Samuel Amintas , Charles Dupin , Marie-Alix Derieppe , Isabelle Moranvillier , Isabelle Lamrissi , Corine Bourdié , Zoe Feurer , Benjamin Fernandez , Tyty Heng-Pradère , François Moreau-Gaudry , Aurélie Bedel , Véronique Vendrely , Sandrine Dabernat
{"title":"Resveratrol and capsaicin as safer radiosensitizers for colorectal cancer compared to 5-fluorouracil","authors":"Samuel Amintas , Charles Dupin , Marie-Alix Derieppe , Isabelle Moranvillier , Isabelle Lamrissi , Corine Bourdié , Zoe Feurer , Benjamin Fernandez , Tyty Heng-Pradère , François Moreau-Gaudry , Aurélie Bedel , Véronique Vendrely , Sandrine Dabernat","doi":"10.1016/j.biopha.2024.117799","DOIUrl":"10.1016/j.biopha.2024.117799","url":null,"abstract":"<div><h3>Background and aim</h3><div>Standard rectal cancer treatment includes neoadjuvant radiotherapy sensitized by 5-fluorouracil (5-FU) chemotherapy. However, 5-FU increased chemoradiotherapy response rate comes with significant toxicity, especially in older, frail patients. The development of alternatives to chemotherapy enabling radiosensitization with limited systemic toxicity is therefore needed to improve patient management. Bioactive food components (BFCs) can exhibit chemo or radio-sensitizing properties against cancer cells. Moreover, the cytotoxic action of BFCs may be tumor-specific, with reduced impact on healthy cells. We hypothesized that BFCs, in particular resveratrol and capsaicin, alone or in association, could lead to specific radio-sensitization of colorectal tumors while offering reduced toxicity compared to 5-FU.</div></div><div><h3>Experimental procedure</h3><div>Colorectal tumor and non-tumor cell lines were treated with resveratrol, capsaicin, or 5-FU, alone or in combination, then irradiated; survival, cell cycle, and apoptosis were analyzed. RAGγ2C−/− mice with xenografts received oral resveratrol, resveratrol + capsaicin, or 5-FU, followed by radiotherapy, with tumor growth and systemic toxicity evaluated.</div></div><div><h3>Key results</h3><div>Resveratrol alone or in association with capsaicin radio-potentiates colorectal tumor cells <em>in vitro</em>, impacting both cell cycle and apoptosis. In a preclinical mouse model, the oral administration of resveratrol and capsaicin, but not resveratrol alone, allowed the radio-sensitization of subcutaneous colorectal tumors with similar efficiency to 5-FU. Moreover, the global as well as the hematological toxicity of the BFC association was lower than those of 5-FU.</div></div><div><h3>Conclusion</h3><div>This work establishes BFCs as effective enhancers of radiotherapy, offering a safer alternative to traditional radiosensitization with chemotherapy.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117799"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
George J. Dugbartey , Lucas N. Penney , Lauren Mills , Max Y. Zhang , Smriti Juriasingani , Sally Major , Patrick McLeod , Winnie Liu , Aaron Haig , Mark E. Wood , Roberta Torregrossa , Matthew Whiteman , Eva Turley , Carl Postenka , Alp Sener
{"title":"AP39, a novel mitochondria-targeted hydrogen sulfide donor, promotes cutaneous wound healing in an in vivo murine model of acute frostbite injury","authors":"George J. Dugbartey , Lucas N. Penney , Lauren Mills , Max Y. Zhang , Smriti Juriasingani , Sally Major , Patrick McLeod , Winnie Liu , Aaron Haig , Mark E. Wood , Roberta Torregrossa , Matthew Whiteman , Eva Turley , Carl Postenka , Alp Sener","doi":"10.1016/j.biopha.2025.117869","DOIUrl":"10.1016/j.biopha.2025.117869","url":null,"abstract":"<div><div>Frostbite injury refers to cold tissue injury which typically affects the peripheral areas of the body, and is associated with limb loss and high rates of morbidity. Historically, treatment options have been limited to supportive care, leading to suboptimal outcomes for affected patients. The pathophysiology of frostbite injury has been understood in recent years to share similarity with that of cold ischemia-reperfusion injury as seen in solid organ transplantation, of which mitochondria play an important contributing role. The present study investigated whether AP39, a novel mitochondria-targeted slow-releasing hydrogen sulfide donor, applied topically in a vehicle cream at 200 nM