Biomedicine & Pharmacotherapy最新文献_第2页

Methanol extract of Euphorbia cotinifolia L. leaf attenuates inflammation and oxidative stress in RAW 264.7 macrophages via TAK1-mediated suppression of NF-κB/MAPK and activation of Nrf2 pathways 大黄叶甲醇提取物通过tak1介导的抑制NF-κB/MAPK和激活Nrf2通路，减轻RAW 264.7巨噬细胞的炎症和氧化应激

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-07-18 DOI: 10.1016/j.biopha.2025.118372

Junho Lee , Salah Uddin , Chohee Jeong , Sang Beom Han , Sayeon Cho

{"title":"Methanol extract of Euphorbia cotinifolia L. leaf attenuates inflammation and oxidative stress in RAW 264.7 macrophages via TAK1-mediated suppression of NF-κB/MAPK and activation of Nrf2 pathways","authors":"Junho Lee , Salah Uddin , Chohee Jeong , Sang Beom Han , Sayeon Cho","doi":"10.1016/j.biopha.2025.118372","DOIUrl":"10.1016/j.biopha.2025.118372","url":null,"abstract":"<div><div><em>Euphorbia cotinifolia</em> L. (<em>E. cotinifolia</em> L.) is distributed in temperate and tropical regions. It exhibits various biological activities, including antioxidant, antimicrobial, and antiviral properties. Although its antioxidant properties have been described, its regulatory molecular mechanisms remain poorly understood and its anti-inflammatory effects have not been studied yet. This study investigated the effects of methanol extract of <em>E. cotinifolia</em> L. (MECL) on inflammation and oxidative stress in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. MECL significantly suppressed the production of inflammatory mediators, including nitric oxide (NO) and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>), by downregulating inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, MECL inhibited the production of key pro-inflammatory cytokines, including interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α), by suppressing of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. It suppressed TAK1 phosphorylation, thereby inhibiting IKKα/β. Consequently, IκBα was stabilized, preventing its degradation and thereby suppressing NF-κB p65 phosphorylation and nuclear translocation. Additionally, MECL attenuated the activation of JNK, ERK, and p38 MAPK signaling. It also activated nuclear factor erythroid 2-related factor 2 (Nrf2), which is a key antioxidant transcription factor, upregulating its target genes, heme oxygenase-1 and NAD(P)H quinone dehydrogenase 1, which are essential for oxidative stress defense. These findings suggested that MECL mitigated inflammation and oxidative stress by regulating TAK1-mediated NF-κB/MAPK signaling and Nrf2 activation. Therefore, it showed potential as a natural therapeutic candidate for inflammatory diseases.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118372"},"PeriodicalIF":6.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic challenges in breast cancer: Navigating the impact of oxidative stress on treatment efficacy and toxicity 乳腺癌的治疗挑战：氧化应激对治疗效果和毒性的影响

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-07-18 DOI: 10.1016/j.biopha.2025.118364

Dariush Haghmorad , Fatemeh Tavassoli Razavi , Yasamin Eivazzadeh , Esmaeil Yazdanpanah , Niloufar Orooji

