Biomolecules & Therapeutics最新文献

{"title":"RNA Therapeutics: Focus on Antisense Oligonucleotides in the Nervous System.","authors":"Betül Ertural, Büşra Nur Çiçek, Işıl Aksan Kurnaz","doi":"10.4062/biomolther.2025.022","DOIUrl":"10.4062/biomolther.2025.022","url":null,"abstract":"<p><p>RNA therapeutics represent a disruptive technology that has transformed drug discovery and manufacturing, gaining significant prominence during the COVID-19 pandemic. RNA therapeutics encompass diverse molecules like antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNAs (miRNAs), RNA aptamers, and messenger RNAs (mRNAs), which can function through different mechanisms. RNA therapeutics are increasingly used to treat various diseases, including neurological disorders. For example, ASO therapies such as nusinersen for spinal muscular atrophy and eteplirsen for Duchenne muscular dystrophy are successful applications of RNA-based treatment. Emerging ASO treatments for Huntington's disease and amyotrophic lateral sclerosis are also promising, with ongoing clinical trials demonstrating significant reductions in disease-associated proteins. Still, delivery of these molecules remains a pivotal challenge in RNA therapeutics, especially for ASOs in penetrating the blood-brain barrier to target neurological disorders effectively. Nanoparticle-based formulations have emerged as leading strategies to enhance RNA stability, reduce immunogenicity, and improve cellular uptake. Despite these advances, significant hurdles remain, including optimizing pharmacokinetics, minimizing off-target effects, and ensuring sustained therapeutic efficacy. Regulatory frameworks are evolving to accommodate the unique challenges of RNA-based therapies, including ASOs with efforts underway to establish comprehensive guidelines for RNA therapeutics, yet there are also sustainable manufacturing issues that need to be considered for long-term feasibility. By addressing these challenges, RNA therapeutics hold immense potential to revolutionize treatment paradigms for neurological disorders. Looking forward, the future of RNA therapeutics in neurology appears promising but requires continued interdisciplinary collaboration and technological innovation.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"572-581"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRL-50481 Ameliorates Lung Inflammation in a Murine Model of Ovalbumin-Induced Allergic Asthma with Co-Exposure to Lipopolysaccharide.","authors":"Oh Seong Kwon, Kyu-Taek Hwang, Won Seok Choi, Ji-Yun Lee","doi":"10.4062/biomolther.2024.167","DOIUrl":"10.4062/biomolther.2024.167","url":null,"abstract":"<p><p>Asthma is an allergic inflammatory disease of the lungs characterized by eosinophilic inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR). Exposure to environmental endotoxins, such as lipopolysaccharide (LPS), can exacerbate asthma severity. Phosphodiesterase (PDE) inactivates cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate, thereby aggravating inflammation. Accordingly, PDE inhibitors could be used to treat asthma. Herein, we studied the effects of BRL-50481 (BRL), a PDE7 inhibitor, in a murine model of ovalbumin (OVA)-induced allergic asthma with co-exposure to LPS. Mice were sensitized, challenged with OVA, and subsequently exposed to LPS. Mice were administered with BRL prior to the OVA challenge. We observed that BRL treatment could suppress hallmark features of asthma, including mediators of eosinophilic and neutrophilic inflammation, such as expression of antigen-specific immunoglobulin (Ig) E, interleukin (IL)-13, IL-6, and mucus hypersecretion. Mice co-exposed to OVA and LPS exhibited marked AHR, which was improved in BRL-treated mice because of inhibition of mucus overproduction. In conclusion, given that PDE7 inhibitors can regulate allergic inflammatory responses, these agents could be potential candidates for treating asthma.