or 1 µM could mitigate frostbite injury and promote wound healing in mice. Frostbite injury was induced continuously for 3 min on the dorsal skin of C57BL/6 mice (<em>Mus musculus</em>) using magnets frozen on dry ice (-80 °C). AP39, delivered via a vehicle cream, was used daily to treat frostbite injury until animals were euthanized on day 15 after induction of frostbite injury. Wound tissues were stained with hematoxylin and eosin along with immunofluorescence staining with cleaved caspase-3, CD31, KI-67, CD163, fibronectin and cytokeratin. While 200 nM AP39 improved granulation tissue maturation (p < 0.001), angiogenesis (p < 0.01) and cell proliferation (p < 0.001) compared to vehicle control, 1 µM AP39 further increased granulation tissue formation compared to other frostbite groups (p < 0.001). Thus, AP39 promoted frostbite wound healing, and therefore could be considered as a treatment option for patients with frostbite injury.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117869"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Danbi Jo , Seo Yoon Choi , Seo Yeon Ahn , Juhyun Song
{"title":"IGF1 enhances memory function in obese mice and stabilizes the neural structure under insulin resistance via AKT-GSK3β-BDNF signaling","authors":"Danbi Jo , Seo Yoon Choi , Seo Yeon Ahn , Juhyun Song","doi":"10.1016/j.biopha.2025.117846","DOIUrl":"10.1016/j.biopha.2025.117846","url":null,"abstract":"<div><div>Obesity is a prevalent metabolic disorder linked to insulin resistance, hyperglycemia, increased adiposity, chronic inflammation, and cognitive dysfunction. Recent research has focused on developing therapeutic strategies to mitigate cognitive impairment associated with obesity. Insulin growth factor-1 (IGF1) deficiency is linked to insulin resistance, glucose intolerance, and the progression of obesity-related central nervous system (CNS) disorders. In this study, we investigated the neuroprotective effects of IGF1 in two obesity models: diet-induced obesity (high-fat diet mice) and genetic obesity (<em>ob/ob</em> mice which is genetically deficient in leptin), and in vitro Neuro2A neuronal cells and primary cortical neurons under insulin resistance conditions. We performed RNA sequencing analysis using the cortex of high-fat diet mice injected with IGF1. Also, we detected cytokine levels in blood of high-fat diet mice injected with IGF1. In addition, we conducted the Barnes maze test as a spatial memory function test and open field test as an anxiety behavior test in <em>ob/ob</em> mice. We measured the levels of proteins and mRNAs related to insulin signaling, including synaptic density proteins in brain cortex of <em>ob/ob</em> mice. Our results showed that IGF1 injection enhanced spatial memory function and synaptic plasticity in obese mice. Furthermore, <em>in vitro</em> data demonstrated that IGF1 treated neurons revealed enhanced neural complexity and improved neurite outgrowth under insulin resistance condition through the AKT-GSK3β-BDNF pathway related to antidepressant, cognitive function and anti-apoptotic mechanisms. Therefore, our results provided that IGF1 have potential to alleviate cognitive impairment by promoting synaptic plasticity and neural complexity in the obese brain.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117846"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Magdalena Kulus , Maryam Farzaneh , Mohadeseh Sheykhi-Sabzehpoush , Farhoodeh Ghaedrahmati , Fatemeh Mehravar , Małgorzata Józkowiak , Hanna Piotrowska-Kempisty , Dorota Bukowska , Paweł Antosik , Marzenna Podhorska-Okołów , Maciej Zabel , Paul Mozdziak , Piotr Dzięgiel , Bartosz Kempisty
