Oladapo F Fagbohun, Amanda Rollins, Lindsey Mattern, Kendra Cipollini, Hp Vasantha Rupasinghe
Cucumaria frondosa (Gennerus, 1767) or orange-footed sea cucumbers are traditional food and are used as natural sources of anti-diabetic, anti-inflammatory, antioxidant, anti-angiogenic, antimicrobial, and anticancer agents. Currently, the introduction of value-added sea cucumber products to the global market has inspired basic research on frondoside A and other saponins in sea cucumbers. These saponins serve as a means of their chemical defence. However, recent studies revealed that exposure to these saponins can lead to irritating symptoms from aerosolization of various holothurins. Moreover, extraction methods are critical to the bioavailability of various bioactive compounds found in sea cucumbers. Therefore, we have critically reviewed recent studies on the chemistry, biosynthesis, and pharmacological properties of frondoside A. Furthermore, the mechanism of actions of frondoside A was postulated and further studies are required for applications in functional foods, nutraceuticals, and pharmaceuticals. Frondoside A was first discovered from Cucumaria frondosa, and it is involved in protein kinase (PI3K/AKT/ERK1/2/p38 MAPK, RAC/CDC42 PAK1, NFκB/MAPK/JNK, and LXR-β) signalling pathways. It is also involved in the suppression of MYC oncogene transcriptional factors implicated and upregulated in over 70% of cancer types. Future research needs to be aimed at optimized green extraction techniques, efficient delivery methods, safety, and efficacy.
Cucumaria frondosa(Gennerus,1767 年)或橙脚海参是传统食品,被用作抗糖尿病、抗炎、抗氧化、抗血管生成、抗菌和抗癌剂的天然来源。目前,高附加值海参产品进入全球市场,激发了对海参中的海参皂苷 A 和其他皂苷的基础研究。这些皂甙是海参化学防御的一种手段。然而,最近的研究表明,接触这些皂苷可能会因各种全皂甙的气溶胶作用而导致刺激症状。此外,提取方法对海参中各种生物活性化合物的生物利用率至关重要。因此,我们对近期有关海参皂苷 A 的化学、生物合成和药理特性的研究进行了批判性回顾。此外,我们还推测了海参皂苷 A 的作用机制,并对其在功能食品、营养保健品和药品中的应用进行了进一步研究。蛇床子甙 A 最早是从葫芦科植物中发现的,它参与蛋白激酶(PI3K/AKT/ERK1/2/p38 MAPK、RAC/CDC42 PAK1、NFκB/MAPK/JNK 和 LXR-β)信号传导途径。它还参与抑制 MYC 癌基因转录因子,70% 以上的癌症类型都与 MYC 癌基因转录因子有牵连并导致其上调。未来的研究需要以优化绿色提取技术、高效给药方法、安全性和有效性为目标。
{"title":"Frondoside A of Cucumaria frondosa (Gennerus, 1767): Chemistry, biosynthesis, medicinal applications, and mechanism of actions.","authors":"Oladapo F Fagbohun, Amanda Rollins, Lindsey Mattern, Kendra Cipollini, Hp Vasantha Rupasinghe","doi":"10.1093/jpp/rgae059","DOIUrl":"https://doi.org/10.1093/jpp/rgae059","url":null,"abstract":"<p><p>Cucumaria frondosa (Gennerus, 1767) or orange-footed sea cucumbers are traditional food and are used as natural sources of anti-diabetic, anti-inflammatory, antioxidant, anti-angiogenic, antimicrobial, and anticancer agents. Currently, the introduction of value-added sea cucumber products to the global market has inspired basic research on frondoside A and other saponins in sea cucumbers. These saponins serve as a means of their chemical defence. However, recent studies revealed that exposure to these saponins can lead to irritating symptoms from aerosolization of various holothurins. Moreover, extraction methods are critical to the bioavailability of various bioactive compounds found in sea cucumbers. Therefore, we have critically reviewed recent studies on the chemistry, biosynthesis, and pharmacological properties of frondoside A. Furthermore, the mechanism of actions of frondoside A was postulated and further studies are required for applications in functional foods, nutraceuticals, and pharmaceuticals. Frondoside A was first discovered from Cucumaria frondosa, and it is involved in protein kinase (PI3K/AKT/ERK1/2/p38 MAPK, RAC/CDC42 PAK1, NFκB/MAPK/JNK, and LXR-β) signalling pathways. It is also involved in the suppression of MYC oncogene transcriptional factors implicated and upregulated in over 70% of cancer types. Future research needs to be aimed at optimized green extraction techniques, efficient delivery methods, safety, and efficacy.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283961","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}
Qingman Luo, Qiao Liu, Kecheng Tang, Bin Zhong, Shengqian Yang, Xiaohui Li
Objectives: Prolonged exposure to chronic hypertension places the heart under excessive strain, resulting in myocardial remodeling. Phillyrin, derived from the natural plant Forsythia suspensa, has been found to possess cardioprotective properties. The objective of this study is to investigate the role and mechanism of phillyrin in hypertension-induced myocardial remodeling in mice.
