Current Research in Pharmacology and Drug Discovery最新文献

Cardiac injury elicited by sub-chronic hookah smoke inhalation, and the alleviating effect of procysteine, 2-oxo-(4R)-4-thiazolidinecarboxylic acid, in BALB/c mice 亚慢性水烟吸入引起的BALB/c小鼠心脏损伤及2-氧-(4R)-4-噻唑烷羧酸半胱氨酸的缓解作用

Q2 Agricultural and Biological Sciences

Current Research in Pharmacology and Drug Discovery

Pub Date : 2026-01-01 Epub Date: 2026-02-16 DOI: 10.1016/j.crphar.2026.100252

Sumaya Beegam , Suhail Al-Salam , Bilal M. Nemmar , Nur Elena Zaaba , Ozaz Elzaki , Badreldin H. Ali , Abderrahim Nemmar

Hookah smoke (HS) inhalation is known to induce cardiovascular dysfunction, including oxidative stress and inflammation. The procysteine, 2-oxo-(4R)-4-thiazolidinecarboxylic acid (OTC) is a prodrug of cysteine, a precursor of glutathione, which is a major intracellular antioxidant. This study aimed to evaluate the possible cardioprotective effects of OTC against HS inhalation-induced cardiac injury in mice. The animals were exposed to HS for 30 min per day, five days per week, for one month, while control mice were exposed to normal air. OTC was administered by gavage at a dose of 80 mg/kg 1 h before each exposure session. OTC prevented HS-induced increase in the concentrations of tumor necrosis factor α, interleukin (IL)-6 and galectin-3 in the heart tissue. HS exposure augmented the levels of markers of oxidative stress and adhesion molecules. The latter effects were significantly abrogated by OTC treatment. Likewise, the cardiac DNA damage and apoptosis triggered by HS inhalation were significantly prevented in mice treated with OTC. The concentrations of NLRP3 inflammasome and IL-1β in the hearts of mice exposed to HS were significantly augmented, and OTC treatment significantly abated this effect. Moreover, while the cardiac expression of phosphorylated nuclear factor κB (NF-κB) was increased, that of sirtuin-1 was significantly decreased by HS inhalation. Both effects were significantly mitigated by OTC administration. Furthermore, HS inhalation induced an elevation in the concentrations of mammalian targets of rapamycin and nuclear factor erythroid-derived 2-like 2 (Nrf2) expression in the heart, and this effect was significantly potentiated in the OTC + HS group. Despite these molecular and biochemical alterations, no detectable differences in cardiac histology were observed among the experimental groups. Collectively, these findings demonstrate that OTC mitigates HS-induced cardiac injury by reducing oxidative stress, inflammation, DNA damage, and apoptosis through mechanisms that involve inhibition of NLRP3 inflammasome activation and NF-κB signaling, together with activation of sirtuin-1 and Nrf2 pathways.

众所周知，吸入水烟会引起心血管功能障碍，包括氧化应激和炎症。半胱氨酸，2-氧-(4R)-4-噻唑烷羧酸（OTC）是半胱氨酸的前药，半胱氨酸是谷胱甘肽的前体，是细胞内主要的抗氧化剂。本研究旨在评价OTC对HS吸入性小鼠心脏损伤可能的保护作用。这些动物每天暴露于HS 30分钟，每周5天，持续一个月，而对照组小鼠暴露于正常空气中。OTC在每次暴露前1小时以80 mg/kg的剂量灌胃给药。OTC可抑制hs诱导的心脏组织肿瘤坏死因子α、白细胞介素-6和半凝集素-3浓度的升高。HS暴露增加了氧化应激和粘附分子标记物的水平。后一种影响被OTC治疗显著消除。同样，OTC对吸入HS引起的小鼠心脏DNA损伤和细胞凋亡也有明显的抑制作用。暴露于HS的小鼠心脏中NLRP3炎症小体和IL-1β的浓度显著增加，OTC治疗显著减轻了这种影响。此外，吸入HS可显著降低sirtuin-1的表达，但可增加心脏磷酸化核因子κB （NF-κB）的表达。这两种效应都被OTC药物显著缓解。此外，吸入HS可引起哺乳动物雷帕霉素靶蛋白浓度和心脏中核因子红细胞衍生2-样2 （Nrf2）表达的升高，且这种作用在OTC + HS组中显著增强。尽管有这些分子和生化改变，但在实验组之间没有观察到心脏组织学上的明显差异。综上所述，这些研究结果表明，OTC通过抑制NLRP3炎性体激活和NF-κB信号传导，以及激活sirtuin-1和Nrf2通路，通过减少氧化应激、炎症、DNA损伤和细胞凋亡，减轻hs诱导的心脏损伤。

