Journal of pharmacological sciences最新文献_第10页

Ramelteon coordinates theta and gamma oscillations in the hippocampus for novel object recognition memory in mice Ramelteon在小鼠的新物体识别记忆中协调海马中的θ和γ振荡

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-06-01 Epub Date: 2025-04-01 DOI: 10.1016/j.jphs.2025.03.013

Kinjiro Takeda , Kisa Watanabe , Sena Iijima , Takeshi Nagahiro , Haruka Suzuki , Kano Izumo , Yuji Ikegaya , Nobuyoshi Matsumoto

{"title":"Ramelteon coordinates theta and gamma oscillations in the hippocampus for novel object recognition memory in mice","authors":"Kinjiro Takeda , Kisa Watanabe , Sena Iijima , Takeshi Nagahiro , Haruka Suzuki , Kano Izumo , Yuji Ikegaya , Nobuyoshi Matsumoto","doi":"10.1016/j.jphs.2025.03.013","DOIUrl":"10.1016/j.jphs.2025.03.013","url":null,"abstract":"<div><div>Object recognition memory is an animal's ability to discriminate between novel and familiar items and is supported by neural activities in not only the perirhinal cortex but also the hippocampus and prefrontal cortex. Since we previously demonstrated that ramelteon enhanced object recognition memory in mice, we sought neural correlates of the memory improvement. We recorded neural activity in the hippocampus and prefrontal cortex of mice while they performed a novel object recognition task. We found that theta oscillations in the hippocampus were enhanced when ramelteon-treated mice explored both novel and familiar objects. Moreover, we showed high coherence in phases at low gamma frequencies between the hippocampus and prefrontal cortex. We assume that theta enhancement is indicative of increased cholinergic activity by melatonin receptor activation. High coherence of low gamma oscillations between the hippocampal and prefrontal network in ramelteon-treated mice sampling novel objects suggests better cognitive operations for discrimination between novelty and familiarity. The current study sheds light upon physiological consequences of melatonin receptor activation, further contributing improved cognitive functions.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 2","pages":"Pages 121-130"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792004","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}

引用次数: 0

Gadoxetic acid-enhanced magnetic resonance imaging predicts early nab-paclitaxel-induced peripheral neuropathy during pancreatic cancer treatment: A pilot study 加多西酸增强磁共振成像预测胰腺癌治疗期间早期nab-紫杉醇诱导的周围神经病变：一项初步研究

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-06-01 Epub Date: 2025-03-19 DOI: 10.1016/j.jphs.2025.03.009

Yusuke Takasaki , Hironao Okubo , Yuka Fukuo , Muneo Ikemura , Hitoshi Ando , Hiroyuki Isayama

{"title":"Gadoxetic acid-enhanced magnetic resonance imaging predicts early nab-paclitaxel-induced peripheral neuropathy during pancreatic cancer treatment: A pilot study","authors":"Yusuke Takasaki , Hironao Okubo , Yuka Fukuo , Muneo Ikemura , Hitoshi Ando , Hiroyuki Isayama","doi":"10.1016/j.jphs.2025.03.009","DOIUrl":"10.1016/j.jphs.2025.03.009","url":null,"abstract":"<div><div>Nab-paclitaxel (nab-PTX) is transported by organic anion-transporting polypeptide (OATP)1B1 and OATP1B3. Chemotherapy-induced peripheral neuropathy (CIPN) is a representative adverse event associated with gemcitabine plus nab-PTX (GnP) in patients with pancreatic cancer. Gadoxetic acid is also transported by OATP1B1 and OATP1B3. We aimed to assess whether the enhancement effect of gadoxetic acid-enhanced magnetic resonance (MR) imaging could predict the development of CIPN for GnP. This study evaluated 27 patients with pancreatic cancer who underwent gadoxetic acid-enhanced MR imaging prior to GnP treatment. The contrast enhancement index (CEI), a measure of liver enhancement on hepato-biliary images, was measured. Plasma concentrations of paclitaxel at 0.5, 6, and 24 h after first administration were also determined in 13 patients. Sixteen of the twenty-seven patients (59.3 %) developed ≥ grade 1 CIPN during the first 8 weeks. We found a negative relationship between the CEI and area under the plasma concentration curve of PTX (r = −0.729, <em>p</em> = 0.003). In multivariate analysis, a CEI <1.84 and concomitant diabetes mellitus were independent predictors of CIPN development (hazard ratio, 5.37, <em>p</em> = 0.027; hazard ratio, 3.68, <em>p</em> = 0.012, respectively). Gadoxetic acid-enhanced MR imaging could be useful in predicting the development of CIPN during GnP therapy.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 2","pages":"Pages 113-120"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768612","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}