{"title":"Therapeutic challenges in breast cancer: Navigating the impact of oxidative stress on treatment efficacy and toxicity","authors":"Dariush Haghmorad , Fatemeh Tavassoli Razavi , Yasamin Eivazzadeh , Esmaeil Yazdanpanah , Niloufar Orooji","doi":"10.1016/j.biopha.2025.118364","DOIUrl":"10.1016/j.biopha.2025.118364","url":null,"abstract":"<div><div>Breast cancer remains one of the most prevalent and challenging malignancies worldwide, necessitating a multifaceted therapeutic approach. Although current treatments- including chemotherapy, radiotherapy, targeted therapy, and hormone therapy- have significantly improved patient outcomes, they are often associated with substantial adverse effects and therapeutic resistance. Emerging evidence underscores the critical role of oxidative stress in mediating both the efficacy and toxicity of these treatments. Reactive oxygen species (ROS), generated either endogenously or as a byproduct of anticancer therapies, contribute to cellular damage, inflammation, and impaired redox homeostasis, ultimately influencing treatment outcomes. This review systematically explores the mechanisms by which oxidative stress modulates the biological response to anthracyclines, taxanes, and ionizing radiation, and highlights its involvement in treatment-induced cardiotoxicity, neurotoxicity, fibrosis, and immune dysregulation. Additionally, we examine the role of oxidative stress in resistance to HER2-targeted and hormone-based therapies. The article further discusses combination therapy-induced synergistic toxicity and outlines current and emerging antioxidant-based strategies- ranging from natural compounds and synthetic agents to nanomedicine and gene modulation- that may mitigate oxidative damage. Understanding the complex interplay between redox biology and therapeutic response offers new opportunities for improving treatment efficacy, minimizing adverse effects, and advancing personalized interventions in breast cancer care.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118364"},"PeriodicalIF":6.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrating neuroprotection, antioxidative effects, and precision medicine in glaucoma management with bioactive compounds 结合神经保护，抗氧化作用和精准医学在青光眼管理与生物活性化合物

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-07-18 DOI: 10.1016/j.biopha.2025.118319

Yan Zhu, Laxmi Moksha, Rebecca Salowe, Vrathasha Vrathasha, Kenneth Pham, Marine-Ayan Ibrahim Aibo, Roy Lee, Mina Halimitabrizi, Isabel Di Rosa, Joan M. O’Brien

{"title":"Integrating neuroprotection, antioxidative effects, and precision medicine in glaucoma management with bioactive compounds","authors":"Yan Zhu, Laxmi Moksha, Rebecca Salowe, Vrathasha Vrathasha, Kenneth Pham, Marine-Ayan Ibrahim Aibo, Roy Lee, Mina Halimitabrizi, Isabel Di Rosa, Joan M. O’Brien","doi":"10.1016/j.biopha.2025.118319","DOIUrl":"10.1016/j.biopha.2025.118319","url":null,"abstract":"<div><div>Glaucoma is a group of progressive optic neuropathies characterized by the degeneration of retinal ganglion cells (RGCs) and their axons, leading to irreversible vision loss or blindness if left untreated. Current glaucoma treatments primarily focus on lowering intraocular pressure (IOP), the only proven method to slow disease progression. However, these treatments do not effectively address RGC loss or promote optic nerve regeneration. Emerging research into both natural and synthetic bioactive compounds offers promising new avenues for glaucoma management. This review explores the multifaceted therapeutic potential of bioactive compounds in glaucoma treatment, focusing on their mechanisms of action in IOP reduction and neuroprotection, as well as antioxidant and anti-inflammatory effects. We further review ongoing clinical trials and discuss significant challenges to clinical translation, including the issues of bioavailability, standardization, long-term safety, and regulatory challenges. Furthermore, this paper highlights the potential of integrating precision medicine into bioactive treatments, emphasizing the value of personalized care based on genetic and phenotypic profiles. Finally, the review discusses the role of combination therapies, which leverage the complementary mechanisms of bioactive compounds and conventional treatments. As research progresses, the development of targeted, bioactive-based therapies could transform glaucoma management, offering more comprehensive and effective options for patients with this vision-threatening disease.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118319"},"PeriodicalIF":6.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HA-PAs hydrogel for enhanced cartilage repair in early osteoarthritis: A novel minimally invasive treatment strategy HA-PAs水凝胶增强早期骨关节炎软骨修复：一种新的微创治疗策略

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-07-18 DOI: 10.1016/j.biopha.2025.118356

Guangjie Li , Jianbao Feng , Fei He , Ge Xu , Chengye Wu , Xiaoming Ma , Yufei Qiao , Zeyu Luo , Pengcheng Du