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引用次数: 0

Breaking biofilm barriers in skin wounds: Membrane-Active antimicrobials in an era of resistance 打破生物膜屏障在皮肤伤口：膜活性抗菌剂在一个耐药的时代

Q2 Agricultural and Biological Sciences

Current Research in Pharmacology and Drug Discovery

Pub Date : 2026-01-01 Epub Date: 2025-12-23 DOI: 10.1016/j.crphar.2025.100249

Lisa Myrseth Hemmingsen , Nataša Škalko-Basnet

Chronic wounds remain a significant challenge for healthcare systems worldwide, placing a considerable burden on both patients and resources. Their management is further complicated by the persistence of biofilm-forming bacteria and an escalating problem of antimicrobial resistance, both of which restrict the effectiveness of conventional therapies. Antimicrobial compounds with a rapid onset of action and activity that is not solely dependent on bacterial metabolism represent promising alternatives for bacterial and biofilm eradication. Among these, membrane-active antimicrobials (MAAs), including antimicrobial peptides, peptidomimetics, and other membrane-disrupting compounds, constitute a particularly interesting group of agents. Recent investigations have revealed diverse mechanisms through which MAAs compromise biofilm integrity, ranging from permeabilization of bacterial membranes to interference with quorum sensing and extracellular polymeric substances. Furthermore, pharmaceutical innovations such as nanoparticle-based carriers, hydrogel matrices, and scaffold-based delivery systems have shown potential to enhance MAA stability, optimize and prolong release profiles, improve antimicrobial and anti-biofilm efficacy, increase tissue penetration, and mitigate cytotoxicity concerns. By integrating insights from microbiology, materials science, and drug development, this short review aims to outline the challenges posed by biofilms in chronic wounds, appraise the antimicrobial and anti-biofilm activity of MAAs, and discuss how advanced delivery strategies might expand their clinical efficacy.

慢性伤口仍然是全球卫生保健系统面临的一个重大挑战，给患者和资源带来了相当大的负担。由于生物膜形成细菌的持续存在和抗菌素耐药性问题的不断升级，它们的管理进一步复杂化，这两者都限制了常规治疗的有效性。具有快速起效和活性且不完全依赖于细菌代谢的抗菌化合物是消灭细菌和生物膜的有希望的替代品。其中，膜活性抗菌剂（MAAs），包括抗菌肽、类肽和其他破坏膜的化合物，构成了一组特别有趣的药物。最近的研究揭示了MAAs损害生物膜完整性的多种机制，从细菌膜的渗透到群体感应和细胞外聚合物的干扰。此外，基于纳米颗粒的载体、水凝胶基质和基于支架的递送系统等药物创新已经显示出增强MAA稳定性、优化和延长释放谱、提高抗菌和抗生物膜功效、增加组织渗透和减轻细胞毒性问题的潜力。通过整合微生物学、材料科学和药物开发方面的见解，本文旨在概述生物膜在慢性伤口中所带来的挑战，评估MAAs的抗菌和抗生物膜活性，并讨论先进的递送策略如何扩大其临床疗效。

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引用次数: 0

Neuroprotective effects of naringenin on nicotine-induced anxiety and depression: Involvement of monoaminergic systems, oxidative stress, and neuroinflammation on male rats 柚皮素对尼古丁诱导的焦虑和抑郁的神经保护作用：雄性大鼠单胺能系统、氧化应激和神经炎症的参与

Q2 Agricultural and Biological Sciences

Current Research in Pharmacology and Drug Discovery

Pub Date : 2026-01-01 Epub Date: 2025-12-04 DOI: 10.1016/j.crphar.2025.100242

Murtaza Haidary , Yahya Samadi , Zakaria Rezai , Atiqullah Sadaqat , Mohammad Ali Ahmadi , Jamshid Gholami , Mohammad Mahdi Mohammadi , Mohammad Taqi Shojae

Introduction

Nicotine withdrawal during adolescence induces severe neurobehavioral disturbances and neurochemical alterations, including anxiety, depression, affective dysregulation, oxidative stress, and neuroinflammation. Current therapeutic options for managing nicotine dependence remain suboptimal. This study investigated the neuroprotective potential of naringenin (NG) in alleviating behavioral and biochemical sequelae of nicotine withdrawal in adolescent rats.