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"692-703"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer Potential of Myricetin against Huh7- and Hep3B-Derived Liver Cancer Stem Cells through the Regulation of Apoptosis, Autophagy, and Stemness.","authors":"Mikyoung Kwon, Hye Jin Jung","doi":"10.4062/biomolther.2025.044","DOIUrl":"10.4062/biomolther.2025.044","url":null,"abstract":"<p><p>Liver cancer stem cells (LCSCs) play a significant role in the development, metastasis, treatment resistance, and recurrence of hepatocellular carcinoma (HCC). Targeting LCSCs offers a novel strategy to overcome treatment resistance in HCC. Myricetin, a flavonol from the flavonoid family, is known for its diverse biological activities, including anticancer effects. However, its potential for eradicating LCSCs had not been thoroughly investigated prior to this study. This study evaluated the effects of myricetin on LCSCs derived from Huh7 and Hep3B cell lines both <i>in vitro</i> and <i>in vivo</i>. LCSCs were treated with myricetin to assess cell proliferation, cell cycle arrest, apoptosis induction, autophagy regulation, stemness and EMT marker expression, and tumor growth suppression using a chicken embryo CAM model. Additionally, the combination therapy of myricetin with chloroquine, an autophagy inhibitor, was explored. Myricetin significantly inhibited the proliferation of Huh7- and Hep3B-derived LCSCs and suppressed tumor growth in the CAM model. It induced cell cycle arrest at the G0/G1 phase and triggered apoptosis through intrinsic and extrinsic pathways. Myricetin also stimulated autophagy by inhibiting the PI3K/AKT/mTOR pathway, reduced the expression of stemness markers, including Sox2, Oct4, Nanog, and ALDH1A1, and suppressed EMT. Combining myricetin with chloroquine enhanced apoptotic effects and further downregulated stemness markers by inhibiting STAT3 activation, demonstrating greater efficacy than myricetin alone. The findings establish myricetin, either as a standalone treatment or in combination with chloroquine, as a promising therapeutic candidate for targeting LCSC growth and overcoming chemotherapy resistance in HCC.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"636-651"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MST3 Regulates AMPK and YAP-Hippo Signaling in Cell Models Relevant to Renal Fibrosis.","authors":"Chee-Hong Chan, Te-Jung Lu, Bo-Ying Bao, Po-Chen Chu, Yu-Kai Chen, Syuan-Long Syu, Wen-Yih Jeng, Te-Ling Lu","doi":"10.4062/biomolther.2025.023","DOIUrl":"10.4062/biomolther.2025.023","url":null,"abstract":"<p><p>YAP is a transcription cofactor in the Hippo pathway that interacts with the TEAD family of transcription factors in the nucleus to promote CTGF expression and stimulate cell growth. YAP hyperactivation is frequently observed in fibrotic diseases. The main kinases in the Hippo pathway, MST1/2, a member of the STE20 family, promote Lats phosphorylation, leading to YAP phosphorylation, which prevents its nuclear entry and thus inhibits cell growth. High cell density induces Lats phosphorylation, causing YAP phosphorylation and its exclusion from the nucleus. Additionally, energy stress, such as glucose deprivation, induces AMPK phosphorylation, which also prevents YAP from entering the nucleus. MST3, another member of the STE20 family, has been shown to regulate cell apoptosis, migration, polarization, and ion homeostasis in previous studies. We hypothesized that MST3 is involved in Hippo pathway-mediated fibrosis. To test this, we overexpressed HA-tagged MST3 (HA-MST3) and a kinase-dead mutant (HA-MST3-KD) in MDCK cells. When cells reached a high density, HA-MST3 was activated to phosphorylate YAP, promoting its nuclear exit and inhibiting cell growth. In contrast, HA-MST3-KD cells showed reduced phosphorylated YAP, resulting in YAP retention in the nucleus, continuous cell growth, and NIH/3T3 cell fibrosis. Interestingly, YAP did not exit the nucleus in HA-MST3-KD cells treated with the YAP inhibitor verteporfin, but it did exit under metformin treatment due to energy stress, accompanied by increased AMPK and YAP phosphorylation, which inhibited MST3-KD-mediated fibrosis. These findings suggest that metformin-induced AMPK activation could provide a therapeutic approach for MST3-KD-mediated fibrosis.