{"title":"HA-PAs hydrogel for enhanced cartilage repair in early osteoarthritis: A novel minimally invasive treatment strategy","authors":"Guangjie Li , Jianbao Feng , Fei He , Ge Xu , Chengye Wu , Xiaoming Ma , Yufei Qiao , Zeyu Luo , Pengcheng Du","doi":"10.1016/j.biopha.2025.118356","DOIUrl":"10.1016/j.biopha.2025.118356","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a degenerative joint disease characterized by joint inflammation, progressive degeneration and destruction of articular cartilage, ultimately resulting in irreversible damage. The treatment of OA is costly, has significant side effects, and yields limited efficacy. To improve OA therapy, we used 3-aminobenzoboronic acid (PBA) as a binding site for proanthocyanidins (PAs), with hyaluronic acid (HA) serving as a drug carrier. A simple method was employed to develop an injectable, biocompatible hydrogel (HA-PAs hydrogel) with sustained-release functionality, aimed is to promote the <em>in vivo</em> repair of cartilage and ligaments by enhancing the expression of collagen and glycosaminoglycans. Characterization results confirmed that HA and PAs crosslinked to form hydrogels through amide and borate ester bonds in PBA. The controlled release function of PAs was further validated through in vitro drug release experiments. The good biocompatibility of HA-PAs hydrogel was further confirmed by CCK-8 assay and cellular live/dead staining. More importantly, compared with PAs alone, the HA-PAs hydrogel exhibited superior ability to promote the expression of collagen and glycosaminoglycans. In a rat enzymatic OA model, the HA-PAs hydrogel significantly reduced joint inflammation in the early stages of cartilage destruction and accelerated cartilage formation. This work provides an inexpensive and efficacious strategy for minimally invasive treatment of early osteoarthritis.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118356"},"PeriodicalIF":6.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of Quercetin in the treatment of kidney diseases: A comprehensive review 槲皮素在肾脏疾病治疗中的作用综述

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-07-17 DOI: 10.1016/j.biopha.2025.118358

Peijian Chen , Xuejing Rao , Ping He , Jieting Liu , Yanhui Chu , Yan Dong , Minglu Ding

{"title":"The role of Quercetin in the treatment of kidney diseases: A comprehensive review","authors":"Peijian Chen , Xuejing Rao , Ping He , Jieting Liu , Yanhui Chu , Yan Dong , Minglu Ding","doi":"10.1016/j.biopha.2025.118358","DOIUrl":"10.1016/j.biopha.2025.118358","url":null,"abstract":"<div><div>Kidney diseases resulting from genetic predisposition, immune dysfunction, hypertension, diabetes, malignancies, hyperuricemia, and unhealthy lifestyle factors are garnering increasing attention due to the essential role of the kidney in maintaining systemic homeostasis. Quercetin (QCT), a polyhydroxy flavonoid abundantly present in the flowers, leaves, and fruits of numerous plants, including over 100 species of Chinese herbs such as <em>Sophora japonica</em> and Tansy, exhibits diverse biological activities and significant medicinal properties. These properties include antioxidant, anticancer, anti-inflammatory, antibacterial, antiviral, hypoglycemic, antihypertensive, immunomodulatory, and cardiovascular protective effects. QCT, generally recognized as safe, confers multiple health benefits, particularly in managing cardiovascular disorders, chronic bronchitis, hypertension, diabetes, and cancer. However, excessive intake may result in side effects. Notably, QCT has demonstrated efficacy in alleviating renal parenchymal injury and fibrosis, and it plays a pivotal role in treating diabetic nephropathy and cardiovascular diseases.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118358"},"PeriodicalIF":6.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Copper metabolism and cuproptosis in Alzheimer's disease: mechanisms and therapeutic potential 阿尔茨海默病中的铜代谢和铜沉积：机制和治疗潜力

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-07-17 DOI: 10.1016/j.biopha.2025.118354

