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Eggplant (Solanum melongena L.) extract improves glucose uptake in LPS-induced inflammation in Caco-2/macrophages co-culture model 在Caco-2/巨噬细胞共培养模型中,茄子提取物可改善脂多糖诱导炎症的葡萄糖摄取
IF 1.8 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-12-04 DOI: 10.1007/s13596-024-00806-6
Atcharaporn Ontawong, Doungporn Amornlerdpison, Teerawat Rattanaphot, Sirinat Pengnet, Kullanat Kuntakhut

The inflammatory bowel disease (IBD) patients have increased intestinal glucose absorption associated with hyperglycemia and diabetes mellitus. Thus, IBD treatment might minimize diabetic mellitus risk. Eggplant extract is frequently prescribed in traditional Chinese medicine and is effective against various diseases, including cancer, cardiovascular disease, and respiratory infections. It contains active compounds; chlorogenic acid (CGA) exhibits anti-inflammatory and anti-hyperglycemic effects. However, the effect of eggplant extract (EPE) on intestinal glucose uptake in IBD is unknown. Thus, this study uses LPS-induced inflammation in a co-culture model to mimic IBD. This work determined the impact of EPE glucose transport in the inflammatory co-culture model—the caco-2 cells in a transwell insert plate on LPS-induced inflammatory THP-1-derived macrophages. Caco-2 cells were treated with various doses of EPE. Inflammatory parameters and intestinal glucose transport function of Caco-2 cells were studied. It was observed that EPE inhibited proinflammatory cytokine gene expression and production. Furthermore, EPE inhibited intestinal glucose absorption under inflammatory conditions. These data suggested that EPE may attenuate inflammatory conditions and glucose absorption in the inflammatory co-cultures model; however, the molecular mechanisms underlying the effects of EPE must be evaluated through further investigation.

Graphical Abstract

炎症性肠病(IBD)患者与高血糖和糖尿病相关的肠道葡萄糖吸收增加。因此,IBD治疗可能会降低糖尿病的风险。茄子提取物经常在中医处方中使用,对多种疾病有效,包括癌症、心血管疾病和呼吸道感染。它含有活性化合物;绿原酸(CGA)具有抗炎和抗高血糖作用。然而,茄子提取物(EPE)对IBD患者肠道葡萄糖摄取的影响尚不清楚。因此,本研究在共培养模型中使用lps诱导的炎症来模拟IBD。本研究确定了炎症共培养模型(transwell插入板中的caco-2细胞)中EPE葡萄糖运输对lps诱导的炎性thp -1来源的巨噬细胞的影响。用不同剂量的EPE处理Caco-2细胞。研究Caco-2细胞炎症参数及肠道葡萄糖转运功能。观察到EPE能抑制促炎细胞因子基因的表达和产生。此外,EPE在炎症条件下抑制肠道葡萄糖吸收。这些数据表明,EPE可以减轻炎症共培养模型中的炎症状况和葡萄糖吸收;然而,EPE作用的分子机制必须通过进一步的研究来评估。图形抽象
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引用次数: 0
Molecular mechanisms of apoptosis induction in KG1a leukemia cells by the Ginkgo biloba extract (EGb) 银杏叶提取物诱导KG1a白血病细胞凋亡的分子机制
IF 1.3 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-25 DOI: 10.1007/s13596-024-00804-8
Farshid Babaei, Soroor Abdzadeh, Nadereh Bakhshandeh, Zahra Derakhshandeh, Mohammad Javad Dehghan-Nayeri, Mohammad Reza Sarafraz Ardakani, Esmaeil Babaei, Majid Mahdavi

Ginkgo biloba is a traditional medicinal herb with anti-cancer, anti-viral, anti-inflammatory, and liver protective properties. In here, we investigated several variables related to Ginkgo biloba extract (EGb)-induced apoptosis in human acute myeloid leukemia KG1a cells. The MTT method was used to quantify cell survival. Following Hoechst 33,258 staining, an inverted microscope to examine the appearance of apoptotic cells was used. Furthermore, to determine the ratio of necrotic to apoptotic cells, annexin V-FITC, propidium iodide (PI) double staining was performed. Using flow cytometry analysis, alterations in the cell cycle were examined. Using the appropriate reagent kits, the activities of caspase-3 was examined. Alterations in multiple apoptosis-associated gene expression were evaluated using a quantitative real-time PCR technique. The MTT results demonstrated that EGb dramatically and dose-dependently reduced the viability of KG1a cells. EGb causes KG1a cells to contract and produce more apoptotic bodies according to observations of their morphology. According to cell cycle studies, EGb arrested the cells in the S phase of cell cycle. The validity of the cell cycle data was confirmed by the decrease in cyclin A expression, and the increase in the expression of p53, p21, cyclin E, and CDK2. qRT-PCR analysis revealed that EGb induces apoptosis by reducing Survivin, raising Noxa, and causing a time-dependent increase in Bax/Bcl-2 transcript. These results suggest EGb induces cell death, potentially offering a promising treatment approach for acute myeloid leukemia.

