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Mechanism of Cistanche deserticola Ma in the Treatment of Myocardial Ischemia-Reperfusion (I/R) Injury Based on Network Pharmacology and In Vitro Experiments 基于网络药理学和体外实验的肉苁蓉治疗心肌缺血再灌注(I/R)损伤的机制
IF 0.7 4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-12-11 DOI: 10.1177/09731296231214855
Yuan-Jia Yue, Yu Li, Huimin Wang, Zhao Ji, Xing Rong, Lin Jiang
To investigate the mechanism of Cistanche deserticola Ma (CDA) in the treatment of myocardial ischemia-reperfusion (I/R) injury by network pharmacology and cell experiments. The main active components of CDA were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). I/R-related targets were identified from DisGeNET, OMIMD, and TTD; the I/R protein–protein interaction (PPI) network was constructed using the STRING input. The targets of CDA that inhibit I/R injury in Matescape and Microshengxin were subjected to Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Cell viability, levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA), and protein expression of phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinase 1 (Akt1) were determined. A total of 236 targets were identified, with PI3K, Akt, epithelial growth factor receptor (EGFR), and another kinase being the major targets, and according to GO and KEGG analysis, CDA was most likely to inhibit I/R through the PI3K-Akt pathway. The optimal concentration of 10% medicated serum of CDA was determined to be the most effective concentration. The levels of LDH and MDA were significantly decreased in the CDA and BEZ23 groups, but the levels of SOD were significantly increased, thereby alleviating cell damage. In addition, the expression of PI3K, Akt, and p-AKT proteins was significantly reduced in the CDA group. CDA alleviates I/R injury through antioxidation and inhibition of the PI3K/Akt signaling pathway.
通过网络药理学和细胞实验研究肉苁蓉(CDA)治疗心肌缺血再灌注(I/R)损伤的机制。CDA的主要活性成分来自中药系统药理学数据库和分析平台(TCMSP)。从DisGeNET、OMIMD和TTD中确定了I/R相关靶点,并利用STRING输入构建了I/R蛋白-蛋白相互作用(PPI)网络。对Matescape和Microshengxin中CDA抑制I/R损伤的靶点进行了基因本体(GO)分析和京都基因组百科全书(KEGG)通路富集分析。测定了细胞活力、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)和丙二醛(MDA)的水平,以及磷脂酰肌醇3-激酶(PI3K)和丝氨酸/苏氨酸激酶1(Akt1)的蛋白表达。共鉴定出236个靶点,其中PI3K、Akt、上皮生长因子受体(EGFR)和另一种激酶是主要靶点,根据GO和KEGG分析,CDA最有可能通过PI3K-Akt途径抑制I/R。10%的CDA药用血清浓度被认为是最有效的浓度。CDA组和BEZ23组的LDH和MDA水平明显下降,但SOD水平明显上升,从而减轻了细胞损伤。此外,CDA组中PI3K、Akt和p-AKT蛋白的表达明显减少。CDA通过抗氧化和抑制PI3K/Akt信号通路减轻了I/R损伤。
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引用次数: 0
Phytochemical Profiling, Antioxidant, and Antifungal Activities of Ethyl Acetate and Chloroformic Extracts from Three Mentha Species 三种薄荷树种的乙酸乙酯和氯仿提取物的植物化学成分分析、抗氧化和抗真菌活性
IF 0.7 4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-12-06 DOI: 10.1177/09731296231202104
N. Bouali, H. Hajlaoui, S. Arraouadi, Mohd Saeed, Munazzah Tasleem, Snoussi Mejdi, Adel Kadri
Phytopathogenic fungi remain the main infectious agents in plants, causing severe damage to the environment and human health. Thus, to reduce the usage of synthetically derived fungicides and perform agricultural crop production, the search for new control strategies including plant extracts constitutes an eco-friendly and safe alternative. This study aimed to quantify the phytochemical constituents of the three plant ( Mentha pulegium L., Mentha spicata L., and Mentha longifolia L.) extracts and to screen their phytochemical composition including total phenolic (TPC), flavonoids (TFC) and condensed tannins contents (TCTC), and to evaluate their antioxidant activities. The efficacy of all mint extracts will be investigated against phytopathogenic fungal species. The three plant extracts were screened to assess their total phenolic, flavonoids, and condensed tannin contents using spectrophotometric assays. The antioxidant activities include 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric ion reducing antioxidant power (FRAP), and β-carotene assays. The antifungal activities were investigated on phytopathogenic species including Botrytis cinerea, Fusarium culmorum, Fusarium oxysporum, Aspergillus niger, Aspergillus flavus, and Trichoderma sp. Quantitative analyses of phytochemical constituents of Mentha genus extracts revealed that both ethyl acetate (EtAc) and chloroformic (Chl) extracts are a rich source of phenols, flavonoids, and condensed tannins. Ethyl acetate extract of M. longifolia (EtAc L) displayed the highest content of phenols (69.9 ± 1.35 mg GAE/g DW) and flavonoids (53.26 ± 2.11 mg CE/g DW), while M. pulegium ethyl acetate extract (EtAc P) has the highest condensed tannins content (2.13 ± 0.4 mg CE/g DW). Moreover, the tested extracts exhibited potent antioxidant activities at low concentrations for EtAc L, followed by M. spicata (EtAc S), and EtAc P (IC50 = 35.76 ± 1.32 µg/mL for scavenging DPPH free radicals; EC50 527.96 ± 5.45 µg/mL for FRAP, and IC50 = 106.3 ± 3.75 µg/mL for β-carotene bleaching test). Finally, all tested extracts were able to inhibit the growth of several phytopathogenic micro-organisms on both agar and broth media. The Mentha extracts derived from the three mint species (i.e., L, P, and S) could be used for their antifungal activities to provide sustainable crop pest management.
