Study on mechanism and molecular docking verification of Angelicae Sinensis Radix and Astragali Radix in treating ischemic stroke

Background:Traditional Chinese medicine(TCM)has been shown to be effective in treating ischemic stroke(IS),and the combination of Angelicae Sinensis Radix(ASR)and Astragali Radix(AR)is a core TCM prescription that is widely acknowledged for its efficacy in IS treatment.This study utilized network pharmacology methods to explore the molecular mechanisms underlying the therapeutic effects of Angelicae Sinensis Radix and Astragali Radix in IS treatment,with preliminary validation conducted through molecular docking.Methods:Information on the structure,targets,main biological functions,and pathways of the active components in Angelicae Sinensis Radix and Astragali Radix was collected using databases such as PubChem,PharmMapper,UniProt,and GeneCards.The results were visualized using software such as Cytoscape 3.6.1,Ledock,and pymol.Results:We retrieved 20 active components and 149 targets associated with the compatibility of Angelicae Sinensis Radix and Astragali Radix from various databases,and GeneCards database was used to search 3350 IS-related gene targets,including 78 key targets of Angelicae Sinensis Radix and Astragali Radix for the treatment of IS.Enrichment analysis of these 78 targets using gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)revealed the involvement of 48 GO terms in the treatment of IS,mainly in biological processes such as metabolism,biological regulation,and stress response.The composition of biological devices such as supercavitary membrane,cell fluid,and extracellular space was also involved.The biological functions mainly included protein binding,ion binding,hydrolytic enzyme activity,and others.The identified pathways were estrogen signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,PI3K-AKT signaling pathway,RAP1 signaling pathway,P53 signaling pathway,PPAR signaling pathway,FOXO signaling pathway,RAS signaling pathway,prolactin signaling pathway,HIF-1 signaling pathway,and TNF signaling pathway.Molecular docking analysis showed that the 17 key active components of Angelicae Sinensis Radix and Astragali Radix had strong binding activity with 13 IS key targets.Conclusion:Through the application of network pharmacology methods,it was found that the use of Angelicae Sinensis Radix and Astragali Radix for treating ischemic stroke mainly targets the MAPK and PI3K-AKT signaling pathways,involving several crucial compounds and genes.Nevertheless,additional in vitro and in vivo studies are needed to verify these findings.

Therapeutic effects of Astragali Radix on diabetic foot:a clinical randomized controlled trial

Objective:This study was conducted to evaluate the efficacy of Astragalus on diabetic foot,as well as the effects on the levels of serum VEGF,bFGF,MMP-2,and inflammatory factors in patients,and to provide a scientific basis for the treatment of diabetic foot with the traditional Chinese medicine Astragalus.Methods:By taking 100 cases of diabetic foot patients who were admitted to the metabolic internal medicine division of the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine and met the criteria of natriuresis during April 2021-April 2023 as the study subjects,and according to the random number method,all patients were divided into the control group and the observation group,with 50 cases in each group.In the control group,only basic treatment was carried out,while in the observation group,Astragalus injection was added based on the control group.After 8 weeks of treatment,the clinical efficacy,serum VEGF,bFGF,MMP-2,and inflammatory factor levels of the patients in the two groups were compared,respectively.Results:The total clinical efficiency of patients in the observation group was significantly better than that in the control group(χ^(2)=5.01,P<0.05).The inflammatory factor indexes decreased substantially in both groups.However,the decrease in the observation group was significantly higher than in the control group(P<0.05).Compared with the control group,serum VEGF and bFGF were considerably higher in the observation group,while MMP-2 was significantly lower(P<0.05).Conclusion:Astragali Radix is clinically effective in the diabetic foot,which can induce vascular endothelial repair and reduce the level of inflammatory factors,to improve the inflammatory state of patients and promote the restoration of ulcerated wound tissue,which is worth promoting in clinical practice.

Analysis of principal isoflavone glycosides and aglycones in Radix astragali

Two major isoflavone glycosides [calycosin 7-O-β-D-glucopyranoside （1） and ononin （2）] and their aglycones [calycosin （3） and formononetin （4）] were simultaneously quantified with HPLC/DAD method. Two unknown compounds were identified as calycosin 7-O-β-D-glucopyranoside-6＇＂-O-malonate （U1） and formononetin 7-O-β-D-glucopymnoside-6＇＂-O-malonate （U2）, respectively, with LC/MS^n. Raw Radix astragli were shown to have higher contents of isoflavone glycosides （1, 2）, but lower contents of aglycones （3, 4） than the processed herbal materials. After being moistened with water and stored up for 24 h at 35 ℃, the glycosides and their m_alonates were almost completely transformed to their corresponding aglycones. The different contents of the isoflavone glycosides and their aglycones in raw and processed Radix astragali materials might be due to enzymolysis of the glycosides during processing.

