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Baicalin Promotes Apoptosis of Human Medullary Breast Cancer via the ERK/p38 MAPK Pathway 黄芩苷通过 ERK/p38 MAPK 通路促进人髓样乳腺癌细胞凋亡
IF 0.7 4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2024-01-04 DOI: 10.1177/09731296231215134
Xianyong Li, Qianqian Tang, Wenwei Li, Dongzai Zhan, Xiangyang Fang, Shengchao Huang, Xiaorong Shui, Jianwen Li
Objectives: The present study aims to examine the effects of baicalin on the human medullary breast carcinoma (MBC) cell line Bcap-37 and to determine whether baicalin regulates Bcap-37 cell apoptosis through the ERK/p38 mitogen-activated protein kinase (MAPK) signaling pathway. Materials and Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Transwell assay were utilized to measure the effects of baicalin on the proliferation and migration ability of Bcap-37 cells, respectively. Flow cytometer analysis was implied to detect the effects of baicalin on Bcap-37 cell apoptosis. Real-time quantitative polymerase chain reaction (RT-PCR) was conducted to observe the influence of baicalin on mRNA expressions of apoptosis-related genes. Western blot was executed to further explore the action of baicalin on apoptosis-related proteins. PD98059 (a specific inhibitor of ERK) and SB203580 (a specific inhibitor of p38 MAPK) were used to further clarify the intrinsic mechanism of baicalin regulating apoptosis in Bcap-37 cells. Results: Compared with the control group, baicalin significantly inhibits the proliferation activity of Bcap-37 cells in a concentration- and time-dependent manner, with a p-value < 0.05. The transwell assay indicated that the migration viability of cells decreased further, followed by the increased concentration of baicalin, and the p-value had a statistical difference. Besides, flow cytometry was conducted to assess the effects of baicalin on the early and late apoptosis rates of Bcap-37 cells, and results showed that baicalin highly promoted the apoptosis level both at the early and late stages with a statistical difference in a concentration-dependent manner ( p < 0.05). Results of RT-PCR presented that, compared with the control group, baicalin significantly activated the mRNA expression of Bax, p38, and p-ERK1 and abolished the mRNA expression of Bcl-2 in every dosing group in a concentration-dependent way ( p < 0.05). Western blot exhibited that, compared with the control group, baicalin promoted the protein expression of caspase-3, caspase-9, Bax, p38, P-ERK, and p53 while playing an opposite function to Bcl-2 in each dosing group ( p values have statistical differences). At last, PD98059 and SB203580 were applied to explore the potential mechanism of baicalin in apoptosis promotion. And results revealed that, compared with the group treated with baicalin alone, protein expression of Bax, p38, p-ERK, caspase-3, and caspase-9 was downregulated obviously in the group treated with both baicalin and PD98059 or SB203580 ( p < 0.05). The p53 expression inhibition showed a difference only when compared to the group adding PD98059. Compared with the blank group, a statistical difference was only observed in Bcl-2 expression in the group treated with baicalin in combination with PD98059 or SB203580 ( p < 0.05). Interestingly, a p53 expression difference was only displayed between the blank group and the g
