OBJECTIVE:To confirm the efficacy of Yiqi Huoxue formula (, YQHX) on heart failure with reduced ejection fraction (HFrEF), and elucidate its potential effect on calcium homeostasis. METHODS:Cardiac specific calcium/calmodulin-dependent protein kinase II delta C isoform (CaMKⅡδC)-overexpression transgenic mice (C-CaMKⅡδC+/- Tg mice) and calcium/calmodulin-dependent protein kinase II delta B isoform (CaMKⅡδB)-overexpression transgenic mice (C-CaMKⅡδB+/- Tg mice) were established by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 technique, and their genotypes and phenotypes were identified thereafter. C57BL/6 mice and transgenic mice were divided into seven groups in random, each containing eight mice. The groups were Control group, CaMKⅡδB model group, CaMKⅡδB treatment group (B Treated), CaMKⅡδB inhibitor group (B Inhibitor), CaMKⅡδC model group (C Model), CaMKⅡδC treatment group (C Treated), CaMKⅡδC inhibitor group (C Inhibitor). B and C Treated groups were given YQHX once a day for 4 weeks by gavage. The cardiac function and structure were evaluated using echocardiogram. The myocardial cellular status and fibrosis were detected by hematoxylin and eosin staining and Masson staining. Calcium transients and calcium leakage from cardiac ventricular myocytes were detected to reflect calcium homeostasis, and the expressions of CaMKⅡδB, CaMKⅡδC, hypertrophy factors, calcium pathway-related genes, and the level of calcium handling proteins were assessed by western blotting and reverse transcription-quantitative polymerase chain reaction. RESULTS:We found CaMKⅡδB and CaMKⅡδC transgenic mice showed HFrEF phenotype. YQHX improved the systolic function of the CaMKⅡδB transgenic mice, reduced the cross-sectional area of cardiomyocytes, inhibited the overexpression of CaMKⅡδB and hypertrophy-related genes (B-type natriuretic peptide, myocyte enhancer factor 2, and atrial natriuretic factor), and increased calcium handling protein sarcoendoplasmic reticulum Ca2+ adenosine triphosphatase 2a (SERCA2a) and calcium capacity. YQHX improved the cardiac systolic function of CaMKⅡδC transgenic mice, reduced the ventricular diameter and cardiomyocyte cross-sectional area, alleviated myocardial fibrosis, increased SERCA2a expression and calcium capacity, and reduced calcium leakage. CONCLUSION:Our results suggest that YQHX improved HFrEF by inhibiting CaMKIIδB overexpression, which may be related to reduced expression of hypertrophy-related factors, and increased SERCA2a expression to increase calcium reserve. In addition, YQHX improved HFrEF by inhibiting CaMKIIδC overexpression, which may be related to reduce calcium leakage, and increase SERCA2a expression to increase calcium reserve.

Gerbera piloselloides Herba (GP) is a traditional herb commonly used for asthma in China. Our previous studies have identified a key group of active components-arbutin, marmesin, and luteolin-that demonstrate significant efficacy in asthma treatment, showing promising therapeutic potential. Although we previously investigated the comparative pharmacokinetics (only absorption process) of 11 main components of GP in both control and asthmatic mice, the pharmacokinetics of these 3 active compounds, including absorption, metabolism, and excretion in rats, remain unclear. This study develops an efficient liquid chromatography (LC) method to explore these pharmacokinetic processes. Ultrahigh-performance LC coupled with triple quadrupole mass spectrometry (UPLC-MS/MS) and Q-Exactive hybrid quadrupole-orbitrap high-resolution accurate MS (UHPLC-Q-Exactive Plus HRMS) were employed to detect these compounds and their metabolites in biological samples. The results indicate that arbutin is rapidly absorbed, with a Tmax of 0.22 +/- 0.15 h and a Cmax of 35 477 +/- 6743 mu g/L, and its cumulative urinary excretion rate is 60.136% +/- 9.539%. Marmesin achieves a Cmax of 503 225 +/- 89 848 mu g/L and a T1/2 of 3.58 +/- 0.075 h, with significantly lower cumulative excretion over 36 h compared to the administered dose. Luteolin demonstrates a characteristic double-peak pharmacokinetic profile, with a Cmax of 22.24 +/- 4.84 ng/L. Notably, arbutin is primarily excreted via urine, whereas marmesin and luteolin are predominantly excreted through bile and urine, respectively. A total of 7 metabolites of arbutin, 13 metabolites of luteolin, and 22 metabolites of marmesin were identified in plasma, feces, urine, and bile, which involves such metabolic pathways as oxidation, reduction, methylation, sulfation, acetylation, hydration, glucuronidation, and glutathione conjugation. This establishes a stable, efficient analytical method for assessing the pharmacokinetic profiles of these key GP components, providing valuable insights for their further therapeutic development.