Molecular mechanism of Radix astragali on improvement of insulin sensitivity of SD rats treated with low dose dexamethasone

Aim To reveal the main active components and the action mechanisms of Radix astragali on insulin sensitivity improvement, we have investigated the effects of polysaccharide portion and saponin portion of Radix astragali extracts on blood biochemical indices and related gene expression of dexamethasone-induced SD rats. Methods SD rats （6 per group） received 2 μg/day subcutaneous dexamethasone for 4 weeks plus same dose （10 g material/kg） of polysaccharide or saponin extracts of Radix astragali. Blood samples, kidney tissues and epididymal fat pads were taken at the end of the experiment. Serum triglyceride （TG）, total cholesterol （TC）, low density lipoprotein cholesterol （LDLC）, high density lipoprotein cholesterol （HDLC）, glucose （GLU） and insulin （INS） levels were measured, respectively, mRNA levels of angiotensinogen in kidney, adiponectin and leptin as well as TNF-α in epididymal fats were determined by RT-PCR assay using GAPDH gene as an internal control. Results Both of polysaccharide and saponin extracts of Radix astragali exhibited positive effects in reducing serum triglycerides, glucose, and insulin levels of dexamethasone-induced SD rats. The saponin group showed more improvements on quantitive insulin sensitivity check index （QUICKI） than the polysaccharide group did. Both of the extracts down-regulated kidney angiotensinogen and fat TNF-α mRNA levels while they were simultaneously up-regulating fat adiponectin and leptin mRNA levels. No significant difference was found between actions of the two extracts. Conclusion Both of polysaccharide and saponin extracts of Radix astragali can improve insulin sensitivity. This action might be closely related to down-regulation of angiotensinogen, TNF-α and up-regulation of adiponectin and leptin expression. The results partly explained the improvement of type Ⅱ diabetes and diabetic nephropathy by Radix astragali. The similar actions of the two crude extracts suggest that unknown key active compounds might exist in both and remain to be discovered.

Protective effect of Radix Astragali injection on immune organs of rats with obstructive jaundice and its mechanism

AIM: To observe the protective effect of Radix Astragali injection on immune organs (lymph nodes, spleen and thymus) of rats with obstructive jaundice (OJ) and its mechanism. METHODS: SD rats were randomly divided into sham-operation group, model control group and Radix Astragali treatment group. On days 7, 14, 21 and 28 after operation, mortality rate of rats, pathological changes in immune organs, expression levels of Bax and nuclear factor (NF)-κB p65 proteins, apoptosis indexes and serum tumor necrosis factor (TNF)-α level in spleen and thymus were observed, respectively.RESULTS: Compared to model control group, the number of dead OJ rats in Radix Astragali treatment group decreased (P > 0.05). The TNF-α level (27.62 ± 12.61 vs 29.55 ± 18.02, 24.61 ± 9.09 vs 31.52 ± 10.95) on days 7 and 21, the pathological severity score for spleen [0.0 (0.0) vs 0.0 (2.0) on days 7 and 14 and for lymph nodes [0.0 (1.0) vs 1.0 (2.0), 1.0 (0.0) vs 2.0 (1.0)] on days 21 and 28, the product staining intensity and positive rate of Bax protein in spleen [0.0 (0.0) vs 1.0 (2.0), 0.0 (1.0) vs 2.0 (1.5) and thymus [0.0 (0.0) vs 1.0 (2.0), 0.0 (1.0) vs 2.0 (1.5)] on days 14 and 28, the apoptotic indexes [0.0 (0.0) vs 0.0 (0.01)] in spleen and thymus [0.0 (0.0) vs 0.0 (0.01) on days 14 and 21 were significantly lower in Radix Astragali treatment group than in model control group (P < 0.05). CONCLUSION: Radix Astragali has protective effects on immune organs of OJ rats by relieving the pathological changes in immune organs, reducing TNF-α level and inhibiting Bax expression and apoptosis in spleen and thymus.

