Biological & pharmaceutical bulletin最新文献_第8页

Glimepiride Modulates LPS-Induced M1 Macrophage Polarization via PPARγ-Mediated Inhibitory Mechanism. 格列美脲通过ppar γ介导的抑制机制调节lps诱导的M1巨噬细胞极化。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00752

Wenkai Wang, Hongrui Liu, Pishan Yang

{"title":"Glimepiride Modulates LPS-Induced M1 Macrophage Polarization via PPARγ-Mediated Inhibitory Mechanism.","authors":"Wenkai Wang, Hongrui Liu, Pishan Yang","doi":"10.1248/bpb.b25-00752","DOIUrl":"10.1248/bpb.b25-00752","url":null,"abstract":"This research intended to explore the role of glimepiride, a sulfonylurea-class medication, in regulating macrophage polarization and clarify its underlying molecular mechanism. In vitro experiments were performed using a lipopolysaccharide (LPS)-induced M1 polarization model in the murine macrophage cell line RAW264.7. Different concentrations (low, medium, and high) of glimepiride were applied to evaluate their effects on the expression of M1 macrophage-specific markers. Transcriptome sequencing was conducted to identify potential regulatory pathways. Small interfering RNA (siRNA) was used to silence target genes, aiming to verify the impacts on downstream signaling pathways and pro-inflammatory cytokine secretion. In vitro experiments revealed that glimepiride markedly suppressed LPS-induced M1 macrophage polarization and diminished the expression levels of M1-specific markers, encompassing cluster of differentiation 86 (CD86) and inducible nitric oxide synthase (iNOS). Transcriptomic profiling indicated that the peroxisome proliferator-activated receptor gamma (PPARγ) pathway was modulated by glimepiride. Functional verification via PPARγ siRNA knockdown revealed that glimepiride mediated its regulatory effects by suppressing the expression of phosphorylated inhibitor of nuclear factor kappa B (IκB)/p65, which in turn restrained M1 macrophage polarization and attenuated pro-inflammatory cytokine release. These findings demonstrate that glimepiride inhibits M1 macrophage polarization through a PPARγ-dependent blockade of the IκB-p65 signaling pathway. This study highlights a novel anti-inflammatory mechanism of glimepiride, providing preclinical evidence for its potential application in anti-inflammatory therapies.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 3","pages":"503-512"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

γ-Linolenic Acid Inhibits Contractile Responses in Pig Basilar Arteries via Prostanoid TP Receptor Antagonism and Ba²⁺-Sensitive K⁺ Channel Activation. γ-亚麻酸通过前列腺素TP受体拮抗和Ba2+敏感K+通道激活抑制猪基底动脉收缩反应

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00185

Kento Yoshioka, Minami Inagaki, Tam Minh Phi, Haruki Kimura, Keigo Osa, Keisuke Obara, Noritaka Nakamichi, Yoshio Tanaka

{"title":"γ-Linolenic Acid Inhibits Contractile Responses in Pig Basilar Arteries via Prostanoid TP Receptor Antagonism and Ba2+-Sensitive K+ Channel Activation.","authors":"Kento Yoshioka, Minami Inagaki, Tam Minh Phi, Haruki Kimura, Keigo Osa, Keisuke Obara, Noritaka Nakamichi, Yoshio Tanaka","doi":"10.1248/bpb.b26-00185","DOIUrl":"https://doi.org/10.1248/bpb.b26-00185","url":null,"abstract":"γ-Linolenic acid (GLA) is an n-6 polyunsaturated fatty acid (PUFA) with reported vasoprotective effects. GLA has been shown to inhibit contractions in pig coronary arteries via competitive antagonism at prostanoid TP receptors. α-Linolenic acid (ALA), an n-3 PUFA and a structural isomer of GLA, has been shown to inhibit contractions in pig basilar arteries (PBAs) via prostanoid TP receptor antagonism and activation of K+ channels. However, the actions of GLA in cerebral arteries remain unclear. In this study, we examined the effects of GLA on contractile responses in PBAs. GLA (10-5-10-4 M) concentration-dependently inhibited contractions induced by the TP receptor agonist U46619 (3 × 10-8 M) and prostaglandin F2α (PGF2α; 3 × 10-6 M). GLA (3 × 10-6-3 × 10-5 M) shifted the concentration-response curve for U46619 to the right. Schild analysis yielded a slope of 1.33 (95% confidence interval: 0.70-1.96), which was not significantly different from unity, but GLA also reduced the maximal response to U46619. The apparent pA2 value was 5.43. GLA (10-4 M) also inhibited PGF2α-induced contractions in the presence of the TP receptor antagonist SQ 29,548 (10-6 M); this inhibitory effect was attenuated by Ba2+ (10-3 M) but not by other tested K+ channel inhibitors. GLA also inhibited endothelin-1 (10-8-3 × 10-8 M)-induced contractions, and this effect was attenuated by Ba2+. These findings indicate that GLA, like ALA, suppresses contractile responses in PBAs through dual mechanisms involving TP receptor antagonism and activation of Ba2+-sensitive K+ channels.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 9","pages":"1416-1419"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Body Mass Index-Related Trends in Adverse Events with Enfortumab Vedotin: Analysis of a Pharmacovigilance Database and Medical Records. 与体重指数相关的维多汀不良事件趋势：对药物警戒数据库和医疗记录的分析

