Journal of pharmacological sciences最新文献_第3页

Resveratrol promotes autophagosome elimination via SIRT1 in cardiomyocytes 白藜芦醇通过心肌细胞中的SIRT1促进自噬体的消除。

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-01-01 DOI: 10.1016/j.jphs.2024.11.006

Atsushi Kuno , Ryusuke Hosoda , Yukika Saga , Naotoshi Iwahara , Yuki Tatekoshi , Ryo Numazawa , Yoshiyuki Horio

{"title":"Resveratrol promotes autophagosome elimination via SIRT1 in cardiomyocytes","authors":"Atsushi Kuno , Ryusuke Hosoda , Yukika Saga , Naotoshi Iwahara , Yuki Tatekoshi , Ryo Numazawa , Yoshiyuki Horio","doi":"10.1016/j.jphs.2024.11.006","DOIUrl":"10.1016/j.jphs.2024.11.006","url":null,"abstract":"<div><div>The processes of autophagy, including autophagosome formation, fusion of autophagosomes with lysosomes, and degradation of autophagosomes by lysosomes, are regulated by various mechanisms. We recently found that treatment with resveratrol, an activator of the NAD<sup>+</sup>-dependent protein deacetylase Sirtuin-1 (SIRT1), in a mouse model prevented autophagosome accumulation in the heart with high mTORC1 activity. In this study, we investigated whether SIRT1 mediates the effects of resveratrol on autophagosome elimination using a cardiomyocyte model. In H9c2 cardiomyocytes, treatment with the mTORC1 activator MHY1485 induced autophagosome accumulation accompanied by increases in fragmented mitochondria within the autophagosomes and levels of intracellular reactive oxygen species (ROS), indicative of impaired autophagy-mediated elimination of mitochondria and resultant oxidative stress. MHY1485 suppressed the fusion of autophagosomes with lysosomes. Co-treatment with resveratrol attenuated the MHY1485-induced increases in autophagosomes, mitochondria within autophagosomes, and levels of ROS. Knockdown of <em>Sirt1</em> reversed the reductions in autophagosomes and ROS levels induced by resveratrol under the condition of MHY1485 treatment. Neither resveratrol treatment nor <em>Sirt1</em> knockdown modulated the phosphorylation levels of UVRAG, a target of mTORC1 for suppression of autophagosome-lysosome fusion. Our findings suggest that SIRT1 mediates the resveratrol-induced promotion of autophagosome elimination in cells with high mTORC1 activity.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 1","pages":"Pages 25-34"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872034","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

Involvement of N-methyl-D-aspartate receptor GluN2C/GluN2D subunits in social behavior impairments in mice exposed to social defeat stress as juveniles

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-12-28 DOI: 10.1016/j.jphs.2024.12.007

Mikio Yoshida , Hikari Katada , Yuya Isozumi , Chiharu Suzuki , Akira Yoshimi , Norio Ozaki , Yukihiro Noda

{"title":"Involvement of N-methyl-D-aspartate receptor GluN2C/GluN2D subunits in social behavior impairments in mice exposed to social defeat stress as juveniles","authors":"Mikio Yoshida , Hikari Katada , Yuya Isozumi , Chiharu Suzuki , Akira Yoshimi , Norio Ozaki , Yukihiro Noda","doi":"10.1016/j.jphs.2024.12.007","DOIUrl":"10.1016/j.jphs.2024.12.007","url":null,"abstract":"<div><div>Glutamatergic system dysfunction is associated with the pathophysiology of stress-related psychiatric disorders. However, the role of N-methyl-D-aspartate (NMDA) receptor GluN2C and GluN2D subunits in the pathophysiology of adverse juvenile experiences remain unclear. This study aimed to investigate the involvement of GluN2C and GluN2D subunits in social behavior impairments in mice exposed to social defeat stress as juveniles. Acute administration of PPDA, a GluN2C/GluN2D antagonist, and ketamine, a non-competitive NMDA receptor antagonist, attenuated social behavior impairments in stressed mice. This attenuating effect of ketamine was partially inhibited by the administration of CIQ, a GluN2C/GluN2D-containing NMDA potentiator. The prefrontal cortex of stressed mice exhibited significantly elevated levels of GluN2C and GluN2D proteins compared to control mice. These findings suggest that activation of GluN2C- and/or GluN2D-containing NMDA receptors contributes to the development of social behavioral impairments induced by juvenile social defeat stress. Moreover, these subunits may play a role in the therapeutic effects of ketamine. Targeting GluN2C/GluN2D subunits of NMDA receptors may be novel therapeutic strategies for stress-related psychiatric disorders in adolescents with adverse juvenile experiences.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 3","pages":"Pages 139-145"},"PeriodicalIF":3.0,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135677","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