Methods: We constructed a mouse model of salt-sensitive hypertension. The mice were treated with varying doses of phillyrin, and their blood pressure, cardiac function, cardiac hypertrophy, fibrosis, inflammation, and other conditions were assessed.
Key findings: Our research findings demonstrated that phillyrin has the potential to lower blood pressure, enhance cardiac function, and mitigate cardiac hypertrophy, fibrosis, and inflammatory responses in deoxycorticosterone acetate-salt hypertension mice. In hypertensive mice, there was an elevated expression of endothelin1 (ET-1) in heart tissue, which can be reduced by phillyrin. Additionally, phillyrin effectively reduced the hypertrophy of H9c2 cells induced by ET-1 stimulation.
Conclusions: Our research highlights the therapeutic capabilities of phillyrin in the treatment of myocardial remodeling through the reduction of ET-1 signaling. These results contribute to the advancement of novel applications for phillyrin and establish a solid conceptual basis for future investigations in this area.
{"title":"Phillyrin improves myocardial remodeling in salt-sensitive hypertensive mice by reducing endothelin1 signaling.","authors":"Qingman Luo, Qiao Liu, Kecheng Tang, Bin Zhong, Shengqian Yang, Xiaohui Li","doi":"10.1093/jpp/rgae018","DOIUrl":"10.1093/jpp/rgae018","url":null,"abstract":"<p><strong>Objectives: </strong>Prolonged exposure to chronic hypertension places the heart under excessive strain, resulting in myocardial remodeling. Phillyrin, derived from the natural plant Forsythia suspensa, has been found to possess cardioprotective properties. The objective of this study is to investigate the role and mechanism of phillyrin in hypertension-induced myocardial remodeling in mice.</p><p><strong>Methods: </strong>We constructed a mouse model of salt-sensitive hypertension. The mice were treated with varying doses of phillyrin, and their blood pressure, cardiac function, cardiac hypertrophy, fibrosis, inflammation, and other conditions were assessed.</p><p><strong>Key findings: </strong>Our research findings demonstrated that phillyrin has the potential to lower blood pressure, enhance cardiac function, and mitigate cardiac hypertrophy, fibrosis, and inflammatory responses in deoxycorticosterone acetate-salt hypertension mice. In hypertensive mice, there was an elevated expression of endothelin1 (ET-1) in heart tissue, which can be reduced by phillyrin. Additionally, phillyrin effectively reduced the hypertrophy of H9c2 cells induced by ET-1 stimulation.</p><p><strong>Conclusions: </strong>Our research highlights the therapeutic capabilities of phillyrin in the treatment of myocardial remodeling through the reduction of ET-1 signaling. These results contribute to the advancement of novel applications for phillyrin and establish a solid conceptual basis for future investigations in this area.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049729","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}
Junjie Zhang, Ao Qi, Jing Shen, Lulu Liu, Chun Cai, Hui Xu
Objectives: Coptisine (Cop), an alkaloid isolated from Rhizoma Coptidis, has a protective effect against central nervous system diseases such as cerebral ischaemia-reperfusion (IR). Dysregulations in fatty acids metabolism are associated with neuroprotection and neuroinflammation. However, the effect of Cop on fatty acids metabolomics during anti-IR remains unclear.
Methods: Cerebral IR rats were established by middle cerebral artery occlusion, and the therapeutic effect of Cop was evaluated by 2, 3, 5-triphenytetrazolium chloride staining and neurological deficits scores. By liquid chromatography-tandem mass spectrometry (LC-MS/MS), fatty acids metabolomics analysis in ischaemic hemisphere and serum were investigated.
Results: We observed Cop (2 mg/kg/qd) was able to reduce cerebral infarct size and ameliorate the neurological function score. Meanwhile decrease in tumour necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) after Cop treatment. Compared with control, down-regulation of cyclopentenone PGs (e.g., PGA2, PGJ2, and 15-deoxy- delta-12,14-PGJ2) was observed in cerebral IR, but upregulation of them when followed by Cop treatment. Similarly, we found the ratios of 14,15-dihydroxyeicosatrienoic acid(14,15-DHET)/arachidonic acid and 11,12-DHET/arachidonic acid was lower in cerebral IR injury relative to control, while their ratios were increased after Cop treatment.
Conclusion: Our results indicated that Cop protect against cerebral IR injury, and its mechanism might be closely associated with antiinflammation and the regulation of arachidonic acid metabolism.