银杏是一种传统的草药,具有抗癌、抗病毒、抗炎和保护肝脏的特性。在这里,我们研究了与银杏叶提取物(EGb)诱导的人急性髓性白血病KG1a细胞凋亡相关的几个变量。MTT法定量细胞存活。在Hoechst 33258染色后,倒置显微镜观察凋亡细胞的外观。此外,通过膜联蛋白V-FITC、碘化丙啶(PI)双染色测定坏死细胞与凋亡细胞的比例。采用流式细胞术分析,检测细胞周期的变化。采用相应的试剂盒检测caspase-3的活性。使用实时定量PCR技术评估多种凋亡相关基因表达的变化。MTT结果表明,EGb显著且剂量依赖性地降低了KG1a细胞的活力。根据形态学观察,EGb使KG1a细胞收缩,产生更多凋亡小体。根据细胞周期研究,EGb阻滞细胞处于细胞周期的S期。细胞周期数据的有效性通过cyclin A表达的减少,p53、p21、cyclin E和CDK2表达的增加得到证实。qRT-PCR分析显示,EGb通过降低Survivin,提高Noxa,并引起Bax/Bcl-2转录物的时间依赖性增加来诱导细胞凋亡。这些结果表明,EGb诱导细胞死亡,可能为急性髓系白血病提供一种有希望的治疗方法。
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引用次数: 0
Exploring the therapeutic potential of Ixora extract: a comprehensive review of mediated studies 探索Ixora提取物的治疗潜力:对介导研究的全面回顾
IF 1.8 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-13 DOI: 10.1007/s13596-024-00797-4
Rabiyah Nadeem, Muhammad Imran, Zohaib Saeed, Muhammad Pervaiz, Umer Younas

Traditional Herbal Medicine Systems, commonly known as Complementary and Alternative Systems of Medicine, is currently one of the most extensively researched subjects. The genus Ixora belongs to the family Rubiaceae, which is commonly referred to as the Madder family. It comprises 500 species and is one of the most investigated herbs today. For centuries, ethnic groups have incorporated various parts of the Ixora plant (flowers, leaves, stems, and roots) into Ayurvedic medicine to treat a range of ailments, including hepatic disorders, diarrhea, cancer, tumors, microbial infections, antioxidants, pain, ulcers, anti-tumor properties, and anti-inflammatory effects. Due to the extensive use of the Ixora genus in traditional medicine, researchers were compelled to examine the phytochemical composition of its various species. Multiple studies on the genus Ixora, which belongs to the Rubiaceae family, have uncovered a rich assortment of phenolic compounds. These include flavonoids, tannins, aromatic acrid oils, poly-sterols, saponins, carbohydrates, fatty acids, peptides, and terpenoids. Over the past 50 years, extensive phytochemical studies have been conducted on the genus Ixora, these studies have not only revealed the composition of the plant extract, but they have also helped to develop a comprehensive pharmacological profile. In doing so, these studies have provided scientific evidence supporting the ethno-medicinal uses of the plant. Every part of various Ixora species is said to possess beneficial properties which have added to its value as a medicinal plant. The purpose of this review is to thoroughly analyze the phytochemical and pharmacological properties of the Ixora genus. Along the way present an updated and categorized compilation of the scientific evidence of its medicinal properties. As a result, it aims to inspire scholars to pursue additional research on this particular genus.

Graphical abstract

传统草药系统,通常被称为补充和替代医学系统,是目前最广泛研究的课题之一。Ixora属属于茜草科,通常被称为茜草科。它包括500种,是当今研究最多的草药之一。几个世纪以来,少数民族将伊克罗拉植物的各个部分(花、叶、茎和根)纳入阿育吠陀药物中,以治疗一系列疾病,包括肝病、腹泻、癌症、肿瘤、微生物感染、抗氧化剂、疼痛、溃疡、抗肿瘤特性和抗炎作用。由于Ixora属在传统医学中的广泛使用,研究人员不得不检查其不同物种的植物化学成分。对Ixora属的多种研究,属于Rubiaceae家族,已经发现了丰富的酚类化合物。这些包括类黄酮、单宁、芳香辛辣油、多元甾醇、皂苷、碳水化合物、脂肪酸、多肽和萜类。在过去的50年里,对Ixora属进行了广泛的植物化学研究,这些研究不仅揭示了植物提取物的组成,而且还有助于建立全面的药理学概况。在这样做的过程中,这些研究提供了支持该植物的民族医药用途的科学证据。据说,各种Ixora物种的每一部分都具有有益的特性,这增加了它作为药用植物的价值。本文综述的目的是全面分析Ixora属的植物化学和药理特性。在此过程中,介绍了其药用特性的最新和分类的科学证据汇编。因此,它旨在激励学者们对这一特殊属进行进一步的研究。图形抽象
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引用次数: 0
Ethnobotanical study of woody medicinal plants used in the traditional pharmacopoeia in the three sub-division of the Mayo-Tsanaga department (Far North, Cameroon) 传统药典中使用的木本药用植物的民族植物学研究在梅奥-察那加省的三个分部(喀麦隆远北)
IF 1.3 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-05 DOI: 10.1007/s13596-024-00796-5
Nai Emmanuel, Tchobsala Daniel, Megueni Clautilde