植物病原真菌是植物感染的主要病原,对环境和人类健康造成严重危害。因此,为了减少合成衍生杀菌剂的使用并进行农作物生产,寻找包括植物提取物在内的新的控制策略构成了一种环保和安全的替代方案。本研究旨在定量测定三种植物(Mentha pulegium L.、Mentha spicata L.和Mentha longifolia L.)提取物的植物化学成分,筛选其总酚(TPC)、总黄酮(TFC)和缩合单宁(TCTC)含量,并评价其抗氧化活性。本文将研究所有薄荷提取物对植物病原真菌的抑制作用。用分光光度法对三种植物提取物的总酚、总黄酮和缩合单宁含量进行了筛选。抗氧化活性包括1,1-二苯基-2-吡啶肼(DPPH)、铁离子还原抗氧化能力(FRAP)和β-胡萝卜素测定。研究了薄荷属植物提取物对灰霉菌、枯萎菌、尖孢镰刀菌、黑曲霉、黄曲霉和木霉等病原菌的抑菌活性。对薄荷属植物提取物的化学成分进行了定量分析,发现乙酸乙酯(EtAc)和氯甲酸(Chl)提取物均含有丰富的酚类物质、类黄酮和缩合单宁。长叶提取物(EtAc L)中酚类物质含量最高(69.9±1.35 mg GAE/g DW),总黄酮含量最高(53.26±2.11 mg CE/g DW),短叶提取物(EtAc P)中缩合单宁含量最高(2.13±0.4 mg CE/g DW)。此外,所测试的提取物在低浓度下对EtAc L具有较强的抗氧化活性,其次是M. spicata (EtAc S)和EtAc P (IC50 = 35.76±1.32 μ g/mL)对DPPH自由基的清除能力;FRAP的EC50为527.96±5.45µg/mL, β-胡萝卜素漂白试验的IC50为106.3±3.75µg/mL)。最后,所有测试的提取物都能抑制几种植物病原微生物在琼脂和肉汤培养基上的生长。从三种薄荷(L、P和S)中提取的薄荷提取物可用于抗真菌活性,为作物病虫害的可持续治理提供依据。
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引用次数: 0
Anti-convulsant Effects of Scutellarein in a PTZ Kindling Model in Mice 黄芩苷在 PTZ 激惹小鼠模型中的抗惊厥作用
IF 0.7 4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-12-04 DOI: 10.1177/09731296231203790
Jun Duan, Jiao Wang, Qian Zhao, Dean Wu, Yang Liu
Background: Epilepsy is a chronic neurological condition with various underlying mechanisms. It is known to affect a multitude of people across the globe, regardless of age and gender. Seizures associated with epilepsy involve the participation of stimulatory glutamatergic mechanisms along with inflammation and oxidative damage. Objectives: In this investigation, the anti-epileptic effect of scutellarein, a phytochemical compound isolated from Erigeron breviscapus (Vant.), has been evaluated in the pentylenetetrazol (PTZ) kindling epilepsy model in mice. Materials and Methods: The experimental mice were categorized into six groups with six animals in each. The first control group was given normal saline. The second group was provided only PTZ through an intraperitoneal route to induce seizures. The third and fourth groups received two oral doses of scutellarein (10 and 20 mg/kg) before 30 min of PTZ induction. Diazepam was intraperitoneally administered to the fifth group as a positive control. The impact of scutellarein on the duration and initiation of clonic and tonic convulsion, mortality, kindling, mobility, and immobility duration in PTZ-induced rodents was estimated. Also, the impact of scutellarein on oxidative stress markers and antioxidant and inflammatory marker levels was also evaluated. Results: Scutellarein treatment was able to reduce PTZ-induced seizures in mice. In PTZ animals, scutellarein lowered the seizure severity by suppressing the onset and duration of convulsions. Scutellarein successfully modulated the PTZ-provoked changes in gamma-aminobutyric acid (GABA), glutamate, and dopamine levels, as well as Ca2+ ATPase and Na+ K+ ATPase activity. Conclusion: Furthermore, it remarkably reduced the oxidative stress markers and decreased the contents of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in PTZ animal brain tissues, confirming its anti-convulsant potential.