研究目的本研究旨在探讨黄芩苷对人类髓样乳腺癌(MBC)细胞系 Bcap-37 的影响,并确定黄芩苷是否通过 ERK/p38 丝裂原活化蛋白激酶(MAPK)信号通路调节 Bcap-37 细胞凋亡。材料与方法:利用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)试验和 Transwell 试验分别测定黄芩苷对 Bcap-37 细胞增殖和迁移能力的影响。流式细胞仪分析用于检测黄芩苷对 Bcap-37 细胞凋亡的影响。实时定量聚合酶链反应(RT-PCR)观察黄芩苷对细胞凋亡相关基因 mRNA 表达的影响。通过 Western 印迹进一步探讨黄芩苷对细胞凋亡相关蛋白的作用。使用ERK特异性抑制剂PD98059和p38 MAPK特异性抑制剂SB203580进一步阐明黄芩苷调节Bcap-37细胞凋亡的内在机制。结果与对照组相比,黄芩苷明显抑制 Bcap-37 细胞的增殖活性,且呈浓度和时间依赖性,P 值小于 0.05。透孔试验表明,黄芩苷浓度增加后,细胞的迁移活力进一步下降,P 值有统计学差异。此外,流式细胞术检测了黄芩苷对 Bcap-37 细胞早期和晚期凋亡率的影响,结果表明黄芩苷对早期和晚期细胞凋亡水平均有显著的促进作用,其浓度依赖性有统计学差异(p < 0.05)。RT-PCR结果表明,与对照组相比,黄芩苷能显著激活各剂量组Bax、p38和p-ERK1的mRNA表达,并抑制Bcl-2的mRNA表达,且呈浓度依赖性(P < 0.05)。Western blot显示,与对照组相比,黄芩苷促进了各剂量组中caspase-3、caspase-9、Bax、p38、P-ERK和p53的蛋白表达,而对Bcl-2的蛋白表达起着相反的作用(p值有统计学差异)。最后,应用PD98059和SB203580探讨了黄芩苷促进细胞凋亡的潜在机制。结果显示,与单用黄芩苷处理组相比,同时使用黄芩苷和 PD98059 或 SB203580 处理组的 Bax、p38、p-ERK、caspase-3 和 caspase-9 蛋白表达明显下调(P < 0.05)。只有与添加 PD98059 的组相比,p53 表达的抑制率才有差异。与空白组相比,只有黄芩苷与 PD98059 或 SB203580 联合治疗组的 Bcl-2 表达有统计学差异(p < 0.05)。有趣的是,只有空白组与黄芩苷和 SB203580 治疗组的 p53 表达存在差异(p < 0.05)。结论我们的研究发现,黄芩苷能抑制 Bcap-37 细胞的增殖和迁移能力。此外,黄芩苷还能通过 ERK/p38 MAPK 信号通路诱导细胞凋亡。
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引用次数: 0
Biological Control of Ustilaginoidea virens Using Chelerythrine Suspension 使用螯合霉素悬浮剂生物防治 Ustilaginoidea virens
IF 0.7 4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2024-01-04 DOI: 10.1177/09731296231217551
Qinghui Wei, Weifeng Song, Xinmin Li, Min Zhao
Background: High efficiency, low toxicity, and environmentally safe pesticides are increasingly being sought and developed to ensure sustainable development and high-yield agricultural production. Chelerythrine has strong inhibitory effects against the mycelial growth of crop pathogens such as Fusarium oxysporum, Anthrax, and grey mold. Our previous studies have shown that chelerythrine inhibits fungus spore germination by up to 86.7% and induces the apoptosis of Ustilaginoidea virens cells. The application of chelerythrine as a green biological pesticide would not only enhance agricultural production but also enhance ecological protection. Materials and Methods: The formulation of a chelerythrine suspension concentrate was selected. According to the ratio of experimental design requirements to preparation sample, six groups were set up in the field assay; the first spraying was performed approximately 7 days before the rice rupture period, and the second spraying was performed after 10 days. The control effect was investigated at the milk-ripe stage. The present study preliminarily investigates the safety of chelerythrine as a pesticide using the oral acute toxicity test for mice. Results: In the present study, the effect of chelerythrine as the main ingredient in suspension concentrate formulations and its field effect on rice false smut (RFS) was investigated. The pesticide in the suspending agent was sprayed twice and had superior effects with regard to the prevention and control of RFS in the field. The control effect was 95.88% at an application rate of 192 mL/ha, with low residue, environmentally safe, and low resistance characteristics. An acute toxicity test following intragastric administration in mice showed that the LD50 of chelerythrine suspension was 1580 mg·kg−1, which was much lower than those of other low-toxicity commercial pesticides. Conclusion: Chelerythrine suspension was a low-toxicity agent and exhibited the characteristics of an environmentally friendly plant pesticide. The application of chelerythrine suspension could facilitate the achievement of the goal of pesticide reduction efficiency.