Protective Effects of Radix Astragali against Anoxic Damages to in vitro Cultured Neurons

To study the protective effects of radix astragali against anoxic damages to in vitro cultured neurons in rats, NaCN was used to develop a hypoxic model of in vitro cultured neurons from newborn rat cerebral cortex. The cellular morphology, A value (cell survival number) and effluxes of lactate dehydrogenase(LDH) and K+ from cells were measured in the radix astragali group and the control group respectively. After 48 h of anoxia, A value was decreased from 0. 325± 0. 031 before anoxia to 0. 145± 0. 011, the effluxes of LDH and K+ were increased from 65. 80± 2. 90 U/L and 5. 23 ± 0. 11mmol/L before anoxia to 148. 80± 8. 40 U/L and 7. 31 ± 0. 18 mmol/L, respectively. It was found that in the anoxic circumstance in the Radix astragali group, the mophological changes were mild, the effluxes of LDH and K+ were decreased and A value increased as compared with those in the control group. It was suggested that Radix astragali could protect the cultured rat neurons against anoxic damages in the anoxic circumstance.

黄芪发酵物通过调节Fas信号通路影响碘缺乏大鼠海马结构和学习记忆功能

目的探讨黄芪发酵物通过调节脂肪酸合成酶(Fas)信号通路对碘缺乏大鼠海马损伤和学习记忆功能的影响,以期选出药效最佳的黄芪制剂。方法60只Wistar大鼠随机分为对照组、模型组、黄芪发酵提取液4.00、2.00、1.00 g·kg^(-1)组和阳性药(左甲状腺素钠9×10^(-3)mg·L^(-1))组。除对照组外,各组大鼠喂养碘缺乏饲料(碘含量为20μg·kg^(-1))90 d构建甲状腺肿大鼠模型。检测各组大鼠血清中游离三碘甲腺原氨酸、游离甲状腺素、促甲状腺激素水平显示造模成功。跳台实验、Morris水迷宫实验检测各组大鼠的学习和记忆水平;酶联免疫吸附试验检测血清乙酰胆碱转移酶、乙酰胆碱酯酶、过氧化氢酶活性和乙酰胆碱、丙二醛含量;观察断头缺氧后存活时间和脑指数;苏木精-伊红染色、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记染色观察海马组织病理学变化;同时,定量逆转录聚合酶链式反应检测Fas、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)、B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2相关X蛋白(Bax)mRNA的相对表达;最后,蛋白质印迹法检测、Caspase-3、Bax、Bcl-2蛋白的表达。结果与对照组比较,模型组大鼠学习记忆能力明显下降,脑组织中乙酰胆碱水平、抗氧化活力降低,海马组织出现不同程度损伤和细胞凋亡,神经细胞排列紊乱、Fas、Caspase-3、Bax基因及蛋白表达增加,Bcl-2表达降低。与模型组相比,黄芪发酵物和阳性药组大鼠跳台潜伏期、错误次数和Morris水迷宫实验逃避潜伏期均明显减少,目标象限停留时间百分率和平台穿越次数均增加;血清乙酰胆碱转移酶、过氧化氢酶活性和乙酰胆碱含量升高,乙酰胆碱酯酶活性和丙二醛含量降低;缺氧后存活时间延长,脑指数增加;海马组织病理损伤得到明显改善;Fas、Caspase-3、Bax mRNA相对表达量减少,Bcl-2表达量增加,Bax/Bcl-2降低;蛋白质印迹法显示,Fas、Caspase-3、Bax蛋白表达量显著减少,Bcl-2蛋白表达增加,具有剂量依赖性。结论黄芪发酵物能够提高碘缺乏大鼠学习记忆水平,可能与抑制Fas信号通路及调节乙酰胆碱代谢、改善能量代谢、减轻氧化应激损伤和抑制凋亡效应有关。

Predicting the grades of Astragali radix using mass spectrometrybased metabolomics and machine learning

Astragali radix(AR,the dried root of Astragalus)is a popular herbal remedy in both China and the United States.The commercially available AR is commonly classified into premium graded(PG)and ungraded(UG)ones only according to the appearance.To uncover novel sensitive and specific markers for AR grading,we took the integrated mass spectrometry-based untargeted and targeted metabolomics approaches to characterize chemical features of PG and UG samples in a discovery set(n=16 batches).A series of five differential compounds were screened out by univariate statistical analysis,including arginine,calycosin,ononin,formononetin,and astragalosideⅣ,most of which were observed to be accumulated in PG samples except for astragalosideⅣ.Then,we performed machine learning on the quantification data of five compounds and constructed a logistic regression prediction model.Finally,the external validation in an independent validation set of AR(n=20 batches)verified that the five compounds,as well as the model,had strong capability to distinguish the two grades of AR,with the prediction accuracy>90%.Our findings present a panel of meaningful candidate markers that would significantly catalyze the innovation in AR grading.