背景:癫痫是一种具有多种潜在机制的慢性神经系统疾病。众所周知,无论年龄和性别,它都会影响全球许多人。与癫痫相关的癫痫发作涉及刺激谷氨酸能机制的参与以及炎症和氧化损伤。目的:研究从灯盏花(Erigeron breviscapus, Vant.)中分离的植物化学物质灯盏花苷(scutellarein)对戊四氮唑(PTZ)点燃癫痫模型小鼠的抗癫痫作用。材料与方法:将实验小鼠分为6组,每组6只。第一对照组给予生理盐水治疗。第二组仅通过腹腔注射PTZ诱导癫痫发作。第三组和第四组在PTZ诱导30 min前口服两剂黄芩苷(10和20 mg/kg)。第五组腹腔注射安定作为阳性对照。估计了黄芩苷对ptz诱导啮齿动物的慢性和强直性惊厥持续时间和开始时间、死亡率、燃烧、活动时间和不活动时间的影响。此外,还评估了黄芩苷对氧化应激标志物、抗氧化和炎症标志物水平的影响。结果:黄芩苷能减轻ptz诱导的小鼠癫痫发作。在PTZ动物中,黄芩苷通过抑制抽搐的发生和持续时间来降低癫痫发作的严重程度。灯花苷成功地调节了ptz引起的γ -氨基丁酸(GABA)、谷氨酸和多巴胺水平的变化,以及Ca2+ atp酶和Na+ K+ atp酶活性。结论:黄芪多糖能显著降低PTZ动物脑组织氧化应激标志物,降低核因子-κB (NF-κB)、肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β)含量,证实其抗惊厥作用。
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引用次数: 0
Valproic Acid Treatment Improves Organ Function, Survival Rate, and Lipid Peroxidation in Fatally Scalded Rats 丙戊酸治疗可改善致命烫伤大鼠的器官功能、存活率和脂质过氧化反应
IF 0.7 4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-12-04 DOI: 10.1177/09731296231211466
Rui Liu, Yu-Tuo Fu, Feng-Qi Jiang, Yi-Jie Ye, Shu-Ming Wang
After hypovolemic shock caused by severe burns, lipid peroxidation is an important factor in tissue edema and multiorgan dysfunction syndrome (MODS). Many studies have shown that valproic acid (VPA) inhibits lipid peroxidation and reduces tissue and organ injury. This study investigated whether the VPA treatment of scalded rats reduced tissue edema by inhibiting lipid peroxidation, thereby improving organ function and survival rate. A total of 60 male Sprague-Dawley rats (weighing: 280–300 g) with a 50% total body surface area (TBSA) full-thickness dermal burn were randomly assigned to the following 3 groups (with 20 rats per group): (I) the no infusion resuscitation (NR) group; (II) the sodium lactate Ringer’s solution (LR) group; and (III) the sodium valproate Ringer’s solution (VR) group. After scalding, the following hemodynamic parameters were measured: Copper2+-Zinc2+-superoxide dismutase (Cu2+-Zn2+-SOD) activity, thiobarbituric acid reactive substances (TBARSs), oxidized glutathione (GSSG), reduced glutathione (GSH), and antioxidant enzyme activities. Organ function parameters and water content were also measured. Another 60 male Sprague-Dawley rats were used to observe the 24-h survival rate of the rats using the same scald model and fluid resuscitation. VPA significantly increased the mean arterial pressure (MAP) and cardiac output (CO), and significantly decreased the pulmonary vascular permeability index (PVPI) and extravascular lung water index (ELWI). VPA also increased plasma Cu2+-Zn2+-SOD activity and decreased the plasma TBARS level. VPA reduced the TBARS level and GSSG in various tissues and increased the concentration of GSH. VPA decreased glutathione peroxidase (GPx) and catalase (CAT) activity, but significantly increased glutathione reductase (GR) activity in various tissues. VPA significantly improved organ functions and decreased water content. VPA significantly improved the survival rate, and the 24-h survival rate of the VR group was double that of the LR group. Resuscitation with VPA reduced tissue edema, protected visceral functions, and improved the survival rate of rats with severe burn shock (BS) by alleviating lipid peroxidation.
严重烧伤引起的低血容量性休克后,脂质过氧化是导致组织水肿和多器官功能障碍综合征(MODS)的重要因素。许多研究表明丙戊酸(VPA)抑制脂质过氧化,减少组织和器官损伤。本研究探讨VPA治疗烫伤大鼠是否通过抑制脂质过氧化作用减轻组织水肿,从而改善脏器功能和生存率。选取体表面积(TBSA)为50%全层皮肤烧伤的雄性Sprague-Dawley大鼠60只(体重280 ~ 300 g),随机分为3组(每组20只):(I)无灌注复苏(NR)组;(II)乳酸钠林格氏溶液(LR)组;丙戊酸钠林格液(VR)组。烫伤后,测定以下血流动力学参数:Copper2+-Zinc2+-超氧化物歧化酶(Cu2+-Zn2+-SOD)活性、硫代巴比妥酸活性物质(TBARSs)、氧化谷胱甘肽(GSSG)、还原性谷胱甘肽(GSH)、抗氧化酶活性。测定器官功能参数和水分含量。另取60只雄性Sprague-Dawley大鼠,采用相同烫伤模型和液体复苏,观察大鼠24小时存活率。VPA显著提高平均动脉压(MAP)和心输出量(CO),显著降低肺血管通透性指数(PVPI)和血管外肺水指数(ELWI)。VPA还能提高血浆Cu2+-Zn2+-SOD活性,降低血浆TBARS水平。VPA降低各组织TBARS水平和GSSG水平,增加GSH浓度。VPA降低了谷胱甘肽过氧化物酶(GPx)和过氧化氢酶(CAT)活性,但显著提高了各组织谷胱甘肽还原酶(GR)活性。VPA显著改善器官功能,降低水分含量。VPA明显提高了生存率,VR组的24小时生存率是LR组的2倍。VPA复苏可减轻严重烧伤休克大鼠的脂质过氧化作用,减少组织水肿,保护内脏功能,提高存活率。
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引用次数: 0
Determination of Four Chemical Components in Qishen Yiqi Dripping Pills by UPLC-MS/MS Method UPLC-MS/MS 法测定七神益气滴丸中的四种化学成分
IF 0.7 4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-12-04 DOI: 10.1177/09731296231203449
Qin Lili, Honglian Zhang, Yanxia Wang, Yingying Liang, Li Qiang, Xuerong Xie
In this study, the ultrahigh performance liquid chromatography mass spectrometry/mass spectrometry (UPLC-MS/MS) method was established to test the contents of protocatechuic acid (C7H6O4), salvianolic acid B (C36H30O16), rosmarinic acid (C19H14O3), and cryptotanshinone (C19H20O3) in Qishen Yiqi dripping pills. Methanol was chosen as the solvent according to a certain material–liquid ratio as a solution, and the ultrasonic extraction method was used to prepare the sample solution. UPLC-MS/MS was used to complete a quantitative analysis of the contents of Qishen Yiqi dripping pills. Then, the chromatographic conditions were shown as follows. The stationary phase was Agilent ZORBAX SB-C18 (2.1 mm × 100 mm, 1.8 µm), and the mobile phase was acetonitrile–0.1% formic acid water. The column temperature was 40℃, the injection volume was 3 µL, and the flow rate was 0.2 mL⋅min–1. Finally, the determination method was built to test four chemical constituents under the multiple reaction monitoring (MRM) analysis mode. The retention times of protocatechuic acid, salvianolic acid B, rosmarinic acid, and cryptotanshinone were 1.26, 1.32, 1.35, and 6.76 min, respectively. In addition, the concentration ranges of four compounds were 0.25–2.0 µg⋅mL–1, 10.0–50.0 µg⋅mL–1, 5.0–50.0 µg⋅mL–1, and 1.0–10.0 µg⋅mL–1, respectively. And the standard curve showed a good linear relationship in a reasonable range ( r2 ≥ 0.9950). The average recovery rate was from 96% to 124%. The contents of protocatechuic acid, salvianolic acid B, rosmarinic acid, and cryptotanshinone were 0.12%–0.022%, 17%–8.4%, and 6.5%–8.6% in seven batches of Qishen Yiqi dripping pills, which were in the range of 23%–31%. The instrument ran stably, and the method had good accuracy and repeatability (relative standard deviation [RSD] ≤ 3%). Additionally, the test result was stable within 10 h. The contents of the four constituents were different among different batches. The quantitative method was established to determine the four chemical components in Qishen Yiqi dripping pills, which could provide a reference for quality evaluation in vivo.