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"33 4","pages":"704-715"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dimethyl Sulfoxide Shifts Human Mesenchymal Stem Cell Differentiation toward Adipogenesis over Osteogenesis.","authors":"Seokyoung Hwang, Sungjin Ahn, Seungchan An, In Guk Park, Junpyo Gong, Yeonjin Lee, Min Ju Lee, Jayhyun Cho, Minkyu Kim, Minsoo Noh","doi":"10.4062/biomolther.2025.005","DOIUrl":"10.4062/biomolther.2025.005","url":null,"abstract":"<p><p>Dimethyl sulfoxide (DMSO) is extensively used as a solvent in bioactive compound screening due to its capacity to solubilize a wide range of chemical compounds. This study demonstrates that DMSO significantly influences lineage commitment in human bone marrow-derived mesenchymal stem cells (hBM-MSCs) by enhancing adipogenesis and inhibiting osteogenesis. At concentrations above 25 mM (0.32% in culture media), DMSO significantly promoted adipogenic differentiation in hBM-MSCs. Under osteogenic conditions, however, DMSO suppressed mineralization and downregulated the expression of osteoblast markers, thereby reducing osteoblast differentiation. Notably, DMSO also increased the adipocyte population within a predominantly osteogenic environment, suggesting it may shift the balance of hBM-MSC lineage commitment toward adipogenesis over osteogenesis. These findings emphasize the importance of careful consideration when utilizing DMSO as a solvent in studies involving hBMMSCs differentiation and the biological evaluation of test compounds.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"728-734"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2',4',6'-Trimethoxyacetophenone Isolated from <i>Lycoris sanguinea</i> Ameliorates Memory Impairment in Methylglyoxal-Induced Depressive Amnesia Mouse Model.","authors":"Eun Ji Ko, Seong-Min Hong, Hoseong Hwang, Jaeyoung Kwon, Hak Cheol Kwon, Sun Yeou Kim","doi":"10.4062/biomolther.2025.065","DOIUrl":"10.4062/biomolther.2025.065","url":null,"abstract":"<p><p>Depressive amnesia, involving memory impairment and mood dysregulation, frequently co-occurs with depression and neurodegenerative diseases. Methylglyoxal (MGO), a reactive glycolytic byproduct, contributes to depressive-like behaviors and cognitive deficits. This study evaluated the therapeutic potential of 2',4',6'-trimethoxyacetophenone (TMA), a bioactive compound from <i>Lycoris sanguinea</i> var. <i>koreana</i>, in a mouse model of MGO-induced depressive amnesia. Mice received MGO (60 mg/kg) followed by TMA (5 or 20 mg/kg), and behavioral tests were conducted to assess mood, cognition, and locomotor activity. TMA significantly reduced immobility in tail suspension and forced swim tests, improved locomotion and exploration in the open field, and restored memory in novel object recognition and Y-maze tests. Histological analysis showed that TMA preserved hippocampal integrity, modulated glucocorticoid receptor expression, and reduced cortisol levels, indicating involvement in stress regulation. TMA also attenuated neuroinflammation by lowering IL-1β and microglial activation while increasing IL-10. Additionally, it reduced amyloidogenic markers, including oligomeric Aβ and amyloid precursor protein. These findings highlight the neuroprotective and antidepressant potential of TMA and support its use as a natural therapeutic candidate for treating depression-related cognitive impairment.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"33 4","pages":"594-605"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Albiflorin, a Monoterpene Glycoside, Protects Myoblasts against Hydrogen Peroxide-Induced Apoptosis by Activating the Nrf2/HO-1 Axis.","authors":"Cheol Park, Hee-Jae Cha, Dong-Gu Kim, Su Hyun Hong, Sung-Kwon Moon, Cheng-Yun Jin, Gi Young Kim, Heui-Soo Kim, Na Yeong Lee, Jung-Hyun Shim, Yung Hyun Choi","doi":"10.4062/biomolther.2025.020","DOIUrl":"10.4062/biomolther.2025.020","url":null,"abstract":"<p><p>Albiflorin, a key active compound in the roots of <i>Paeonia lactiflora</i> Pall, is known to have multiple health benefits. Although albiflorin has been shown to exert its major pharmacological effects via its antioxidant activity, its efficacy in the muscles has not been evaluated. In this study, we