The conservation and rational management of medicinal plants require preliminary studies of ethnobotanical. It is for this reason that the present study on the woody medicinal plants of the three sub-division of Mayo-Tsanaga subjected to anarchic exploitation was undertaken. The aim of this study was to contribute to a better understanding of woody medicinal plants used in traditional pharmacopoeia, with a view to their sustainable management for conservation and use by the population. The study was carried out with herbalists, traditional practitioners, phytotherapists or any other person who uses plants for therapeutic purposes in three sub-divisions of the Mayo-Tsanaga division through the use of ethnobotanical survey forms. The results were processed using Statgraphics plus 5.0 version 11.0 and the Excel spreadsheet program. Following our series of surveys, the studies enabled us to identify 97 plant species used in the traditional medicine, belonging to 72 genera and 31 families. The most represented families are Fabaceaea (21 species), Combretaceae (9 species), Anacardiaceae (8 species) and Malvaceae (7 species). The most popular species used in traditional pharmacopoeia were Boswellia dalzielii (81.3%), Khaya senegalensis (80.3%), Ximenia americana (78.2%), Bauhinia rufescens (73.4%), Tamarindus indica (77.4%), Haematostaphis barteri (73.6%), Sarcocephalus latifolius (73.9%), Kigelia africana (71.8%), Guiera senegalensis (70.8%) and Sclerocarya birrea (69.3%).The results of this study showed that the bark was the most frequently plant part used in the preparation of medicine. The majority of traditional medicines were prepared in the form of decoction and oral route is their common mode of administration. This study is a source of information that contribute to the knowledge of medicinal plant flora with a view to sustainable management and to safeguard of the local popular know-how. It can also be used as a database for developing this valuable resource with a view of discovering new active ingredients for use in pharmacology and the pharmaceutical industry.

药用植物的保护和合理管理需要对民族植物学进行初步研究。因此,本文对梅奥-察那加三个分支遭受无政府开发的木本药用植物进行了研究。本研究的目的是为了更好地了解传统药典中使用的木本药用植物,以期对其进行可持续管理,以供种群保护和利用。通过使用民族植物学调查表格,在Mayo-Tsanaga分部的三个分部与草药医师、传统从业者、植物治疗师或任何其他将植物用于治疗目的的人进行了研究。使用Statgraphics plus 5.0 version 11.0和Excel电子表格程序处理结果。通过一系列调查,我们鉴定出了97种中药植物,隶属于31科72属。代表性科为豆科(21种)、combretacae科(9种)、Anacardiaceae(8种)和malvacae科(7种)。传统药典中使用最多的种为:达氏乳香(81.3%)、塞内加尔海参(80.3%)、美洲Ximenia(78.2%)、紫荆(73.4%)、印度柽柳(77.4%)、巴氏血丝虫(73.6%)、latifolcephalus Sarcocephalus(73.9%)、非洲Kigelia(71.8%)、塞内加尔Guiera senegalensis(70.8%)和birclerocarya(69.3%)。本研究结果表明,树皮是制备药物中最常用的植物部分。传统药物以汤剂为主,口服给药是其常用的给药方式。这项研究是一个信息来源,有助于了解药用植物区系,以期可持续管理和保护当地的流行知识。它也可以作为开发这一宝贵资源的数据库,以发现新的有效成分用于药理学和制药工业。
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引用次数: 0
The possible involvement of KATP channels in cholestatic pruritus in mice 小鼠胆汁淤积性瘙痒中KATP通道的可能参与
IF 1.3 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-04 DOI: 10.1007/s13596-024-00802-w
Arya Afrooghe, Maryam Shayan, Nazgol-Sadat Haddadi, Asma Rashki, Shahabaddin Solaimanian, Maryam Shokrian Zeini, Ahmad-Reza Dehpour