Materials and methods

Male adolescent Wistar rats were allocated into eight groups and subjected to nicotine exposure (1 mg/kg) and NG treatment (50 or 100 mg/kg) across nicotine exposure and withdrawal phases. Behavioral assays (OFT, EPM, FST) were employed to evaluate anxiety- and depression-like behaviors. Neurochemical assessments of dopamine, serotonin, their metabolites (DOPAC, 5-HIAA), MAO-A activity, oxidative stress markers (MDA, Nit), antioxidant enzymes (SOD, CAT, TT), and neuroinflammatory/neurodegenerative biomarkers (GFAP, IL-10, BDNF, NSE) were conducted in prefrontal cortex (PFC) homogenates.

Results

Nicotine withdrawal significantly induced anxiety- and depression-like behaviors, disrupted monoaminergic balance, elevated MAO-A activity, and triggered oxidative and neuroinflammatory responses in the PFC. NG administration, particularly at 100 mg/kg across both phases, significantly ameliorated behavioral impairments, restored neurotransmitter homeostasis, inhibited MAO-A, suppressed lipid peroxidation and nitrosative stress, enhanced antioxidant defenses, reduced GFAP and NSE expression, and restored IL-10 and BDNF levels.

Conclusion

NG exerts anxiolytic, antidepressant, antioxidant, and anti-inflammatory effects, likely via modulation of monoaminergic pathways and suppression of neuroinflammation and oxidative stress. These findings underscore the potential of NG as a promising candidate for mitigating neuropathological effects associated with nicotine withdrawal-induced neuropathology, particularly during adolescence.

青春期尼古丁戒断会引起严重的神经行为障碍和神经化学改变，包括焦虑、抑郁、情感失调、氧化应激和神经炎症。目前用于控制尼古丁依赖的治疗方案仍然不够理想。本研究探讨柚皮素（NG）在缓解青少年大鼠尼古丁戒断后行为和生化后遗症中的神经保护作用。材料与方法将成年Wistar大鼠分为8组，分别在尼古丁暴露和戒断阶段接受尼古丁暴露（1 mg/kg）和NG治疗（50或100 mg/kg）。行为测试（OFT， EPM， FST）用于评估焦虑和抑郁样行为。在前额皮质（PFC）匀浆中进行多巴胺、血清素及其代谢物（DOPAC、5-HIAA）、MAO-A活性、氧化应激标志物（MDA、Nit）、抗氧化酶（SOD、CAT、TT）和神经炎症/神经退行性生物标志物（GFAP、IL-10、BDNF、NSE）的神经化学评估。结果尼古丁戒断显著诱导焦虑和抑郁样行为，破坏单胺能平衡，提高MAO-A活性，并引发PFC. NG给药（特别是在两个阶段均为100 mg/kg时）的氧化和神经炎症反应，显著改善行为障碍，恢复神经递质稳态，抑制MAO-A，抑制脂质过氧化和亚硝酸盐应激，增强抗氧化防御。GFAP和NSE表达降低，IL-10和BDNF水平恢复。结论ng具有抗焦虑、抗抑郁、抗氧化和抗炎作用，可能通过调节单胺能通路和抑制神经炎症和氧化应激来实现。这些发现强调了NG作为缓解尼古丁戒断引起的神经病理相关神经病理效应的潜力，特别是在青少年时期。

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引用次数: 0

Synergistic effect of oxaliplatin and nanocurcumin in dendrosomal carrier to inhibits ovarian cancer cells invasion and metastasis through the long non-coding RNA MEG3 奥沙利铂和纳米姜黄素在树状体载体上通过长链非编码RNA MEG3抑制卵巢癌细胞侵袭转移的协同作用