黄芪-莪术对C5a介导JAK2/STAT3通路调控Lewis肺癌小鼠Th17/Treg细胞平衡影响的实验研究

目的探讨黄芪-莪术影响C5a介导JAK2/STAT3通路调控肿瘤微环境中Th17/Treg细胞平衡,从而阐明其在此途径抑制肿瘤进展的相关机制。方法40只雄性C57BL/6小鼠按随机数字表法分为空白对照组、模型对照组、中药干预组、阳性对照药(PMX53)组,每组各10只。腋下接种Lewis细胞建立肺癌小鼠模型,于接种后第3天开始,中药干预组按8.2 g/kg剂量给予中药浓煎液灌胃,模型对照组和PMX53组予等容积灭菌双蒸水灌胃,连续14 d;PMX53组分别于第3、6、9、12、15天按1mg/kg剂量给予腹腔注射PMX53,模型对照组和中药干预组同时腹腔注射等容PBS溶液。每2 d测算各组小鼠肿瘤体积、绘制肿瘤生长曲线;于第15天处死,剖取瘤块,ELISA法检测血清C5a、IL6、IL-10、IL-17、TGF-β等因子水平,流式细胞术检测并计算外周血和肿瘤组织中Th17/Treg细胞比例,Western Blot和Real-time PCR法检测肿瘤组织中JAK2/STAT3信号通路相关蛋白及mRNA表达。结果与模型对照组比较,中药干预组和PMX53组肿瘤生长较缓慢,补体C5a、JAK2和STAT3蛋白及mRNA水平、p-JAK2/JAK2、p-STAT3/STAT3比值、Treg占比均降低,SOCS3蛋白及mRNA水平、Th17/Treg比例增高,差异有统计学意义(P<0.05)。结论黄芪-莪术可降低补体C5a进而抑制JAK2/STAT3通路活化,并调节肿瘤微环境中Th17/Treg平衡达到抑制肿瘤生长的作用。

Simultaneous separation and determination of four main isoflavonoids in Astragali Radix by an isocratic LC/ESI-MS method

A simple, reliable and rapid isocratic liquid chromatography(LC)-mass spectrometric detection(MS) coupled with electrospray ionization(ESI) method for simultaneous separation and determination of calycosin-7-O-β-D-glucoside, ononin, calycosin and formonometin in Astragali Radix was developed. After the samples were extracted with ethanol, the optimum separation conditions for these analytes were achieved using water and acetonitrile(70:30, v/v) containing 0.2%(v/v) acetic acid as a mobile phase and a 2.0 mm×150 mm Hypersil-Keystone C18 column. Selective ion monitoring(SIM) mode and [M+H]+ ions at m/z 447, 431, 285 and 269 were used for quantitative analysis of four main active components above mentioned. The calibration curves were linear in the range of 0.4-175.0 μg/mL for calycosin-7-O-β-D-glucoside, 0.2-146.0 μg/m L for ononin, 0.4-210.0 μg/mL for calycosin and 0.5-217.0 μg/mL for formonetion, respectively. The limits of quantification(LOQ) and detection(LOD) were 0.4 μg/mL and 0.08 μg/m L for calycosin-7-O-β-D-glucoside, 0.2 μg/mL and 0.06 μg/m L for ononin, 0.4 μg/mL and 0.1 μg/mL for calycosin, 0.5 μg/m L and 0.1 μg/m L formonetion, respectively. The standard recoveries were in the range of 96.5%-104.7%. The developed method has successfully been used for the determination of four main flavonoids in Astragali Radix from various sources and can be used for identification, differentiation and quality evaluation of Astragali Radix.