本研究建立了超高效液相色谱-质谱联用(UPLC-MS/MS)法测定芪肾益气滴丸中原儿茶酸(C7H6O4)、丹酚酸B (C36H30O16)、迷迭香酸(C19H14O3)、隐丹参酮(C19H20O3)的含量。按一定的料液比选择甲醇作为溶剂作为溶液,采用超声波提取法制备样品溶液。采用UPLC-MS/MS对芪肾益气滴丸的含量进行定量分析。然后,色谱条件如下:固定相为Agilent ZORBAX SB-C18 (2.1 mm × 100 mm, 1.8µm),流动相为乙腈- 0.1%甲酸水。柱温40℃,进样量3µL,流速0.2 mL⋅min-1。最后,在多重反应监测(MRM)分析模式下,建立检测四种化学成分的测定方法。原儿茶酸、丹酚酸B、迷迭香酸和隐丹参酮的保留时间分别为1.26、1.32、1.35和6.76 min。4种化合物的浓度范围分别为0.25 ~ 2.0µg⋅mL-1、10.0 ~ 50.0µg⋅mL-1、5.0 ~ 50.0µg⋅mL-1和1.0 ~ 10.0µg⋅mL-1。标准曲线在合理范围内呈良好的线性关系(r2≥0.9950)。平均回收率为96% ~ 124%。七批芪肾益气滴丸中原儿茶酸、丹酚酸B、迷迭香酸、隐丹参酮的含量分别为0.12% ~ 0.022%、17% ~ 8.4%、6.5% ~ 8.6%,含量范围为23% ~ 31%。仪器运行稳定,方法准确度和重复性好(相对标准偏差[RSD]≤3%)。10 h内检测结果稳定。不同批次的四种成分含量不同。建立气肾益气滴丸中4种化学成分的定量测定方法,为体内质量评价提供参考。
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引用次数: 0
Gastrodin Ameliorates Knee Joint Inflammation and Pain in Osteoarthritis Rats and Prevents Chondrocyte Injury by Regulating PI3K/Akt/FoxO1 Pathway 天麻素通过调节 PI3K/Akt/FoxO1 通路改善骨关节炎大鼠膝关节炎症和疼痛并防止软骨细胞损伤
IF 0.7 4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-11-24 DOI: 10.1177/09731296231203860
Jiang-Long Shi, Li-Yun Liu, Yu-Ting Dong, Tao Shen
Several studies have demonstrated the anti-inflammatory properties of gastrodin. However, its specific role and mechanism in the context of osteoarthritis (OA) remain unclear. The objective of this study was to explore the function and mechanism of gastrodin in both in vivo and in vitro OA models. In this study, the targets of gastrodin against osteoarthritis were analyzed using bioinformatics methods. The effect of gastrodin on neutrophil infiltration and inflammatory cytokines in OA synovial tissue was evaluated using H&E staining. The levels of inflammatory cytokines were determined using ELISA and Q-PCR. The extracellular matrix degradation-related proteins and PI3K/AKT/FoxO1 signaling pathway were tested using western blotting. Bioinformatics analysis predicted that the target of gastrodin against OA might act on the FoxO pathway. The use of gastrodin resulted in a significant reduction in the infiltration of neutrophils in the synovial tissue of rats, as observed through H&E staining. Additionally, gastrodin was found to attenuate IL-1β-induced inhibition of chondrocyte viability, pro-inflammatory cytokine production, and extracellular matrix degradation. This effect can be attributed to the suppression of PI3K/AKT/FoxO1 by gastrodin. These findings indicate that gastrodin is a treatment for OA.
