Breakthrough progress has been made in the molecular mechanism research and clinical application of PD-1/PD-L1 in the regulation of immunosuppression and tolerance mainly in human and mouse fields, but is relatively slow in other species. The eukaryotic expression vectors pECFP-Fc-1 and pEYFP-Fc-L1 for high expression of canine PD-1 and PD-L1 proteins were constructed and transfected into human embryonic kidney 293 T cells. Fluorescence microscopy, laser scanning confocal microscopy, and immunofluorescence technology were used to identify the expression and membrane localization of the target proteins in human embryonic kidney 293 T cells. The binding activity of the target proteins expressed on the model cell was identified by eukaryotic expression vector co-transfection and immunocoprecipitation. The results showed that canine PD-1 and PD-L1 proteins were expressed on the membrane surfaces of their respective positively transfected cells. The cell membrane complex was further analyzed by co-immunoprecipitation technology, PD-L1 protein components were successfully detected in the pull-down complex of canine PD-1 antibody, and the two target proteins expressed in the model cells showed good mutual binding activity. Further research is needed to evaluate high throughput and a reliable method for screening drugs that block the PD-1 and PD-L1 pathway.

IMPORTANCE:The programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) pathway transmits negative immunoregulatory signals. Blocking this pathway using peptides or antibodies can restore immunity. OBJECTIVE:To evaluate the immune function of epitope peptides interacting with porcine PD-1 or PD-L1. METHODS:We optimized and synthesized peptides (PD-L14QN-GF and PD-L14QN-AF) using the solid-phase method and assessed their effects on peripheral blood mononuclear cell (PBMC) proliferation and PD-1 and cytokine expression after porcine reproductive and respiratory syndrome virus (PRRSV) infection in vitro and on antibody responses to a porcine circovirus type 2 (PCV2) vaccine in vivo. RESULTS:The optimized peptides PD-L14QN-GF and PD-L14QN-AF exhibited lower binding free energy and higher stability when interacting with the PD-1 target protein. Under both PRRSV-infected and non-infected conditions in vitro, both peptides enhanced the proliferation of PBMCs, inhibited PRRSV RNA replication, and downregulated PD-1 transcription levels. Additionally, PD-L14QN-GF and PD-L14QN-AF upregulated the mRNA transcription and protein secretion of interleukin (IL)-2, IL-10, and interferon-γ to varying degrees. In vivo experiments demonstrated that PD-L14QN-GF significantly increased the antibody titer and seroconversion rate of the PCV2 vaccine. CONCLUSIONS AND RELEVANCE:PD-L14QN-GF and PD-L14QN-AF induced stronger immune responses than PD-L14. PD-L14QN-GF has potential as an immune-enhancing adjuvant.

Endothelial dysfunction (ED) serves as the pathological basis for various cardiovascular diseases. Guanosine triphosphate cyclopyrrolone 1 (GCH1) emerges as a pivotal protein in sustaining nitric oxide (NO) production within endothelial cells, yet it undergoes degradation under oxidative stress, contributing to endothelial cell dysfunction. Citronellal (CT), a monoterpenoid, has been shown to ameliorate endothelial dysfunction induced by in atherosclerosis rats. However, whether CT can inhibit the degradation of GCH1 protein is not clear. It has been reported that ubiquitination may play a crucial role in regulating GCH1 protein levels and activities. However, the specific E3 ligase for GCH1 and the molecular mechanism of GCH1 ubiquitination remain unclear. Using data-base exploration analysis, we find that the levels of the E3 ligase Smad-ubiquitination regulatory factor 2 (Smurf2) negatively correlate with those of GCH1 in vascular tissues and HUVECs. We observe that Smurf2 interacts with GCH1 and promotes its degradation via the proteasome pathway. Interestingly, ectopic Smurf2 expression not only decreases GCH1 levels but also reduces cell proliferation and reactive oxygen species (ROS) levels, mostly because of increased GCH1 accumulation. Furthermore, we identify BH 4/eNOS as downstream of GCH1. Taken together, our results indicate that CT can obviously improve vascular endothelial injury in Type 1 diabetes mellitus (T1DM) rats and reverse the expressions of GCH1 and Smurf2 proteins in aorta of T1DM rats. Smurf2 promotes ubiquitination and degradation of GCH1 through proteasome pathway in HUVECs. We conclude that the Smurf2-GCH1 interaction might represent a potential target for improving endothelial injury.