Cholestatic itch dramatically impairs the quality of life of affected patients; however, the therapeutic choices are limited and far from sufficient. ATP-sensitive potassium channels (KATP channels) contribute to transmitting signals, including itch. Here, we investigated the role of KATP channels in cholestatic pruritus in mice induced by bile duct ligation (BDL). KATP channel openers (diazoxide and minoxidil) and blockers (glibenclamide) were administered via the intraperitoneal route in BDL and sham-operated (Sham) mice. After the open-field test, the scratching behavior in response to the intradermal vehicle injection was videotaped for one hour. We investigated the probable alterations in the dermal expression of genes encoding the KATP channel (Kcnj8 and Kcnj11) via RT-qPCR analysis. We detected increased scratching responses in cholestatic mice regarding intradermal vehicle injection, representing cholestatic pruritus. KATP channel openers, diazoxide (10 mg/kg, i.p.), and minoxidil (10 mg/kg, i.p.) attenuated scratching responses in the bile duct ligated mice. On the other hand, KATP channel blocker glibenclamide (3 mg/kg, i.p.) intensified the scratching behavior. Moreover, pre-treatment with the sub-effective dose of glibenclamide (1 mg/kg, i.p.) reversed the anti-pruritic effects of diazoxide (10 mg/kg, i.p.) and minoxidil (10 mg/kg, i.p.). The open-field test revealed that the scratching behavior was not affected by locomotor activity. Our finding of RT-qPCR analysis also showed an increase in the expression of Kcnj11 in BDL mice. We conclude that KATP channels are possibly involved in cholestatic itch. Further studies are needed to elucidate the other associations between cholestasis and itch.

胆汁淤积性瘙痒严重损害患者的生活质量;然而,治疗的选择是有限的,远远不够。atp敏感钾通道(KATP通道)有助于传递信号,包括瘙痒。在此,我们研究了KATP通道在胆管结扎(BDL)引起的小鼠胆汁淤积性瘙痒中的作用。在BDL和假手术(Sham)小鼠中通过腹腔给药KATP通道打开剂(二氮和米诺地尔)和阻滞剂(格列本脲)。裸场试验结束后,对皮内车辆注射后的抓痕行为进行1小时的录像。我们通过RT-qPCR分析研究了编码KATP通道的基因(Kcnj8和Kcnj11)在皮肤表达中的可能变化。我们检测到胆汁淤积小鼠在皮内注射时抓挠反应增加,这代表了胆汁淤积性瘙痒。KATP通道开放剂、二氮氧化合物(10mg /kg, i.p)和米诺地尔(10mg /kg, i.p)可减轻胆管结扎小鼠的抓伤反应。另一方面,KATP通道阻滞剂格列本脲(3mg /kg, i.p)加剧了抓伤行为。此外,用亚有效剂量的格列苯脲(1mg /kg, i.p)预处理可以逆转二氮氧化合物(10mg /kg, i.p)和米诺地尔(10mg /kg, i.p)的止痒作用。野外实验显示,运动活动对抓痕行为没有影响。我们的RT-qPCR分析也显示Kcnj11在BDL小鼠中的表达增加。我们得出结论,KATP通道可能参与胆汁淤积性瘙痒。需要进一步的研究来阐明胆汁淤积和瘙痒之间的其他联系。
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引用次数: 0
Curcumin and 2-DG synergistically target the glio-oncogenesis trigger IL-6 and down-regulate the stemness in glioblastoma model in-vitro 姜黄素和2-DG协同靶向胶质母细胞瘤模型中胶质肿瘤发生触发因子IL-6并下调干细胞性
IF 1.8 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-30 DOI: 10.1007/s13596-024-00800-y
Kavita Peter, Puneet Gandhi, Santosh Kumar Kar

Glioblastoma is the most lethal brain tumor; despite available multimodal therapies. This poor survival is an outcome of many contributing factors the major is resistance due to inflammation and the presence of a subset of cells called glial stem-cells (GSCs). A rationale combination of drugs which act by targeting multiple mechanisms to inhibit cancer cells and GSCs would be more potent in abrogating chemoresistance. In this study, we aimed to target cancer hallmarks using a natural polyphenol in combination with 2-deoxyglucose, a glycolytic inhibitor on the heterogeneous human U-87 Glioblastoma model. The U-87 glioblastoma cells were treated with curcumin, 2-deoxyglucose and combination of both. Cell proliferation was determined by MTT assay and combination index was analyzed. Cell cycle inhibition and apoptosis were assessed by flow cytometry. The tumorigenicity of the cells was evaluated by clonogenic and soft agar assay. Migration efficacy of the cells was assessed by wound healing assay while the inflammation trigger Il-6 was assessed by ELISA. The changes in expression of molecular marker of stemness were analyzed by immuno-cytochemistry. Curcumin enhanced the cytotoxic effect of 2-deoxyglucose in GB cancer cells. The combination of CUR (20µM) and 2-DG (4mM) showed a synergistic effect in reducing cell viability with a combination index of less than 0.9. The polyphenol induced apoptosis, arrested the cells in S and G2/M phase of the cell cycle, inhibited anchorage dependent, anchorage independent clone forming efficacy, cell migration capacity as well as stemness while 2-DG downregulated IL-6 expression potently. Our novel combination exhibited the potential to reduce glio-oncogenesis trigger Il-6 and inhibit GSCs responsible for relapse and resistance. The study suggests that our tailor-made combination using established drugs can target multiple cancer signaling molecules to yield optimal therapeutic outcome and is the right approach to address stemness attributed resistance.