OBJECTIVE:To evaluate the effect of Yiqi Liangxue Shengji prescription (, YQLXSJ) on cardiac function and outcomes in acute myocardial infarction (AMI) patients with myocardial ischemia-reperfusion injury (MIRI) and to determine its clinical efficacy. METHODS:This prospective, randomized, double-blind, placebo-controlled trial enrolled hospitalized patients with AMI who underwent percutaneous coronary intervention and experienced MIRI either intraoperatively or postoperatively. Participants were randomly allocated to the treatment group, which received YQLXSJ, or the control group, which received a placebo, concurrent with standard Western Medicine therapy. The intervention period lasted 8 weeks. The primary outcome measure was left ventricular ejection fraction (LVEF), determined by echocardiography. Secondary outcomes included N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) levels, left ventricular internal diameter, major adverse cardiovascular events (MACE), angina pectoris scores, and Chinese medicine evidence scores. RESULTS:Following 8 weeks of intervention, the treatment group demonstrated a significant increase in LVEF and a marked reduction in NT-proBNP when compared to the control group. There was also a significant decrease in peak cTnI levels, Chinese medicine evidence scores, and angina pectoris scores. The control group's left ventricular end-systolic diameter (LVESD) significantly increased compared to baseline after 8 weeks (P < 0.05), whereas the treatment group's LVESD showed no significant change from baseline (P > 0.05). Although the treatment group showed a downward trend in MACE incidence compared to the control group, this difference was not statistically significant (P > 0.05). CONCLUSIONS:This study demonstrated that the addition of YQLXSJ to standard therapy can improve cardiac function and alleviate clinical symptoms in AMI patients with MIRI, and also showed a potential to mitigate the incidence of MACE. Furthermore, YQLXSJ displayed a favorable safety profile in clinical application.

Background Gerberae Piloselloidis Herba (GPH) exhibits notable efficacy in alleviating allergic asthma. Previous studies in our research have identified a mixture of luteolin, arbutin, and marmesin as effective components of GPH in treating allergic asthma. However, the underlying mechanism remains unclear. This study aims to elucidate the molecular mechanism of these active components. Method Using an ovalbumin (OVA)-induced allergic asthma mouse model, various treatment groups were administered, including GPH, the active component mixture (termed "Mixture") containing luteolin, arbutin, and marmesin, and a positive drug (dexamethasone, DEX). Relevant indices were assessed, including behavioral characteristics, inflammatory cell counts, cytokine levels, histopathological examination of lung tissue, apoptosis, and expression of key proteins such as Caspase-3, Bax, Bcl-2, PI3K, p-PI3K, Akt, and p-Akt. The effect of the Mixture on the PI3K/Akt signaling pathway was further verified using the PI3K inhibitor LY294002. Results The Mixture significantly alleviated asthma symptoms, decreased IgE levels, cytokine levels (IL-4, IL-5, IL-13 and TNF-α), and the number of inflammatory cells in serum or bronchoalveolar lavage fluid (BALF), leading to the alleviation of lung pathological lesions. Additionally, the Mixture reduced the expression of Bax and Caspase-3 while increasing Bcl-2 expression, resulting in mitigated apoptosis in lung tissue. Furthermore, there appeared a decrease in the levels of PI3K and p-PI3K, as well as the ratio of p-Akt to Akt in the Mixture group, indicating the suppression of PI3K and Akt phosphorylation. Interestingly, the effects of the Mixture were comparable to those of GPH, LY294002, or the combination of LY294002 with the Mixture. Conclusion The study confirms that the Mixture containing luteolin, arbutin, and marmesin indeed alleviates allergic asthma induced by OVA in mice by suppressing the PI3K/Akt signaling pathway. These findings highlight the potential of the GPH-derived Mixture as a novel therapeutic for the treatment of allergic asthma.