目的:从黄连中分离出的一种生物碱--黄连碱(Cop)对脑缺血再灌注等中枢神经系统疾病具有保护作用。脂肪酸代谢失调与神经保护和神经炎症有关。然而,Cop 对抗 IR 期间脂肪酸代谢组学的影响仍不清楚:方法:通过大脑中动脉闭塞建立脑 IR 大鼠,并通过 2,3,5-三苯基氯化四氮唑染色和神经功能缺损评分评估 Cop 的治疗效果。通过液相色谱-串联质谱法(LC-MS/MS),研究了缺血半球和血清中脂肪酸代谢组学分析:结果:我们观察到科普(2 毫克/千克/天)能够缩小脑梗塞面积,改善神经功能评分。同时,经 Cop 治疗后,肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)均有所下降。与对照组相比,环戊烯酮类 PGs(如 PGA2、PGJ2 和 15-脱氧-δ-12,14-PGJ2)在脑 IR 中出现下调,但在 Cop 治疗后出现上调。同样,我们发现在脑 IR 损伤中,14,15-二羟基二十碳三烯酸(14,15-DHET)/花生四烯酸和 11,12-DHET/ 花生四烯酸的比例相对于对照组较低,而在经过 Cop 治疗后,它们的比例上升:我们的研究结果表明,Cop 对脑 IR 损伤有保护作用,其机制可能与抗炎和调节花生四烯酸代谢密切相关。
{"title":"Coptisine protects against transient focal cerebral ischaemic injury by regulation of arachidonic acid metabolism.","authors":"Junjie Zhang, Ao Qi, Jing Shen, Lulu Liu, Chun Cai, Hui Xu","doi":"10.1093/jpp/rgae026","DOIUrl":"10.1093/jpp/rgae026","url":null,"abstract":"<p><strong>Objectives: </strong>Coptisine (Cop), an alkaloid isolated from Rhizoma Coptidis, has a protective effect against central nervous system diseases such as cerebral ischaemia-reperfusion (IR). Dysregulations in fatty acids metabolism are associated with neuroprotection and neuroinflammation. However, the effect of Cop on fatty acids metabolomics during anti-IR remains unclear.</p><p><strong>Methods: </strong>Cerebral IR rats were established by middle cerebral artery occlusion, and the therapeutic effect of Cop was evaluated by 2, 3, 5-triphenytetrazolium chloride staining and neurological deficits scores. By liquid chromatography-tandem mass spectrometry (LC-MS/MS), fatty acids metabolomics analysis in ischaemic hemisphere and serum were investigated.</p><p><strong>Results: </strong>We observed Cop (2 mg/kg/qd) was able to reduce cerebral infarct size and ameliorate the neurological function score. Meanwhile decrease in tumour necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) after Cop treatment. Compared with control, down-regulation of cyclopentenone PGs (e.g., PGA2, PGJ2, and 15-deoxy- delta-12,14-PGJ2) was observed in cerebral IR, but upregulation of them when followed by Cop treatment. Similarly, we found the ratios of 14,15-dihydroxyeicosatrienoic acid(14,15-DHET)/arachidonic acid and 11,12-DHET/arachidonic acid was lower in cerebral IR injury relative to control, while their ratios were increased after Cop treatment.</p><p><strong>Conclusion: </strong>Our results indicated that Cop protect against cerebral IR injury, and its mechanism might be closely associated with antiinflammation and the regulation of arachidonic acid metabolism.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140189886","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}
Reem Fekry Diab, Tamer M Abdelghany, Shadeed Gad, Asmaa M Elbakry
Purpose: Although resveratrol (RES) is an efficacious molecule, its therapeutic activity is impeded by significant limitations, such as rapid oral absorption, poor oral bioavailability, and low water solubility. Therefore, the preparation of RES in different pharmaceutical carriers represents an important tool to enhance its therapeutic applications. This study aims to potentiate the anti-cancer activity of RES by formulating it into a novel nanocarrier called Smart Lipid.
Methods: RES-loaded Smart Lipids were prepared by high-shear hot homogenization method utilizing a 21 × 32 factorial design with three factors at different levels: the total lipid concentration, the concentration of surfactant, and the type of surfactant. The responses were evaluated based on entrapment efficiency percentages and particle size.
Results: Our novel optimized RES-loaded Smart Lipid formula showed small particle size (288.63 ± 5.55 nm), good zeta potential (-16.44 ± 0.99 mV), and an entrapment efficiency of 86.346 ± 3.61% with spherical, clearly distinct, and no signs of fusion by transmission electron microscopy. Further characterization was done using differential scanning calorimetry, which showed no interaction between the drug and other components as the optimum lyophilized formula showed a peak at 54.75°C, which represents the lipid mixture, with an undetectable characteristic peak of the drug, which indicates entrapment of the drug, and the structure of the compounds was confirmed by Fourier transform-infrared spectroscopy, in which the majority of the drug's characteristic peaks disappeared when loaded into Smart Lipid, which may indicate Smart Lipid's ability to reduce the stretching and bending between bonds in RES. In addition, the optimized formula showed a sustained release pattern compared to RES suspension. Finally, the cytotoxic activity of the optimized RES-loaded Smart Lipid on different cell lines (human breast adenocarcinoma (MCF7), human hepatocellular carcinoma (HepG2), and human colon cancer cells (HT29)) was assessed through MTT assay (7-fold reduction in the IC50, from 3.7 ± 0.5 μM for free RES to 0.5 ± 0.033 μM for Smart Lipid loaded formula against MCF7, 3-fold reduction in the IC50 against HepG2 cells, from 10.01 ± 0.35 to 3.16 ± 0.21 μMm, and a more than 10-fold reduction in the IC50 from more than 100 to 10 ± 0.57 μM against HT-29 cells) and its effect on cell cycle progression and apoptosis induction were assessed using flow cytometry and annexin V kit, respectively. Our results showed that RES-loaded Smart Lipid significantly reduced cell viability, induced cell cycle arrest at G0/G1 phase, and apoptosis compared to free formula and free RES suspension.