{"title":"Exosomes and non-coding RNAs: Exploring their roles in human myocardial dysfunction","authors":"Magdalena Kulus , Maryam Farzaneh , Mohadeseh Sheykhi-Sabzehpoush , Farhoodeh Ghaedrahmati , Fatemeh Mehravar , Małgorzata Józkowiak , Hanna Piotrowska-Kempisty , Dorota Bukowska , Paweł Antosik , Marzenna Podhorska-Okołów , Maciej Zabel , Paul Mozdziak , Piotr Dzięgiel , Bartosz Kempisty","doi":"10.1016/j.biopha.2025.117853","DOIUrl":"10.1016/j.biopha.2025.117853","url":null,"abstract":"<div><div>Myocardial dysfunction, characterized by impaired cardiac muscle function, arises from diverse etiologies, including coronary artery disease, myocardial infarction, cardiomyopathies, hypertension, and valvular heart disease. Recent advancements have highlighted the roles of exosomes and non-coding RNAs in the pathophysiology of myocardial dysfunction. Exosomes are small extracellular vesicles released by cardiac and other cells that facilitate intercellular communication through their molecular cargo, including ncRNAs. ncRNAs are known to play critical roles in gene regulation through diverse mechanisms, impacting oxidative stress, fibrosis, and other factors associated with myocardial dysfunction. Dysregulation of these molecules correlates with disease progression, presenting opportunities for therapeutic interventions. This review explores the mechanistic interplay between exosomes and ncRNAs, underscoring their potential as biomarkers and therapeutic agents in myocardial dysfunction. Emerging evidence supports the use of engineered exosomes and modified ncRNAs to enhance cardiac repair by targeting signaling pathways associated with fibrosis, apoptosis, and angiogenesis. Despite promising preclinical results, delivery, stability, and immunogenicity challenges remain. Further research is needed to optimize clinical translation. Understanding these intricate mechanisms may drive the development of innovative strategies for diagnosing and treating myocardial dysfunction, ultimately improving patient outcomes.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117853"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rabia Ashfaq, Anita Kovács, Szilvia Berkó, Mária Budai-Szűcs
{"title":"Smart biomaterial gels for periodontal therapy: A novel approach","authors":"Rabia Ashfaq, Anita Kovács, Szilvia Berkó, Mária Budai-Szűcs","doi":"10.1016/j.biopha.2025.117836","DOIUrl":"10.1016/j.biopha.2025.117836","url":null,"abstract":"<div><div>Periodontitis, a chronic inflammatory condition of the oral cavity, is characterized by the progressive destruction of the supporting structures of the teeth. The pathogenic effects of periodontopathogens extend beyond the local periodontal environment, contributing to systemic health complications, thereby underscoring the need for effective therapeutic strategies. Current standard treatments, which involve mechanical debridement coupled with systemic anti-inflammatory and antibiotic therapies, are often associated with limited efficacy, adverse effects, and the emergence of antibiotic resistance. Recent advancements in localized drug delivery systems present an innovative alternative, offering site-specific targeting with sustained therapeutic action. Smart drug delivery platforms, designed to respond to the unique microenvironment of periodontal pockets, undergo physicochemical transformations such as gelation or controlled drug release, enhancing treatment efficacy. This review comprehensively explores the etiological and prognostic factors of periodontitis, critical diagnostic biomarkers, and an in-depth analysis of stimuli-responsive biomacromolecule-based gels. These systems are evaluated for their structural properties, biological compatibility, and therapeutic potential while addressing their limitations and barriers to clinical translation. By integrating insights into the interplay between material properties and biological performance, this review highlights the future role of these advanced delivery systems in overcoming challenges in periodontal healthcare. Such approaches aim to bridge the gap between bench-side innovation and bedside application, offering the transformative potential to enhance therapeutic outcomes and improve patient quality of life in managing periodontal diseases.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117836"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ji Hyun Oh , Mi Gyeong Jeong , Soheun Lee , Jihae Lim , Jio Kang , Myung Ae Bae , Jin-Hee Ahn , Jeong-Ho Hong , Eun Sook Hwang