ABSTRACT Influenza is an important zoonotic disease that persistently threatens global public health. While it is widely acknowledged that probiotics can modulate the host response to protect the host against infectious disease, the prophylactic efficacy on respiratory viral infection and the detailed mechanism remains elusive. Lactobacillus , the most commonly used probiotic widely applied in food production, has garnered significant attention. In our study utilizing both C57BL/6 and BALB/c mouse models, we explored the protective effect against two strains of influenza virus, A/Mink/China/01/2014(H9N2) and A/California/04/2009(H1N1), through the administration of Lactiplantibacillus plantarum strain 16 ( L. plantarum 16) and Lacticaseibacillus rhamnosus strain P118 ( L. rhamnosus P118), aiming to identify robust probiotic strains with antiviral properties. Our findings indicate that administering L. plantarum 16 or L. rhamnosus P118 alone does not provide sufficient protection against influenza. However, the co-administration of L. plantarum 16 and L. rhamnosus P118 dramatically reduces viral titers in the respiratory tract and lung, thereby markedly alleviating the clinical symptoms, improving prognosis, and reducing mortality. The mechanisms underlying this effect involve the modulation of host gut microbiota and metabolism through the co-administration of L. plantarum 16 and L. rhamnosus P118, resulting in enrichment of Firmicutes and enhancement of phenylalanine-related metabolism, ultimately leading to an augmentation of the antiviral immune response. Notably, we identified that the circulating metabolic molecule 2-Hydroxycinnamic acid plays a significant role in combating influenza. Our data suggest the potential utility of L. plantarum 16 and L. rhamnosus P118 two-bacterium or 2-Hydroxycinnamic acid in preventing influenza. IMPORTANCE Vaccination represents the most optimal strategy to control influenza. Nevertheless, influenza viruses constantly evolve due to antigenic drift and shift, leading to the need for regular updates on influenza vaccines. Additionally, vaccination failure poses significant challenges to influenza prevention. Therefore, it is essential and beneficial to identify novel or universal antiviral measures to protect against influenza. While cumulative data suggest that probiotics offer protection against infectious diseases, the specific mechanisms, such as the effective metabolites or components, remain largely unknown. Our research discovered the capacity of combinational two-bacterium Lactiplantibacillus plantarum 16 and Lacticaseibacillus rhamnosus P118 to fight against influenza infection in a mouse model. The protection may occur through modulating the host’s gut microbiota and metabolism, further influencing the host’s antiviral immune response. Notably, we have identified a novel metabolic molecule, 2-Hydroxycinnamic acid, capable of enhancing antiviral response and restricting viral replication in vivo .