多项研究已经证明了天麻素的抗炎特性。然而,它在骨关节炎(OA)中的具体作用和机制仍不清楚。本研究的目的是探索天麻素在体内和体外 OA 模型中的功能和机制。本研究利用生物信息学方法分析了天麻素对骨关节炎的作用靶点。利用 H&E 染色法评估了天麻素对 OA 滑膜组织中性粒细胞浸润和炎性细胞因子的影响。炎性细胞因子的水平通过 ELISA 和 Q-PCR 进行测定。使用 Western 印迹法检测了细胞外基质降解相关蛋白和 PI3K/AKT/FoxO1 信号通路。生物信息学分析预测,天麻素抗OA的靶点可能作用于FoxO通路。通过H&E染色观察到,使用天麻素后,大鼠滑膜组织中的中性粒细胞浸润明显减少。此外,研究还发现天麻素能减轻 IL-1β 诱导的对软骨细胞活力、促炎细胞因子产生和细胞外基质降解的抑制作用。这种效应可归因于天麻素对 PI3K/AKT/FoxO1 的抑制。这些研究结果表明,天麻素可以治疗 OA。
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引用次数: 0
Screening of Chenopodium hybridum L. for Anti-ovarian Cancer Compounds Using UPLC-Q-Exactive MS and Partial Least Squares Analysis 利用 UPLC-Q-Exactive MS 和偏最小二乘法分析筛选陈皮中的抗卵巢癌化合物
IF 0.7 4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-11-22 DOI: 10.1177/09731296231198930
Shuli Yang, Duanduan Cheng, Xueqin Feng, Ruixin Lin
Extracts of Chenopodium hybridum L. leaves and stems exerted a significant antiproliferative effect on human A2780 ovarian cancer cells, but C. hybridum active components have not been reported. Here, a method is described for screening of C. hybridum extracts for potential bioactive components that inhibit A2780 cell proliferation. First, the spectrum–effect relationship between UPLC-Q-Exactive MS chromatograms and C. hybridum extract antiproliferative effect against A2780 cells was established to evaluate extract bioactive components using partial least squares (PLS) analysis. The results indicated that the optimal reflux extraction process for preparing C. hybridum extracts with antiproliferative activity involved a suspension of C. hybridum material in 8 volumes of 70% ethanol followed by heating and refluxing twice for 60 min/reflux step and then repeating the extraction and pooling of both the extracts. Chromatographic results revealed five compounds with potential anti-ovarian cancer activities based on inhibition of A2780 cell proliferation: isorhamnetin-3-O-β-D-furanosyl(1↓2)-O-[α-L-rhamnpyranosyl(1↓6)]-β-D-glucopyranoside, kaempferol-3-O-β-D-glucopyranoside-7-O-α-L-pyranoside, kaempferol-3-O-[α-L-rhamnopyranosyl(1″↓2″)]-β-D-galactopyranoside, quercetin-3,7-di-rhamnose, and isorhamnetin-3-acacia disaccharide. Network pharmacological screening revealed nine core cellular targets that potentially interacted with these compounds. These results were verified through molecular docking studies that supported the involvement of these compounds in observed C. hybridum A2780 cell antiproliferative effects, thus indicating C. hybridum active components may have value in ovarian cancer treatments.
Chenopodium hybridum L.叶和茎的提取物对人类 A2780 卵巢癌细胞有显著的抗增殖作用,但杂交草的活性成分尚未见报道。本文介绍了一种筛选杂交乌头提取物中可抑制 A2780 细胞增殖的潜在生物活性成分的方法。首先,利用偏最小二乘法(PLS)分析建立了UPLC-Q-Exactive MS色谱图与杂交草提取物抗A2780细胞增殖效果之间的谱效关系,以评估提取物中的生物活性成分。结果表明,制备具有抗增殖活性的杂交乌头提取物的最佳回流提取工艺是将杂交乌头材料悬浮于 8 体积的 70% 乙醇中,然后加热回流两次,每次 60 分钟/回流步骤,然后重复提取并汇集两种提取物。色谱结果显示,根据对 A2780 细胞增殖的抑制作用,有五种化合物具有潜在的抗卵巢癌活性:异鼠李素-3-O-β-D-呋喃糖基(1↓2)-O-[α-L-鼠李吡喃糖基(1↓6)]-β-D-吡喃葡萄糖苷,山奈酚-3-O-β-D-吡喃葡萄糖苷-7-O-α-L-吡喃糖苷、山奈酚-3-O-[α-L-吡喃鼠李糖基(1″↓2″)]-β-D-吡喃半乳糖苷、槲皮素-3,7-二鼠李糖和异鼠李素-3-金合欢二糖。网络药理学筛选发现了可能与这些化合物相互作用的九个核心细胞靶点。这些结果通过分子对接研究得到了验证,证明这些化合物参与了所观察到的杂交草 A2780 细胞抗增殖作用,从而表明杂交草的活性成分可能具有治疗卵巢癌的价值。
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引用次数: 0
Shexiang Tongxin Dropping Pretreated Mesenchymal Stem Cells-derived Exosomes Attenuate Cardiac Ischemia/Reperfusion Injury by Modulating miR-182-5p and miR-199a-3p-mediated Inflammatory Responses 佘香通心滴入预处理间充质干细胞来源的外泌体通过调节miR-182-5p和mir -199a-3p介导的炎症反应减轻心脏缺血/再灌注损伤
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-11-07 DOI: 10.1177/09731296231207232
Ling-Yan Li, Ling-Fang Zhou, Jia Shi, Zong-Jun Liu, Jun-Qing Gao
Background Previous research has highlighted the regulatory role of miR-182-5p in targeting TLR4 during the pathogenesis of allergic rhinitis. In a different context, TLR4 has been identified as a crucial factor in the development of lung ischemia-reperfusion injury, where its upregulation is believed to initiate the injury process. Additionally, miR-199a-3p has been shown to possess cardioprotective properties in simulated ischemia/reperfusion (I/R) injury models. Materials and Methods HE and TUNEL were performed to evaluate the cardiac injury and cellular apoptosis of I/R mice under distinct conditions. Real-time PCR was used to analyze the expression of microRNAs (miRNAs) and mRNAs under differential conditions. Results Pretreatment by Shexiang Tongxin Dropping (SXTXD) has been shown to significantly augment the therapeutic efficacy of MSC-derived exosomes (MSC-EXOs) in attenuating cardiac injury in I/R mice. MSC-EXOs effectively restored the repressed miR-182/miR-199a-3p expressions and activated TLR4/CD44 expressions in I/R mice, while SXTXD pretreatment remarkably strengthened the efficiency of MSC-EXOs. Moreover, SXTXD pretreatment notably reinforced the capability of MSC-EXOs to maintain cardiac parameters, including iNOS and interleukin-1β (IL-1β). Furthermore, the luciferase assay indicated that miR-182-5p and miR-199a-3p effectively suppressed the luciferase activities of TLR4 and CD44, respectively, through binding to the 3´ UTR. The overexpression of miR-182-5p and miR-199a-3p significantly suppressed the expression of TLR4 and CD44 in H2C6 and RAW264.7 cells. Conclusion In conclusion, our investigation indicates that MSC-derived exosomes, pretreated with SXTXD, hold promise in mitigating cardiac I/R injury by modulating inflammatory responses through the miR-182-5p/TLR4 axis and miR-199a-3p/CD44 axis. These findings suggest potential therapeutic strategies for addressing I/R-related cardiac complications.