背景:为了确保农业的可持续发展和高产,人们越来越多地寻求和开发高效、低毒、对环境安全的农药。白屈菜红碱对作物病原体(如镰刀菌、炭疽病和灰霉病)的菌丝生长有很强的抑制作用。我们之前的研究表明,白屈菜红碱对真菌孢子萌发的抑制率高达 86.7%,并能诱导 Ustilaginoidea virens 细胞凋亡。应用红霉素作为绿色生物农药,不仅能提高农业生产,还能加强生态保护。材料与方法:选择了红霉素悬浮浓缩液的配方。根据实验设计要求与制备样品的比例,田间试验设 6 组,第一次喷药在水稻破口期前约 7 天进行,第二次喷药在水稻破口期后 10 天进行。对照效果在乳熟期进行调查。本研究使用小鼠口服急性毒性试验初步调查了作为杀虫剂的白屈菜碱的安全性。研究结果本研究调查了作为悬浮浓缩制剂主要成分的白屈菜红碱对水稻假穗病(RFS)的影响及其田间效果。悬浮剂中的农药经两次喷洒后,在田间对 RFS 的防控效果显著。施药量为 192 毫升/公顷时,防治效果为 95.88%,具有低残留、环境安全和低抗性的特点。小鼠胃内给药急性毒性试验表明,白屈菜红碱悬浮剂的半数致死剂量为 1580 毫克-千克-1,远低于其他低毒性商用农药。结论白屈菜红碱悬浮剂是一种低毒性药剂,具有环境友好型植物杀虫剂的特点。应用白屈菜红碱悬浮剂有助于实现农药减量增效的目标。
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引用次数: 0
A Review on Exploring the Phytochemical and Pharmacological Significance of Indigofera astragalina 探索黄芪的植物化学和药理意义综述
IF 0.7 4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2024-01-03 DOI: 10.1177/09731296231215911
V. Rajani, S. Umadevi, C. Naga Raju
Indigofera astragalina, a versatile medicinal plant, has gained significant attention because of its rich phytochemical composition and diverse therapeutic properties. I. astragalina contains sterols, phenolics, alkaloids, and flavonoids, making it ideal for a variety of therapeutic purposes. In this review, an in-depth look at the phytoconstituents and their biological activity is presented. The anti-microbial properties of the plant extracts have been demonstrated against drug-resistant Enterococcus and Staphylococcus aureus strains resistant to vancomycin and methicillin. Moreover, the plant exhibits moderate to potent anti-protozoal activity against Trypanosoma brucei and weak anti-protozoal activity against Plasmodium falciparum. In various cancer cell lines, astragalin extracts have demonstrated significant cytotoxic effects, suggesting their potential as anti-cancer agents. Due to its high phenolic content, the plant has an antioxidant effect, which has contributed to its traditional use for managing oxidative stress. In addition, I. astragalina is packed with essential amino acids, minerals (such as iron, manganese, and zinc), and vitamins. The comprehensive analysis of I. astragalina emphasizes its important role in drug discovery, nutrition, and healthcare, as well as its tremendous therapeutic potential.
黄芪(Indigofera astragalina)是一种用途广泛的药用植物,因其丰富的植物化学成分和多样的治疗特性而备受关注。黄芪含有甾醇、酚类、生物碱和黄酮类化合物,是多种治疗用途的理想选择。本综述深入探讨了黄芪的植物成分及其生物活性。该植物萃取物的抗微生物特性已被证实可抗耐万古霉素和甲氧西林的耐药肠球菌和金黄色葡萄球菌。此外,该植物对布氏锥虫具有中度到强效的抗原虫活性,对恶性疟原虫的抗原虫活性较弱。在各种癌细胞系中,黄芪提取物都表现出显著的细胞毒性作用,表明其具有抗癌潜力。由于酚类物质含量高,黄芪具有抗氧化作用,这也是黄芪在传统上用于控制氧化应激的原因之一。此外,黄芪还富含人体必需的氨基酸、矿物质(如铁、锰和锌)和维生素。对黄芪的全面分析强调了它在药物发现、营养和保健方面的重要作用,以及巨大的治疗潜力。
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引用次数: 0
Calycosin Protects against Focal Cerebral Ischemia/Reperfusion Injury via Inhibiting the HMGB1/TLR4/NF-κB Signaling Pathway 萼萼素能通过抑制 HMGB1/TLR4/NF-κB 信号通路保护局灶性脑缺血/再灌注损伤
IF 0.7 4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-12-30 DOI: 10.1177/09731296231215158
Yong Wang, Shifeng Wang, Peng Zhang, Shengjun Xiao, Huizhong Shi, Zihan Chen
Background: The rate of disability and mortality associated with cerebral ischemia/reperfusion injury (CIRI) is high due to limited treatment options, making it a major challenge to clinical management. Calycosin is a biologically active compound hostile to inflammatory, neuroprotective, and tumor effects. Whether calycosin has an ischemia/reperfusion effect or mechanism is unclear. Materials and Methods: For in vivo experiments, we randomly divided rats into five groups: blank control group, middle cerebral artery occlusion/reperfusion (MCAO/R) surgical group, calycosin + MCAO/R group (5 mg/kg), calycosin + MCAO/R group (10 mg/kg), and calycosin + MCAO/R group (20 mg/kg). Molding of the middle cerebral artery was performed. Calycosin’s neuroprotective effects were evaluated using the neurological deficit score, brain edema rate, and cerebral infarct volume. For in vitro experiments, we divided PC12 cells into five groups: blank control group, oxygen and glucose deprivation/reperfusion (OGD/R) group, calycosin + OGD/R group (1 × 10−6 mol/L), calycosin + OGD/R group (4 × 10−6 mol/L), and calycosin + OGD/R group (16 × 10−6 mol/L). The optimal concentration of calycosin on PC12 cells was determined using the cell counting kit-8 (CCK-8) cell activity assay. The expression of nuclear factor kappa-B (NF-κB)-related factors was detected using real-time quantitative polymerase chain reaction and Western blotting. Results: In rats, the MCAO/R model resulted in elevated neurological deficit scores, increased brain infarct volumes, and increased brain edema rates. The OGD/R model decreased rat adrenal pheochromocytoma (PC12) cell activity, and calycosin had a significant cerebral protective effect on PC12 cells under OGD/R conditions. In addition, calycosin can inhibit the activation of the NF-κB pathway, and its neuroprotective effect may be related to the NF-κB pathway. Conclusion: Calycosin can reduce focal CIRI, and the neuroprotective effect of calycosin may be related to the inhibition of the high mobility group protein 1/toll-like receptor 4 (TLR4)/NF-κB signaling pathways.