Conclusion: Loading RES into this novel kind of nanocarrier enhanced RES absorption, cellular accumulation, and improved its anticancer properties.
目的:虽然白藜芦醇(RES)是一种有效的分子,但其治疗活性却受到口服吸收快、口服生物利用度差和水溶性低等显著限制。因此,用不同的药物载体制备 RES 是提高其治疗应用的重要工具。本研究旨在通过将 RES 制备成一种名为智能脂质的新型纳米载体来增强 RES 的抗癌活性:方法:采用高剪切热均质法制备负载 RES 的 Smart Lipids,该方法采用 21 × 32 因子设计,包含三个不同水平的因素:总脂质浓度、表面活性剂浓度和表面活性剂类型。根据夹带效率百分比和颗粒大小对反应进行了评估:结果:通过透射电子显微镜观察,我们的新型优化 RES 加载智能脂质配方显示出较小的粒径(288.63 ± 5.55 nm)、良好的 zeta 电位(-16.44 ± 0.99 mV)和 86.346 ± 3.61% 的夹持效率,且颗粒呈球形,清晰分明,无融合迹象。使用差示扫描量热法进行了进一步表征,结果表明药物与其他成分之间没有相互作用,因为最佳冻干配方在 54.75°C 出现了一个代表脂质混合物的峰值,检测不到药物的特征峰,这表明药物被包埋了,而且通过傅里叶变换红外光谱法确认了化合物的结构,其中大部分药物的特征峰在装入 Smart Lipid 后消失了,这可能表明 Smart Lipid 能够减少 RES 中键之间的伸展和弯曲。此外,与 RES 悬浮液相比,优化配方显示出一种持续释放模式。最后,通过 MTT 试验评估了优化后的负载 RES 的 Smart Lipid 对不同细胞系(人乳腺癌(MCF7)、人肝癌(HepG2)和人结肠癌细胞(HT29))的细胞毒活性(IC50 降低了 7 倍,从游离 RES 的 3.7 ± 0.5 μM 降至 0.5 ± 0.033 μM)。033 μM,对HepG2细胞的IC50降低了3倍,从10.01 ± 0.35 μMm降至3.16 ± 0.21 μMm,对HT-29细胞的IC50降低了10多倍,从100多μM降至10 ± 0.57 μM),并使用流式细胞仪和annexin V试剂盒分别评估了其对细胞周期进展和凋亡诱导的影响。结果表明,与游离配方和游离 RES 悬浮液相比,负载 RES 的 Smart Lipid 能显著降低细胞活力,诱导细胞周期停滞在 G0/G1 期,并诱导细胞凋亡:结论:将 RES 添加到这种新型纳米载体中可增强 RES 的吸收和细胞蓄积,提高其抗癌性能。
{"title":"Novel resveratrol smart lipids; design, formulation, and biological evaluation of anticancer activity.","authors":"Reem Fekry Diab, Tamer M Abdelghany, Shadeed Gad, Asmaa M Elbakry","doi":"10.1093/jpp/rgae009","DOIUrl":"10.1093/jpp/rgae009","url":null,"abstract":"<p><strong>Purpose: </strong>Although resveratrol (RES) is an efficacious molecule, its therapeutic activity is impeded by significant limitations, such as rapid oral absorption, poor oral bioavailability, and low water solubility. Therefore, the preparation of RES in different pharmaceutical carriers represents an important tool to enhance its therapeutic applications. This study aims to potentiate the anti-cancer activity of RES by formulating it into a novel nanocarrier called Smart Lipid.</p><p><strong>Methods: </strong>RES-loaded Smart Lipids were prepared by high-shear hot homogenization method utilizing a 21 × 32 factorial design with three factors at different levels: the total lipid concentration, the concentration of surfactant, and the type of surfactant. The responses were evaluated based on entrapment efficiency percentages and particle size.</p><p><strong>Results: </strong>Our novel optimized RES-loaded Smart Lipid formula showed small particle size (288.63 ± 5.55 nm), good zeta potential (-16.44 ± 0.99 mV), and an entrapment efficiency of 86.346 ± 3.61% with spherical, clearly distinct, and no signs of fusion by transmission electron microscopy. Further characterization was done using differential scanning calorimetry, which showed no interaction between the drug and other components as the optimum lyophilized formula showed a peak at 54.75°C, which represents the lipid mixture, with an undetectable characteristic peak of the drug, which indicates entrapment of the drug, and the structure of the compounds was confirmed by Fourier transform-infrared spectroscopy, in which the majority of the drug's characteristic peaks disappeared when loaded into Smart Lipid, which may indicate Smart Lipid's ability to reduce the stretching and bending between bonds in RES. In addition, the optimized formula showed a sustained release pattern compared to RES suspension. Finally, the cytotoxic activity of the optimized RES-loaded Smart Lipid on different cell lines (human breast adenocarcinoma (MCF7), human hepatocellular carcinoma (HepG2), and human colon cancer cells (HT29)) was assessed through MTT assay (7-fold reduction in the IC50, from 3.7 ± 0.5 μM for free RES to 0.5 ± 0.033 μM for Smart Lipid loaded formula against MCF7, 3-fold reduction in the IC50 against HepG2 cells, from 10.01 ± 0.35 to 3.16 ± 0.21 μMm, and a more than 10-fold reduction in the IC50 from more than 100 to 10 ± 0.57 μM against HT-29 cells) and its effect on cell cycle progression and apoptosis induction were assessed using flow cytometry and annexin V kit, respectively. Our results showed that RES-loaded Smart Lipid significantly reduced cell viability, induced cell cycle arrest at G0/G1 phase, and apoptosis compared to free formula and free RES suspension.</p><p><strong>Conclusion: </strong>Loading RES into this novel kind of nanocarrier enhanced RES absorption, cellular accumulation, and improved its anticancer properties.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175116","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}
Amine Ali El Sala, Ghada Khawaja, Mahmoud Khalil, Sherine Abdel Salam
Objectives: Improving response rates in colorectal cancer (CRC) is an urgent clinical need. This study aimed to explore the synergistic action of Lebanese rosemary essential oil (REO) and 5-fluorouracil (5-FU) in HCT116 CRC cells.