examined the protective activity of albiflorin against oxidative injury in C2C12 murine myoblasts. C2C12 cells were pretreated with nontoxic concentrations of albiflorin and exposed to hydrogen peroxide (H₂O₂) to mimic oxidative stress. Albiflorin pretreatment inhibited H₂O₂-mediated decrease in cell viability and extracellular release of lactate dehydrogenase, and reduced comet tail formation, 8-hydroxy-2'-deoxyguanosine production, and phosphorylated form of histone 2AX expression, which are representative biomarkers of DNA damage. Albiflorin also blocked H₂O₂-induced apoptosis by inhibiting the activation of caspase-3, which is associated with the maintenance of mitochondrial membrane stability by decreasing the Bax/Bcl-2 expression ratio. Additionally, albiflorin markedly suppressed H₂O₂-induced accumulation of reactive oxygen species (ROS) and decreased glutathione levels, while increasing the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) and activating heme oxygenase-1 (HO-1) in the presence of H₂O₂. However, artificial inhibition of HO-1 activity using zinc protoporphyrin (ZnPP) markedly abrogated the protective effects of albiflorin against ROS production and mitochondrial damage in H₂O₂-treated cells. ZnPP significantly reversed the protective effects of albiflorin against H₂O₂-induced apoptosis and decreased cell viability. Taken together, these findings suggest that albiflorin protects myoblasts from oxidative stress-induced DNA damage and apoptosis by activating Nrf2/HO-1 signaling, thus highlighting its potential in the management of myofunctional homeostasis.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"716-727"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Niclosamide Alleviated Skin Inflammation and Restored the Balance between Effector and Regulatory T Cells in Skin.","authors":"Bo Mi Kang, Eunyoung Seo, Jung Min Ahn, Bo Ri Kim, Gwanyoung Kim, Kyungmin Lee, Seunghyun Choi, Taeheon Kim, Yunjee Lee, Wonwoo Choi, Chong Won Choi, Sang Woong Youn","doi":"10.4062/biomolther.2024.210","DOIUrl":"10.4062/biomolther.2024.210","url":null,"abstract":"<p><p>Niclosamide is an oral anthelmintic agent and was reported to also have anti-inflammatory effects by suppressing STAT3 signaling pathways. In this study, we investigated the effect of niclosamide on skin inflammatory diseases to determine its potential as a therapeutic drug. We investigated the effects of niclosamide on two models of skin inflammatory diseases: imiquimod -induced psoriasis-like skin inflammation and LL-37-induced rosacea mouse models. Our experimental results showed that niclosamide ameliorated the psoriasis-like skin inflammation and reduced proinflammatory cytokine production in the psoriasis mouse model. Moreover, niclosamide restored the imbalance between IL-17-expressing γδT cells and Tregs in the psoriasis model. Topical application of niclosamide significantly decreased the abundance of IL-17A⁺ γδT cells, which was increased by imiquimod. Moreover, niclosamide significantly increased the abundance of CD4⁺Foxp3⁺ Tregs. In the LL-37-induced rosacea mouse model, niclosamide significantly reduced the number of inflammatory cells including neutrophils and mast cells that play major roles in initiating inflammation and inducing uncontrolled dermal vessel function in rosacea. Lastly, niclosamide significantly reduced the number of p-STAT3-positive cells in mouse skin, which was increased by treatment with imiquimod or LL-37. We found an anti-inflammatory effect of niclosamide in psoriasis and rosacea mouse models and demonstrated the ability of niclosamide in controlling skin inflammation by recalibrating T cell differentiation and restoring T cell regulatory function. Niclosamide, as a STAT3 inhibitor, is a promising therapeutic for skin inflammation, particularly for preventing the relapse of disease by restoring regulatory cell functions.