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00050

Motoki Kei, Shiori Sato, Ryosuke Yamaga, Satoko Karaki, Yoshihiro Uesawa, Toshimasa Ito

{"title":"Body Mass Index-Related Trends in Adverse Events with Enfortumab Vedotin: Analysis of a Pharmacovigilance Database and Medical Records.","authors":"Motoki Kei, Shiori Sato, Ryosuke Yamaga, Satoko Karaki, Yoshihiro Uesawa, Toshimasa Ito","doi":"10.1248/bpb.b26-00050","DOIUrl":"https://doi.org/10.1248/bpb.b26-00050","url":null,"abstract":"Enfortumab vedotin (EV) is an antibody-drug conjugate used to treat advanced urothelial carcinoma. Although effective, it frequently causes adverse events, particularly skin toxicity. Body mass index (BMI) has been suggested as a risk factor for EV toxicity, but evidence from large-scale studies remains limited. This study investigated the association between BMI and EV toxicity using a national pharmacovigilance database and single-center clinical data. Adverse event reports from the Japanese Adverse Drug Event Report (JADER) database (2004-2025) were stratified by BMI (<22 vs. ≥22 kg/m2). Reporting odds ratios were calculated, and event frequencies were compared using z-tests. Additionally, a retrospective review of medical records was conducted for 17 EV-treated patients at a single institution. Data on dosing and adverse events were collected, and Fisher's exact test was applied. In JADER, a BMI ≥22 kg/m2 was associated with increased reporting of skin disorders, pruritus, and toxic epidermal necrolysis (p < 0.05), whereas a BMI <22 kg/m2 was associated with more reports of pyelonephritis (p = 0.007). In the clinical cohort, patients with skin toxicity had a higher BMI (25.1 vs. 17.7 kg/m2, p = 0.004) and received higher EV doses relative to ideal body weight (IBW) (108.3 vs. 79.9%, p = 0.007) than those without skin toxicity. A high BMI was associated with an increased risk of certain EV-related skin toxicities, potentially exacerbated by dosing based on actual versus IBW, whereas a low BMI may increase susceptibility to infections such as pyelonephritis. Individualizing risk assessment and dosing based on patient physique may improve the safety and efficacy of EV therapy.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 9","pages":"1425-1437"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the Therapeutic Impact of Targeting Brk in Epithelial-Derived Cancer Cells. 探讨靶向Brk对上皮源性癌细胞的治疗作用。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00303

Ryohei Kozaki, Shingo Hotta, Koji Teraishi, Cuifang Li, Kenji Oritani, Tadashi Matsuda

引用次数: 0

Effects of Oxygen-Permeable Plates on Cytochrome P450 and Flavin-Containing Monooxygenase in HepaRG Spheroid Cultures. 透氧板对HepaRG球形培养细胞色素P450和含黄素单加氧酶的影响

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00489

Naoki Takaoka, Momoka Morita, Jun Takahashi, Katsuhiro Esashika, Shigeru Ohta, Seigo Sanoh