Methods: We tested the cell viability of monotherapy and combination therapy. The combination index was calculated using CompuSyn software to evaluate drug-drug interactions and the level of synergistic cytotoxicity. We also evaluated cell migration and cytopathology. Furthermore, cell apoptosis-related proteins (i.e. Bax and Bcl-2) were measured by Western blot analysis.
Key findings: The REO/5-FU combination synergistically reduced cell viability, effectively decreased cell migration, and increased the Bax/Bcl-2 ratio in HCT116 cells. This triggered a proapoptotic morphology and initiated an apoptotic cascade in HCT116 cells, as indicated by a higher Bax/Bcl-2 ratio.
Conclusions: Our results provide evidence of the REO/5-FU combination as a better approach to improve 5-FU anticancer efficacy and allow the use of lower 5-FU doses due to the adjuvant effect of REO.
{"title":"Rosemary essential oil potentiates the antitumour activity of 5-fluorouracil in human colorectal carcinoma cells.","authors":"Amine Ali El Sala, Ghada Khawaja, Mahmoud Khalil, Sherine Abdel Salam","doi":"10.1093/jpp/rgae022","DOIUrl":"10.1093/jpp/rgae022","url":null,"abstract":"<p><strong>Objectives: </strong>Improving response rates in colorectal cancer (CRC) is an urgent clinical need. This study aimed to explore the synergistic action of Lebanese rosemary essential oil (REO) and 5-fluorouracil (5-FU) in HCT116 CRC cells.</p><p><strong>Methods: </strong>We tested the cell viability of monotherapy and combination therapy. The combination index was calculated using CompuSyn software to evaluate drug-drug interactions and the level of synergistic cytotoxicity. We also evaluated cell migration and cytopathology. Furthermore, cell apoptosis-related proteins (i.e. Bax and Bcl-2) were measured by Western blot analysis.</p><p><strong>Key findings: </strong>The REO/5-FU combination synergistically reduced cell viability, effectively decreased cell migration, and increased the Bax/Bcl-2 ratio in HCT116 cells. This triggered a proapoptotic morphology and initiated an apoptotic cascade in HCT116 cells, as indicated by a higher Bax/Bcl-2 ratio.</p><p><strong>Conclusions: </strong>Our results provide evidence of the REO/5-FU combination as a better approach to improve 5-FU anticancer efficacy and allow the use of lower 5-FU doses due to the adjuvant effect of REO.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068462","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}
Objectives: In our study, we aimed to examine how δ(9)-tetrahydrocannabinol (THC) administration to hyperinsulinemia (HI) model rats would change endoplasmic reticulum stress (ERS), apoptosis, inflammation, and oxidative stress in cardiac tissue.
Methods: Rats were divided into four groups (n = 32): Control (C), THC, HI, and Treatment (Tre). Fructose (10%) in the drinking water was given to HI and Tre rats for 12 weeks. 1.5 mg/kg/d THC was given intraperitoneally to THC and Tre rats in the last 4 weeks of the experiment. The mRNA expressions of ERS and apoptosis markers in the cardiac tissue were detected. TNF-α concentration and oxidative stress were also analyzed.
Key findings: THC treatment in rats with HI ameliorated the overexpression of GRP-78, IRE1α, ATF6, ATF4, CHOP, Cas-12, Cas-8, Cas-9, and Cas-3 mRNAs, markers of ERS and apoptosis (P < .0001 for all). In addition, THC has been shown to reduce inflammation in the Tre group by causing a decrease in increased cardiac TNF-α levels (P < .01). Moreover, THC prevented cardiac tissue damage by regulating the degraded oxidative stress marker levels and antioxidant enzyme activities in HI.