{"title":"SMEPPI: An indenone derivative that selectively inhibits M1 macrophage activation and enhances phagocytic activity","authors":"Ji Hyun Oh , Mi Gyeong Jeong , Soheun Lee , Jihae Lim , Jio Kang , Myung Ae Bae , Jin-Hee Ahn , Jeong-Ho Hong , Eun Sook Hwang","doi":"10.1016/j.biopha.2025.117856","DOIUrl":"10.1016/j.biopha.2025.117856","url":null,"abstract":"<div><div>SMEPPI is a small molecule synthesized as a derivative of KR-62980 that has anti-diabetic and anti-inflammatory activities. Despite the established physiological effects of KR-62980, the effects and benefits of SMEPPI remain largely unexplored. This study investigated the immunomodulatory functions of SMEPPI on macrophages and inflammatory diseases. SMEPPI did not affect the differentiation and maturation of bone marrow-derived monocytes into macrophages, nor did it affect the proliferation of M1 or M2 macrophages. Although SMEPPI did not affect M2 macrophage polarization, it significantly inhibited IL-1β and IL-6 cytokine production in both M1 macrophages and activated RAW264.7 macrophages. Importantly, SMEPPI inhibited the expression and phosphorylation of NF-κB p65 through inhibition of Akt expression, preventing its translocation to the nucleus. It also promoted p65 degradation through the stimulation of the proteasomal degradation pathway by inducing the expression of proteasome-related genes, thereby inhibiting p65 transcriptional activity. SMEPPI also enhanced the expression of various molecules associated with macrophage phagocytosis, including CD68, CD33, and lectins, thereby increasing phagocytic activity. Moreover, SMEPPI mitigated lipopolysaccharides-induced acute lung injury by suppressing IL-1β and IL-6 production in M1 macrophages and reduced mortality related to severe lung injury. These findings indicate that SMEPPI effectively regulates inflammatory diseases by impeding p65-induced cytokine production and enhancement of phagocytosis by M1 macrophages.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117856"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jae Ho Lee , Kyeong Hyeon Lee , Ji Hyeon Ryu , Min Jae Kim , Eunji Kim , Seo-Yeon Lee , Sang-Cheol Han , Byung Tae Choi , Yong-Il Shin , Hwa Kyoung Shin
{"title":"LM22A-4-loaded smart mesoporous balls enhance neuroprotection and functional recovery after ischemic stroke","authors":"Jae Ho Lee , Kyeong Hyeon Lee , Ji Hyeon Ryu , Min Jae Kim , Eunji Kim , Seo-Yeon Lee , Sang-Cheol Han , Byung Tae Choi , Yong-Il Shin , Hwa Kyoung Shin","doi":"10.1016/j.biopha.2025.117863","DOIUrl":"10.1016/j.biopha.2025.117863","url":null,"abstract":"<div><div>Stroke is globally recognized as the second leading cause of death, significantly impairing both motor and cognitive functions. Enhancing regeneration after stroke is crucial for restoring these functions and necessitates strategies to promote neuroregeneration to achieve better post-stroke outcomes. Brain-derived neurotrophic factor (BDNF) plays a key role in neuroregeneration by influencing motor ability, learning, memory, and rehabilitation after stroke. However, challenges such as the substantial protein size, short half-life of BDNF, and blood-brain barrier hinder its efficient delivery to the brain. In this study, LM22A-4, a BDNF mimetic, was utilized and delivered through a Smart Mesoporous Ball (SMB-3) system to target the ischemic injured brain and explore its potential therapeutic effects in a mouse ischemic stroke model. Treatment with LM22A-4-loaded SMB-3 (LM22A-4-SMB-3) markedly restored neurological, motor, and cognitive deficits following ischemic stroke compared to LM22A-4 alone. Additionally, administration of LM22A-4-SMB-3 reduced apoptotic cell death and glial activation, as evidenced by the TUNEL assay results, and decreased GFAP and Iba-1 expression levels. Furthermore, the phosphorylation of TrkB and Akt, but not that of Erk, was considerably increased in the LM22A-4-SMB-3-treated group. Treatment also enhanced the number of BrdU+/NeuN+ cells, with a marked reduction in post-stroke brain atrophy. These findings suggest that LM22A-4-SMB-3 can attenuate ischemic damage and recover neurological, motor, and cognitive functions by increasing p-TrkB and p-Akt levels and promoting neurogenesis. Therefore, SMB-3-mediated delivery of LM22A-4 presents a potentially applicable delivery system, and LM22A-4-SMB-3 use could be considered a novel therapeutic strategy to improve post-stroke outcomes.