{"title":"Effects of Oxygen-Permeable Plates on Cytochrome P450 and Flavin-Containing Monooxygenase in HepaRG Spheroid Cultures.","authors":"Naoki Takaoka, Momoka Morita, Jun Takahashi, Katsuhiro Esashika, Shigeru Ohta, Seigo Sanoh","doi":"10.1248/bpb.b25-00489","DOIUrl":"10.1248/bpb.b25-00489","url":null,"abstract":"Three-dimensional (3D) hepatocyte spheroid cultures offer an advanced in vitro model for investigating liver function and drug metabolism; however, oxygen diffusion limitations restrict spheroid size and functionality. In the present study, we developed a 3D spheroid culture system using HepaRG, a human hepatoma-derived cell line that retains drug-metabolizing enzymes, and oxygen-permeable plates composed of 4-polymethyl-1-pentene (PMP) to improve oxygen availability and metabolic performance. Morphological analysis showed enhanced spheroid circularity and compactness in the PMP culture, implying enhanced cell-cell adhesion. Hypoxic imaging revealed that PMP plate-based cultures markedly reduced central hypoxia, enabling the formation of spheroids with up to 20000 cells. Using clozapine, a low-clearance antipsychotic drug with limited metabolic elimination that is metabolized by monooxygenases, including CYP3A4 and flavin-containing monooxygenase (FMO), we observed an enhanced decline in clozapine levels in PMP plates compared with the clozapine levels seen in the conventional polystyrene plates. Furthermore, the mRNA and protein-expression levels of CYP3A4 and FMO3 were upregulated in the spheroids cultured on PMP plates. These results suggest that improved oxygenation enhances hepatic functionality in 3D cultures by maintaining cell viability and promoting the expression of drug-metabolizing enzymes. Therefore, the PMP plate-based spheroid model offers a practical and physiologically relevant platform for investigating drug metabolism and hepatotoxicity.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 1","pages":"90-98"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intracellular Signaling Pathways for Erythropoietin-Induced Cell Proliferation in Primary Cultured Hepatocytes. 促红细胞生成素诱导原代培养肝细胞增殖的细胞内信号通路。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00596

Hajime Moteki, Masahiko Ogihara, Mitsutoshi Kimura

{"title":"Intracellular Signaling Pathways for Erythropoietin-Induced Cell Proliferation in Primary Cultured Hepatocytes.","authors":"Hajime Moteki, Masahiko Ogihara, Mitsutoshi Kimura","doi":"10.1248/bpb.b25-00596","DOIUrl":"10.1248/bpb.b25-00596","url":null,"abstract":"The mechanisms by which erythropoietin (EPO) promotes hepatocyte proliferation in primary cultures of adult rat hepatocytes were studied. EPO stimulated cell proliferation in a time- and dose-dependent manner, significantly increasing the number of hepatocyte nuclei and DNA synthesis. EPO-induced hepatocyte proliferation was completely suppressed by specific inhibitors targeting Janus kinase 2 (JAK 2), phospholipase C (PLC), protein kinase C (PKC), intracellular Ca2+ mobilization, mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK), and mammalian target of rapamycin (mTOR). In contrast, inhibition of signal transducer and activator of transcription 3/5 (STAT 3/5) or granule secretion had no effect, indicating that EPO acts through a pathway distinct from the classical JAK2-STAT signaling pathway. Western blot analysis showed rapid phosphorylation of ERK 2, but not ERK 1, following EPO stimulation. In addition, EPO induced phosphorylation of PLC and C-rapidly accelerated fibrosarcoma (C-Raf), with PKC acting downstream of PLC and upstream of C-Raf. In contrast, intracellular Ca2+ concentration and activated Ras were transiently increased in hepatocytes after EPO stimulation, and EPO-induced activated Ras was significantly suppressed by the specific PKC inhibitor GF109203X. These results indicate that EPO engages the JAK2/PLC/PKC-Ca2+ signaling cascade, leading to the sequential activation of Ras, C-Raf, and ERK2, ultimately promoting hepatocyte proliferation in vitro.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 2","pages":"281-290"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Roles of Temperature and Reactive Oxygen Species in Circadian Rhythms and Thermosensitivity. 温度和活性氧在昼夜节律和热敏性中的作用。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00811