金雀根、黄芪及其配伍对糖尿病肾脏疾病大鼠JNK/SAPK信号通路的影响

目的探究金雀根、黄芪及其配伍对糖尿病肾脏疾病(DKD)模型大鼠肾脏保护作用及机制。方法将60只SD大鼠随机分为正常组、模型组、恩格列净组(10 mg/kg)、金雀根组(3.1 g/kg)、黄芪组(3.1 g/kg)、金雀根加黄芪组(6.2 g/kg),除正常组外,各组大鼠行左侧肾摘除手术并腹腔注射链脲佐菌素(STZ,35 mg/kg)建立DKD模型,各组分别给予相应药物灌胃8周。期间定期检测FBG、24 h尿微量蛋白(24 h U-mAlb)。给药8周后处死大鼠,检测Scr、BUN、Cystatin C水平,HE、PAS、Masson染色观察肾组织病理改变,免疫组织化学法检测巨噬细胞标志蛋白CD68、iNOS表达,Western blot法检测肾组织JNK/SAPK通路蛋白JNK、p-JNK和TNF-α、IL-1β、ICAM-1表达,ELISA法检测血清TNF-α、IL-1β、ICAM-1水平。结果与正常组比较,模型组大鼠FBG、24 h U-mAlb、BUN、Scr、Cystatin C水平均升高(P<0.01),肾组织出现病理损伤,肾组织和血清TNF-α、IL-1β、ICAM-1水平升高(P<0.01),肾组织JNK和p-JNK蛋白表达升高(P<0.01);与模型组比较,各给药组大鼠FBG、24 h U-mAlb、BUN、Scr、Cystatin C水平均降低(P<0.05,P<0.01),肾组织病理损伤减轻,肾组织和血清TNF-α、IL-1β、ICAM-1水平降低(P<0.01),肾组织JNK和p-JNK蛋白表达降低(P<0.01);金雀根组与黄芪组比较各指标均无明显变化(P>0.05);与金雀根组或黄芪组比较,金雀根加黄芪组各指标均有不同程度的改善(P<0.05,P<0.01)。结论金雀根、黄芪及其配伍可改善DKD大鼠肾功能,抑制M1型巨噬细胞,减少炎症因子分泌,减轻肾脏病理损伤,其机制可能与抑制JNK/SAPK信号通路激活有关,金雀根与黄芪配伍药效较好。

Analysis on Genetic Diversity of Radix Astragali by ISSR Markers

Radix Astragali has been an important traditional Chinese herbal medicine for over 2000 years. It is derived from two plant species, namely, Astragalus mongholicus [Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao] and Astragalus membranaceus [Astragalus membranaceus (Fisch.) Bge.] (Leguminosae ), according to the Pharmacopoeia of the People’s Republic of China. In this study, the genetic diversity and genetic relationships of Radix Astragali in China were analyzed by Inter-Simple Sequence Repeat (ISSR) markers. A total of 25 highly polymorphic ISSR primers were selected to amplify 95 Radix Astragali samples. Among 273 DNA bands amplified, 213 are polymorphic (percentage of polymorphic bands: 78%). The average value of the amplified bands was 10.9 for each primer, and the number varied from 4 to 20. The genetic diversity of the 95 Radix Astragali samples was analyzed by using POPGENE 1.32 software. The Nei’s genetic diversity index (h) and Shannon’s information index (I ) were 0.3590 and 0.5308, respectively, which indicated the abundant genetic diversity of Radix Astragali . The level of genetic diversity in A. membranaceus (h: 0.3109, I : 0.4657) was slightly lower than that in A. mongholicus (h: 0.3364, I : 0.4969). Considering the average genetic similarity coefficient by NTSYS analysis to cluster the A. membranaceus of nine habitats and A. mongholicus of five habitats, Radix Astragali samples were clustered into two groups according to place of origin. This clustering is different from traditional clustering, which divides groups according to species. Results obtained from this study will provide a theoretical basis for the molecular study on germplasm resources of Radix Astragali .