背景:由于治疗方法有限,脑缺血再灌注损伤(CIRI)的致残率和死亡率都很高,成为临床治疗的一大挑战。钙苷是一种生物活性化合物,具有抗炎、保护神经和肿瘤的作用。钙苷是否具有缺血/再灌注效应或机制尚不清楚。材料与方法:在体内实验中,我们将大鼠随机分为五组:空白对照组、大脑中动脉闭塞/再灌注(MCAO/R)手术组、钙苷+MCAO/R组(5 mg/kg)、钙苷+MCAO/R组(10 mg/kg)和钙苷+MCAO/R组(20 mg/kg)。对大脑中动脉进行造模。使用神经功能缺损评分、脑水肿率和脑梗死体积评估卡利科辛的神经保护作用。体外实验中,我们将 PC12 细胞分为五组:空白对照组、缺氧缺糖再灌注(OGD/R)组、钙苷 + OGD/R 组(1 × 10-6 mol/L)、钙苷 + OGD/R 组(4 × 10-6 mol/L)和钙苷 + OGD/R 组(16 × 10-6 mol/L)。使用细胞计数试剂盒-8(CCK-8)细胞活性测定法确定了钙黄绿素对 PC12 细胞的最佳浓度。采用实时定量聚合酶链反应和 Western 印迹法检测核因子卡巴-B(NF-κB)相关因子的表达。结果在大鼠中,MCAO/R 模型导致神经功能缺损评分升高、脑梗塞体积增大和脑水肿率升高。OGD/R模型降低了大鼠肾上腺嗜铬细胞瘤(PC12)细胞的活性,而在OGD/R条件下,钙黄素对PC12细胞有显著的脑保护作用。此外,钙黄素还能抑制NF-κB通路的激活,其神经保护作用可能与NF-κB通路有关。结论钙松素可减轻局灶性CIRI,其神经保护作用可能与抑制高迁移率基团蛋白1/类托尔受体4(TLR4)/NF-κB信号通路有关。
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引用次数: 0
Mechanism of Schisandra chinensis in Treatment of Insomnia by Sleep–Wake Cycle Based on Network Pharmacology 基于网络药理学的五味子通过睡眠-觉醒周期治疗失眠的机制
IF 0.7 4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-12-26 DOI: 10.1177/09731296231216171
Ke Liang, Tie Qiao, Ning Sun, Ning Jiang, Fangxiao Li, Haoxuan Jiang, Yutong Jiang
Schisandra chinensis (SC) is the dried fruit of SC of Magnoliaceae, which has been used to treat many diseases, such as asthma, cough, insomnia, spontaneous sweating, and so on, for more than 2000 years. Lignans are important active ingredients of SC for improving insomnia, but it is not clear the exact material basis and mechanism of action. This study aimed to discover the mechanism by which SC treats insomnia through network pharmacology. It was used to study the chemical constituents of SC by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). The SC–Insomnia network and the protein–protein interaction (PPI) network were set up using network pharmacology to research the mechanisms by which SC treats insomnia. The targets found in network pharmacology were proven by enzyme-linked immunosorbent assays (ELISA) and real-time polymerase chain reactions (RT-PCR). It identified 26 monomer compounds, all of which were lignans. From the SC–Insomnia and PPI networks, seven main active lignans were discovered, which could play an important part in treating insomnia, along with 11 targets that play an important part in the sleep−wake cycle. It was verified by the expression of GABA with ELISA and GABRA1 with RT-PCR. Based on network pharmacology, the mechanism by which SC treats insomnia is through the sleep–wake cycle. It was a foundation to rationally apply SC for treating insomnia in the clinic.