目的:观察芪参桃红颗粒对压力负荷心力衰竭模型小鼠不同时期胸主动脉缩窄(Transverse Aortic Constriction,TAC)术后2周、4周心肌重构的干预作用及对自噬和相关微RNA(miRNA)的影响.方法:将90只C57小鼠随机分为:模型组(M组)、芪参桃红颗粒组(后简称QSTH,T组)、QSTH+雷帕霉素组(TR组)、QSTH+3-甲基腺嘌吟组(T3M组)、依那普利组(E组),假手术组(S组).于术后2周、4周,监测心功能,行苏木精-伊红(HE)染色、Masson染色、凋亡检测并定量分析,于透射电镜下观察左室组织自噬体形成情况,并对S组、M组、T组左室组织行miRNA测序并验证.结果:术后2周时,T组在提高左心射血分数方面优于其他组(P＜0.05),术后4周时,T组、E组在提高左室心射血分数方面优于其他组;除S组,其他组可见不同程度心脏几何形状变形、心肌肥厚.T组和E组相比较其他组,心肌纤维凋亡百分比更低(P＜0.05).除S组,其他组可见自噬滤泡、自噬体及自噬溶酶体,肌纤维细胞排列紊乱.M组相较于S组,测序结果提示新陈代谢通路、溶酶体通路与心肌自噬的联系非常密切并且其富集因子较高,具有显著的差异性;在T组较M组中,哺乳动物雷帕霉素靶蛋白(mTOR)、溶酶体通路富集明显,与自噬密切相关.结论:QSTH有效改善由压力负荷导致的心力衰竭小鼠的心功能及其心肌重构,其作用机制可能是基于miRNA调节自噬通量以产生相应的保护作用.

目的:基于网络药理学及分子对接预测党参治疗射血分数保留性心力衰竭的相关靶点及信号通路,探讨其发挥治疗作用的潜在机制.方法:利用中药系统网络药理学数据库与分析平台(TCMSP)检索党参的有效成分;通过Swiss Target Prediction数据库预测其潜在靶点;通过检索DisGeNET数据库获得射血分数保留性心力衰竭的相关靶点后,构建"药物-疾病"共同靶点韦恩图;使用Cytoscape 3.7.2软件构建"党参-有效成分-潜在靶点"网络;利用STRING数据库构建靶蛋白质-蛋白质相互作用(PPI)网络图;借助Cytoscape软件获取核心成分、关键靶点;利用Metascape数据库进行基因本体(GO)功能与京都基因和基因组百科全书(KEGG)通路富集分析;采用分子对接将核心成分与关键靶点进行结果验证.结果:筛选获得党参作用于射血分数保留性心力衰竭有效成分16个,疾病共同靶点116个,关键靶点5个;GO功能富集获得党参治疗射血分数保留性心力衰竭生物学过程主要富集在丝裂原活化蛋白激酶(MAPK)级联反应的正调控、循环系统过程、激素水平的调节、调节离子传输、细胞对氮化合物的反应等;KEGG通路主要富集在癌症、环磷酸鸟苷/蛋白激酶信号通路、内分泌抵抗等;分子对接验证党参有效成分与关键靶点具有强结合能.结论:通过网络药理学方法初步探讨了党参治疗射血分数保留性心力衰竭的作用机制,为下一步的临床和基础研究提供思路和方向.

OBJECTIVE:To explore the cardioprotective effects of astragaloside IV (AS-IV) in heart failure (HF).METHODS:PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Web of Science, Wanfang Database, Chinese Bio-medical Literature and Retrieval System (SinoMed), China Science and Technology Journal Database (VIP), and China National Knowledge Infrastructure (CNKI) were searched from inception to November 1, 2021 for animal experiments to explore AS-IV in treating HF in rats or mice. The left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular weight-to-body weight (LVW/BW) and B-type brain natriuretic peptide (BNP) were recorded. The qualities of included studies were assessed by the risk of bias according to the Cochrane handbook. Meta-analysis was performed using Stata 13.0.RESULTS:Twenty-one articles involving 558 animals were considered. Compared with the control group, AS-IV improved cardiac function, specifically by increasing LVEF (mean difference (MD)=6.97, 95% confidence interval (CI)=5.92 to 8.03, P<0.05; fixed effects model) and LVFS (MD=7.01, 95% CI=5.84 to 8.81, P<0.05; fixed effects model), and decreasing LVEDD (MD=-4.24, 95% CI=-4.74 to -3.76, P<0.05; random effects model) and LVESD (MD=-4.18, 95% CI=-5.26 to -3.10, P<0.05; fixed effects model). In addition, the BNP and LVW/BW levels were decreased in the AS-IV treatment group (MD=-9.18, 95% CI=-14.13 to -4.22, P<0.05; random effects model; MD=-1.91, 95% CI=-2.42 to -1.39, P<0.05; random effects model).CONCLUSIONS:AS-IV is a promising therapeutic agent for HF. However, this conclusion needs to be clinically validated in the future.