The primary and initial manifestations of hypertension encompass arterial hypoelasticity and histiocyte senescence. Oxidative stress plays a pivotal role in the progression of senescence. Elevated intracellular oxidative stress levels will directly induce cell damage, disrupt normal physiological signal transduction, which can cause mitochondrial dysfunction to accelerate the process of senescence. Alizarin, an anthraquinone active ingredient isolated from Rubia cordifolia L., has a variety of pharmacological effects, including antioxidant, anti-inflammatory and anti-platelet. Nevertheless, its potential in lowering blood pressure (BP) and mitigating hypertension-induced vascular senescence remains uncertain. In this study, we used spontaneously hypertensive rats (SHR) and human umbilical vein endothelial cells (HUVECs) to establish a model of vascular senescence in hypertension. Our aim was to elucidate the mechanisms underpinning the vascular protective effects of Alizarin. By assessing systolic blood pressure (SBP) and diastolic blood pressure (DBP), H&E staining, SA-β-Gal staining, vascular function, oxidative stress levels, calcium ion concentration and mitochondrial membrane potential, we found that Alizarin not only restored SBP and increased endothelium-dependent relaxation (EDR) in SHR, but also inhibited oxidative stress-induced mitochondrial damage and significantly delayed the vascular senescence effect in hypertension, and the mechanism may be related to the activation of VEGFR2/eNOS signaling pathway.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic metabolic liver diseases worldwide. Perillaldehyde (4-propyl-1-en-2-ylcyclohexene-1-aldehyde, PA) is a terpenoid compound extracted from Perilla, which has effective pharmacological activities such as anti-inflammatory, antidepressant, and anticancer. This study aimed to explore the pharmacological effects of PA in intervening with NAFLD and reveal its potential mechanisms. Firstly, we identified the core targets of PA intervention therapy for NAFLD through network pharmacology and molecular docking techniques. After that, in vitro animal experiments such as H&E and Masson staining, immunofluorescence, immunohistochemistry, and Western blot were conducted to validate the results network effectively pharmacology predicted. Network pharmacology analysis suggested that PPAR-α may be the core target of PA intervention in NAFLD. H&E and Masson staining showed that after low-dose (50 mg/kg) PA administration, there was a noticeable improvement in fat deposition in the livers of NAFLD mice, and liver tissue fibrosis was alleviated. Immunohistochemical and immunofluorescence analysis showed that low dose (50 mg/kg) PA could reduce hepatocyte apoptosis, decrease the content of pro-apoptosis protein Bax, and increase the expression of anti-apoptosis protein Bcl-2 in NAFLD mice. Western blot results confirmed that low-dose (50 mg/kg) PA could increase the expression of PPAR-α and inhibit the expression of NF-κB in NAFLD mice. Our study indicated that PA could enhance the activity of PPAR-α and reduce the level of NF-κB in NAFLD mice, which may positively affect the prevention of NAFLD.

Previous studies have shown that puerarin plays a key role in protecting humans and animals from cardiovascular diseases. The exact mechanism of the therapeutic effect of puerarin on various cardiovascular diseases (protective effect on cardiomyocytes) is still unclear. In the present study, we identify the role of puerarin in an animal model of experimental heart failure (HF) and explore its underlying mechanisms. The HF rat model is induced by intraperitoneal injection of adriamycin (ADR), and puerarin is administered intragastrically at low, medium, and high concentrations. We demonstrate that puerarin significantly improves myocardial fibrosis and inflammatory infiltration and, as a result, improves cardiac function in ADR-induced HF rats. Mechanistically, we find for the first time that puerarin inhibits overactivated Na+/H+ exchange isoform 1 (NHE1) in HF, which may improve HF by decreasing Na+ and Ca2+ ion concentrations and attenuating mitochondrial damage caused by calcium overload; on the other hand, puerarin inhibits the activation of the p38 pathway in HF, reduces the expressions of TGF-β and proinflammatory cytokines, and suppresses myocardial fibrosis. In conclusion, our results suggest that Puerarin is an effective drug against HF and may play a protective role in the myocardium by inhibiting the activation of p38 and its downstream NHE1.