Long-term efficacy and safety of Huangqi(Radix Astragali Mongolici)-based Traditional Chinese Medicine in diabetic peripheral neuropathy:a Meta-analysis of randomized controlled trials

OBJECTIVE:To assess the long-term effectiveness of Huangqi(Radix Astragali Mongolici,HQ)-based Traditional Chinese Medicine(TCM)in the treatment of diabetic peripheral neuropathy(DPN).METHODS:Nine databases were searched to retrieve available randomized controlled trials that compared HQbased TCM and Western Medicines in the treatment of DPN.The methodological quality of the included studies was assessed using the Cochrane bias risk tool,and RevMan 5.4 was used for data analysis.The effect estimates of interest were risk ratio(RR),mean difference(MD)or standardized mean difference(SMD)with 95%confidence interval(CI).RESULTS:The results from 48 available studies assessing 3759 patients demonstrated that cases administered HQ-based TCM[RR=1.30,95%CI(1.21,1.40),P<0.00001]or HQ-based TCM combined with Western Medicines[RR=1.25,95%CI(1.19,1.31),P<0.00001]exhibited higher total efficacy rates than individuals who received Western Medicine alone.The results showed that the HQ-based TCM group had decreased Toronto Clinical Scoring System scores[MD=-1.50,95%CI(-1.83,-1.17),P<0.00001],and reduced serum interleukin 6[SMD=-0.57,95%CI(-0.87,-0.27),P=0.0002]and tumor necrosis factors-αlevels[SMD=-0.60,95%CI(-0.95,-0.25),P=0.0009].In addition,both HQ-based TCM and HQbased TCM combined with Western Medicine increased nerve conduction velocity and decreased glycaemia compared with Western Medicine alone.In terms of blood lipids,oxidative stress and adverse drug reactions,there were no significant differences between the HQ-based TCM groups and the Western Medicine control group.CONCLUSION:The current Meta-analysis revealed that HQ-based TCM yields higher efficacy and safety than Western Medicine alone for the treatment of DPN,although further well-designed RCTs are required to validate these findings.

基于UHPLC-Q-Orbitrap-MS比较不同产地黄芪饮片的成分差异

目的探究黄芪的3个重要产地(山西浑源与朔州、甘肃渭源与岷县、陕西子洲)所产黄芪饮片的成分差异,为其基原鉴定与质量研究提供参考依据。方法用超高效液相色谱-四级杆/静电场轨道阱高分辨质谱技术(UHPLC-Q-Orbitrap-MS)测定3个不同产地黄芪饮片的化学成分。以变量投影重要性(VIP)>1、P<0.05为标准,筛选获得其显著差异成分,用SIMCA软件对所得化合物及差异化合物进行聚类分析、偏最小二乘法判别分析(partial least squares discriminant analysis,PLS-DA)。结果4-羟基肉桂酸、胱氨酸、刺芒柄花素等21个化合物在甘肃、陕西、山西3个产地黄芪之间存在显著差异,其中甘肃与山西产地的黄芪差异性成分有1个,山西与陕西产地的黄芪差异成分有11个,甘肃与陕西产地的黄芪差异成分有18个。结论基于UHPLC-QOrbitrap-MS液质联用技术及聚类分析、PLS-DA等成分分析方法所得21个差异性成分,可为不同产地及品种黄芪饮片的来源鉴定及质量控制提供理论依据。

Network pharmacology research and experimental verification of Huangqi(Astragalus Radix)and Jinyingzi(Rosae Laevigatae Fructus)in treating benign prostatic hyperplasia

Objective This study aimed to analyze the mechanism of action of Huangqi(Astragalus Radix,HQ)-Jinyingzi(Rosae Laevigatae Fructus,JYZ)in the treatment of benign prostatic hyperplasia(BPH)based on network pharmacology and to verify the prediction through animal experimentation.Methods Based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine(BATMAN-TCM)databases,and literature,the active components and related target genes of HQ and JYZ were screened.The BPH target genes were screened based on the DisGeNET and GeneGards databases,and Excel was used to merge and remove duplicates.The Perl language was used to obtain drug-BPH target genes by intersecting shared target genes.A drug-component-target gene network diagram was constructed using Cytoscape software.The drug-BPH intersection target genes were inputted into the STRING database,and the key target genes were selected according to the degree algorithm.The output formed the basis for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses to determine the potential mechanism of HQ and JYZ in BPH treatment.High,medium,and low doses of HQ and JYZ extract were used to intervene in BPH rats,and then the prostate volume,wet weight,and prostate index of the BPH rats were determined.Changes in prostate histopathology and microvessel density(MVD)were evaluated using immunohistochemistry,and the optimal HQ and JYZ extract dose was confirmed.Finally,the optimal dose was used to intervene in a BPH rat model,and AKT1 and VEGF expressions were examined by immunohistochemistry.Results Based on network pharmacology,33 active components and 772 target genes were identified from HQ and JYZ,along with 817 BPH target genes and 112 drug-BPH common target genes.Among them were 10 key target genes,including AKT1,JUN,MAPK1,IL-6,TNF,ESR1,and VEGFA.KEGG enrichment analysis revealed 135 signaling pathways,including PI3K/AKT,IL-17,TNF,p53,MAPK,VEGF,JAK-STAT,and NF-κB pathways.The animal experiment showed that HQ and JYZ significantly improved prostate volume,wet weight,prostate index,and prostate histopathology of BPH rats,reducing MVD.In addition,HQ and JYZ inhibited the expression of AKT1 and VEGF in the prostate tissue of rats,promoted epithelial cell apoptosis,and inhibited angiogenesis,consistent with the prediction.Conclusion The combination of HQ and JYZ is effective for BPH therapy through multi-compound and multi-target collaboration.Its possible mechanism in treating BPH includes regulation of AKT1,VEGF protein,PI3K/Akt,and VEGF signaling pathways related to apoptosis,angiogenesis,and inflammation,with potential for clinical use and research.