以往的研究已经强调了miR-182-5p在变应性鼻炎发病过程中靶向TLR4的调控作用。在不同的背景下,TLR4已被确定为肺缺血-再灌注损伤发展的关键因素,其上调被认为启动了损伤过程。此外,在模拟缺血/再灌注(I/R)损伤模型中,miR-199a-3p已被证明具有心脏保护特性。材料与方法采用HE法和TUNEL法观察不同条件下I/R小鼠心脏损伤及细胞凋亡情况。采用Real-time PCR分析不同条件下microRNAs (miRNAs)和mrna的表达。结果麝香通心滴剂(SXTXD)预处理可显著增强间充质干细胞来源的外泌体(MSC-EXOs)对I/R小鼠心脏损伤的治疗作用。在I/R小鼠中,MSC-EXOs可有效恢复被抑制的miR-182/miR-199a-3p表达,激活TLR4/CD44表达,而SXTXD预处理可显著增强MSC-EXOs的效率。此外,SXTXD预处理显著增强了MSC-EXOs维持心脏参数的能力,包括iNOS和白细胞介素-1β (IL-1β)。此外,荧光素酶检测表明,miR-182-5p和miR-199a-3p分别通过结合3´UTR有效抑制TLR4和CD44的荧光素酶活性。过表达miR-182-5p和miR-199a-3p可显著抑制H2C6和RAW264.7细胞中TLR4和CD44的表达。总之,我们的研究表明,经SXTXD预处理的间充质干细胞来源的外泌体通过miR-182-5p/TLR4轴和miR-199a-3p/CD44轴调节炎症反应,有望减轻心脏I/R损伤。这些发现提示了解决I/ r相关心脏并发症的潜在治疗策略。
{"title":"Shexiang Tongxin Dropping Pretreated Mesenchymal Stem Cells-derived Exosomes Attenuate Cardiac Ischemia/Reperfusion Injury by Modulating miR-182-5p and miR-199a-3p-mediated Inflammatory Responses","authors":"Ling-Yan Li, Ling-Fang Zhou, Jia Shi, Zong-Jun Liu, Jun-Qing Gao","doi":"10.1177/09731296231207232","DOIUrl":"https://doi.org/10.1177/09731296231207232","url":null,"abstract":"Background Previous research has highlighted the regulatory role of miR-182-5p in targeting TLR4 during the pathogenesis of allergic rhinitis. In a different context, TLR4 has been identified as a crucial factor in the development of lung ischemia-reperfusion injury, where its upregulation is believed to initiate the injury process. Additionally, miR-199a-3p has been shown to possess cardioprotective properties in simulated ischemia/reperfusion (I/R) injury models. Materials and Methods HE and TUNEL were performed to evaluate the cardiac injury and cellular apoptosis of I/R mice under distinct conditions. Real-time PCR was used to analyze the expression of microRNAs (miRNAs) and mRNAs under differential conditions. Results Pretreatment by Shexiang Tongxin Dropping (SXTXD) has been shown to significantly augment the therapeutic efficacy of MSC-derived exosomes (MSC-EXOs) in attenuating cardiac injury in I/R mice. MSC-EXOs effectively restored the repressed miR-182/miR-199a-3p expressions and activated TLR4/CD44 expressions in I/R mice, while SXTXD pretreatment remarkably strengthened the efficiency of MSC-EXOs. Moreover, SXTXD pretreatment notably reinforced the capability of MSC-EXOs to maintain cardiac parameters, including iNOS and interleukin-1β (IL-1β). Furthermore, the luciferase assay indicated that miR-182-5p and miR-199a-3p effectively suppressed the luciferase activities of TLR4 and CD44, respectively, through binding to the 3´ UTR. The overexpression of miR-182-5p and miR-199a-3p significantly suppressed the expression of TLR4 and CD44 in H2C6 and RAW264.7 cells. Conclusion In conclusion, our investigation indicates that MSC-derived exosomes, pretreated with SXTXD, hold promise in mitigating cardiac I/R injury by modulating inflammatory responses through the miR-182-5p/TLR4 axis and miR-199a-3p/CD44 axis. These findings suggest potential therapeutic strategies for addressing I/R-related cardiac complications.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"285 S3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135475205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Modulations by L-Carvone and Thymoquinone to Exert Protection on Bone Marrow Cells Against Benzene-induced Toxicities Through Anti-inflammatory Pathways in SD Rats l -香芹酮和百里醌通过抗炎途径对SD大鼠骨髓细胞苯致毒性的保护作用
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-11-07 DOI: 10.1177/09731296231201510
Enjun Kong, Yan Xu, Hong Jin, Tahani Awad Alahmadi, Samer Hasan Hussein Al Ali
Background Adverse effects of benzene (BZ) exposure toxicities were documented by many researchers worldwide. BZ exposure causes many hematological abnormalities that might be treated with naturally occurring phytocompounds. Aim In this experimental study, we evaluated the anti-inflammatory effect of L-carvone and thymoquinone together (LCTQ) against BZ-induced inflammatory toxicities in Sprague-Dawley (SD) rats. Introduction BZ exposure could cause an excess formation of immature blood cells to enter the peripheral bloodstream. Phytocompounds namely L-carvone (LC) and thymoquinone (TQ) have confirmed anti-inflammatory effects against various diseases. Materials and Methods Rats were divided into four different groups such as control, LCTQ group, BZ pathologic group, and treatment group (LCTQ+BZ). After 