Dandan Meng , Guizhi Luo , Ping Liu

{"title":"Copper metabolism and cuproptosis in Alzheimer's disease: mechanisms and therapeutic potential","authors":"Dandan Meng , Guizhi Luo , Ping Liu","doi":"10.1016/j.biopha.2025.118354","DOIUrl":"10.1016/j.biopha.2025.118354","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a neurodegenerative disorder with an increasing incidence rate year by year. The pathogenesis of AD is complex and closely related to protein misfolding and aggregation, neuroinflammation, oxidative stress, mitochondrial dysfunction, and other factors. Cuproptosis is a newly discovered form of programmed cell death caused by excessive intracellular copper. Unlike other known forms of cell death, it shows significant potential in the treatment of neurodegenerative diseases. Copper binds to the acylated components of the tricarboxylic acid cycle, causing protein toxicity stress, which ultimately leads to cell cuproptosis. AD is characterized by pathological features such as β-amyloid plaque formation and excessive phosphorylation of tau protein, which are closely linked to the cuproptosis mechanism. However, the specific relationship between the pathogenesis of AD and copper metabolism remains unclear. This article summarizes the metabolism of copper in the brain, the mechanisms of cuproptosis, and the pathogenesis of cuproptosis in AD, and also discusses the regulation of cuproptosis in the treatment of AD. This article provides a basis for targeted research on cuproptosis in AD.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118354"},"PeriodicalIF":6.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Focused ultrasound-triggered escitalopram delivery using microbubble-liposome complexes for rapid and sustained serotonin regulation in depression therapy 聚焦超声触发艾司西酞普兰递送使用微泡脂质体复合物快速和持续调节血清素在抑郁症治疗中

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-07-17 DOI: 10.1016/j.biopha.2025.118373

Chen-Cheng Tsai , Ching-Hsiang Fan , Chia-Wei Lin , Ayache Bouakaz , Chih-Kuang Yeh

{"title":"Focused ultrasound-triggered escitalopram delivery using microbubble-liposome complexes for rapid and sustained serotonin regulation in depression therapy","authors":"Chen-Cheng Tsai , Ching-Hsiang Fan , Chia-Wei Lin , Ayache Bouakaz , Chih-Kuang Yeh","doi":"10.1016/j.biopha.2025.118373","DOIUrl":"10.1016/j.biopha.2025.118373","url":null,"abstract":"<div><div>Serotonin plays a pivotal role in the pathophysiology of major depressive disorder, with a deficiency therein being a hallmark of the condition. However, the efficacies of conventional treatments for depression involving the regulation of serotonin are limited by delayed onset, high drug dosing, and requirement for daily administration due to the obstacle of the blood-brain barrier. This study investigated an innovative approach that combines focused ultrasound (FUS) with escitalopram-loaded liposomes (Esc-lip) tethered to microbubbles (Esc-MBs) for targeted drug delivery to the serotonin-transporter-rich hippocampus. This approach elevates the serotonin level rapidly and sustainably with minimal drug doses and repeated treatments. Esc-MBs were synthesized by encapsulating escitalopram within biotinylated liposomes conjugated to MBs' outer surface. The results demonstrated that exposing Esc-MBs to FUS at 1 MHz and 600 kPa for 160 cycles and 1800 s induced the transient release of free Esc and Esc-lip, resulted in the local accumulation of escitalopram in the hippocampus of a chronic unpredictable mild stress model of depression. After Esc-MBs with FUS treatment, the intracerebral levels of escitalopram and serotonin immediately elevated 32.2-fold and 1.1-fold, respectively, higher than for oral administration, and these levels remained high at 144 h after the treatment. We have also demonstrated that the proposed Esc-MBs with FUS treatment strategy can ameliorate depression-like behaviors in an animal model of depression, achieving therapeutic outcomes comparable to those for the oral administration of escitalopram. These results highlight the potential of this strategy for addressing critical unmet needs in depression therapy.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118373"},"PeriodicalIF":6.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Increased cellular uptake and proteasome inhibition of carfilzomib through the optimized self-nanoemulsifying drug delivery system 通过优化的自纳米乳化给药系统增加卡非佐米的细胞摄取和蛋白酶体抑制