基于PINK1/MFN2/Parkin通路探讨金雀根和黄芪配伍对糖尿病肾病大鼠的影响

目的探讨金雀根和黄芪配伍对糖尿病肾病(DKD)大鼠的影响。方法将SD大鼠随机分为正常组、模型组、恩格列净组、金雀根组、黄芪组、配伍组,每组10只。采用单侧切除肾脏联合腹腔注射链脲佐菌素(STZ)复制DKD大鼠模型,造模成功后灌胃相应剂量药物8周。第0、4、8周检测24 h尿微量白蛋白(24 h U-mALB);ELISA法检测Scr、BUN、CysC、MDA水平及SOD活性;荧光探针法检测肾组织ROS表达;HE、PAS、Masson、PASM-Masson染色观察肾组织病理结构改变;免疫组织化学法检测肾组织NOX4、Drp1、MFN2、P62表达;Western blot法检测肾组织PINK1、MFN2、Parkin、LC3-Ⅱ/Ⅰ、P62、p-Drp1蛋白表达。结果与模型组比较,各给药组大鼠24 h U-mALB、BUN、Scr、CysC水平均降低(P<0.01),肾组织病理性结构损伤改善;血清和组织MDA水平降低(P<0.01),SOD活性升高(P<0.01);肾组织PINK1、MFN2、Parkin、LC3-Ⅱ/Ⅰ蛋白表达升高(P<0.05,P<0.01),p-Drp1、P62蛋白表达降低(P<0.01),其中配伍组作用优于单用药组(P<0.05,P<0.01)。结论金雀根和黄芪配伍可能是通过调控PINK1/MFN2/Parkin通路改善线粒体动力学,激活线粒体自噬,抑制氧化应激,减轻肾脏病理损伤,改善DKD大鼠肾功能。

Progress of Radix Astragali and Radix Angelicae Sinensis in the treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis(IPF)is a chronic,progressive,fibrotic interstitial lung disease.Current treatment options for IPF are limited.Radix Astragali(RA)and Radix Angelicae Sinensis(RAS),according to 5:1 ratio composed of Danggui Buxue decoction(DGBXD),which have played an essential role in the treatment of IPF.This article reviewed the experimental research,clinical research,and progress of RA and RAS(DGBXD)treating IPF to provide a deeper scientific basis for the future experimental research and clinical research.