胶质母细胞瘤是最致命的脑肿瘤;尽管有多模式治疗。这种低存活率是许多因素共同作用的结果,主要是炎症引起的耐药性和一种称为神经胶质干细胞(GSCs)的细胞亚群的存在。通过靶向多种机制来抑制癌细胞和GSCs的药物组合将更有效地消除化疗耐药。在这项研究中,我们的目标是使用天然多酚与2-脱氧葡萄糖(一种糖酵解抑制剂)联合在异质人U-87胶质母细胞瘤模型上靶向癌症特征。用姜黄素、2-脱氧葡萄糖及两者联合治疗U-87胶质母细胞瘤细胞。MTT法测定细胞增殖情况,并分析联合指数。流式细胞术检测细胞周期抑制和细胞凋亡。用克隆法和软琼脂法评价细胞的致瘤性。采用创面愈合法检测细胞迁移效能,ELISA法检测炎症触发因子Il-6。用免疫细胞化学方法分析干性分子标志物的表达变化。姜黄素增强了2-脱氧葡萄糖对GB癌细胞的细胞毒作用。CUR(20µM)和2-DG (4mM)联合使用对细胞活力有协同降低作用,联合指数小于0.9。多酚诱导细胞凋亡,阻滞细胞周期S期和G2/M期,抑制锚定依赖性、锚定非依赖性克隆形成效率、细胞迁移能力和细胞干性,2-DG显著下调IL-6表达。我们的新组合显示出减少神经胶质瘤发生触发因子Il-6和抑制负责复发和耐药性的GSCs的潜力。该研究表明,我们使用现有药物的量身定制组合可以针对多种癌症信号分子产生最佳治疗效果,是解决干细胞耐药的正确方法。
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引用次数: 0
Protective effects of Sphaeranthus indicus floral extract against BPS-induced testicular damage in rats occurs through downregulation of RIPK1/3-MLK-driven necroptosis and Fas-FasL-mediated apoptosis 白球花提取物对bps诱导的大鼠睾丸损伤的保护作用是通过下调ripk1 /3- mlk驱动的坏死下垂和fas - fasl介导的细胞凋亡来实现的
IF 1.8 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-29 DOI: 10.1007/s13596-024-00803-9
Shabnoor Iqbal, Timothy Omara, Ivan Kahwa, Usman Mir Khan

Bisphenol S (BPS) is one of the monomers preferred in the manufacturing of polycarbonate plastics. Unfortunately, its estrogenic and genotoxic effects are similar to those of bisphenol A. The protective effects of Sphaeranthus indicus floral extract (SFE) against reprotoxic effects of BPS (50 µg/kg per body weight) in rats exposed to it via drinking water was investigated. Different SFE doses (25, 50, and 100 mg/kg) were administered via oral gavage for 10 weeks. High-performance liquid chromatography (HPLC) results indicated that SFE was rich in polyphenols, with rutin and quercetin being important bioactive molecules modulating BPS-induced necroptosis and apoptosis. Biochemical analyses unveiled that rats administered BPS only exhibited considerable elevation of biomarkers of nitro-oxidative stress, necroptotic (RIPK1/RIPK3 and MLKL), and apoptotic mediators (Fas/FasL and caspase 3/caspase-8). These events caused changes in sperm characteristics (sperm motility, sperm head, and sperm viability), sperm count, and hormonal profile (thyroid stimulating hormone, luteinizing hormone, and follicle-stimulating hormone) of the rats. Histological analysis suggested that there was pronounced sloughing of Sertoli cells, reduced spermatogenic cell density, increased levels of seminiferous tubules, and disorganized morphometric parameters related to seminiferous tubules. The SFE supplementation in rats with BPS-containing water restored nitro-oxidative stress biomarkers, which led to the reduction of necroptosis and apoptosis. Reinstatement of all the biomarkers of oxidative stress, inflammation, necroptosis, and apoptosis after SFE supplementations restored the hormonal profile and normal histoarchitecture of the testes. Virtual screening elucidated that the key regulators of the necroptosis are RIPK3-rutin and RIPK1-quercetin complexes. Further studies are needed to assess its pharmacodynamics, kinetics, and effective concentration for daily use in humans.