Background: Previous studies have shown that Puerarin plays a key role in protecting humans and animals from cardiovascular diseases. The therapeutic effects (protective role in cardiomyocytes) of Puerarin in various cardiovascular diseases mainly through the regulation of Na+, K+, and Ca2+ channels and the concentration of these ions in cardiomyocytes, but the exact mechanism is unclear. Purpose: In the present study, we identified the role of Puerarin in an animal model of experimental heart failure and explored its underlying mechanisms.Study design and Methods: The heart failure model of rats was induced by Adriamycin (ADR) intraperitoneal injection, and Puerarin was treated by intragastric administration with low, medium, and high concentrations.Results: We demonstrated that Puerarin significantly improved myocardial fibrosis and as a result improved cardiac function in ADR-induced heart failure (HF) rats. Mechanistically, we found for the first time that Puerarin inhibited the over-activated Na+/H+ exchange isoform 1 (NHE1) in HF, which may improve HF by decreasing Na+ and Ca2+ ion concentrations; on the other hand, Puerarin can interfere with JNK/p38 pathway, inhibit myocardial fibrosis and alleviate mitochondrial damage.Conclusion: Our results suggest that Puerarin is an effective drug against HF and may play a protective role in the myocardium by inhibiting the activation of JNK/p38 and its downstream NHE1.

Chinese herbal medicine plays an important role in regulating the nutritional metabolism of poultry and maintaining or improving normal physiological functions and animal health. The present study investigated the effects of dietary supplementation with Qiling Jiaogulan Powder (QLJP) on pulmonary fibrosis and pulmonary arteriole remodeling in low temperature-exposed broilers. Seven-day-old Ross 308 broilers (n = 240) were reared adaptively to 14 days of age. The broilers were randomly divided into six groups: A control group (basal diet and normal feeding temperature); model group (basal diet); low-, medium- and high-dose QLJP groups (basal diet supplemented with 1 g/kg, 2 g/kg, 4 g/kg QLJP); and L-Arg group (basal diet supplemented with 10 g/kg L-arginine). Additionally, all the broilers, except the broilers in the control group, from the age of 14 days old, had a house temperature continuously lowered by 2 °C each day until it reached 12 °C at 21 days of age, and the low temperature was maintained until the end of the experiment. There were four replicates per group and 10 birds per replicate. The results showed that the structure of the lung tissue was clearer and basically intact in the broilers in the QLJP groups, with a small number of collagen fibers formed, and the content of hydroxyproline (HYP) was significantly reduced. QLJP improved pulmonary arteriole lesions, such as tunica media thickening, intimal hyperplasia, arterial wall hypertrophy, and lumen narrowing. QLJP reduced the relative media thickness (%) and relative medial area (%) of the pulmonary arteriole, and significantly decreased the expression level of the alpha-smooth muscle actin (α-SMA) protein in pulmonary arteriole, which alleviated pulmonary arteriole remodeling. The quantitative real-time PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA) results showed that QLJP treatment significantly reduced the gene and protein levels of transforming growth factor-beta l (TGF-β1) and Smad2 in the lung and downregulated the gene and protein levels of collagen type I alpha 1 (COL1A1) and matrix metalloproteinase 2 (MMP2). In conclusion, the results of our study suggested that dietary supplementation with QLJP improved pulmonary fibrosis and pulmonary arteriole remodeling by inhibiting the expression of genes related to the TGF-β1/Smad2 signaling pathway and inhibited the occurrence and development of pulmonary arterial hypertension in low-temperature-exposed broilers.