基于心肌重塑和心功能标志物NT-proBNP、H-FABP水平探讨黄芪注射液治疗慢性心力衰竭的作用

【目的】基于心肌重塑和心功能标志物N端脑钠肽前体(NT-proBNP)、心型脂肪酸结合蛋白(H-FABP)水平探讨黄芪注射液治疗慢性心力衰竭的作用。【方法】将80例心气虚型慢性心力衰竭患者随机分为对照组和研究组,每组各40例。对照组给予西医常规治疗,研究组在对照组的基础上给予黄芪注射液治疗,疗程为1周。观察2组患者治疗前后Lee氏心衰计分、中医证候积分、明尼苏达心力衰竭生活质量调查问卷(MLHFQ)评分及6 min步行距离的变化情况,检测2组患者治疗前后左室射血分数(LVEF)、每搏输出量(SV)和左室舒张末期内径(LVEDD)等心功能指标以及血清NT-proBNP、H-FABP的水平变化,并评估2组患者的临床疗效。【结果】(1)疗效方面,治疗1周后,研究组的总有效率为90.00%(36/40),对照组为62.50%(25/40),组间比较(χ^(2)检验),研究组的疗效明显优于对照组(P<0.01)。(2)结局指标方面,治疗后,2组患者的Lee氏心衰计分、中医证候积分及MLHFQ评分均较治疗前明显下降(P<0.01),且研究组的下降幅度均明显优于对照组(P<0.01)。(3)6 min步行距离方面,治疗后,2组患者的6 min步行距离均较治疗前明显增加(P<0.05或P<0.01),且研究组的增加幅度明显优于对照组(P<0.05)。(4)实验室指标方面,治疗后,2组患者的血清NT-proBNP、H-FABP水平均较治疗前明显下降(P<0.01),且研究组的下降幅度均明显优于对照组(P<0.01)。(5)心功能指标方面,治疗后,2组患者的LVEF、SV水平均较治疗前明显升高(P<0.01),且研究组的升高幅度均明显优于对照组(P<0.01);而2组患者的LVEDD治疗前后及治疗后组间比较,差异均无统计学意义(P>0.05)。【结论】在西医常规治疗基础上联合黄芪注射液治疗心气虚型慢性心力衰竭患者疗效确切,能有效缓解患者临床症状,改善患者心功能,提高患者生活质量。

Potential mechanism of Astragali radix-Angelicae sinensis radix in the treatment of spinal cord injury based on network pharmacology and molecular docking

Objective:Using network pharmacology and molecular docking technology to explore the possible mechanism of Huangqi(Astragali radix)-Danggui(Angelicae sinensis radix)on the treatment of spinal cord injury.Methods:The active components and the targets related to Astragali radix-Angelicae sinensis radix were screened out on the Traditional Chinese Medicine Systems Pharmacology database.Genes of spinal cord injury were searched by Genecards and the Online Mendelian Inheritance in Man databases.The intersection targets between herbs and diseases were obtained through online Venn diagrams.A components-targets-pathways network was established on Cytoscape 3.8.1 software.The STRING database was used to construct the intersection protein interaction network and screen out core targets.Gene Ontology biological processes and enrichment analysis based on the Kyoto Encyclopedia of Genes and Genes of intersection proteins were performed via DAVID database.Finally,the molecular docking with key components and core targets were performed in AutoDock software.Results:The 22 chemical components including quercetin,kaempferol were collected from Astragali radix-Angelicae sinensis radix.It acts on 110 targets,and interleukin-6,tumor necrosis factor,mitogen-activated protein kinase,tumor antigen p53 were considered as the major targets.50 pathways like Interleukin-17 signaling pathway,tumor necrosis factor signaling pathway and mitogen-activated protein kinase signaling pathway participate in biological processes such as positive transcription regulation and lipopolysacchanide response.The molecular docking revealed that the core targets had stronger binding activity with its corresponding active components.Conclusion:Astragali radix-Angelicae sinensis radix has the characteristics of multi-component,multi-target,and multi-pathway effects in treating spinal cord injury.Its potential mechanism may be related to preventing inflammation,improving microcirculation,inhibiting neuronal apoptosis,protecting damaged nerve cells and promoting nerve repair and regeneration.

Transcriptome Analysis of Gene in Mouse M-1 Cells Revealing the Functional Mechanism of Astragali Radix Extract

Astragali Radix (AR), the dried root of legumes, belongs to the Qi-invigorating herbs in traditional Chinese medicine and plays an important role in the treatment of many diseases. In order to understand the mechanism of action of AR extract. We used AR extract to treat M-1, mouse kidney cells, and used transcriptome sequencing technology to detect the genomic transcription level of the cells under the action of AR at different concentrations and times. The results showed that after a low concentration of AR treatments on the cells, the expression of genes related to cell growth and cellular immune response changed significantly, among which multiple genes are related to mitochondrial function, while high concentrations of AR affected the expression of histones and disease-related genes. It showed that the low concentration of AR extract can achieve the effect of invigorating Qi by regulating the function of mitochondria. In addition, several important genes and pathways were identified as potential targets of AR activation. The research not only clarified the main molecular biological mechanism of AR invigorating Qi, but also provided experimental basis and cellular physiology reference for the further clinical application of AR.