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117863"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hepatoprotective effect of the Sechium HD-Victor hybrid extract in a model of liver damage induced by carbon tetrachloride in mice","authors":"Edelmiro-Santiago Osorio , Ramírez-Padilla María-Guadalupe , Mendoza-Núñez Víctor-Manuel , Cadena-Íñiguez Jorge , Soto-Hernández Marcos , Rosado-Pérez Juana , Romero-López Ernesto , Weiss-Steider Benny , Gavia-García Graciela , Arista-Ugalde Taide-Laurita , Cisneros-Solano Víctor-Manuel , Aguiñiga-Sánchez Itzen","doi":"10.1016/j.biopha.2025.117831","DOIUrl":"10.1016/j.biopha.2025.117831","url":null,"abstract":"<div><div><em>Sechium</em> spp., is a vegetable species renowned for its pharmacological properties, including hepatoprotective activity. This species can crossbreed with its wild relatives, leading to the creation of an HD-Victor hybrid with higher levels of flavonoids, cucurbitacins, and phenolic acids compared to the <em>Sechium edule</em>. However, the antioxidant and hepatoprotective properties of this hybrid are not well-known. We investigated the hepatoprotective effect of HD-Victor hybrid extract on a hepatic-damage mouse model induced by carbon tetrachloride (CCl₄). We conducted a phytochemical characterization and quantified its antioxidant activity. Subsequently, we evaluated the extract at different concentrations, testing the potential to mitigate liver damage induced by CCl₄. After, we performed tests to assess liver function through AST, ALT, ALP and albumin, antioxidant levels, and histopathological examination. Our findings reveal that HD-Victor hybrid extract is rich in flavonoids, phenolic acids, and cucurbitacins and shows DPPH-free radical inhibition, protection in liver function, and increased antioxidant levels. Therefore, the <em>Sechium</em> HD-Victor hybrid extract exerts a protective effect against hepatic damage induced by oxidative stress, showing its potential as a hepatoprotective agent.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117831"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Myung-A Jung , Joo Young Lee , Yu Jin Kim , Kon-Young Ji , Mi Han Le , Dong Ho Jung , Yun Hee Kim , Wook Jin Kim , Byeong Cheol Moon , Bu-Yeo Kim , Taesoo Kim
{"title":"Inula japonica Thunb. and its active compounds ameliorate airway inflammation by suppressing JAK-STAT signaling","authors":"Myung-A Jung , Joo Young Lee , Yu Jin Kim , Kon-Young Ji , Mi Han Le , Dong Ho Jung , Yun Hee Kim , Wook Jin Kim , Byeong Cheol Moon , Bu-Yeo Kim , Taesoo Kim","doi":"10.1016/j.biopha.2025.117852","DOIUrl":"10.1016/j.biopha.2025.117852","url":null,"abstract":"<div><div>Asthma, a chronic inflammatory disease, remains a global health challenge due to its complex pathophysiology and the limited treatment efficacy. This study explored the effect of <em>Inula japonica</em> Thunb. water extract (IJW) on asthma and its protective mechanisms. To assess the effects of IJW, we established an experimental asthma model in BALB/c mice using ovalbumin (OVA). Airway hyper-responsiveness (AHR) in response to methacholine was measured. We quantified inflammatory cell infiltration and cytokine and chemokine levels in bronchoalveolar lavage fluid (BALF), as well as total IgE levels in serum. Staining with hematoxylin and eosin and periodic acid–Schiff was used to examine the impact of IJW on lung pathology. We performed RNA sequencing to identify differentially expressed genes, which were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. We used interleukin (IL)-4/IL-13-treated human bronchial epithelial (HBE) cells to explore the associated mechanisms. IJW showed therapeutic effects against OVA-induced asthma by alleviating AHR, peribronchial inflammation, mucus hypersecretion, and collagen fiber deposition. It reduced total IgE levels in the serum and IL-4, IL-5, IL-13, eotaxin, macrophage-derived chemokines, and periostin levels in BALF. In IL-4/IL-13-treated HBE cells, IJW and its components suppressed the Janus kinase-signal transducer and activator of the transcription (JAK-STAT) signaling. These findings support IJW’s potential as a pharmacological agent for allergic airway inflammation and asthma.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117852"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}