10 weeks of the experimental period, body weight changes, hematological parameters, pro-inflammatory cytokines, oxidative stress, RBC antioxidants, bone marrow cellular abnormalities, and bone marrow DNA fragmentation were evaluated. Results BZ toxicity showed abnormal loss of body weight, altered hematological parameters, increased pro-inflammatory cytokines, abnormal cellular oxidative status, and DNA damage. LCTQ treatment showed significant ( p < 0.05) increase in body weight, normalized hematological parameters such as red blood cells, hemoglobin, white blood cells (lymphocytes and eosinophils), platelets (PLT), and hematocrit with RBC parameters, reduction of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), controlled oxidative stress, normalized enzymatic antioxidants in the RBC cells, normalized nucleated cells, megakaryocyte cells, and controlled DNA fragmentation were observed. Conclusion The current study showed an anti-inflammatory effect of LCTQ through the control of inflammation against benzene-induced toxicities in rats.
背景苯(BZ)暴露毒性的不良影响已被世界各地的许多研究人员所记录。接触BZ会导致许多血液学异常,这些异常可以用天然植物化合物来治疗。目的观察左旋香芹酮和百里醌(LCTQ)对bz诱导的SD大鼠炎症毒性的抗炎作用。BZ暴露会导致过量的未成熟血细胞进入外周血。植物化合物如l -香芹酮(LC)和百里醌(TQ)已被证实对多种疾病具有抗炎作用。材料与方法将大鼠分为4组,分别为对照组、LCTQ组、BZ病理组和治疗组(LCTQ+BZ)。实验10周后,观察小鼠体重变化、血液学参数、促炎因子、氧化应激、红细胞抗氧化剂、骨髓细胞异常和骨髓DNA断裂。结果BZ毒性表现为体重异常下降、血液学参数改变、促炎细胞因子升高、细胞氧化状态异常和DNA损伤。LCTQ治疗显着(p <0.05)体重增加,血液学参数如红细胞、血红蛋白、白细胞(淋巴细胞和嗜酸性粒细胞)、血小板(PLT)和红细胞红细胞压积正常化,促炎细胞因子如肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β)和白细胞介素-6 (IL-6)减少,氧化应激得到控制,红细胞、有核细胞、巨核细胞中的酶促抗氧化剂正常化,并观察到有控制的DNA断裂。结论本研究表明,白芍多糖具有抗炎作用,其作用机制是通过抑制大鼠苯中毒引起的炎症反应。
{"title":"Modulations by L-Carvone and Thymoquinone to Exert Protection on Bone Marrow Cells Against Benzene-induced Toxicities Through Anti-inflammatory Pathways in SD Rats","authors":"Enjun Kong, Yan Xu, Hong Jin, Tahani Awad Alahmadi, Samer Hasan Hussein Al Ali","doi":"10.1177/09731296231201510","DOIUrl":"https://doi.org/10.1177/09731296231201510","url":null,"abstract":"Background Adverse effects of benzene (BZ) exposure toxicities were documented by many researchers worldwide. BZ exposure causes many hematological abnormalities that might be treated with naturally occurring phytocompounds. Aim In this experimental study, we evaluated the anti-inflammatory effect of L-carvone and thymoquinone together (LCTQ) against BZ-induced inflammatory toxicities in Sprague-Dawley (SD) rats. Introduction BZ exposure could cause an excess formation of immature blood cells to enter the peripheral bloodstream. Phytocompounds namely L-carvone (LC) and thymoquinone (TQ) have confirmed anti-inflammatory effects against various diseases. Materials and Methods Rats were divided into four different groups such as control, LCTQ group, BZ pathologic group, and treatment group (LCTQ+BZ). After 10 weeks of the experimental period, body weight changes, hematological parameters, pro-inflammatory cytokines, oxidative stress, RBC antioxidants, bone marrow cellular abnormalities, and bone marrow DNA fragmentation were evaluated. Results BZ toxicity showed abnormal loss of body weight, altered hematological parameters, increased pro-inflammatory cytokines, abnormal cellular oxidative status, and DNA damage. LCTQ treatment showed significant ( p < 0.05) increase in body weight, normalized hematological parameters such as red blood cells, hemoglobin, white blood cells (lymphocytes and eosinophils), platelets (PLT), and hematocrit with RBC parameters, reduction of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), controlled oxidative stress, normalized enzymatic antioxidants in the RBC cells, normalized nucleated cells, megakaryocyte cells, and controlled DNA fragmentation were observed. Conclusion The current study showed an anti-inflammatory effect of LCTQ through the control of inflammation against benzene-induced toxicities in rats.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"285 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135475204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
GRg1 Ameliorates Insulin Resistance Through Activation of the PI3K/AKT/GSK-3β Pathway in HepG2 Cells GRg1通过激活HepG2细胞中的PI3K/AKT/GSK-3β通路改善胰岛素抵抗
4区 医学 Q4 CHEMISTRY, MEDICINAL Pub Date : 2023-11-03 DOI: 10.1177/09731296231198284
Xunjun Shen, Yamei Jin, Yuting Chen, Huadi Yang