目的:系统评价口服中成药治疗微血管性心绞痛(MVA)的疗效及安全性.方法:计算机检索中国知网(CNKI)、万方(WanFang Data)、维普(VIP)、中国生物医学文献数据库(SinoMed)、PubMed、Web of Science、the Cochrane Library、EMbase等数据库,收集口服中成药联合常规西药治疗MVA的随机对照试验(RCTs),检索时限为建库至2022年4月.应用Cochrane协作网偏倚风险评估工具对纳入研究进行质量评价,使用RevMan 5.4和Stata 12.0软件进行数据分析.结果:共纳入19项研究,涉及1555例病人,试验组802例,对照组753例.Meta分析结果显示,与对照组相比,试验组心绞痛症状减轻[RR=1.17,95％CI(1.09,1.25),P<0.00001],心电图(ECG)运动试验持续时间延长[MD=53.88,95％CI(38.24,69.51),P<0.00001],静息ECG疗效提高[RR=1.24,95％CI(1.09,1.41),P=0.001],血清一氧化氮(NO)浓度升高[MD=14.43,95％CI(6.49,22.37),P=0.0004],血清内皮素1(ET-1)浓度降低[MD=-20.34,95％CI(-27.32,-13.37),P<0.00001],血清超敏C反应蛋白(hs-CRP)浓度降低[MD=-2.01,95％CI(-3.23,-0.78),P=0.001],且不增加不良反应发生率.结论:现在证据表明,在常规西药治疗的基础上口服中成药能减轻MVA病人临床症状,改善心肌缺血及冠状动脉微血管内皮功能,具有较好的安全性,但本研究纳入文献质量整体较低,结论仍需多中心、大样本的随机对照试验验证.

Objective To observe the therapeutic effect of Yiqi Fumai Recipe on tumor necrosis factor-α（TNF-α）and interleukin-6（IL-6）in the patients with paroxysmal atrial fibrillation（PAF,syndrome of qi deficiency and blood stasis）.Methods A total of 64 PAF patients with the syndrome of qi deficiency and blood stasis treated in Dongzhimen Hospital of Beijing University of Chinese Medicine and Fengtai District Hospital of Traditional Chinese Medicine from January 2020 to December 2021 were selected and assigned into a control group（n=32）and an observation group（n=32）according to the random number table method.The control group（1 patient dropped out）received routine treatment, and the observation group was additionally treated with Yiqi Fumai Recipe.After 4 weeks of treatment, the clinical efficacy and safety of the two groups were evaluated.The frequency and duration of atrial fibrillation attack, the TCM symptom scores, and the serum levels of tumor necrosis factor-α（TNF-α）and interleukin-6（IL-6）were compared between the two groups as well as between before and after treatment.Results The total effective rate in the observation group（96.88%,31/32）was higher than that in the control group（74.19%,23/31）（P＜0.05）.The treatment decreased the frequency and duration of atrial fibrillation in the two groups（P＜0.05）,and the observation group showed lower frequency and duration of atrial fibrillation than the control group（P＜0.05）.The treatment decreased the scores of palpitations, shortness of breath, chest tightness, dizziness, and fatigue in the two groups（P＜0.05）,and the symptom scores in the ob-servation group were lower than those in the control group（P＜0.05）.The treatment down-regulated the levels of TNF-α and IL-6 in the two groups（P＜0.05）,and the levels in the observation group were lower than those in the control group（P＜0.05）.During the treatment period, neither group showed significant abnormalities in the blood routine, stool routine, urine routine, or liver and kidney functions, and no serious adverse reactions occurred.Conclusion Yiqi Fumai Recipe can lower the serum levels of TNF-α and IL-6,mitigate clinical symptoms, and reduce the frequency and shorten the duration of atrial fibrillation attack, demonstrating significant therapeutic effect on PAF patients.