Conclusions: Our findings suggest that THC treatment in rats with HI exhibited a significant effect in ameliorating cardiac tissue damage by improving the antioxidant defense system, inflammation, apoptosis, ERS, and oxidative stress.
研究目的我们的研究旨在探讨高胰岛素血症(HI)模型大鼠服用δ(9)-四氢大麻酚(THC)会如何改变心脏组织的内质网应激(ERS)、细胞凋亡、炎症和氧化应激:大鼠分为四组(n = 32):方法:将大鼠分为四组(n = 32):对照组(C)、THC 组、HI 组和治疗组(Tre)。给 HI 和 Tre 大鼠在饮用水中添加果糖(10%),持续 12 周。在实验的最后 4 周,给 THC 和 Tre 大鼠腹腔注射 1.5 mg/kg/d THC。检测心脏组织中 ERS 和细胞凋亡标志物的 mRNA 表达。还分析了 TNF-α 浓度和氧化应激:主要研究结果:THC 治疗 HI 大鼠可改善 ERS 和细胞凋亡标志物 GRP-78、IRE1α、ATF6、ATF4、CHOP、Cas-12、Cas-8、Cas-9 和 Cas-3 mRNA 的过度表达(P < .0001)。此外,THC 还能降低心脏 TNF-α 水平,从而减轻 Tre 组的炎症反应(P < .01)。此外,THC 还通过调节 HI 中降解的氧化应激标记物水平和抗氧化酶活性来防止心脏组织损伤:我们的研究结果表明,通过改善抗氧化防御系统、炎症、细胞凋亡、ERS 和氧化应激,THC 治疗 HI 大鼠对改善心脏组织损伤有显著效果。
{"title":"Δ(9)-tetrahydrocannabinol protects cardiac tissue against endoplasmic reticulum and oxidative stresses, apoptosis, and inflammation in rats with hyperinsulinemia.","authors":"Zeynep Mine Coskun Yazici, Karolin Yanar, Sema Bolkent","doi":"10.1093/jpp/rgae023","DOIUrl":"10.1093/jpp/rgae023","url":null,"abstract":"<p><strong>Objectives: </strong>In our study, we aimed to examine how δ(9)-tetrahydrocannabinol (THC) administration to hyperinsulinemia (HI) model rats would change endoplasmic reticulum stress (ERS), apoptosis, inflammation, and oxidative stress in cardiac tissue.</p><p><strong>Methods: </strong>Rats were divided into four groups (n = 32): Control (C), THC, HI, and Treatment (Tre). Fructose (10%) in the drinking water was given to HI and Tre rats for 12 weeks. 1.5 mg/kg/d THC was given intraperitoneally to THC and Tre rats in the last 4 weeks of the experiment. The mRNA expressions of ERS and apoptosis markers in the cardiac tissue were detected. TNF-α concentration and oxidative stress were also analyzed.</p><p><strong>Key findings: </strong>THC treatment in rats with HI ameliorated the overexpression of GRP-78, IRE1α, ATF6, ATF4, CHOP, Cas-12, Cas-8, Cas-9, and Cas-3 mRNAs, markers of ERS and apoptosis (P < .0001 for all). In addition, THC has been shown to reduce inflammation in the Tre group by causing a decrease in increased cardiac TNF-α levels (P < .01). Moreover, THC prevented cardiac tissue damage by regulating the degraded oxidative stress marker levels and antioxidant enzyme activities in HI.</p><p><strong>Conclusions: </strong>Our findings suggest that THC treatment in rats with HI exhibited a significant effect in ameliorating cardiac tissue damage by improving the antioxidant defense system, inflammation, apoptosis, ERS, and oxidative stress.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101770","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}
Objectives: The aim of this study was to investigate the protective effect of neuropeptide W (NPW) on ovarian ischemia-reperfusion-induced oxidative injury and ovarian steroid metabolism.
Methods: Rats were randomly divided into control and ischemia groups that received either saline or NPW (0.1 or 5 μg/kg/day). Bilateral ovarian ischemia was performed for 3 h followed by a 72-h reperfusion. Blood, ovary, and uterus samples were collected for biochemical and histological assessments.
Key findings: Treatment with either dose of NPW alleviated oxidative injury of the ovaries with a significant suppression in free radical formation and decreased histopathological injury in both the ovarian and uterine tissues, along with reduced lipid peroxidation and neutrophil accumulation in the uterus. Moreover, NPW treatment reversed the decrease in aromatase expression with a concomitant reduction in the expression of the inactivity enzyme estrogen sulfotransferase. Also, downregulation of estrogen receptor-α (ERα) expression in the injured ovarian tissue was abolished by NPW treatment, which implicates that the protective effect of NPW on the female reproductive system may involve the upregulation of the ERα-mediated signaling pathway.
Conclusions: Our study demonstrated for the first time that NPW protects against ovarian oxidative injury and reinforces ovarian steroidogenic activity, which is accompanied by the upregulation of ERα expression in the ovaries.