Background Insulin resistance (IR) is a pathological state closely associated with various diseases, with hepatic insulin resistance playing a pivotal role. Insulin resistance can be improved by Ginsenoside Rg1 (GRg1), which is known as one of the most biologically active compounds found in ginseng. Nevertheless, the precise role and mechanisms of GRg1 in ameliorating hepatic insulin resistance are still unknown. Objectives We wanted to demonstrate the impact of GRg1 on hepatic insulin resistance and explore the underlying mechanisms in our work. Materials and Methods We mimicked insulin resistance conditions by culturing HepG2 cells in 30 mM glucose for 24 h. The effects of GRg1 on cellular glucose consumption and the key kinases of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β) pathway were evaluated. To assess if the PI3K/AKT/GSK-3β pathway is crucial for GRg1’s protective effect against insulin resistance, the compound LY294002, which inhibits PI3K, was employed. Results In HepG2 cells, GRg1 markedly increased glucose uptake while exhibiting no cytotoxicity. Additionally, GRg1 activated the PI3K/AKT/GSK-3β pathway, as indicated by the increased phosphorylation of insulin receptor substrates-1 (IRS-1), AKT, and GSK-3β. Treatment with LY294002 significantly reversed the promotive effects of GRg1 on cellular glucose consumption and PI3K/AKT/GSK-3β pathway activation. Conclusion Taken together, our present study revealed GRg1 exerted a protective effect against hepatic insulin resistance induced by high glucose through PI3K/AKT/GSK-3β pathway, suggesting its potential as a beneficial therapeutic medication.
胰岛素抵抗(Insulin resistance, IR)是一种与多种疾病密切相关的病理状态,肝脏胰岛素抵抗在其中起着举足轻重的作用。人参皂苷Rg1 (GRg1)可以改善胰岛素抵抗,它被认为是人参中最具生物活性的化合物之一。然而,GRg1在改善肝脏胰岛素抵抗中的确切作用和机制尚不清楚。我们希望在我们的工作中证明GRg1对肝脏胰岛素抵抗的影响,并探索其潜在机制。材料和方法模拟HepG2细胞在30 mM葡萄糖中培养24 h,观察GRg1对细胞葡萄糖消耗和磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B (AKT)/糖原合成酶激酶-3β (GSK-3β)通路关键激酶的影响。为了评估PI3K/AKT/GSK-3β通路是否在GRg1对胰岛素抵抗的保护作用中起关键作用,我们使用了抑制PI3K的化合物LY294002。结果在HepG2细胞中,GRg1显著增加葡萄糖摄取,但无细胞毒性。此外,GRg1激活了PI3K/AKT/GSK-3β通路,胰岛素受体底物-1 (IRS-1)、AKT和GSK-3β磷酸化增加。LY294002显著逆转了GRg1对细胞葡萄糖消耗和PI3K/AKT/GSK-3β通路激活的促进作用。综上所述,我们的研究表明GRg1通过PI3K/AKT/GSK-3β通路对高糖诱导的肝脏胰岛素抵抗具有保护作用,提示其可能是一种有益的治疗药物。
{"title":"GRg1 Ameliorates Insulin Resistance Through Activation of the PI3K/AKT/GSK-3β Pathway in HepG2 Cells","authors":"Xunjun Shen, Yamei Jin, Yuting Chen, Huadi Yang","doi":"10.1177/09731296231198284","DOIUrl":"https://doi.org/10.1177/09731296231198284","url":null,"abstract":"Background Insulin resistance (IR) is a pathological state closely associated with various diseases, with hepatic insulin resistance playing a pivotal role. Insulin resistance can be improved by Ginsenoside Rg1 (GRg1), which is known as one of the most biologically active compounds found in ginseng. Nevertheless, the precise role and mechanisms of GRg1 in ameliorating hepatic insulin resistance are still unknown. Objectives We wanted to demonstrate the impact of GRg1 on hepatic insulin resistance and explore the underlying mechanisms in our work. Materials and Methods We mimicked insulin resistance conditions by culturing HepG2 cells in 30 mM glucose for 24 h. The effects of GRg1 on cellular glucose consumption and the key kinases of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β) pathway were evaluated. To assess if the PI3K/AKT/GSK-3β pathway is crucial for GRg1’s protective effect against insulin resistance, the compound LY294002, which inhibits PI3K, was employed. Results In HepG2 cells, GRg1 markedly increased glucose uptake while exhibiting no cytotoxicity. Additionally, GRg1 activated the PI3K/AKT/GSK-3β pathway, as indicated by the increased phosphorylation of insulin receptor substrates-1 (IRS-1), AKT, and GSK-3β. Treatment with LY294002 significantly reversed the promotive effects of GRg1 on cellular glucose consumption and PI3K/AKT/GSK-3β pathway activation. Conclusion Taken together, our present study revealed GRg1 exerted a protective effect against hepatic insulin resistance induced by high glucose through PI3K/AKT/GSK-3β pathway, suggesting its potential as a beneficial therapeutic medication.","PeriodicalId":19895,"journal":{"name":"Pharmacognosy Magazine","volume":"52 18","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135820139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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