Q2 Agricultural and Biological Sciences

Current Research in Pharmacology and Drug Discovery

Pub Date : 2026-01-01 Epub Date: 2025-12-02 DOI: 10.1016/j.crphar.2025.100243

Elahe Seyed Hosseini , Marziyeh Alizadeh Zarei , Zahra Shabani , Hamed Haddad Kashani , Hossein Nikzad

Background

Ovarian cancer (OC) remains one of the most lethal gynecological malignancies worldwide. The long non-coding RNA MEG3 (Maternally Expressed Gene 3), located on chromosome 14q32.3, has been identified as a tumor suppressor in various cancers. This study investigated the impact of siRNA-mediated MEG3 silencing in the context of dendrosomal nanocurcumin (DNC) and Oxaliplatin (OXA) treatments on ovarian cancer cell lines, focusing on the expression of genes associated with apoptosis and metastasis, including Bcl-2, BAX, MMP-2, and MMP-9.

Methods

Cell viability was assessed using the MTT assay; apoptosis and cell cycle progression were evaluated via flow cytometry and Annexin V-FLUOS staining. Cell migration and invasion were examined using the transwell assay, and gene expression levels were quantified by real-time PCR.

Results

MEG3 expression significantly increased in both cell lines upon DNC and OXA treatment in a time-dependent manner, with the most pronounced effect in OVCAR3 cells (P < 0.01–0.001). MEG3 silencing significantly attenuated the anticancer efficacy of both agents. Notably, MMP-2 expression increased in DNC (P < 0.01) and combination therapy (P < 0.001), while MMP-9 was upregulated following OXA treatment (P < 0.01) after MEG3 knockdown.

Conclusion

These results suggest that MEG3 knockdown impairs the anti-metastatic properties of DNC and OXA by modulating MMP-2 and MMP-9 expression. The combination of DNC and OXA holds promise as an effective therapeutic strategy in OC, and MEG3 may serve as a potential biomarker and therapeutic target, particularly in drug-resistant ovarian cancer.

卵巢癌（OC）仍然是世界范围内最致命的妇科恶性肿瘤之一。位于染色体14q32.3上的长链非编码RNA MEG3（母系表达基因3）已被确定为多种癌症的肿瘤抑制因子。本研究探讨了sirna介导的MEG3沉默在树状体纳米黄素（DNC）和奥沙利铂（OXA）治疗下对卵巢癌细胞系的影响，重点研究了与凋亡和转移相关的基因Bcl-2、BAX、MMP-2和MMP-9的表达。方法采用MTT法测定细胞活力；通过流式细胞术和Annexin V-FLUOS染色评价细胞凋亡和细胞周期进展。transwell法检测细胞迁移和侵袭，real-time PCR法检测基因表达水平。结果经DNC和OXA处理后，两种细胞系中meg3的表达均呈时间依赖性增加，其中OVCAR3细胞中meg3的表达最明显（P < 0.01-0.001）。MEG3沉默显著降低了两种药物的抗癌效果。值得注意的是，MMP-2在DNC和联合治疗中表达增加（P < 0.01），而在MEG3敲低后，OXA治疗后MMP-9表达上调（P < 0.01）。结论MEG3敲低可通过调节MMP-2和MMP-9的表达，从而影响DNC和OXA的抗转移特性。DNC和OXA的联合治疗有望成为卵巢癌的有效治疗策略，而MEG3可能作为潜在的生物标志物和治疗靶点，特别是在耐药卵巢癌中。

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引用次数: 0

Therapeutic potential, pharmacological role and molecular mechanisms of adelmidrol, an analogue of palmitoylethanolamide 棕榈酰乙醇酰胺类似物阿德米多的治疗潜力、药理作用和分子机制

Q2 Agricultural and Biological Sciences

Current Research in Pharmacology and Drug Discovery

Pub Date : 2026-01-01 Epub Date: 2026-01-10 DOI: 10.1016/j.crphar.2026.100250

Bushra Zia , Abdulrahman Alkaabi , Niraj Kumar Jha , Sameer Mirza , Sandeep B Subramanya , Shreesh Ojha