双酚S (BPS)是制造聚碳酸酯塑料的首选单体之一。结果表明,Sphaeranthus indicus花提取物(Sphaeranthus indicus flower extract, SFE)对BPS(50µg/kg /体重)对大鼠生殖毒性的保护作用与双酚a相似。不同剂量的SFE(25、50和100 mg/kg)灌胃10周。高效液相色谱(HPLC)结果表明,SFE中含有丰富的多酚类物质,其中芦丁和槲皮素是调节bps诱导的坏死坏死和细胞凋亡的重要生物活性分子。生化分析显示,给予BPS的大鼠仅表现出氮氧化应激、坏死(RIPK1/RIPK3和MLKL)和凋亡介质(Fas/FasL和caspase 3/caspase-8)的生物标志物显著升高。这些事件引起了大鼠精子特征(精子活力、精子头和精子活力)、精子数量和激素特征(促甲状腺激素、促黄体激素和促卵泡激素)的变化。组织学分析表明,支持细胞明显脱落,生精细胞密度降低,精小管水平升高,精小管相关形态学参数紊乱。在含bps水的大鼠中补充SFE可以恢复氮氧化应激生物标志物,从而减少坏死和细胞凋亡。补充SFE后,所有氧化应激、炎症、坏死性下垂和细胞凋亡的生物标志物恢复了睾丸的激素水平和正常的组织结构。虚拟筛选结果表明,ripk3 -芦丁和ripk1 -槲皮素复合物是坏死性坏死的关键调控因子。需要进一步的研究来评估其药效学、动力学和人类日常使用的有效浓度。
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引用次数: 0
Annona muricata ethanolic extract protects BALB/c mice against colitis-associated colon cancer through modulation of cytokine levels and KRAS and APC expression 番荔枝乙醇提取物通过调节细胞因子水平和KRAS和APC表达,保护BALB/c小鼠免受结肠炎相关结肠癌的侵袭
IF 1.8 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-26 DOI: 10.1007/s13596-024-00798-3
María del Rosario Huizar-López, Anne Santerre, Jaime Coronilla-Martínez, Xóchitl Rocío Ávila-Dávila, Pablo Cesar Ortiz-Lazareno, Josefina Casas-Solís

Annona muricata (L.) is used worldwide in folk medicine to treat numerous ailments. In vitro studies have reported that the phytocomponents of this plant have anti-inflammatory, antioxidant, and cytotoxic properties against multiple tumoral cells, including colon cancer cell lines. However, few studies have tested its antitumoral potential in vivo, especially against colitis-associated colon cancer (CAC), whose main risk factor is inflammation. This study assessed, for the first time, the protective properties of A. muricata in a murine model of CAC at the histopathological, immunological, and molecular levels. CAC was induced chemically in BALB/c mice using azoxymethane (AOM) and dextran sulfate salt (DSS). The ethanolic extract of A. muricata leaves was administered preventively or simultaneously with CAC induction. At the end of the experimental period, which lasted six months, colon and liver histopathology were assessed through hematoxylin and eosin staining. Circulating cytokines were evaluated by flow cytometry, and KRAS oncogene and APC tumor-suppressor gene expression by RT-qPCR. The ethanolic extract of A. muricata decreased circulating cytokine levels (IL-10, IL-1β, INF-γ, and IL-12) compared to the AOM-DSS group and protected colon architecture. The preventive administration of A. muricata also decreased the expression of oncogenic KRAS but increased the expression of APC tumor-suppressor mRNA in the colon of BALB/c mice. Administering A. muricata extract alone had no adverse effect on the studied parameters. Hence, our findings support the ethnobotanical use of A. muricata.

Graphical abstract

凤仙花(L.)在世界各地的民间医学中被用来治疗许多疾病。体外研究报道,这种植物的植物成分具有抗炎、抗氧化和对多种肿瘤细胞(包括结肠癌细胞系)的细胞毒性。然而,很少有研究在体内测试其抗肿瘤潜力,特别是对结肠炎相关的结肠癌(CAC),其主要危险因素是炎症。本研究首次从组织病理学、免疫学和分子水平评估了田中草对小鼠CAC模型的保护作用。采用氮氧甲烷(AOM)和硫酸葡聚糖盐(DSS)化学诱导BALB/c小鼠CAC。采用预防性或与CAC诱导同时施用的方法。6个月试验期结束时,采用苏木精和伊红染色法观察大鼠结肠和肝脏组织病理学变化。流式细胞术检测循环细胞因子,RT-qPCR检测KRAS癌基因和APC抑癌基因表达。与AOM-DSS组相比,muricata乙醇提取物降低了循环细胞因子(IL-10、IL-1β、INF-γ和IL-12)水平,并保护了结肠结构。在BALB/c小鼠的结肠中,预防性给药也降低了致癌KRAS的表达,但增加了APC肿瘤抑制mRNA的表达。单独给药对实验参数无不良影响。因此,我们的研究结果支持了muricata的民族植物学用途。图形抽象
{"title":"Annona muricata ethanolic extract protects BALB/c mice against colitis-associated colon cancer through modulation of cytokine levels and KRAS and APC expression","authors":"María del Rosario Huizar-López,&nbsp;Anne Santerre,&nbsp;Jaime Coronilla-Martínez,&nbsp;Xóchitl Rocío Ávila-Dávila,&nbsp;Pablo Cesar Ortiz-Lazareno,&nbsp;Josefina Casas-Solís","doi":"10.1007/s13596-024-00798-3","DOIUrl":"10.1007/s13596-024-00798-3","url":null,"abstract":"<div><p><i>Annona muricata</i> (L.) is used worldwide in folk medicine to treat numerous ailments. In vitro studies have reported that the phytocomponents of this plant have anti-inflammatory, antioxidant, and cytotoxic properties against multiple tumoral cells, including colon cancer cell lines. However, few studies have tested its antitumoral potential in vivo, especially against colitis-associated colon cancer (CAC), whose main risk factor is inflammation. This study assessed, for the first time, the protective properties of <i>A. muricata</i> in a murine model of CAC at the histopathological, immunological, and molecular levels. CAC was induced chemically in BALB/c mice using azoxymethane (AOM) and dextran sulfate salt (DSS). The ethanolic extract of <i>A. muricata</i> leaves was administered preventively or simultaneously with CAC induction. At the end of the experimental period, which lasted six months, colon and liver histopathology were assessed through hematoxylin and eosin staining. Circulating cytokines were evaluated by flow cytometry, and KRAS oncogene and APC tumor-suppressor gene expression by RT-qPCR. The ethanolic extract of <i>A. muricata</i> decreased circulating cytokine levels (IL-10, IL-1β, INF-γ, and IL-12) compared to the AOM-DSS group and protected colon architecture. The preventive administration of <i>A. muricata</i> also decreased the expression of oncogenic KRAS but increased the expression of APC tumor-suppressor mRNA in the colon of BALB/c mice. Administering <i>A. muricata</i> extract alone had no adverse effect on the studied parameters. Hence, our findings support the ethnobotanical use of <i>A. muricata</i>.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":7613,"journal":{"name":"Advances in Traditional Medicine","volume":"25 2","pages":"553 - 565"},"PeriodicalIF":1.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Acupuncture ameliorates liver injury induced by platinum treatment through the Notch signaling pathway 针刺可通过Notch信号通路改善铂治疗所致肝损伤
IF 1.8 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-26 DOI: 10.1007/s13596-024-00799-2
Dongdong Yu, Wenzhe Wang, Xueyuan Du, Yingchun Teng, Liqin Chao, Huanhuan Zhang, Shidong Fan, Xingyu Wei, Chen Zhang