五味子(Schisandra chinensis,SC)是木兰科植物五味子的干燥果实,2000 多年来一直被用于治疗多种疾病,如哮喘、咳嗽、失眠、自汗等。木犀草木脂素是木犀草改善失眠的重要活性成分,但其确切的物质基础和作用机制尚不清楚。本研究旨在通过网络药理学发现 SC 治疗失眠的机制。该研究采用超高效液相色谱-四极杆飞行时间质谱(UPLC-QTOF-MS)对SC的化学成分进行了研究。利用网络药理学建立了SC-失眠网络和蛋白质-蛋白质相互作用(PPI)网络,以研究SC治疗失眠的机制。通过酶联免疫吸附试验(ELISA)和实时聚合酶链反应(RT-PCR)证实了网络药理学中发现的靶点。研究发现了 26 种单体化合物,全部都是木酚素。从 SC-Insomnia 和 PPI 网络中发现了七种主要的活性木酚素,它们可能在治疗失眠症中发挥重要作用,同时还发现了 11 个在睡眠-觉醒周期中发挥重要作用的靶标。通过酶联免疫吸附法检测 GABA 的表达,通过 RT-PCR 检测 GABRA1 的表达,验证了这一点。根据网络药理学,SC 治疗失眠症的机制是通过睡眠-觉醒周期。这为在临床上合理应用SC治疗失眠症奠定了基础。
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引用次数: 0
Gentianella turkestanorum (Gand.) Holub, a Chinese Herbal Medicine that can Alleviate T2DM in Db/db Mice, and its Active Mechanism of Action 能缓解 Db/db 小鼠 T2DM 的中药龙胆草及其活性作用机制
IF 0.7 4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-12-26 DOI: 10.1177/09731296231215577
Ying Wei, Jiaxin Sun, Liya Su, Tunhai Xu
The increasing prevalence of type 2 diabetes mellitus (T2DM) on a global scale has created a pressing demand for novel treatments. Gentianella turkestanorum (Gand.) Holub, a traditional Chinese herbal medicine, has been found to possess hypoglycemic effects. However, the mechanism of its action remains unclear. This study was to investigate the impact and mechanism of G. turkestanorum’s water extract (WEG) in reducing insulin resistance (IR) in T2DM. Db/db mice were administered WEG for 8 weeks, during which their body weight, blood glucose (BG), oral glucose tolerance test, islet tolerance test, fasting insulin, total cholesterol, triglyceride, high-density lipoprotein, and low-density lipoprotein were monitored. Additionally, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in db/db mice were measured using enzyme-linked immunosorbent assay (ELISA). The study also evaluated the impact of WEG on liver injury through hematoxylin-eosin staining. The expression levels of key proteins and genes in both insulin signaling and inflammation-related pathways were detected using western blotting and real-time quantitative polymerase chain reaction. WEG has the potential to regulate glycolipid metabolism, reduce inflammation, and alleviate IR. The mechanism of action may involve promoting the insulin signaling pathway and inhibiting inflammation. Gentianella turkestanorum could be a viable treatment option for T2DM and IR.
2 型糖尿病(T2DM)在全球范围内的发病率不断上升,对新型治疗方法的需求十分迫切。龙胆草(Gentianella turkestanorum (Gand.) Holub)是一种传统中药材,具有降血糖作用。然而,其作用机制仍不清楚。本研究旨在探讨土鳖虫水提取物(WEG)在降低 T2DM 胰岛素抵抗(IR)方面的影响和机制。给 Db/db 小鼠服用 WEG 8 周,监测其体重、血糖(BG)、口服葡萄糖耐量试验、胰岛耐量试验、空腹胰岛素、总胆固醇、甘油三酯、高密度脂蛋白和低密度脂蛋白。此外,还使用酶联免疫吸附试验(ELISA)测定了 db/db 小鼠体内肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的水平。研究还通过苏木精-伊红染色评估了WEG对肝损伤的影响。研究人员还利用西部印迹法和实时定量聚合酶链反应检测了胰岛素信号转导和炎症相关通路中关键蛋白和基因的表达水平。WEG具有调节糖脂代谢、减轻炎症和缓解红外热的潜力。其作用机制可能涉及促进胰岛素信号通路和抑制炎症。龙胆草可能是治疗 T2DM 和 IR 的一种可行方法。
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引用次数: 0
Analysis of Shared Mechanisms and Chinese Herbal Medicines Between Osteoporosis and Type 2 Diabetes 骨质疏松症与 2 型糖尿病的共同机制及中药分析
IF 0.7 4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-12-23 DOI: 10.1177/09731296231215568
Huawen Yang, Fanwei Luo, Zhongyu Xiong
Osteoporosis (OP) and type 2 diabetes (T2D) are commonly encountered metabolic disorders in clinical practice, but the comorbidity mechanism has not been clarified. This study explored the underlying mechanisms for utilizing bioinformatics methods. Furthermore, it predicted traditional Chinese medicines (TCMs) with preventive and therapeutic effects. GSE35958 and GSE43950 were retrieved and downloaded from the GEO database, and differential expression analysis was performed to identify differentially expressed genes (DEGs) with similar expression patterns in OP and T2D. Then, the common DEGs were uploaded to the STRING database to construct a protein interaction network. Enrichment analysis of the screened genes was conducted using R language packages. Relevant TCMs were searched and screened based on gene targets using the Encyclopedia of traditional Chinese medicine (ETCM) database. Molecular docking of active ingredients of the TCMs and related gene targets was performed using AutoDock Vina software. By analyzing the gene expression microarrays, GSE35958 and GSE43950, 34 genes with the same expression pattern shared by OP and T2D were identified. Among these genes, 32 were upregulated and two were downregulated. Protein interaction network analysis revealed that tumor necrosis factor, vascular endothelial growth factor A, and CD44 might play key roles in the co-pathogenesis of T2D and OP. TCMs, including Wolfberry (枸杞), Ginseng (人参), and Yam (山药), were screened based on key genes. Molecular docking results demonstrated binding activity between all active ingredients and the related gene targets. This study explored the potential molecular co-pathogenesis of OP and T2D through bioinformatic analysis and preliminarily predicted traditional herbal medicines that may have preventive and therapeutic effects.