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-07-17 DOI: 10.1016/j.biopha.2025.118368

Taek-Seon Yun , Young-Guk Na , Jong-Suep Baek , Hong-Ki Lee , Cheong-Weon Cho

{"title":"Increased cellular uptake and proteasome inhibition of carfilzomib through the optimized self-nanoemulsifying drug delivery system","authors":"Taek-Seon Yun , Young-Guk Na , Jong-Suep Baek , Hong-Ki Lee , Cheong-Weon Cho","doi":"10.1016/j.biopha.2025.118368","DOIUrl":"10.1016/j.biopha.2025.118368","url":null,"abstract":"<div><div>Carfilzomib (CFZ) is a potent second-generation proteasome inhibitor that blocks the ubiquitin-proteasome pathway, inducing apoptosis in cancer cells. Currently, commercially available CFZ formulations contain large amounts of excipients, require intravenous (IV) infusion, and have a short half-life of less than 1 h. Recent research trends have focused on developing alternative CFZ formulations to address these limitations; however, all attempts thus far have been restricted to injectable formulations. In this study, we developed a self-nanoemulsifying drug delivery system (SNEDDS) containing CFZ based on a Quality by Design (QbD) approach (CFZ-SN) to enhance the oral bioavailability of CFZ. The uniform, nanosized CFZ-SN droplets exhibited significantly improved water solubility and drug release profiles compared to raw CFZ. Furthermore, CFZ encapsulated in the optimized droplets demonstrated stability against enzymatic and lipolytic degradation in vivo. The uptake and permeation of CFZ-SN in enterocytes were notably enhanced through inhibition of the P-glycoprotein (P-gp) efflux pump. Additionally, CFZ-SN significantly increased cellular uptake and proteasome inhibition in cancer cells. Overall, our findings suggest that CFZ-SN has the potential to enable oral administration of CFZ, offering a promising alternative to existing injectable formulations.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118368"},"PeriodicalIF":6.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bromelain enhances nitric oxide bioavailability: Bradykinin’s link to TRPV1/Ca2+ /AMPK/autophagy signaling 菠萝蛋白酶提高一氧化氮的生物利用度：缓激肽与TRPV1/Ca2+ /AMPK/自噬信号传导的联系

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-07-17 DOI: 10.1016/j.biopha.2025.118376

Wen-Hua Chen , Yi-Ying Wu , Man-Chen Hsu , Chia-Hui Chen , Julia Chu-Ning Hsu , Tzong-Shyuan Lee