引用次数: 0

Receptor-mediated Gi-3 activation in mammalian and human brain membranes: Reestablishment method and its application to nociceptin/orphanin FQ opioid peptide (NOP) receptor/Gi-3 interaction 受体介导的Gi-3在哺乳动物和人类脑膜中的激活：重建方法及其在伤害肽/孤儿蛋白FQ阿片肽（NOP）受体/Gi-3相互作用中的应用

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-06-01 Epub Date: 2025-03-31 DOI: 10.1016/j.jphs.2025.03.014

Yuji Odagaki , Masakazu Kinoshita , Makoto Honda , J. Javier Meana , Luis F. Callado , Jesús A. García-Sevilla , Miklós Palkovits , Dasiel Oscar Borroto-Escuela , Kjell Fuxe

{"title":"Receptor-mediated Gi-3 activation in mammalian and human brain membranes: Reestablishment method and its application to nociceptin/orphanin FQ opioid peptide (NOP) receptor/Gi-3 interaction","authors":"Yuji Odagaki , Masakazu Kinoshita , Makoto Honda , J. Javier Meana , Luis F. Callado , Jesús A. García-Sevilla , Miklós Palkovits , Dasiel Oscar Borroto-Escuela , Kjell Fuxe","doi":"10.1016/j.jphs.2025.03.014","DOIUrl":"10.1016/j.jphs.2025.03.014","url":null,"abstract":"<div><div>Functional activation of heterotrimeric guanine nucleotide-binding proteins (G-proteins) via G-protein-coupled receptors (GPCRs) has been extensively explored using guanosine-5′-<em>O</em>-(3-[<sup>35</sup>S]thio)triphosphate ([<sup>35</sup>S]GTPγS) binding assay. However, the conventional method is primarily applicable to G<sub>i/o</sub> family without discrimination among G-protein subtypes. Therefore, this study aims to reestablish a novel method termed “[<sup>35</sup>S]GTPγS binding/immunoprecipitation assay” by identifying a most suitable anti-Gα<sub>i-3</sub> antibody instead of the previously utilized, now withdrawn antibody. In the initial screening of commercially available anti-Gα<sub>i-3</sub> antibodies, two were identified and one was selected for further investigations based on efficacy with adenosine—the most potent agonist in our previous research. After optimizing experimental conditions with rat and postmortem human brain membranes, the stimulatory effects of various agonists were evaluated. Some agonists, including nociceptin, exhibited sufficient stimulatory effects for further pharmacological characterization. Nociceptin increased [<sup>35</sup>S]GTPγS binding to Gα<sub>i-3</sub> in a concentration-dependent manner, response that was insensitive to naloxone but potently inhibited using (±)-J-113397. The method described in this study provides a valuable strategy for determining the intrinsic efficacy of ligands at various GPCRs. This includes nociceptin/orphanin FQ opioid peptide (NOP) receptor selectively coupled to Gα<sub>i-3</sub>, providing insights into the pharmacological concept of “functional selectivity.”</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 2","pages":"Pages 131-138"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791936","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}

引用次数: 0

The citrus flavonoid nobiletin prevents the development of doxorubicin-induced heart failure by inhibiting apoptosis 柑橘类黄酮皂素通过抑制细胞凋亡来防止阿霉素诱导的心力衰竭的发生

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-06-01 Epub Date: 2025-03-19 DOI: 10.1016/j.jphs.2025.03.011

Yoichi Sunagawa , Sonoka Iwashimizu , Masaya Ono , Saho Mochizuki , Kenshiro Iwashita , Rina Sato , Satoshi Shimizu , Masafumi Funamoto , Kana Shimizu , Toshihide Hamabe-Horiike , Yasufumi Katanasaka , Akira Murakami , Tomohiro Asakawa , Makoto Inai , Toshiyuki Kan , Maki Komiyama , Philip Hawke , Kiyoshi Mori , Yoshiki Arakawa , Koji Hasegawa , Tatsuya Morimoto