Adelmidrol is a bioactive semi-synthetic compound with significant therapeutic potential, particularly in resolving inflammation since inflammation plays a key role in the pathogenesis of several diseases. The mechanisms of action of adelmidrol are multifaceted, involving interactions with specific receptors like the PPAR-γ and modulation of signaling pathways associated with inflammation. Adelmidrol demonstrates efficacy in conditions such as inflammatory bowel disease, colon inflammation, and urothelial inflammation by regulating the level of pro-inflammatory cytokines. In dermatological conditions like atopic and allergic dermatitis, adelmidrol plays a key role in modulating immune responses and enhancing skin barrier function by reducing inflammation while offering an alternative to conventional therapies. Additionally, adelmidrol plays a critical role in wound healing and diabetic foot ulcers by facilitating cell migration and proliferation, thus accelerating wound closure and reducing infection risk. Adelmidrol has been shown to reduce joint inflammation and improve functionality, making it a candidate for adjunct therapy in musculoskeletal disorders like osteoarthritis. The compound also addresses pulmonary conditions, such as pulmonary fibrosis, by mitigating inflammatory responses and improving respiratory function. Furthermore, applications of adelmidrol in liver diseases, including liver ischemia and non-alcoholic steatohepatitis (NASH), highlight its potential in resolving hepatic inflammation. This review emphasizes the therapeutic promise of adelmidrol across various inflammatory diseases, advocating for further clinical studies to establish its full potential and optimize its clinical use all the while providing an overview of the properties, mechanisms of action, and therapeutic applications of adelmidrol.

阿德米铎是一种具有显著治疗潜力的生物活性半合成化合物，特别是在治疗炎症方面，因为炎症在几种疾病的发病机制中起着关键作用。阿德米多尔的作用机制是多方面的，包括与PPAR-γ等特定受体的相互作用以及与炎症相关的信号通路的调节。阿德米铎通过调节促炎细胞因子的水平，在炎症性肠病、结肠炎症和尿路上皮炎症等疾病中显示出疗效。在像特应性和过敏性皮炎这样的皮肤病中，阿德米特罗在调节免疫反应和增强皮肤屏障功能方面发挥着关键作用，通过减少炎症，同时提供传统疗法的替代方案。此外，阿德米多在伤口愈合和糖尿病足溃疡中起关键作用，促进细胞迁移和增殖，从而加速伤口愈合和降低感染风险。阿德米多尔已被证明可以减少关节炎症并改善功能，使其成为骨关节炎等肌肉骨骼疾病辅助治疗的候选药物。该化合物还通过减轻炎症反应和改善呼吸功能来治疗肺部疾病，如肺纤维化。此外，阿德米多尔在肝脏疾病，包括肝缺血和非酒精性脂肪性肝炎（NASH）中的应用，突出了其在解决肝脏炎症方面的潜力。本综述强调了阿德米多尔治疗各种炎症性疾病的前景，提倡进一步的临床研究，以充分发挥其潜力并优化其临床应用，同时概述了阿德米多尔的性质、作用机制和治疗应用。

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引用次数: 0

Corrigendum to “Pharmacogenetics association with long-term clinical evolution in a kidney transplant patients cohort” [Curr. Res. Pharmacol. Drug Discov. 9 (2025) 100230] “药物遗传学与肾移植患者长期临床发展的关联”的勘误表[Curr。研究》杂志。药物发现。9 (2025)100230]

Q2 Agricultural and Biological Sciences

Current Research in Pharmacology and Drug Discovery

Pub Date : 2026-01-01 Epub Date: 2025-12-11 DOI: 10.1016/j.crphar.2025.100247

Luis Sendra , Gladys G. Olivera-Pasquini , Enrique G. Zucchet , Fabiana D.V. Genvigir , María Isabel Beneyto , Julio Hernández-Jaras , María José Herrero , Salvador F. Aliño

引用次数: 0

Arctiin targets oxidative stress and inflammation, restores Neuregulin-1, and improves neurobehavioral outcomes in neonatal hypoxic-ischemic brain injury 牛蒡子肽靶向氧化应激和炎症，恢复神经调节蛋白1，改善新生儿缺氧缺血性脑损伤的神经行为结局。

Q2 Agricultural and Biological Sciences

Current Research in Pharmacology and Drug Discovery

Pub Date : 2026-01-01 Epub Date: 2026-02-17 DOI: 10.1016/j.crphar.2026.100253

Skandar Babak , Tahereh Safari , Hamed Fanaei

Objective

Hypoxic-ischemic brain damage (HIBD) represents a major cause of neonatal morbidity and mortality, resulting from perinatal oxygen deprivation and impaired cerebral blood flow. This study aims to investigate the neuroprotective effects of Arctiin, a bioactive lignan derived from Arctium lappa, recognized for its potent antioxidant and anti-inflammatory properties, in a neonatal rat model of HIBD.