骨质疏松症(OP)和 2 型糖尿病(T2D)是临床上常见的代谢性疾病,但其合并机制尚未明确。本研究利用生物信息学方法探索了其潜在机制。此外,研究还预测了具有预防和治疗作用的传统中药。研究人员从 GEO 数据库中检索并下载了 GSE35958 和 GSE43950,并进行了差异表达分析,以确定 OP 和 T2D 中具有相似表达模式的差异表达基因(DEGs)。然后,将共同的 DEGs 上传到 STRING 数据库,构建蛋白质相互作用网络。使用 R 语言包对筛选出的基因进行富集分析。利用中药百科全书(ETCM)数据库根据基因靶点搜索和筛选相关中药。使用 AutoDock Vina 软件对中药有效成分和相关基因靶点进行分子对接。通过分析基因表达微阵列 GSE35958 和 GSE43950,确定了 34 个基因在 OP 和 T2D 中具有相同的表达模式。在这些基因中,32个基因上调,2个基因下调。蛋白质相互作用网络分析显示,肿瘤坏死因子、血管内皮生长因子 A 和 CD44 可能在 T2D 和 OP 的共同发病机制中发挥关键作用。根据关键基因对枸杞、人参和山药等中药进行了筛选。分子对接结果表明,所有有效成分都与相关基因靶点具有结合活性。本研究通过生物信息学分析探讨了 OP 和 T2D 的潜在分子共发病机制,并初步预测了可能具有预防和治疗作用的传统中药。
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引用次数: 0
Bioinformatics Analyzes the Mechanisms of Codonopsis Radix in Treating Ovarian Cancer 生物信息学分析党参治疗卵巢癌的机制
IF 0.7 4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-12-15 DOI: 10.1177/09731296231204151
Zhenhui Chen, Yan Zhou, Yun Shen, Yanrong Ye
Codonopsis Radix (CR), a renowned traditional Chinese medicine (TCM) formula, has been widely applied for its immunomodulatory, antitumor, antioxidant, neuroprotective, and antiviral effects. However, the multitarget mechanism of CR in ovarian cancer (OC) remains to be elucidated. We applied bioinformatics and molecular docking techniques to explore possible pharmacological targets, bioactivities, and molecular mechanisms of CR for OC treatment. We identified 40 common genes associated with CR and OC and obtained core genes through a protein–protein interaction network. Enrichment analysis revealed that mitochondrial electron transport was the key biological process involved. Based on the analysis, we selected estrogen receptor 1 (ESR1) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) as the key target genes for molecular docking. In the final verification analysis, we evaluated the effect of the PIK3CA mutation on the survival rate of patients with OC and determined that the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway was the key pathway in the OC treatment. These results suggest that CR inhibits the activity of mitochondrial complex II, reduces adenosine triphosphate (ATP) production by mitochondrial electron transport, inhibits PI3K/AKT phosphorylation, and promotes apoptosis in OC cells.