{"title":"The citrus flavonoid nobiletin prevents the development of doxorubicin-induced heart failure by inhibiting apoptosis","authors":"Yoichi Sunagawa , Sonoka Iwashimizu , Masaya Ono , Saho Mochizuki , Kenshiro Iwashita , Rina Sato , Satoshi Shimizu , Masafumi Funamoto , Kana Shimizu , Toshihide Hamabe-Horiike , Yasufumi Katanasaka , Akira Murakami , Tomohiro Asakawa , Makoto Inai , Toshiyuki Kan , Maki Komiyama , Philip Hawke , Kiyoshi Mori , Yoshiki Arakawa , Koji Hasegawa , Tatsuya Morimoto","doi":"10.1016/j.jphs.2025.03.011","DOIUrl":"10.1016/j.jphs.2025.03.011","url":null,"abstract":"<div><h3>Background</h3><div>The anthracycline anticancer drug doxorubicin (DOX) induces myocardial cell death and heart failure. The aim of the present study was to investigate whether nobiletin (NOB), a natural flavonoid isolated from citrus peel, has a protective effect against DOX-induced cardiotoxicity.</div></div><div><h3>Methods and results</h3><div>H9C2 cells were pretreated with 100 μM NOB and then treated with 1 μM DOX. An MTT assay revealed that NOB improved the decreased cell viability induced by DOX. A TUNEL assay showed that NOB treatment improved DOX-induced apoptosis in H9C2 cells. Western blotting indicated that DOX-induced increases in cleaved caspase-3 and -9 expression were significantly suppressed by NOB treatment. Motion field imaging of human iPS cell-derived cardiomyocyte sheets showed that NOB significantly suppressed a DOX-induced reduction of their contractile function. Next, to investigate the effect of NOB in vivo, DOX was intraperitoneally administered to mice. Echocardiography showed that oral administration of NOB reduced DOX-induced left ventricular systolic dysfunction, and a TUNEL assay showed that oral administration also inhibited apoptosis in the mouse heart.</div></div><div><h3>Conclusions</h3><div>These results indicate that NOB treatment suppressed DOX-induced cardiotoxicity by reducing apoptosis. Further study of the mechanism of this effect may lead to the development of a novel therapy for DOX-induced heart failure.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 2","pages":"Pages 84-94"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683457","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}

引用次数: 0

Suppressing SPARC gene with siRNA exerts therapeutic effects and inhibits MMP-2/9 and ADAMTS1 overexpression in a murine model of ischemia/reperfusion-induced acute kidney injury 用siRNA抑制SPARC基因在小鼠缺血/再灌注急性肾损伤模型中发挥治疗作用，抑制MMP-2/9和ADAMTS1过表达

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-06-01 Epub Date: 2025-03-21 DOI: 10.1016/j.jphs.2025.03.010

Hiroe Toba , Denan Jin , Shinji Takai

{"title":"Suppressing SPARC gene with siRNA exerts therapeutic effects and inhibits MMP-2/9 and ADAMTS1 overexpression in a murine model of ischemia/reperfusion-induced acute kidney injury","authors":"Hiroe Toba , Denan Jin , Shinji Takai","doi":"10.1016/j.jphs.2025.03.010","DOIUrl":"10.1016/j.jphs.2025.03.010","url":null,"abstract":"<div><div>Secreted protein acidic and rich in cysteine (SPARC), a collagen-binding matricellular protein, is reported to facilitate inflammation and fibrosis in various tissues including the kidneys. Ischemia/reperfusion (I/R) is a major process of acute kidney injury. To investigate whether SPARC inhibition might attenuate renal I/R injury, we injected small interfering RNA (siRNA) targeting SPARC into male BALB/c mice one day before 45 min of renal ischemia followed by 72 h of reperfusion. Serum creatinine concentration, blood urea nitrogen, histological tubular damage, tubulointerstitial fibrosis, and expression of collagen I and transforming growth factor-β were increased after I/R. Expression of 4-hydroxy-2-nonenal, an oxidative stress marker, and the inflammatory cytokines monocyte chemoattractant protein-1 and tumor necrosis factor-α, were also upregulated in I/R kidneys. Overexpression of SPARC mRNA was observed after I/R, and immunohistochemistry revealed that SPARC was localized mainly in damaged tubuloepithelial cells. Additionally, a disintegrin and metalloproteinase with thrombospondin type 1 motif (ADAMTS1) expression colocalized with SPARC. Injection of siRNA targeting SPARC attenuated renal dysfunction, histological abnormalities, collagen deposition, oxidative stress, and renal inflammation. In addition, SPARC gene knockdown suppressed the I/R-induced increases in ADAMTS1 and matrix metalloproteinase-2/9 expression. In conclusion, I/R-induced SPARC could be a novel therapeutic target against acute kidney injury.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 2","pages":"Pages 103-112"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705001","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}