Materials and methods

Neonatal rats at postnatal day 8 were randomly assigned to four groups: Sham-operated (SHAM), Hypoxia-Ischemia (HI), Hypoxia-Ischmia with Solvent control (HI/SO), and Hypoxia-Ischemia treated with Arctiin (HI/Arc). HIBD was induced via unilateral carotid artery ligation followed by exposure to hypoxia. The HI/Arc group was administered Arctiin orally at a dosage of 60 mg/kg daily for seven consecutive days. Behavioral performance, biochemical parameters, histological integrity, and gene expression profiles were assessed to evaluate the neuroprotective efficacy of Arctiin.

Results

Arctiin administration resulted in a significant reduction in C-reactive protein (CRP), and total oxidant capacity (TOC). Simultaneously, it enhanced total antioxidant capacity (TAC) and brain-derived neurotrophic factor (BDNF) levels. Histological analysis showed diminished infarct volume in the Arctiin-treated group. Moreover, gene expression studies revealed significant restoration of Neuregulin-1 (NRG-1) in group treated by arctiin. Neurobehavioral assessments further confirmed significant improvements in sensorimotor function in the Arctiin-treated group.

Conclusion

Our study provides evidence indicating that Arctiin mitigates hypoxic-ischemic brain damage in rat pups through a synergistic mechanism involving the suppression of inflammation and oxidative stress, coupled with the upregulation of critical neuroprotective genes and proteins, specifically NRG-1 gene expression and BDNF protein levels. Future studies should investigate the precise molecular pathways downstream of NRG-1 that mediate Arctiin's neuroprotective effects.

目的：缺氧缺血性脑损伤（HIBD）是新生儿发病率和死亡率的主要原因，由围产期缺氧和脑血流受损引起。牛蒡子素是一种从牛蒡子中提取的生物活性木脂素，以其有效的抗氧化和抗炎特性而闻名，本研究旨在研究牛蒡子素对HIBD新生大鼠模型的神经保护作用。材料与方法：将出生第8天的新生大鼠随机分为4组：假手术组（SHAM）、缺氧缺血组（HI）、缺氧缺血与溶剂对照组（HI/SO）和牛角苷治疗的缺氧缺血组（HI/Arc）。HIBD是通过单侧颈动脉结扎后缺氧诱导的。HI/Arc组给予牛蒡苷60 mg/kg / d口服，连续7天。通过评估行为表现、生化参数、组织学完整性和基因表达谱来评价牛蒡苷的神经保护作用。结果：牛蒡子苷可显著降低c -反应蛋白（CRP）和总氧化能力（TOC）。同时，它还能提高总抗氧化能力（TAC）和脑源性神经营养因子（BDNF）水平。组织学分析显示，牛蒡肽治疗组梗死体积减小。此外，基因表达研究显示，动蛋白处理组神经调节蛋白-1 （NRG-1）显著恢复。神经行为评估进一步证实了牛蒡素治疗组感觉运动功能的显著改善。结论：我们的研究表明，牛蒡子苷通过抑制炎症和氧化应激的协同机制，以及上调关键神经保护基因和蛋白，特别是NRG-1基因表达和BDNF蛋白水平，减轻了大鼠幼崽缺氧缺血性脑损伤。未来的研究应进一步探索NRG-1下游介导牛蒡子苷神经保护作用的确切分子通路。

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引用次数: 0

Anti-Shigella activity and killing kinetics of compounds from MMV Pathogen and COVID Boxes: Identifying leads against Shigellosis MMV病原菌和COVID - box化合物的抗志贺氏菌活性和杀伤动力学：鉴定抗志贺氏菌病的线索