{"title":"Neuropeptide W protects against ovarian oxidative injury and reinforces ovarian steroidogenic activity via the upregulation of ERα expression.","authors":"Sevil Arabacı Tamer, Leyla Semiha Şen, Kasım Güneş, Meral Yüksel, Şule Çetinel, Berrak Ç Yeğen","doi":"10.1093/jpp/rgad098","DOIUrl":"10.1093/jpp/rgad098","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study was to investigate the protective effect of neuropeptide W (NPW) on ovarian ischemia-reperfusion-induced oxidative injury and ovarian steroid metabolism.</p><p><strong>Methods: </strong>Rats were randomly divided into control and ischemia groups that received either saline or NPW (0.1 or 5 μg/kg/day). Bilateral ovarian ischemia was performed for 3 h followed by a 72-h reperfusion. Blood, ovary, and uterus samples were collected for biochemical and histological assessments.</p><p><strong>Key findings: </strong>Treatment with either dose of NPW alleviated oxidative injury of the ovaries with a significant suppression in free radical formation and decreased histopathological injury in both the ovarian and uterine tissues, along with reduced lipid peroxidation and neutrophil accumulation in the uterus. Moreover, NPW treatment reversed the decrease in aromatase expression with a concomitant reduction in the expression of the inactivity enzyme estrogen sulfotransferase. Also, downregulation of estrogen receptor-α (ERα) expression in the injured ovarian tissue was abolished by NPW treatment, which implicates that the protective effect of NPW on the female reproductive system may involve the upregulation of the ERα-mediated signaling pathway.</p><p><strong>Conclusions: </strong>Our study demonstrated for the first time that NPW protects against ovarian oxidative injury and reinforces ovarian steroidogenic activity, which is accompanied by the upregulation of ERα expression in the ovaries.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065384","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}
Zhimin Shi, Rui Wang, Jie Huang, Qian Qian, Menglin Hu, Hengguo Zhang, Linfei Feng, Hao Gu, Yuanyin Wang
Background: Tongue squamous cell carcinoma (TSCC) exhibits an aggressive biological behavior of lymph node and distant metastasis, which contributes to poorer prognosis and results in tongue function loss or death. In addition to known regulators and pathways of cell migration in TSCC, it is important to uncover pivotal switches governing tumor metastasis.
Methods: Cancer cell migration-associated transcriptional and epigenetic characteristics were profiled in TSCC, and the specific super-enhancers (SEs) were identified. Molecular function and mechanism studies were used to investigate the pivotal switches in TSCC metastasis.
Results: Ameboidal-type cell migration-related genes accompanied by transcriptional and epigenetic activity were enriched in TSCC. Meanwhile, the higher-ranked SE-related genes showed significant differences between 43 paired tumor and normal samples from the TCGA TSCC cohort. In addition, key motifs were detected in SE regions, and transcription factor-related expression levels were significantly associated with TSCC survival status. Notably, BATF and ATF3 regulated the expression of ameboidal-type cell migration-related MMP14 by switching the interaction with the SE region.
Conclusion: SEs and related key motifs transcriptional regulate tumor metastasis-associated MMP14 and might be potential therapeutic targets for TSCC.
{"title":"Super-enhancer-driven ameboidal-type cell migration-related MMP14 expression in tongue squamous cell carcinoma switched by BATF and ATF3.","authors":"Zhimin Shi, Rui Wang, Jie Huang, Qian Qian, Menglin Hu, Hengguo Zhang, Linfei Feng, Hao Gu, Yuanyin Wang","doi":"10.1093/jpp/rgae063","DOIUrl":"https://doi.org/10.1093/jpp/rgae063","url":null,"abstract":"<p><strong>Background: </strong>Tongue squamous cell carcinoma (TSCC) exhibits an aggressive biological behavior of lymph node and distant metastasis, which contributes to poorer prognosis and results in tongue function loss or death. In addition to known regulators and pathways of cell migration in TSCC, it is important to uncover pivotal switches governing tumor metastasis.</p><p><strong>Methods: </strong>Cancer cell migration-associated transcriptional and epigenetic characteristics were profiled in TSCC, and the specific super-enhancers (SEs) were identified. Molecular function and mechanism studies were used to investigate the pivotal switches in TSCC metastasis.</p><p><strong>Results: </strong>Ameboidal-type cell migration-related genes accompanied by transcriptional and epigenetic activity were enriched in TSCC. Meanwhile, the higher-ranked SE-related genes showed significant differences between 43 paired tumor and normal samples from the TCGA TSCC cohort. In addition, key motifs were detected in SE regions, and transcription factor-related expression levels were significantly associated with TSCC survival status. Notably, BATF and ATF3 regulated the expression of ameboidal-type cell migration-related MMP14 by switching the interaction with the SE region.</p><p><strong>Conclusion: </strong>SEs and related key motifs transcriptional regulate tumor metastasis-associated MMP14 and might be potential therapeutic targets for TSCC.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248278","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}
Wei Yu, Yaping Zhao, Iqra Ilyas, Li Wang, Peter J Little, Suowen Xu
The incidence and mortality rate of atherosclerotic cardiovascular disease (ASCVD) is increasing yearly worldwide. Recently, a growing body of evidence has unveiled the anti-atherosclerotic properties of fisetin, a natural polyphenol compound. In this article, we reviewed the pharmacologic actions of fisetin on experimental atherosclerosis and its protective effects on disease-relevant cell types such as endothelial cells, macrophages, vascular smooth muscle cells, and platelets. Based on its profound cardiovascular actions, fisetin holds potential for clinical translation and could be developed as a potential therapeutic option for atherosclerosis and its related complications. Large-scale randomized clinical trials are warranted to ascertain the safety and efficacy of fisetin in patients with or high risk for ASCVD.