Background: Vascular endothelial dysfunction is the initial cause of the occurrence and development of atherosclerosis. Citronellal, a natural product extracted from Citronella, has anti-thrombotic, anti-hypertensive, anti-diabetic cardiomyopathy and anti-atherosclerotic vascular endothelial injury, but the specific mechanism is still unclear. The purpose of this study is to explore the hypothesis that CT may inhibit the ectopic expression of miR-133a in vascular endothelium to reduce AS ED through AP-2α/circRNA_102979 pathway.Methods: Citronellal inhibits the ectopic expression of miR-133a in vascular endothelium through AP-2α/circRNA_102979 pathway to reduce vascular endothelial injury in vivo and in vitro.Findings: In vivo and in vitro experiments, citronellal intervention significantly reduced the levels of total cholesterol, triglyceride and low density lipoprotein, and effectively reduced the atherosclerotic plaque area of mice. By inducing the ectopic expression of miR-133a in vascular endothelium, citronellal intervention increased the expression levels of AP-2α and circRNA_102979 in vascular endothelium, increased the adsorption effect of circRNA_102979 on miR-133a and removed the inhibitory effect of miR-133a on target genes. Thereby reducing vascular endothelial injury.Interpretation: In this study, we analyzed the new mechanism of citronellal protecting vascular endothelial function and provided a new target for the development of cardiovascular protective drugs.Funding This research was supported by National Natural Science Foundation of China (82271460, U1804197, 81874312), Research Foundation of Henan Province (202300410308, HNGD2022067), National High-End Foreign Expert Recruitment Plan of China(G2022026006L) Research Foundation of Xinxiang Medical University (XYBSKYZZ505319, XYBSKYZZ201626).Declaration of Interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in thispaper.Ethical Approval: Animal research is carried out in strict accordance with the recommendations inthe "Guidelines for the Care and Use of Laboratory Animals" of the National Institutes of Health, and all animal research programs are implemented after being reviewed and approved by the Animal Protection and Use Committee of Xinxiang Medical College.

为了提高临床药理学教学水平,针对当前教学现状面临的主要问题,文章提出了网络教学的改进方法,并对教学改革进行了探讨.通过对新乡医学院2020年度第一学期临床药理学网络教学过程中问卷调查和考试成绩的分析,文章探讨了网络教学模式在临床药理学课程中的应用及反馈,并从多方面评价了网络授课的效果.学生对网络教学模式的认可度很高,能够提高学生的学习积极性和解决问题的能力.实践证明,特殊封闭环境下网络教学的实施不仅保障了临床药理学课程的教学进度和质量,而且还充分发挥了学生的学习主动性.为保障临床药理学教学课程的顺利实施,需要有效发挥网络教学的优势,同时利用多种手段融合使用以达到良好的教学效果.

文章旨在评估日粮脂肪类型对不同环境温度下肉牛生长性能、瘤胃发酵和血液指标的影响.试验将初重为(544.09±2.53)kg的120头肉牛随机分为4组,每组5个重复,每个重复6头.试验采用2×2因子设计,即2种油脂类型(大豆油和包被脂肪),2种环境温度(18℃和26℃),分别对应T1～T4,试验持续4周.日粮脂肪类型及日粮类型和温度的交互效应对肉牛的末重、日增重、采食量和料重比均无显著影响(P>0.05).无论日粮类型如何,高温组肉牛的末重、日增重和饲料效率均显著高于低温组(P<0.05).环境温度对瘤胃pH、挥发性脂肪酸、乙酸和丙酸浓度的影响也无显著差异(P>0.05).无论日粮脂肪类型如何,低温组瘤胃氨氮浓度和乙酸与丙酸比值均显著高于高温组(P<0.05).无论环境温度如何,包被脂肪组血清胆固醇、高密度脂蛋白和磷浓度均显著高于大豆油组(P<0.05).不论日粮脂肪类型如何,低温组血清葡萄糖和钙浓度显著高于高温组(P<0.05),但皮质醇浓度显著降低(P<0.05).结论:全混合日粮添加包被脂肪可以改善血清胆固醇和高密度脂蛋白浓度,且对肉牛生长性能无负面影响.高温(26℃)环境较低温(18℃)提高了肉牛的增重和饲料效率.

文章旨在评估日粮添加不同水平的海藻对肉鸡生长性能、抗氧化及免疫性能的影响.试验将840只平均体重为(58.01±0.67)g的1日龄肉鸡随机分为4组,每组5个重复,每个重复42只鸡.对照组和处理组分别饲喂基础日粮+0、1.5％、2.5％和3.5％海藻,试验共开展42 d.结果:与对照组相比,3.5％海藻组42 d肉鸡体重显著提高1.39％(P<0.05),但22～42 d采食量及1～42 d料重比较对照组显著降低5.19％和4.80％(P<0.05).3.5％海藻组22～42 d肉鸡料重比较对照组和1.5％海藻组分别显著降低7.2％和5.69％(P<0.05).对照组血清胆固醇、甘油三酯和高密度脂蛋白浓度显著高于3.5％海藻组(P<0.05),同时,对照组和1.5％海藻组血清总脂浓度较3.5％海藻组分别显著提高11.86％和7.73％(P<0.05).与对照组相比,处理组血清超氧化物歧化酶活性分别显著提高10.78％、12.49％和11.89％(P<0.05).与对照组相比,1.5％～3.5％海藻组42 d肉鸡抗绵羊红细胞抗体滴度分别显著提高20.63％、15.61％和18.52％(P<0.05).结论:在本试验条件下,综合考虑生长性能、血清抗氧化和抗体滴度,1～42 d肉鸡日粮中海藻适宜的添加水平为3.5％.