Q2 Agricultural and Biological Sciences

Current Research in Pharmacology and Drug Discovery

Pub Date : 2026-01-01 Epub Date: 2026-02-02 DOI: 10.1016/j.crphar.2026.100251

Lauve Rachel Tchokouaha Yamthe , Francine Kengne Mediesse , Yanick Kevin Melogmo Dongmo , Sonia Raissa Matchuenkam Gayap , Darline Dize , Patrick Valere Tsouh Fokou , Fabrice Fekam Boyom

Background

Shigellosis is a leading diarrheal disease, posing critical public health challenges in low- and middle-income countries. Rising antibiotic resistance exacerbates treatment limitations.

Methods

We screened 560 compounds from the MMV Pathogen and COVID Boxes for in vitro activity against Shigella flexneri, S. sonnei, and S. dysenteriae via resazurin-based microdilution. Cytotoxicity (RAW 264.7 cells) and killing kinetics against S. flexneri were assessed.

Results

From the primary screen, 13 compounds (9 from the Pathogen Box, 4 from the COVID Box) showed potent anti-Shigella activity against S. flexneri (MIC ≤10 μM). Among these, seven non-antibiotic Pathogen Box compounds exhibited low-micromolar MICs (0.31–5 μM) and low cytotoxicity (CC₅₀ > 100 μM). The known antibiotic levofloxacin (MMV687798) showed broad-spectrum activity (MIC 0.15–2.5 μM). MMV1804312 (salinomycin) was the most active COVID Box hit (MIC 1.25 μM). Time-kill assays revealed rapid, concentration-dependent bactericidal activity (≥3-log reduction within 4–6 h) for Pathogen Box compounds MMV675997 and MMV021660, while MMV000858 displayed bacteriostatic action.

Conclusion

This study identifies several novel, non-antibiotic leads from the MMV Pathogen Box with potent anti-Shigella activity and favorable cytotoxicity profiles, offering promising starting points for further development against drug-resistant shigellosis.

志贺氏菌病是一种主要的腹泻病，对低收入和中等收入国家的公共卫生构成重大挑战。抗生素耐药性的上升加剧了治疗的局限性。方法从MMV病原菌和COVID盒中筛选560个化合物，通过瑞祖林为基础的微量稀释，检测其对福氏志贺氏菌、sonnei链球菌和痢疾链球菌的体外活性。细胞毒性（RAW 264.7细胞）和对flexneri的杀伤动力学进行了评估。结果13个化合物（9个来自病原菌盒，4个来自COVID盒）对MIC≤10 μM的flexneri具有较强的抗志贺氏菌活性。其中，7种非抗生素病原菌盒化合物具有低微摩尔MICs （0.31 ~ 0.31 μM）和低细胞毒性（CC50 > 100 μM）。已知抗生素左氧氟沙星（MMV687798）具有广谱活性（MIC 0.15 ~ 2.5 μM）。MMV1804312 （salinomycin）是最活跃的COVID - Box hit （MIC 1.25 μM）。时间杀伤实验显示，病原菌盒化合物MMV675997和MMV021660具有快速、浓度依赖性的杀菌活性（4-6 h内降低≥3对数），而MMV000858具有抑菌作用。结论本研究从MMV病原菌盒中发现了几种新的非抗生素先导物，它们具有有效的抗志贺氏菌活性和良好的细胞毒性特征，为进一步开发耐药志贺氏菌病提供了有希望的起点。

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引用次数: 0

Targeting telomere dynamics with plant-derived compounds: Molecular strategies against aging 用植物源性化合物靶向端粒动力学：抗衰老的分子策略

Q2 Agricultural and Biological Sciences

Current Research in Pharmacology and Drug Discovery

Pub Date : 2025-01-01 Epub Date: 2025-11-07 DOI: 10.1016/j.crphar.2025.100238

Raushanara Akter, Adwiza Chakraborty Bishakha, Raisha Rajib, Asef Raj, Mashwiyat Samrin Roja, Fouzia Noor