目的:系统评价破格救心汤加减联合常规西药治疗心力衰竭的有效性及安全性.方法:检索中国知网(CNKI)、万方医学数据库、维普中文科技期刊数据库(VIP)、中国生物医学文献数据库(CBM)、PubMed、EMbase、the Cochrane Library 7个数据库,检索时限为建库至2021年12月1日.纳入破格救心汤加减治疗心力衰竭的临床随机对照试验(RCT),采用Cochrane系统评价的方法对所纳入的文献进行质量评价,借助Review Manager 5.4及Stata SE 16软件进行Meta分析.结果:最终纳入10项RCT,涉及病人884例.Meta分析结果显示,与对照组(常规西药)比较,试验组(破格救心汤加减联合常规西药)左室射血分数增加[MD=6.16,95％CI(5.41,6.92),P<0.00001],左室舒张末期内径减小[MD=-4.04,95％CI(-5.90,-2.18),P<0.0001],N末端脑钠肽前体(NT-proBNP)水平降低[MD=-1232.13,95％CI(-1391.21,-1073.05),P<0.00001],脑钠肽(BNP)水平降低[SMD=-0.71,95％CI(-1.06,-0.36),P<0.00001],6 min步行距离增加[MD=77.17,95％CI(25.96,128.38),P=0.003],临床总有效率提高[RR=1.28,95％CI(1.17,1.39),P<0.00001],且药物不良反应较少,安全性良好.结论:现有证据表明,破格救心汤加减联合常规西药治疗心力衰竭的疗效优于常规西药,且不良反应少;鉴于纳入文献研究质量不高,仍需更多高质量的RCT进一步验证本结论.

目的:采用芪参六味方干预自发性高血压大鼠(SHR)心肌纤维化(MF)模型,观察其对大鼠MF的影响并探讨其作用机制.方法:SHR大鼠15只,分为模型组、中药组和氯沙坦钾组,每组5只.另魏-凯二氏大鼠(WKY)5只作为对照组.干预12周后检测各组大鼠超声心动图,处死后取左室心肌组织进行相关检测.采用Masson染色及苦味酸-天狼猩红染色,观察心肌组织胶原含量与分布;采用Western blot法测定各组大鼠心肌组织中Ⅰ型胶原(Collagen Ⅰ)、Ⅲ型胶原(Collagen Ⅲ)、基质金属蛋白酶(MMP)-9、基质金属蛋白酶抑制剂(TIMP)-1、转化生长因子(TGF)-β1、Smad2、Smad3蛋白的表达;采用RT-PCR法检测TGF-β1、Smad2、Smad3 mRNA的表达.结果:干预12周后,与模型组比较,中药组镜下胶原纤维明显减少,排列较均匀,E/E'、心肌组织胶原纤维面积百分比、Collagen Ⅰ/Collagen Ⅲ 明显降低(P＜0.05),Collagen Ⅰ、Collagen Ⅲ、MMP-9、TGF-β1、Smad2、Smad3 蛋白表达量均降低(P＜0.05),TGF-β1、Smad2 mRNA表达量下降(P＜0.05).结论:芪参六味方可通过调控TGF-β1/Smad2/3信号通路,减轻细胞外基质的沉积,改善SHR大鼠心肌纤维化.

目前,器官纤维化已成为一个全球共同关注的健康问题,其中心肌纤维化由于伴随于多种心血管疾病而广受关注.那么心肌纤维化究竟是什么?它容易发生在心脏的哪个部位?会导致什么样的后果?心肌纤维化为什么会引起大家的广泛关注?