This work aims to investigate whether acupuncture can ameliorate liver injury caused by platinum-based therapy and relevant mechanism. The liver indices of patients receiving and not receiving acupuncture were analyzed based on the clinical statistics, and it was found that after acupuncture treatment, the aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin (ALB), and γ-glutamyltranspeptidase of the patients were significantly improved. Then, the animal experiments were conducted for verification. After treatment with cisplatin (DDP) modeling and acupuncture, the HE and Masson staining results of the livers of mice showed that the liver injuries were reduced, and the indexes of platelets, AST and ALT became normal after acupuncture treatment. The gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that acupuncture may ameliorates liver injury through the Notch signaling pathway. Under the effect of blocker γ-secretase inhibitor (DAPT) for the Notch signaling pathway, the expressions of inflammatory factors and the genes and proteins related to the Notch signaling pathway were all up-regulated, while the alleviation of liver injury by acupuncture was inhibited. These results suggest that acupuncture can ameliorate platinum treatment-induced liver injury through the Notch signaling pathway.

本研究旨在探讨针刺是否能改善铂基疗法所致肝损伤及其机制。通过临床统计分析接受和未接受针灸治疗患者的肝脏指标,发现针灸治疗后,患者的天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、白蛋白(ALB)、γ-谷氨酰转肽酶均有明显改善。然后进行动物实验验证。经顺铂(DDP)造模和针刺治疗后,小鼠肝脏HE、Masson染色结果显示,针刺治疗后肝脏损伤减轻,血小板、AST、ALT指标恢复正常。基因本体论和京都基因与基因组百科富集分析表明,针刺可能通过Notch信号通路改善肝损伤。在Notch信号通路阻断剂γ-分泌酶抑制剂(DAPT)的作用下,炎症因子及Notch信号通路相关基因和蛋白的表达均上调,针刺对肝损伤的缓解作用受到抑制。提示针刺可通过Notch信号通路改善铂治疗所致肝损伤。
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引用次数: 0
Metabolite profiling and wound healing potential of Gynura cusimbua in zebrafish model 斑马鱼模型中虎纹Gynura的代谢物分析和伤口愈合潜力
IF 1.8 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-10-23 DOI: 10.1007/s13596-024-00788-5
Anuradha Moirangthem, Shandyarani Devi Laishram, Sonia Sougrakpam, Sushma Khuraijam, Sharmila Laishram, Sushil K. Chaudhary, Sachin Jorvekar, Roshan M. Borkar, Pulok K. Mukherjee, Nanaocha Sharma