Telomeres, the repetitive DNA–protein complexes capping eukaryotic chromosomes, preserve genomic stability and regulate cellular replicative capacity. Progressive telomere shortening, coupled with diminished telomerase activity, is a hallmark of aging and contributes to cellular senescence, tissue degeneration, and the onset of age-related diseases. Conversely, telomerase overactivation in malignant cells enables uncontrolled proliferation, positioning telomere biology as a dual therapeutic target in longevity and oncology. Plant-derived compounds possess diverse structural classes such as polyphenols, flavonoids, triterpenoid saponins, polysaccharides, lignans, alkaloids, carotenoids, amino acids, and fatty acids that can modulate telomere length and telomerase activity via multiple molecular pathways. These include antioxidant and anti-inflammatory actions, regulation of key genes such as hTERT, SIRT1, and c-Myc, modulation of PI3K/Akt, JAK/STAT, and ERK signaling, and stabilization or destabilization of G-quadruplex DNA structures. Compounds such as resveratrol, epigallocatechin gallate, astragaloside IV, cycloastragenol, and ginsenoside Rg1 have demonstrated telomerase activation or inhibition in a context-dependent manner, influenced by concentration, cell type, and disease state. This review categorizes plant-derived positive and negative telomere/telomerase modulators, detailing their sources, mechanisms of action, experimental evidence, and the formulation challenges that hinder clinical translation, such as low bioavailability, instability, and variability in phytochemical content. By integrating molecular insights with pharmacological perspectives, this review highlights the potential of plant-derived agents as multi-target interventions in aging and cancer. Advancing this field will require rigorous pharmacokinetic profiling, standardized preparations, and longitudinal clinical studies to bridge the gap between laboratory findings and real-world therapeutic outcomes.

端粒是覆盖在真核生物染色体上的重复dna -蛋白质复合物，它保持基因组的稳定性并调节细胞的复制能力。进行性端粒缩短，加上端粒酶活性降低，是衰老的标志，并有助于细胞衰老，组织变性和年龄相关疾病的发病。相反，端粒酶在恶性细胞中的过度激活会导致不受控制的增殖，使端粒生物学成为长寿和肿瘤的双重治疗靶点。植物源性化合物具有多种结构类别，如多酚、类黄酮、三萜皂苷、多糖、木脂素、生物碱、类胡萝卜素、氨基酸和脂肪酸，它们可以通过多种分子途径调节端粒长度和端粒酶活性。这些包括抗氧化和抗炎作用，关键基因如hTERT、SIRT1和c-Myc的调节，PI3K/Akt、JAK/STAT和ERK信号的调节，以及g -四重体DNA结构的稳定或不稳定。诸如白藜芦醇、表没食子儿茶素没食子酸酯、黄芪甲苷IV、环黄芪醇和人参皂苷Rg1等化合物已经证明端粒酶的激活或抑制以依赖于环境的方式进行，受浓度、细胞类型和疾病状态的影响。本文对植物源性端粒/端粒酶阳性和阴性调节剂进行了分类，详细介绍了它们的来源、作用机制、实验证据以及阻碍临床转化的配方挑战，如低生物利用度、不稳定性和植物化学含量的可变性。通过结合分子和药理学的观点，本综述强调了植物源性药物作为多靶点干预衰老和癌症的潜力。推进这一领域将需要严格的药代动力学分析、标准化的制剂和纵向临床研究，以弥合实验室发现和现实世界治疗结果之间的差距。

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引用次数: 0

Corrigendum to “Metabolic and clinical effect of alpha-lipoic acid administration in schizophrenic subjects stabilized with atypical antipsychotics: A 12-week, open-label, uncontrolled study” [Curr. Res. Pharmacol. Drug Discov. 3 (2022) 100116] “非典型抗精神病药物稳定的精神分裂症患者服用α硫辛酸的代谢和临床效果：一项为期12周、开放标签、非对照研究”的更正[Curr。研究》杂志。药物发现，3 (2022)100116]

Q2 Agricultural and Biological Sciences

Current Research in Pharmacology and Drug Discovery

Pub Date : 2025-01-01 Epub Date: 2025-03-12 DOI: 10.1016/j.crphar.2025.100215

Fiammetta Iannuzzo , Gianpaolo Antonio Basile , Domenica Campolo , Giovanni Genovese , Gianluca Pandolfo , Loretta Giunta , Domenica Ruggeri , Antonino Di Benedetto , Antonio Bruno

引用次数: 0