引用次数: 0

Hirsutine attenuated oxidative stress and autophagy in diabetic kidney disease through Keap1/Nrf2 pathway hirsutin通过Keap1/Nrf2通路减弱糖尿病肾病的氧化应激和自噬

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-06-01 Epub Date: 2025-04-07 DOI: 10.1016/j.jphs.2025.04.002

Yao Zhang , Bing Yang , Miao Tan, Jinchuan Tan

{"title":"Hirsutine attenuated oxidative stress and autophagy in diabetic kidney disease through Keap1/Nrf2 pathway","authors":"Yao Zhang , Bing Yang , Miao Tan, Jinchuan Tan","doi":"10.1016/j.jphs.2025.04.002","DOIUrl":"10.1016/j.jphs.2025.04.002","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the therapeutic potential and renal protective mechanisms of hirsutine in diabetic kidney disease (DKD).</div></div><div><h3>Methods</h3><div>A DKD model was induced in Sprague-Dawley rats using a high-fat diet (HFD) and streptozotocin (STZ). High glucose (HG)-stimulated HK-2 cells served as an <em>in vitro</em> model. Reactive oxygen species (ROS) levels in kidney tissues were measured using dihydroethidium (DHE) staining. ELISA was performed to measure MDA, SOD, and GSH in both rat tissues and HK-2 cells. Western blot and immunofluorescence analyses evaluated renal fibrosis, the Nrf2 signaling pathway, and autophagy-related proteins (Beclin 1, LC3I/II, P62).</div></div><div><h3>Results</h3><div>Hirsutine treatment significantly improved metabolic and renal parameters in rats, enhancing renal function and reducing fibrosis, as shown by lower levels of Vimentin, Collagen-IV, and α-SMA. It alleviated oxidative stress, indicated by reduced ROS and MDA levels and increased SOD and GSH activity. Additionally, hirsutine enhanced autophagy, reflected by higher Beclin 1 and LC3I/II levels and decreased P62 expression. By disrupting the Keap1-Nrf2 interaction, hirsutine increased Nrf2 levels and upregulated antioxidative enzymes like NQO1, SOD-2, and HO-1.</div></div><div><h3>Conclusion</h3><div>Hirsutine exhibited renoprotective effects in DKD by modulating the Keap1/Nrf2 pathway, mitigating oxidative stress and promoting autophagy, making it a promising candidate for treatment.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 2","pages":"Pages 143-153"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

A novel lysophosphatidic acid receptor 1 antagonist with high brain penetrability has a curative effect in the empathic pain-related fibromyalgia model 一种新型高脑穿透性溶血磷脂酸受体1拮抗剂在共情性疼痛相关纤维肌痛模型中具有疗效

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-06-01 Epub Date: 2025-04-11 DOI: 10.1016/j.jphs.2025.03.012

Hiroyuki Neyama , Naoki Dozono , Yasuka Sahara , Kenji Nishikawa , Hiroshi Ueda

引用次数: 0

Acute curcumin administration enhances delta oscillations in the hippocampus underlying object memory improvement 急性姜黄素管理增强了海马体的delta振荡，从而改善了对象记忆

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-06-01 Epub Date: 2025-03-15 DOI: 10.1016/j.jphs.2025.03.007

Sena Iijima , Kinjiro Takeda , Takeshi Nagahiro , Kisa Watanabe , Yuji Ikegaya , Nobuyoshi Matsumoto

引用次数: 0

Mirogabalin and pregabalin alleviate nociplastic sensitization induced by chemogenetic activation of the central amygdala neurons in rodents 米罗巴林和普瑞巴林可减轻鼠类中央杏仁核神经元化学激活引起的致伤性敏化

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-06-01 Epub Date: 2025-03-11 DOI: 10.1016/j.jphs.2025.03.004