Objective:To observe the effect and mechanism of diagnostic low intensity ultrasound combined with microbubbles on myocardial microcirculation in rats with diabetic cardiomyopathy (DCM).Methods:The healthy male SD rats were induced DCM by streptozotocin through intraperitoneal injection and fed with high fat diet. The rats were randomly divided into normal control group ( n=15), DCM model group (DCM group, n=15), and the SonoVue microbubble + US group (US+ MB group, n=15). After 2 weeks of intervention using diagnostic ultrasound combined with VFLASH, all rats underwent conventional echocardiograph to examine the cardiac function. The rats were sacrificed and myocardial tissue was stained with CD31 immunohistochemistry to quantify myocardial microvascular density (MVD). The expressions of PI3K-Akt-eNOS pathway protein in rats myocardium were detected by Western blot. Results:The left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) in the US+ MB grouph were significantly increased compared with DCM group [(68.97±4.84) % vs (57.76±6.03)%, (34.01±3.97)% vs (27.70±3.24)%, all P<0.05]. The MVD in US+ MB group was significantly higher than that in the DCM group(27.66±3.39 vs 10.67±1.63, P<0.05). The protein level of phosphatidylinositol 3-kinase(PI3K), protein kinase B(PKB/Akt) and PI3K phosphorylation in myocardial tissue of rats increased significantly in US+ MB group compared with DCM group [(0.44±0.04)% vs (0.28±0.05)%, (0.36±0.04)% vs (0.21±0.05)%, (0.42±0.06)% vs (0.26±0.05)%, all P<0.05]. However, the protein level of endothelial nitric oxide synthase(eNOS) and p-eNOS were slightly increased in US+ MB group, but there was no obvious statistical difference compared to the DCM group [(0.37±0.05)% vs (0.29±0.07)%, (0.26±0.05)% vs (0.23±0.03)%, all P>0.05]. Conclusions:Diagnostic low intensity ultrasound combined with microbubbles can enhance myocardial microcirculation and improve myocardial function to some extent, and the mechanism may be related to the activation of PI3K-Akt-eNOS pathways.

The authors have withdrawn this preprint due to author disagreement.

为研究阿苯达唑和吡喹酮对兔豆状囊尾蚴病的治疗效果,将30只患豆状囊尾蚴的病兔随机分为3组,分别用阿苯达唑、吡喹酮和淀粉进行2个疗程的治疗,从临床症状、体质量变化、白细胞分类变化、病理学宏观、微观和超微结构检查等方面进行比较观察.结果 证明2种药物对兔豆状囊尾蚴病的治疗主要有3点不同:一是阿苯达唑可使豆状囊尾蚴头节的齿钩破坏,吸盘闭锁,并发生凝固性坏死和钙化,囊液充分吸收;而吡喹酮主要引起头节和原始体节起泡、破溃和崩解,皮层破坏,平滑肌收缩,吸盘口闭合,死亡的虫体呈扭曲状,囊液吸收不充分.二是阿苯达唑可引起嗜酸性粒细胞增多,但反应较慢;吡喹酮能在较短的时间内引起嗜酸性粒细胞明显增多.三是阿苯达唑治疗组的增长速度比吡喹酮治疗组的快,差异显著,而2治疗组的增长速度均比对照组的快,差异非常显著.总之,阿苯达唑和吡喹酮对兔豆状囊尾蚴病均有较好的疗效,但以前者更好.