党参(CR)是一种著名的传统中药配方,因其免疫调节、抗肿瘤、抗氧化、神经保护和抗病毒作用而被广泛应用。然而,CR在卵巢癌(OC)中的多靶点作用机制仍有待阐明。我们应用生物信息学和分子对接技术探索了 CR 治疗卵巢癌的可能药理靶点、生物活性和分子机制。我们确定了 40 个与 CR 和 OC 相关的常见基因,并通过蛋白相互作用网络获得了核心基因。富集分析表明,线粒体电子传递是所涉及的关键生物过程。根据分析结果,我们选择了雌激素受体 1(ESR1)和磷脂酰肌醇-4,5-二磷酸 3-激酶催化亚基α(PIK3CA)作为分子对接的关键目标基因。在最后的验证分析中,我们评估了 PIK3CA 突变对 OC 患者生存率的影响,并确定磷脂肌醇 3 激酶/蛋白激酶 B(PI3K/AKT)通路是 OC 治疗的关键通路。这些结果表明,CR能抑制线粒体复合体II的活性,减少线粒体电子传递产生的三磷酸腺苷(ATP),抑制PI3K/AKT磷酸化,促进OC细胞凋亡。
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引用次数: 0
Auraptene Alleviates Paclitaxel-induced Neuropathy in Mice 金合欢烯能缓解紫杉醇诱导的小鼠神经病变
IF 0.7 4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-12-13 DOI: 10.1177/09731296231198573
Zihong Cong, Jun Wang, M. Hashemzaei, Suiyun Xu
Paclitaxel administration causes peripheral neuropathy. Auraptene is a natural bioactive monoterpene with anti-inflammatory and anti-neuropathic effects that is widely used. We aimed to study auraptene effects on paclitaxel-induced neuropathy. This study was comprised of two steps of evaluation of the preventive and treatment effects of auraptene in mice. In the first step, mice were randomly allocated into three groups of six animals, including the negative control (NEG CTL): animals injected with paclitaxel (PTX) together with normal saline, PTX (paclitaxel 2 mg/kg given on days 1, 3, 5, and 7), and PREVENTION: PTX + auraptene 100 mg/kg on days 1, 3, 5, and 7. In the second step, animals were allocated into six groups of six: NEG CTL (normal saline), PTX (paclitaxel 10 mg/kg given on days 1, 3, 5, and 7), PTX AUR (PTX + auraptene 50, 75, and 100 mg/kg), and a positive control (PTX-treated animals receiving imipramine 10 mg/kg). Intraperitoneal injection of PTX 2 mg/kg on days 1, 3, 5, and 7 was used in order to induce neuropathy. In both steps of the study, a hot plate test was done on day 7 in order to determine the response to heat. After the scarification of animals, the interleukin-6 (IL-6) level in the sciatic nerve was assessed by western blotting. In the preventive group, auraptene could reduce hyperalgesia significantly. In the treatment step, the AUR 100 mg/kg compared to NEG CTL groups had significantly increased heat latency. The expression of IL-6 protein in the sciatic nerve was remarkably decreased in both the preventive and treatment groups compared to NEG CTL. Taken together, our results confirmed that AUR could decrease paclitaxel-induced hyperalgesia in mice and IL-6 protein content in sciatic nerve samples.
紫杉醇会导致周围神经病变。金合欢烯是一种天然生物活性单萜,具有抗炎和抗神经病变的作用,已被广泛使用。我们旨在研究金合欢萜对紫杉醇诱导的神经病变的影响。这项研究包括两个步骤,分别评估枳椇烯对小鼠的预防和治疗效果。第一步,将小鼠随机分为三组,每组六只,包括阴性对照组(NEG CTL):注射紫杉醇(PTX)和生理盐水;PTX(紫杉醇 2 mg/kg,第 1、3、5 和 7 天注射);预防组:PTX + 奥拉庚定 100 mg/kg,第 1、3、5 和 7 天注射。第二步,将动物分为六组,每组六只:NEG CTL(普通生理盐水)、PTX(紫杉醇 10 毫克/千克,第 1、3、5 和 7 天给药)、PTX AUR(PTX + 痩素 50、75 和 100 毫克/千克)和阳性对照组(PTX 治疗动物接受咪唑安定 10 毫克/千克)。在第 1、3、5 和 7 天腹腔注射 2 毫克/千克 PTX,以诱导神经病变。研究的两个步骤都在第 7 天进行热板试验,以确定动物对热的反应。动物瘢痕化后,用 Western 印迹法评估坐骨神经中的白细胞介素-6(IL-6)水平。在预防组中,枳实苷能显著减轻痛觉减退。在治疗步骤中,与NEG CTL组相比,AUR 100 mg/kg组的热潜伏期明显增加。与 NEG CTL 组相比,预防组和治疗组坐骨神经中 IL-6 蛋白的表达均明显降低。综上所述,我们的研究结果证实,AUR可降低紫杉醇诱导的小鼠痛觉减退和坐骨神经样本中IL-6蛋白的含量。
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引用次数: 0
