌损伤的保护作用.
目的 研究丹参-红花药对对异丙肾上腺素(isoprenaline hydrochloride,ISO)诱导的心肌缺血大鼠的保护作用及其机制.方法 大鼠随机分为对照组、模型组、复方丹参滴丸(73mg/kg)组和丹参-红花低、中、高剂量(4、8、16g/kg)组,给予相应药物干预7d.于第6天开始ig药物1h后,大鼠于0℃的冰浴中寒冷刺激4 min,sc ISO(85mg/kg),连续2 d.采用2,3,5-氯化三苯基四氮唑(2,3,5-triphenyltetrazolium chloride,TTC)染色法测定各组大鼠心肌梗死面积;采用TUNEL法检测各组大鼠心肌细胞凋亡情况;采用苏木素-伊红(HE)染色法观察各组大鼠心肌组织病理变化;采用ELISA法检测各组大鼠血浆中肌酸激酶同工酶(creatine kinase,CK)、天冬氨酸转氨酶(aspartate aminotransferase,AST)、乳酸脱氢酶(lactate dehydrogenase,LDH)、CK-肌红蛋白(myoglobin,MB)活性及心肌肌钙蛋白-Ⅰ(cardiac troponin-Ⅰ,CTn-Ⅰ)、CTn-T、C 反应蛋白(C-reaction protein,CRP)、MB、N 末端利钠肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)和 B 型脑利钠肽(B-brain natriuretic peptides,BNP)水平;采用Western blotting检测各组大鼠心肌组织中磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)、磷酸化 PI3K(phosphorylated PI3K,p-PI3K)、磷酸肌醇依赖性蛋白激酶 1(pyruvate dehydrogenase kinase isozyme 1,PDK1)、蛋白激酶 B(protein kinase B,Akt)、p-Akt、内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)、p-eNOS、B 淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)、核因子-κBp65(nuclear factor-κB p65,NF-KBp65)、p-NF-κBp65、Bcl-2 相关 X 蛋白(Bcl-2 associated X protein,Bax)、细胞色素 C(cytochrome C,Cyt C)、半胱氨酸天冬氨酸蛋白酶-3(cystein-asparate protease-3,Caspase-3)和Caspase-9蛋白表达.结果 丹参-红花药对显著抑制ISO诱导的心肌缺血模型大鼠的心肌梗死面积(P<0.01);改善心肌组织病理变化;显著抑制心肌细胞的凋亡(P<0.05、0.01);显著降低血浆中心肌酶活性以及心肌蛋白水平(P<0.05、0.01);显著上调心肌组织中Bcl-2、PDK1、p-eNOS、p-PI3K和p-Akt 蛋白表达水平(P<0.05、0.01),降低 Bax、Cyt C、剪切型 Caspase-3(cleaved Caspase-3)、cleaved Caspase-9 和 p-NF-κBp65蛋白表达水平(P<0.05、0.01).结论 丹参-红花药对能够通过调控PI3K/PDK1/Akt信号通路,从而发挥对ISO诱导的心肌缺血的保护作用.
In the recent years, a growing number of studies have shown that the occurrence of myocardial ischemia (MI) is closely related to the gut microbiota (GM). The Danshen-Honghua herb pair (DHHP), a classic combination in traditional Chinese herbal formulas, has been widely applied throughout history to cure cardiovascular disease, exhibiting remarkable clinical efficacy to treat ischemic heart disease (IHD). However, the intrinsic regulation mechanism of DHHP in treating MI remains unclear. This study aims to investigate the possible protective mechanism of DHHP in rats with acute myocardial ischemia (AMI) induced by isoproterenol (ISO) through 16S rRNA gene sequencing technique. Pharmacodynamic results showed that DHHP significantly ameliorated the pathological changes and improved the abnormal cardiac enzymes levels in the AMI rats. In addition, GM analysis demonstrated that DHHP effectively ameliorated the ISO-induced dysbiosis of the GM community, mainly by enhancing the GM diversity and increasing the relative abundance of Bacteroides, Roseburia, unclassified_f__Lachnospiraceae, and Lachnospiraceae_NK4A136_group, the abundance ratio of Bacteroidetes to Firmicutes, and decreasing the relative abundance of Escherichia-Shigella and Enterococcus. In summary, this study revealed that DHHP could improve ischemic myocardial injury in rats, and that its regulation mechanism is associated with significantly ameliorating the composition of GM, thus contributing to further our understanding of the anti-MI mechanisms of DHHP.
目的 探讨丹参-红花药对抗心肌缺血的机制.方法 将60只SD雄性大鼠随机分为空白对照组(A组,等体积纯净水)、模型组(B组,等体积纯净水)、复方丹参滴丸组(C组,73 mg/kg)及丹参-红花低、中、高剂量组(D1组、D2组、D3组,原药材4,8,16 g/kg),各10只,各组大鼠灌胃给予相应药物或纯净水,每天1次,连续7 d.于第6天、第7天灌胃给药1 h后,除A组外,其余各组均皮下注射盐酸异丙肾上腺素(85 mg/kg)以复制急性心肌缺血大鼠模型.观察大鼠心肌病理形态、心肌细胞凋亡情况,采用酶联免疫吸附法检测大鼠心肌酶水平;采用多指标综合指数法计算各组总效应值和偏最小二乘回归分析(PLS-DA)得分,筛选效果最佳的剂量组进行肠道菌群多样性分析.结果 D3组的综合指数最高(7.68),其次是D2组(7.18),D3组和D2组PLS-DA得分差异较小,选用D2组进行肠道菌群多样性分析;与B组比较,D2组放线菌门、TM7菌门、厚壁菌门/拟杆菌门、乳杆菌属、棒状杆菌属、葡萄球菌属和SMB53菌属的相对丰度显著升高(P<0.05或P<0.01),拟杆菌门、软壁菌门、脱铁杆菌门、颤螺菌属和罗斯氏菌属的相对丰度显著降低(P<0.05或P<0.01).结论 丹参-红花药对可能通过调节肠道菌群而发挥抗心肌缺血的作用.