Aims : This study aimed to evaluate the effects and mechanisms of tertiary butylhydroquinone (TBHQ) on insulin resistance (IR) and diabetic liver steatosis. Methods : Male ApoE -/- mice were received streptozocin (STZ) injection and a high-sugar-high-fat diet to form type 2 diabetes mellitus (T2DM). Then, the mice were given TBHQ for six weeks. Body weight, fasting blood-glucose (FBG), postprandial blood glucose (PBG), insulin and oral glucose tolerance test (OGTT) were detected on all the mice. Hematoxylin-eosin staining and western-blot were performed to detect the morphological structure and the target proteins expression in liver tissues. In vitro, HepG2 cells were induced by HClO and insulin to develop IR. Western-blot was used to evaluate the related proteins expression. Hoechst staining was conducted to measure cell apoptosis. Results : Mice that received STZ injection and a high-sugar-high-fat diet developed T2DM. TBHQ reduced blood glucose level, improved glucose tolerance, alleviated liver steatosis in diabetic mice. Moreover, TBHQ significantly increased AMPKα2, GLUT4 and GSK3β expression, up-regulated PI3K and AKT phosphorylation level in diabetic mice liver. Notably, TBHQ down-regulated HClO and insulin-induced cell IR and inhibited cell apoptosis via AMPKα2/PI3K/AKT pathway. Conclusion : TBHQ alleviated IR and liver steatosis in T2DM mice and the mechanism may relate to AMPKα2/PI3K/AKT pathway.

Retrospective analysis of data from 14,528 lung cancer patients with multiple primary malignant neoplasm (MPMN) revealed that 2.5% (364/14,528) were MPMN cases and 96.2% (350/364) were diagnosed with two primary malignancies, 3.6% (13/364) with three primary malignancies, and 0.3% (1/364) with four primary malignancies. Among 350 lung cancer patients diagnosed with two primary malignancies, 26.6% (93/350) had lung cancer diagnosed first (LCF) and 73.4% (257/350) had other cancers diagnosed initially (OCF), whereas synchronous MPMN (SMPMN) accounted for 21.1% (74/350) and metachronous MPMN (MMPMN) accounted for 78.9% (276/350) of the cases. Detection of first primary neoplasms were at an early stage for LCF patients and the age of the first lung cancer diagnosis was 59.3 years vs. 55.4 years in the OCF group ( P = 0.008), whereas the onset age of second primary neoplasm diagnosis was similar in both groups (62.5 and 61.6 years, P = 0.544). Median survival times of MMPMN and SMPMN patients in the LCF group were 6.83 and 2.42 years and in the OCF group 8.67 years and 2.25 years, respectively. Multivariate analysis showed that SMPMN, LCF and the age of the primary cancer diagnosed first ( ≥ 60 years) and NSCL staging > II were significant independent factors for inferior prognosis of patients.

目的 为提高临床药物治疗学教学水平,分析当前教学现状存在的问题,提出教学改进办法,进行教学改革探讨.方法 通过授课过程中调查问卷和对比授课后考试成绩,从多方面探讨改革效果.结果对问卷调查总结和考试成绩分析得出,采用改进办法后学生成绩提高明显;同时,学生的及格率明显高于采用传统教学模式的学生;通过教学改进后来看,学生的学习积极性有了很大提高,考试中综合运用能力高于传统教学模式的学生;从对学生调查回访可知,学生对改进的教学方法认可度很高.实践证明,新的教学模式能够开阔学生视野,提高解决问题的能力.结论 新的教学改进办法有利于提高教学效果.

目的 以葛根传统的降糖功效(中医称“止消渴”)作为研究对象,揭示葛根主要活性成分的作用靶点,探讨其多成分-多靶点-多通路的作用机制.方法 针对葛根中27个活性成分,采用反向药效团匹配方法进行作用靶点预测和作用机制探讨.通过对PharmMapper数据库和DrugBank数据库中降糖药物靶点的比对筛选,借助String数据库挖掘靶点信息关系,并采用Cytoscape软件构建成分-靶点-通路网络.结果 葛根降糖的潜在活性成分主要有18个,涉及9个靶点和25条代谢通路,其中潜在活性成分主要包括葛根素、3'-羟基葛根素、3'-甲氧基葛根素和大豆素等;潜在作用靶点主要有胰岛素受体、血管紧张素转换酶2、过氧化物酶体增殖活化受体γ等;代谢通路主要有低氧诱导因子-1(hypoxia-inducible factor-1,HIF-1)信号通路、肾素-血管紧张素系统、FoxO信号通路和腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)信号通路等.结论 本实验运用网络药理学方法和技术,从分子网络层面揭示了葛根主要活性成分降糖作用的多靶点预测、多通路的作用模式,为葛根降糖作用机制的深入探讨提供了理论依据和线索.