Takahito Miyake

{"title":"Roles of Temperature and Reactive Oxygen Species in Circadian Rhythms and Thermosensitivity.","authors":"Takahito Miyake","doi":"10.1248/bpb.b25-00811","DOIUrl":"10.1248/bpb.b25-00811","url":null,"abstract":"Noxious temperature changes and high levels of reactive oxygen species (ROS) have traditionally been regarded as harmful stimuli. However, there is now substantial evidence for the importance of small-to-moderate changes in temperature and ROS levels-well below the thresholds that induce cell death or physiological dysfunction-as fundamental signaling cues that regulate a wide range of physiological functions in mammals. In this review, I summarize our recent findings on the regulatory roles of slight fluctuations in temperature and intracellular ROS in biological processes. In particular, this review focuses on two key examples: (A) the effects of subtle changes in physiological circadian body temperature fluctuations on the translational efficiency of the core clock gene Period2 and (B) the role of non-toxic levels of ROS as essential intracellular signals that modulate transient receptor potential ion channel activity and cold sensitivity. Our findings challenge longstanding assumptions that circadian clocks are governed solely by transcriptional and post-translational mechanisms and that the temperature sensitivity of ion channels arises exclusively from direct thermal gating. We demonstrated the pivotal roles of the translational control of mRNA and mitochondrial responses in the temperature-mediated maintenance of circadian clock function and ion channel activity. These insights provide conceptual advances relevant to chronobiology, neuroscience, and pharmacology.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 4","pages":"618-624"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Economic Burden of Cachexia in Japanese Lung Cancer Patients: A Retrospective Claims Database Analysis. 日本肺癌患者恶病质的经济负担：回顾性索赔数据库分析。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00791

Munenobu Kashiwa

{"title":"Economic Burden of Cachexia in Japanese Lung Cancer Patients: A Retrospective Claims Database Analysis.","authors":"Munenobu Kashiwa","doi":"10.1248/bpb.b25-00791","DOIUrl":"10.1248/bpb.b25-00791","url":null,"abstract":"Cancer cachexia is associated with poor clinical outcomes in lung cancer patients; however, its economic impact in Japan remains largely uncharacterized. This study quantified the incremental healthcare costs associated with cachexia in Japanese lung cancer patients using nationwide claims data. We conducted a retrospective cohort study using the Japan Medical Data Center Claims Database. Deceased lung cancer patients were classified into cachexia (n = 447) and control (n = 10464) groups based on International Classification of Diseases, 10th Revision diagnosis codes. Between-group cost differences were assessed using generalized linear models with a gamma distribution, adjusting for survival time, demographics, histology, metastasis, and comorbidities. Within-patient cost changes were analyzed using fixed-effects regression, comparing 6-month periods before and after cachexia diagnosis. Cachexia was independently associated with 13.5% higher total medical costs (rate ratio: 1.14, 95% confidence interval [CI]: 1.06-1.21, p < 0.001). Within-patient analysis demonstrated a 57.9% cost increase in the month of diagnosis (from ¥371360 to ¥586405), with costs remaining 21.7% elevated post-diagnosis. Cost composition shifted from procedures (1.3 vs. 5.4%) toward home care (8.6 vs. 5.7%) in cachexia patients. Median survival following cachexia diagnosis was only 1.0 month, with 71% of patients dying within 3 months. Anamorelin use increased from 2.4 to 29.8% post-diagnosis, although 70.2% of patients did not receive this therapy. Cachexia diagnosis in lung cancer patients is associated with substantial cost increases in Japan. The extremely short survival after diagnosis and the shift toward supportive care highlight the need for earlier recognition and intervention. These findings provide essential data for the economic evaluation of cachexia therapies.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 5","pages":"809-817"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ninjurin-1 Negatively Regulates Humoral and Cellular Immune Responses Induced by the Saponin-Based Adjuvant Quil-A in Mice. 忍尿素-1负向调控皂素基佐剂quila诱导的小鼠体液和细胞免疫反应。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00786