Gerberae Piloselloidis Herba, a traditional Chinese medicine, is often employed to treat such lung-related diseases as coughs, asthma, and pulmonary carbuncles in southwest China. Our previous study demonstrated that its active fraction, prepared from Gerberae Piloselloidis Herba, exerts an obvious beneficial effect on asthma. However, the pharmacokinetics of its major constituents remain unclear. Therefore, an ultra-performance mass spectrometry-electrospray ionization-tandem mass spectrometry method was successfully established to simultaneously perform the pharmacokinetics of the main 11 components of the active fraction between normal and ovalbumin-induced asthmatic mice. Compared to the normal group, in asthmatic mice the peak concentration of arbutin, marmesin, caffeoylquinic acids, and flavonoid glycosides clearly increased, while for luteolin it significantly declined; the area under the curve for arbutin and luteolin showed an increase, but the values of marmesin, caffeoylquinic acids, and flavonoid glycosides revealed a decline; the peak time for arbutin, caffeoylquinic acids and flavonoid glycosides decreased, while for marmesin and luteolin it significantly augmented; apart from marmesin, the half-life for all compounds shortened significantly. It is indicated that the pathology of asthma could lead to an alteration in the pharmacokinetic profiles of the 11 components in plasma, providing a reference for further exploration of the pharmacodynamic basis of the anti-bronchial effect of Gerberae Piloselloidis Herba.

Xuanbai Chengqi Decoction (XBCQD), a classic traditional Chinese medicine, has been widely used to treat COVID-19 in China with remarkable curative effect. However, the chemical composition and potential therapeutic mechanism is still unknown. Here, we used multiple open-source databases and literature mining to select compounds and potential targets for XBCQD. The COVID-19 related targets were collected from GeneCards and NCBI gene databases. After identifying putative targets of XBCQD for the treatment of COVID-19, PPI network was constructed by STRING database. The hub targets were extracted by Cytoscape 3.7.2 and MCODE analysis was carried out to extract modules in the PPI network. R 3.6.3 was used for GO enrichment and KEGG pathway analysis. The effective compounds were obtained via network pharmacology and bioinformatics analysis. Drug-likeness analysis and ADMET assessments were performed to select core compounds. Moreover, interactions between core compounds and hub targets were investigated through molecular docking, molecular dynamic (MD) simulations and MM-PBSA calculations. As a result, we collected 638 targets from 61 compounds of XBCQD and 845 COVID-19 related targets, of which 79 were putative targets. Based on the bioinformatics analysis, 10 core compounds and 34 hub targets of XBCQD for the treatment of COVID-19 were successfully screened. The enrichment analysis of GO and KEGG indicated that XBCQD mainly exerted therapeutic effects on COVID-19 by regulating signal pathways related to viral infection and inflammatory response. Meanwhile, the results of molecular docking showed that there was a stable binding between the core compounds and hub targets. Moreover, MD simulations and MM-PBSA analyses revealed that these compounds exhibited stable conformations and interacted well with hub targets during the simulations. In conclusion, our research comprehensively explained the multi-component, multi-target, and multi-pathway intervention mechanism of XBCQD in the treatment of COVID-19, which provided evidence and new insights for further research.

心肌出现纤维化后不可逆转,而这又是多种心血管疾病从发生到走向终末期的必经阶段,所以抑制心肌纤维化的发生发展极为关键.除了西医治疗手段,目前中医药对心肌纤维化的干预作用逐渐得到挖掘,通过临床研究肯定了多种中药抑制心肌纤维化的疗效,并且其中的作用机制也正在逐步得到证实.

心肌纤维化是高血压、冠心病及心力衰竭等多种心血管疾病的共同病理过程,是心肌重构的主要表现之一,持续进展可导致不良心血管事件的发生.引起心肌纤维化的根本原因是各种致心肌纤维化相关疾病,因此,积极防治包括高血压、冠心病、心肌病、心肌炎、心脏瓣膜病、心包炎等基础疾病,是预防心肌纤维化的根本.