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"735-745"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triggering Mechanisms of Hepatocyte Repopulation during Liver Regeneration.","authors":"Eui Jin Lee, Na Young Lee, Myeung Gi Choi, Ho Jae Ryu, Ja Hyun Koo","doi":"10.4062/biomolther.2025.035","DOIUrl":"10.4062/biomolther.2025.035","url":null,"abstract":"<p><p>Liver regeneration is a complex process involving hepatocyte proliferation and differentiation, which is essential for restoring liver function after liver injury. Hepatocyte repopulation plays a central role in this regenerative process, and extensive research has aimed to elucidate the triggering mechanisms of hepatocyte proliferation as well as the origins of new hepatocytes. Partial hepatectomy, drug-induced liver injuries, and other genetic mouse models have been widely employed to investigate the regenerative machinery of the liver. However, the exact sources of regenerating hepatocytes remain controversial. While substantial evidence supports the model in which pre-existing hepatocytes self-duplicate to replenish the liver, alternative hypotheses suggest that biliary epithelial cells and hepatic progenitor cells also contribute under certain injury conditions. Recently, advanced techniques, including lineage tracing and spatial transcriptomics, have been utilized to track cell lineages and analyze changes in cell composition during liver regeneration, greatly advancing the field. Given that hepatocytes perform the majority of liver functions, understanding the contributing signaling pathways of hepatocyte repopulation is the most critical among the whole process of liver regeneration. Therefore, this review specifically focuses on summarizing current findings in the cellular and molecular mechanisms underlying hepatocyte repopulation during liver regeneration.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"582-593"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumenol Inhibits Mast Cells Activation in Ovalbumin-Induced Anaphylaxis Model Mice through Modulation of the Fc Epsilon Receptor I Signaling Pathway.","authors":"Yun-Mi Kang, Ki-Shuk Shim, Sung-Wook Chae, So-Hyeon Bok, Dae-Hun Park, Kyungho Kim, Bonggi Lee, Su-Yeon Park, Taesoo Kim, Ki Mo Kim","doi":"10.4062/biomolther.2025.041","DOIUrl":"10.4062/biomolther.2025.041","url":null,"abstract":"<p><p>Curcumenol, a sesquiterpene isolated from <i>Curcuma zedoaria</i>, has a variety of therapeutic effects, such as neuroprotective, antitumor and hepatoprotective effects. This study elucidates whether curcumenol can inhibit ovalbumin (OVA)-induced allergic reactions in a mouse and monoclonal anti-2,4,6-dinitrophenyl (DNP)-immunoglobulin (IgE)/bovine serum albumin (BSA)-mediated allergic reactions in mouse bone marrow-derived mast cells (BMMCs) and rat basophilic leukemia cells (RBL-2H3). IgE-mediated passive cutaneous anaphylaxis and ovalbumin (OVA)-induced anaphylaxis mouse models were performed. β-hexosaminidase release and mast cell degranulation were analyzed <i>in vitro</i>. Western blot analyses were performed to validate the effect of curcumenol on FcεRI signaling pathway. Molecular docking analysis were performed to evaluate curcumenol and tyrosine kinase interaction. Curcumenol alleviated OVA-induced anaphylactic allergic symptoms by increasing rectal temperature in a dosedependent manner. In addition, it reduced the levels of plasma histamine, IgE, and interleukin-4 in mouse model. Curcumenol inhibited IgE-BSA-stimulated β-hexosaminidase release and mast cell degranulation in a dose-dependent manner in BMMCs and RBL-2H3. Curcumenol also inhibited the activation of Src family tyrosine kinases (Fyn and Lyn) and the downstream spleen tyrosine kinase (Syk) in the FcεRI signaling pathway in BMMCs. Furthermore, curcumenol suppressed the activation of Akt, PLCγ1, and mitogen-activated protein kinase signaling. Molecular docking analysis revealed that curcumenol could bind to Fyn and Lyn kinases, thereby suppressing Src family tyrosine kinase signaling. This study suggests that curcumenol inhibits IgE-mediated allergic reactions by suppressing the activation Lyn and Fyn Src family kinases in OVA-challenged model animals. Therefore, curcumenol could be used as an effective alternative therapeutic for allergic diseases.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"670-679"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}