Gynura cusimbua (D. Don) S. Moore is a medicinal plant traditionally used to accelerate wound healing. Scientifically, it has been reported to exhibit anti-inflammatory, anti-ulcer, hypoglycemic and anti-angiogenic activities. However, no report on wound healing activity of this plant has been studied scientifically so far. Thus, our study presents a scientific evaluation of wound healing potential of hydroalcoholic extract of Gynura cusimbua leaves. To identify the major phytoconstituents of hydroalcoholic extract, LCMS analysis was carried out. Protein denaturation inhibition method and membrane stabilization test was utilized to check anti- inflammatory activity of the extract. Caudal fin regeneration experiment on adult zebrafish was conducted to study wound healing potential of the extract. Developmental toxicity was studied in zebrafish embryos to rule out toxicity in the model species after systemic administration of the extract. LCMS analysis detected a total of 774 metabolites consisting of flavonoids, terpenoids, polyphenols, lipids, organic acids, phenolic acids as well as cinnamic and coumaric acid derivatives. In vitro anti-inflammatory tests revealed the extract exhibited anti-inflammatory activity in a dose dependent manner. No developmental toxicity was observed after exposure to the extract. Regeneration of caudal fin was observed in fishes exposed to the extract with significant increase in the 800 µg/mL treatment group at 5dpa and 7dpa. Neutrophil accumulation along the wounded area was observed to be highest at 24hpa. To the best of our knowledge, our study is the first report showing the wound healing potential of Gynura cusimbua with no developmental toxicity after exposure in the zebrafish model.

秋葵(D. Don) S.摩尔是一种药用植物,传统上用于加速伤口愈合。科学上,它已被报道具有抗炎、抗溃疡、降血糖和抗血管生成的活性。然而,目前还没有关于该植物伤口愈合活性的科学研究报道。因此,本研究对虎木叶水酒精提取物的创面愈合潜力进行了科学评价。为了确定水醇提取物的主要植物成分,进行了LCMS分析。采用蛋白变性抑制法和膜稳定法检测提取物的抗炎活性。对成年斑马鱼进行尾鳍再生实验,研究其伤口愈合潜力。在斑马鱼胚胎中研究了发育毒性,以排除系统给药后对模式物种的毒性。LCMS分析共检测到774种代谢物,包括黄酮类、萜类、多酚类、脂类、有机酸、酚酸以及肉桂酸和香豆酸衍生物。体外抗炎试验显示提取物具有剂量依赖性的抗炎活性。暴露于提取物后未观察到发育毒性。在5dpa和7dpa浓度为800µg/mL时,尾鳍再生显著增加。在24hpa时观察到沿伤区中性粒细胞积累最多。据我们所知,我们的研究是第一个在斑马鱼模型暴露后显示Gynura cusimbua伤口愈合潜力而没有发育毒性的报告。
{"title":"Metabolite profiling and wound healing potential of Gynura cusimbua in zebrafish model","authors":"Anuradha Moirangthem,&nbsp;Shandyarani Devi Laishram,&nbsp;Sonia Sougrakpam,&nbsp;Sushma Khuraijam,&nbsp;Sharmila Laishram,&nbsp;Sushil K. Chaudhary,&nbsp;Sachin Jorvekar,&nbsp;Roshan M. Borkar,&nbsp;Pulok K. Mukherjee,&nbsp;Nanaocha Sharma","doi":"10.1007/s13596-024-00788-5","DOIUrl":"10.1007/s13596-024-00788-5","url":null,"abstract":"<div><p><i>Gynura cusimbua</i> (D. Don) S. Moore is a medicinal plant traditionally used to accelerate wound healing. Scientifically, it has been reported to exhibit anti-inflammatory, anti-ulcer, hypoglycemic and anti-angiogenic activities. However, no report on wound healing activity of this plant has been studied scientifically so far. Thus, our study presents a scientific evaluation of wound healing potential of hydroalcoholic extract of <i>Gynura cusimbua</i> leaves. To identify the major phytoconstituents of hydroalcoholic extract, LCMS analysis was carried out. Protein denaturation inhibition method and membrane stabilization test was utilized to check anti- inflammatory activity of the extract. Caudal fin regeneration experiment on adult zebrafish was conducted to study wound healing potential of the extract. Developmental toxicity was studied in zebrafish embryos to rule out toxicity in the model species after systemic administration of the extract. LCMS analysis detected a total of 774 metabolites consisting of flavonoids, terpenoids, polyphenols, lipids, organic acids, phenolic acids as well as cinnamic and coumaric acid derivatives. In vitro anti-inflammatory tests revealed the extract exhibited anti-inflammatory activity in a dose dependent manner. No developmental toxicity was observed after exposure to the extract. Regeneration of caudal fin was observed in fishes exposed to the extract with significant increase in the 800 µg/mL treatment group at 5dpa and 7dpa. Neutrophil accumulation along the wounded area was observed to be highest at 24hpa. To the best of our knowledge, our study is the first report showing the wound healing potential of <i>Gynura cusimbua</i> with no developmental toxicity after exposure in the zebrafish model.</p></div>","PeriodicalId":7613,"journal":{"name":"Advances in Traditional Medicine","volume":"25 2","pages":"537 - 551"},"PeriodicalIF":1.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Advances in Traditional Medicine
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