Manami Yajima , Yukari Takahashi , Yasuhito Uezono , Fusao Kato

{"title":"Mirogabalin and pregabalin alleviate nociplastic sensitization induced by chemogenetic activation of the central amygdala neurons in rodents","authors":"Manami Yajima , Yukari Takahashi , Yasuhito Uezono , Fusao Kato","doi":"10.1016/j.jphs.2025.03.004","DOIUrl":"10.1016/j.jphs.2025.03.004","url":null,"abstract":"<div><div>Nociplastic pain represents the third mechanistic descriptor of pain, alongside neuropathic and nociceptive pain, as proposed in 2017 by the International Association for the Study of Pain (IASP). It describes pain occurring in the absence of nociceptor activation, tissue damage, or neuropathy. The underlying brain mechanisms of nociplastic pain remain poorly understood. Despite the potentially large patient population with chronic pain of this class, effective pharmacological treatments for nociplastic pain are still limited, highlighting the urgent need for drug development using appropriate preclinical models.</div><div>In this study, we investigated the anti-sensitization effects of two gabapentinoids—mirogabalin besylate (MGB) and pregabalin (PGB)—using a rodent model of nociplastic pain. This model involves experimental excitation of central amygdala neurons via designer receptors exclusively activated by designer drugs (DREADDs), causing widespread sensitization. Administration of an artificial ligand, deschloroclozapine (DCZ; 0.1 mg/kg, i.p.), significantly reduced the 50 %-paw withdrawal threshold, which was significantly elevated by MGB (10 mg/kg, i.p.) and PGB (30 mg/kg, i.p.), restoring it to levels not significantly different from the pre-DCZ baseline. We conclude that MGB and PGB alleviate widespread sensitization in this nociplastic pain model, likely through their action on α<sub>2</sub>δ-1 subunits within brain circuits that regulate pain sensitivity.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 2","pages":"Pages 77-83"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683458","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}

引用次数: 0

Puerarin improves MASLD by remodeling intestinal microenvironment to promote mitochondrial fusion and autophagy 葛根素通过重塑肠道微环境促进线粒体融合和自噬来改善MASLD

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-01 Epub Date: 2025-03-04 DOI: 10.1016/j.jphs.2025.03.001

Chunbin Sun , Mei Du , Shuang Sha , Si Wang , Lei Li , Jiong Hou , Li Li , Jiali Yuan , Jinyuan Yan , Zhongshan Yang

{"title":"Puerarin improves MASLD by remodeling intestinal microenvironment to promote mitochondrial fusion and autophagy","authors":"Chunbin Sun , Mei Du , Shuang Sha , Si Wang , Lei Li , Jiong Hou , Li Li , Jiali Yuan , Jinyuan Yan , Zhongshan Yang","doi":"10.1016/j.jphs.2025.03.001","DOIUrl":"10.1016/j.jphs.2025.03.001","url":null,"abstract":"<div><div>Pueraria Mirifica (Willd. Ohwi) is a medicine with anti-inflammatory and lipid-lowering properties. Puerarin is one of the main active components of Pueraria. The aim of this study was to investigate the possible mechanisms of Pueraria in the treatment of non-alcoholic fatty liver disease. The therapeutic effect of the drug was demonstrated by serum and liver pathology indicators. The mechanism of action of puerarin was demonstrated by intestinal microbial changes and short-chain fatty acid content tests. The mechanism of puerarin alleviating Metabolic dysfunction-associated steatotic liver disease (MASLD) by regulating intestinal flora was predicted by bioinformatics. The relationship between flora and liver was revealed by q-PCR detection of mRNA expression level of liver metabolic genes. And the mechanism of puerarin action was further verified by intestinal microbial clearance experiments. Puerarin reduced vacuolar-like changes, lipid deposition, and inflammatory cell infiltration in the livers of high-fat diet (HFD) model mice. The gut microbiota abundance and diversity were remodeled, short-chain fatty acid content was increased, and the intestinal mucosal barrier was repaired, accompanied by a reduction in inflammatory cytokines. Puerarin regulated mRNA expression of hepatic lipid metabolism genes to alleviate MASLD. These results suggested that puerarin treats MASLD by treating altering bacterial metabolism and anti-inflammation.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 1","pages":"Pages 27-41"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578355","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}

引用次数: 0