Lactobacillus plantarum Enhanced the Cardioprotective Efficacy of Arctiin in Isoproterenol Cardiac Injury in BALB/c Mice 植物乳杆菌增强了阿克替林对 BALB/c 小鼠异丙肾上腺素心肌损伤的保护作用
IF 0.7 4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-12-11 DOI: 10.1177/09731296231211453
Kun Jiang, Yanjun Jia, T. Alahmadi, S. Hussein-Al-Ali, Yajing Wei
Isoproterenol is a drug used for the treatment of bradycardia that has many side effects due to its non-selective β-adrenoceptor agonist properties. In this study, we evaluated an in vivo experimental model for isoproterenol (ISO) cardiac injury using BALB/c mice and protective treatment with a combined optimized dose of Arctiin (AR) and Lactobacillus plantarum (LP) (ARLP; 30 mg/kg b.w. AR and viable 106 CFU/mL LP p.o.) together. Isoproterenol causes cardiac injury in many instances. Arctiin is a naturally occurring lignin glycoside present in many herbal medicinal plants that has many beneficial effects for humans. Lactobacillus plantarum is yet another beneficial probiotic that benefits largely to humans. Male BALB/c mice in appropriate groups (6 animals each) were treated with ARLP for 7 days with ISO administration (100 mg/kg i.p.) on days 5 and 6. On the 8th day, animals were sacrificed. Serum and heart samples were collected for further processing. CK-MB, cardiac troponin, AST, ALT, LDH, GST, GPx, CAT, SOD, GSH, GSSG, MDA, nuclear factor kappa B (NFκB), TNF-α, and IL-6 by ELISA and gene expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) were estimated in samples. Mice administered with ISO showed a prominent rise in the serum marker enzyme activities and tissue oxidative stress markers (MDA and GSSG). Furthermore, marked reductions in body weight and enzymatic and non-enzymatic antioxidant levels were noticed in ISO toxicity. Alterations in proinflammatory cytokines (TNF-α and IL-6) and Nrf2 levels by RT-PCR were analyzed. Histopathology of the heart also indicated cardiac injury in ISO-intoxicated mice. ARLP pretreatment prevented all these cardiac injuries and exerted significant ( p ≤ 0.05) prophylactic protection toward cardiac tissue. Further, we analyzed the possible interactions between AR and LP in vitro, to understand the influence of ARonLP, which showed no significant suppressive/antibacterial activity on LP. In conclusion, ARLP exerts a strong cardioprotective and anti-inflammatory activity in cardiovascular injury.
异丙肾上腺素是一种用于治疗心动过缓的药物,由于其具有非选择性β肾上腺素受体激动剂的特性,因此有很多副作用。在这项研究中,我们使用 BALB/c 小鼠评估了异丙肾上腺素(ISO)心脏损伤的体内实验模型,并同时使用优化剂量的阿克替林(AR)和植物乳杆菌(LP)(ARLP;30 mg/kg b.w. AR 和可存活 106 CFU/mL LP p.o.)进行保护性治疗。异丙肾上腺素在许多情况下会造成心脏损伤。辛辣素是一种天然木质素苷,存在于许多草本药用植物中,对人体有许多益处。植物乳杆菌是另一种对人体有益的益生菌。雄性 BALB/c 小鼠按适当的组别(每组 6 只)接受为期 7 天的 ARLP 治疗,并在第 5 天和第 6 天注射 ISO(100 毫克/千克)。第 8 天,动物被处死。收集血清和心脏样本作进一步处理。通过 ELISA 法检测 CK-MB、心肌肌钙蛋白、AST、ALT、LDH、GST、GPx、CAT、SOD、GSH、GSSG、MDA、核因子卡巴 B(NFκB)、TNF-α 和 IL-6,并评估样本中核因子红细胞 2 相关因子 2(Nrf2)的基因表达。小鼠服用 ISO 后,血清标记酶活性和组织氧化应激标记物(MDA 和 GSSG)显著升高。此外,ISO毒性还导致体重、酶和非酶抗氧化剂水平明显下降。通过 RT-PCR 分析了促炎细胞因子(TNF-α 和 IL-6)和 Nrf2 水平的变化。心脏组织病理学检查也显示了 ISO 毒性小鼠的心脏损伤。ARLP 预处理可防止所有这些心脏损伤,并对心脏组织产生显著的预防性保护(p ≤ 0.05)。此外,我们还在体外分析了 AR 和 LP 之间可能存在的相互作用,以了解 AR 对 LP 的影响,结果显示 AR 对 LP 没有明显的抑制/抗菌活性。总之,ARLP在心血管损伤中具有很强的心脏保护和抗炎活性。
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