{"title":"Bromelain enhances nitric oxide bioavailability: Bradykinin’s link to TRPV1/Ca2+ /AMPK/autophagy signaling","authors":"Wen-Hua Chen , Yi-Ying Wu , Man-Chen Hsu , Chia-Hui Chen , Julia Chu-Ning Hsu , Tzong-Shyuan Lee","doi":"10.1016/j.biopha.2025.118376","DOIUrl":"10.1016/j.biopha.2025.118376","url":null,"abstract":"<div><div>Bromelain, a protease enzyme extracted from the pineapple stem, is suggested to protect against atherosclerosis, non-alcohol fatty liver diseases, and coagulation dysfunction. However, the mechanism underlying the vascular protection of bromelain in the cardiovascular system is not fully understood. In this study, we explored the role of the kininogen-bradykinin system in bromelain-mediated nitric oxide (NO) bioavailability in endothelial cells (ECs). NO bioavailability was examined by Griess’s assay, western blot analysis was used to assess protein expression, the level of urea and arginine was evaluated by conventional assay kits. <em>In vivo</em> angiogenesis was performed by Matrigel plug assay. In ECs, bromelain increased NO production by increasing intracellular levels of Ca<sup>2+</sup>, activating AMP-activated protein kinase (AMPK), and phosphorylating endothelial nitric oxide synthase (eNOS). Concurrently, bromelain activated the AMPK-regulated autophagy-urea cycle pathway and increased intracellular levels of L-arginine, the precursor of NO, resulting in an increase in NO biosynthesis. Inhibition of bradykinin receptor B<sub>2</sub> (B<sub>2</sub>R) or transient receptor potential vanilloid 1 (TRPV1) prevented the activation of Ca<sup>2+</sup>-AMPK-eNOS signaling, autophagy-urea cycle pathway, and NO biosynthesis by bromelain in ECs. Mechanistically, bromelain cleaved kininogen into bradykinin and activated B<sub>2</sub>R-TRPV1-Ca<sup>2+</sup>-AMPK-eNOS pathway and autophagy-urea cycle-L-arginine pathway, and these two events may work in concert to promote NO production in ECs. <em>In vivo</em> experiments showed that inhibition of B<sub>2</sub>R, TRPV1, eNOS, or autophagy activity attenuated bromelain-induced angiogenesis in Matrigel. This study presents novel understanding into the molecular mechanisms underlying the vascular protection of bromelain in the cardiovascular system.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118376"},"PeriodicalIF":6.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Melatonin facilitates the anti-EV71 activity by inhibiting apoptosis through the regulation of the Caspase-7 signaling pathway 褪黑素通过调节Caspase-7信号通路抑制细胞凋亡，促进抗ev71活性

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-07-16 DOI: 10.1016/j.biopha.2025.118338

Zhengyun Liu , Jiarong Xie , Mingxia Xiong , Haiyan Yang , Huan Wang

{"title":"Melatonin facilitates the anti-EV71 activity by inhibiting apoptosis through the regulation of the Caspase-7 signaling pathway","authors":"Zhengyun Liu , Jiarong Xie , Mingxia Xiong , Haiyan Yang , Huan Wang","doi":"10.1016/j.biopha.2025.118338","DOIUrl":"10.1016/j.biopha.2025.118338","url":null,"abstract":"<div><div>To investigate the impacts and potential underlying mechanisms of melatonin on enterovirus 71(EV71). Three-day-old ICR mice were randomly divided into seven groups: control group, vehicle group, melatonin 10, 50, and 100 mg/kg group, ribavirin 50 mg/kg group, and melatonin 50 mg/kg combined ribavirin 50 mg/kg group. The mice were intracranial injected with 50 μL EV71 (5 ×10<sup>3</sup> TCID<sub>50</sub>) and treated with different medications once a day for four days. Clinical scores, body weights of mice were recorded, and the expression of VP1 protein in the hindlimb muscles and brainstem was analyzed using western blot. In vitro, CCK-8 assays were employed to assess cell proliferation, Reed-Muench method was used to calculate viral titers, western blot was conducted to evaluate the expression of VP1 and caspase-7 proteins, flow cytometry and TMRE staining were utilized to assess cell apoptosis, molecular docking was performed to calculate binding activity. Melatonin significantly alleviated the clinical symptoms induced by EV71 and effectively suppressed the expression of VP1 protein in the hindlimb muscles and brainstem of mice. In vitro, Melatonin effectively reduced the TCID<sub>50</sub> and the expression of VP1 protein and rescued the apoptosis induced by EV71; Melatonin enhanced the fluorescence intensity of TMRE compared to the infected group; the binding energy between melatonin and caspase-7 was calculated to be −7.2 kcal/mol, and melatonin inhibited the expression of caspase-7 protein after EV71 infection. Melatonin inhibited EV71 replication both in vivo and vitro, and its mechanism may involve preventing EV71-induced apoptosis by inhibiting the expression of cleaved caspase-7.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"190 ","pages":"Article 118338"},"PeriodicalIF":6.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0