{"title":"The natural polyphenol fisetin in atherosclerosis prevention: a mechanistic review.","authors":"Wei Yu, Yaping Zhao, Iqra Ilyas, Li Wang, Peter J Little, Suowen Xu","doi":"10.1093/jpp/rgae053","DOIUrl":"https://doi.org/10.1093/jpp/rgae053","url":null,"abstract":"<p><p>The incidence and mortality rate of atherosclerotic cardiovascular disease (ASCVD) is increasing yearly worldwide. Recently, a growing body of evidence has unveiled the anti-atherosclerotic properties of fisetin, a natural polyphenol compound. In this article, we reviewed the pharmacologic actions of fisetin on experimental atherosclerosis and its protective effects on disease-relevant cell types such as endothelial cells, macrophages, vascular smooth muscle cells, and platelets. Based on its profound cardiovascular actions, fisetin holds potential for clinical translation and could be developed as a potential therapeutic option for atherosclerosis and its related complications. Large-scale randomized clinical trials are warranted to ascertain the safety and efficacy of fisetin in patients with or high risk for ASCVD.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908547","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}
Objectives: Inflammatory cytokine secretion and gut microbiota dysbiosis play crucial roles in ulcerative colitis. In this research, the protective effects of peimisine on colitis mice were investigated.
Methods: The protective effects were evaluated by the disease activity index, colonic length, hematoxylin-eosin, and AB/PAS Staining. The protective mechanisms were analyzed by ELISA, Western-blot, immunohistochemistry staining, immunofluorescence staining, and 16S rRNA gene analysis.
Key findings: The results showed that peimisine treatment could reduce the disease activity index, prevent colonic shortening, and alleviate colon tissue damage. Peimisine treatment also decreased the levels of MCP-1, IL-1β, IL-6, IFN-γ, TNF-α and affected macrophage polarization and Th17/Treg cell balance by downregulating the expression of jak1/2, p-jak1/2, stat1/3, and p-stat1/3. Moreover, peimisine treatment significantly increased the abundances of beneficial microbes (e.g. Ruminococcaceae UCG-014 and Lachnospiraceae_NK4A136_group) and decreased the abundances of harmful microbes (e.g. Bacteroides and Escherichia).
Conclusions: Peimisine can ameliorate colitis by inhibiting Jak-Stat signaling pathway, reversing gut microbiota alterations, suppressing macrophage M1 polarization, maintaining the Th17/Treg cell balance, and reducing sustained inflammatory cytokines-related inflammatory injury.
{"title":"Peimisine ameliorates DSS-induced colitis by suppressing Jak-Stat activation and alleviating gut microbiota dysbiosis in mice.","authors":"Yue Li, Xia Yang, Jicheng Han, Bing Bai, Yaru Li, Chao Shang, Shanzhi Li, Zhiru Xiu, Zirui Liu, Chenchen Ge, Guangze Zhu, Ningyi Jin, Jinbo Fang, Yiquan Li, Xiao Li, Yilong Zhu","doi":"10.1093/jpp/rgad091","DOIUrl":"10.1093/jpp/rgad091","url":null,"abstract":"<p><strong>Objectives: </strong>Inflammatory cytokine secretion and gut microbiota dysbiosis play crucial roles in ulcerative colitis. In this research, the protective effects of peimisine on colitis mice were investigated.</p><p><strong>Methods: </strong>The protective effects were evaluated by the disease activity index, colonic length, hematoxylin-eosin, and AB/PAS Staining. The protective mechanisms were analyzed by ELISA, Western-blot, immunohistochemistry staining, immunofluorescence staining, and 16S rRNA gene analysis.</p><p><strong>Key findings: </strong>The results showed that peimisine treatment could reduce the disease activity index, prevent colonic shortening, and alleviate colon tissue damage. Peimisine treatment also decreased the levels of MCP-1, IL-1β, IL-6, IFN-γ, TNF-α and affected macrophage polarization and Th17/Treg cell balance by downregulating the expression of jak1/2, p-jak1/2, stat1/3, and p-stat1/3. Moreover, peimisine treatment significantly increased the abundances of beneficial microbes (e.g. Ruminococcaceae UCG-014 and Lachnospiraceae_NK4A136_group) and decreased the abundances of harmful microbes (e.g. Bacteroides and Escherichia).</p><p><strong>Conclusions: </strong>Peimisine can ameliorate colitis by inhibiting Jak-Stat signaling pathway, reversing gut microbiota alterations, suppressing macrophage M1 polarization, maintaining the Th17/Treg cell balance, and reducing sustained inflammatory cytokines-related inflammatory injury.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440899","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}