现代社会,各种心血管疾病的发病率只增不减,高血压、冠心病、心梗、心衰这些病名对于大多数人来说已经是耳熟能详.但正因为常见,就有很多人不重视.不只是在疾病出现前不重视预防,即使已经明确诊断了心血管疾病,也有很多人不就医、不吃药、不监测等.这样的做法是万万不可取的.可能短时间内没有明显的身体不舒服,但是长久如此就会造成非常严重的危害,包括我们今天聊到的心肌纤维化.但心肌纤维化并非"不治之症",有多种治疗手段可以改善症状、抑制纤维化进展、保留心脏功能,提高生活质量.

Ethnopharmacological relevance: Gerberae Piloselloidis Herba (GPH), a commonly used traditional medicine in China, is derived from Gerbera piloselloides (Linn.) Cass. It is featured by its special bioactivities as antitussive, expectorant, anti-asthma, anti-bacterial, anti-tumor, uterine analgesia, and immunity-enhancing. With a long history of medication in ethnic minority areas in China, it is often used as an effective treatment for cough and sore throat as well as allergic asthma. Although our previous investigation also has discovered GPH performed effective treatment on allergic asthma, its underlying mechanism remains unclear. Aim of the study: This research aims to reveal the pharmacological mechanism of GPH in the treatment for allergic asthma through combination of plasma pharmacology and network pharmacology. Materials and methods: Firstly, the components of GPH in blood samples were identified using UHPLC- Q-Orbitrap HRMS. An interaction network of "compound-target-disease" was constructed based on the compounds confirmed in blood and on their corresponding targets of allergic asthma acquired from disease gene databases, predicting the possible biological targets and potential signal pathways of GPH with the network pharmacology analysis. Then, a molecular docking between the blood ingredients and the core targets was carried out using the Autodock Vina software. Subsequently, after establishing a mouse model with allergic asthma induced by ovalbumin (OVA), the effect of GPH on allergic asthma was evaluated by analyzing a series of indicators including behavior, lung pathological changes, inflammatory factors in serum and bronchoalveolar lavage fluid (BALF). Finally, the key pathway and targets predicted by network pharmacology and molecular docking were further verified using Western blot analysis. Results: Eleven chemical constituents (such as arbutin, neochlorogenic acid, chlorogenic acid, etc.) were identified through the analysis of plasma samples, on which basis a total of 142 genes intersecting GPH and allergic asthma were collected by network pharmacology. After performing enrichment analysis of these genes in gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG), it was found that arbutin-related targets mainly focused on phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signal pathway, while luteolin and marmesin-related targets tended to locate at Interleukin-17 (IL-17) signal pathway. Meanwhile, the findings of molecular docking suggested that such components as arbutin, luteolin and marmesin entering into blood had good binding with the core targets related to PI3K/Akt and IL-17 pathways. In addition, GPH improved the OVAinduced asthma symptoms, the alveolar septa thickening and the infiltration of inflammatory cell around bronchi and bronchioles as well as reduced the levels of IgE, IL-8 and TNF- a in serum or BALF. Furthermore, GPH could inhibit the phosphorylation level of Akt and the expression of PI3K, an efficacy supported by the findings by way of Western blot which suggests that GPH in the treatment of allergic asthma was linked to PI3K/Akt signal pathway. Conclusion: In this study, a comprehensive strategy to combine the UPLC-Q-Orbitrap HRMS with network pharmacology was employed to clarify the mechanism of GPH against allergic asthma, a finding where GPH may inhibit PI3K/Akt signal pathway to protect mice from OVA-induced allergic asthma. This study provides a deeper understanding of the pharmacological mechanism of GPH in treatment of asthma, offering a scientific reference for further research and clinical application of GPH in terms of allergic asthma.