Meigui Shao, Michihiro Takahama, Naoki Takemura, Tatsuya Saitoh

{"title":"Ninjurin-1 Negatively Regulates Humoral and Cellular Immune Responses Induced by the Saponin-Based Adjuvant Quil-A in Mice.","authors":"Meigui Shao, Michihiro Takahama, Naoki Takemura, Tatsuya Saitoh","doi":"10.1248/bpb.b25-00786","DOIUrl":"https://doi.org/10.1248/bpb.b25-00786","url":null,"abstract":"Adjuvants are co-administered with antigens to enhance vaccine-induced protection. Saponins are plant-derived compounds with adjuvant properties, some of which are used in licensed vaccines. Macrophages and dendritic cells (DCs) exposed to saponin-based adjuvants have been reported to exhibit NLRP3-dependent interleukin-1 beta (IL-1β) release, and NLRP3 signaling has been shown to limit their adjuvant activity. Saponin-based adjuvants also induce plasma membrane rupture (PMR) and the release of high-molecular-weight intracellular molecules; however, the molecular mechanisms that mediate PMR and its impact on adjuvant-induced immune responses remain unclear. Here, we investigated the involvement of Ninjurin-1 (NINJ1), a key executor of PMR, in Quil-A-induced PMR and its immunological consequences. Upon stimulation with the saponin mixture Quil-A, peritoneal macrophages and bone marrow-derived dendritic cells (BMDCs) showed NLRP3-independent PMR but NLRP3-dependent IL-1β release. Quil-A-induced PMR was almost completely suppressed in Ninj1-/- peritoneal macrophages and BMDCs compared with wild-type cells, whereas IL-1β release remained unaffected by NINJ1 deficiency. Immunization with Quil-A and ovalbumin (OVA) increased OVA-specific serum immunoglobulin G (IgG), IgG2b, and IgG2c levels in Ninj1-/- mice compared with wild-type mice. Splenocytes from Ninj1-/- mice produced higher levels of interferon-gamma upon stimulation with class I- and class II-restricted OVA peptides than those from wild-type mice. Ninj1-/- mice also showed a higher frequency of OVA-bearing cells, particularly monocyte-derived DCs, in the draining lymph nodes. These results demonstrate that NINJ1 is critical for Quil-A-induced PMR and that NINJ1-mediated PMR negatively regulates Quil-A-induced humoral and cellular immune activation by restricting antigen delivery via antigen-presenting cells.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 2","pages":"371-379"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chronotropic, Inotropic, and Lusitropic Effects of Flavonoids. 黄酮类化合物的变时、变肌和变肌作用。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00486

Kazuo Noguchi, Chinami Ueda, Saki Umeda, Haruna Kanae, Maika Seki, Shogo Hamaguchi, Iyuki Namekata, Hikaru Tanaka

{"title":"Chronotropic, Inotropic, and Lusitropic Effects of Flavonoids.","authors":"Kazuo Noguchi, Chinami Ueda, Saki Umeda, Haruna Kanae, Maika Seki, Shogo Hamaguchi, Iyuki Namekata, Hikaru Tanaka","doi":"10.1248/bpb.b25-00486","DOIUrl":"https://doi.org/10.1248/bpb.b25-00486","url":null,"abstract":"We summarized the recent findings on the acute myocardial effects of several flavonoids, whose long-term beneficial effects through antioxidant activity has attracted attention. Polymethoxyflavones, such as sudachitin, demethoxysudachitin, and nobiletin, showed chronotropic and inotropic effects; the effects were milder than those of β-adrenoceptor agonists. Their strength of action appeared to be related to the number of methoxy groups in the chemical structure. Sudachitin also showed strong vasorelaxant effect causing full relaxation. Quercetin showed positive lusitropic effects in both normal and diabetic myocardium; this was probably mediated by enhancement of Ca2+ sequestration into the sarcoplasmic reticulum by the Ca2+ ATPase. Hesperetin inhibited the spontaneous firing of action potential in the pulmonary vein myocardium; the chronotropic inotropic and lusitropic effects were weak or not observed. Thus, each flavonoid compound has characteristic pharmacological effects probably through their action on specific cellular targets. Further investigation of their effects would provide insights for the development of therapeutic agents for heart diseases such as heart failure and arrhythmia.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 1","pages":"12-23"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0