Okanin alleviates symptoms of nociceptive-like responses in diabetic peripheral neuropathy in type 1 diabetic Wistar rats by regulating the AGEs/NF-κB/Nrf-2 pathway Okanin通过调节AGEs/NF-κB/Nrf-2通路，减轻1型糖尿病Wistar大鼠糖尿病周围神经病变损伤样反应症状

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-11-22 DOI: 10.1016/j.jphs.2024.11.003

Mohammad Rafiq Ganie , Nadeem Khan , Manish Shukla , Shreya Sood , Sushma Devi , Poonam Arora , Manish Kumar , Imtiyaz Ahmed Najar , Jianlei Tang

{"title":"Okanin alleviates symptoms of nociceptive-like responses in diabetic peripheral neuropathy in type 1 diabetic Wistar rats by regulating the AGEs/NF-κB/Nrf-2 pathway","authors":"Mohammad Rafiq Ganie , Nadeem Khan , Manish Shukla , Shreya Sood , Sushma Devi , Poonam Arora , Manish Kumar , Imtiyaz Ahmed Najar , Jianlei Tang","doi":"10.1016/j.jphs.2024.11.003","DOIUrl":"10.1016/j.jphs.2024.11.003","url":null,"abstract":"<div><div>Elevated reactive species and AGEs contribute to deregulation of transcription factors <em>e.g.</em>, NF-κB and Nrf2 in diabetic peripheral neuropathy (DPN). Okanin, a bioactive chalcone, is active against redox imbalance, immune response, and pro-inflammatory events. The current investigation assessed effects of okanin in streptozotocin-induced DPN in rats. Wistar rats were divided into 6 groups (<em>n</em> = 6): Control, DPN, Okanin 2.5, Okanin 5, Okanin 10, and Gpn (Gabapentin). After 6 weeks of streptozotocin (55 mg/kg) injection, okanin (2.5, 5, 10 mg/kg), and gabapentin (50 mg/kg), were administered for 4 weeks. The streptozotocin-induced reduction in body weight, and increased feed/water intake, insulin, glucose, and HbA1c levels were mitigated by okanin or gabapentin. In DPN rats, Okanin or gabapentin ameliorated insulin resistance and β-cell function, inflammatory indices, and oxidative stress in the sciatic nerve of rodents thereby culminating in a decrease in hyperalgesia and allodynia. Okanin and streptozotocin-treated rats had significantly declined levels of AGEs, the receptor for AGEs, and NF-κB, and an upsurge in Nrf2 expression. In streptozotocin-induced DPN model, okanin ameliorates nociceptive-like responses by regulating the AGEs/NF-κB/Nrf2 pathway, suggesting that okanin has therapeutic value against DPN which needs further studies involving human subjects.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 1","pages":"Pages 12-24"},"PeriodicalIF":3.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743708","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

Paclitaxel-induced peripheral neuropathy in male rats attenuated by calmangafodipir, a superoxide dismutase mimetic 紫杉醇诱导的雄性大鼠外周神经病变可通过超氧化物歧化酶模拟物卡马福地平（Calangafodipir）得到缓解

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-11-20 DOI: 10.1016/j.jphs.2024.11.004

Takehiro Kawashiri , Kohei Mori , Haruna Ishida , Mami Ueda , Kozo Yao , Fumiko Nagahama , Keisuke Mine , Yusuke Mori , Yusuke Koura , Shunsuke Fujita , Takao Shimazoe , Daisuke Kobayashi

引用次数: 0

Different sensitivities of porcine coronary arteries and veins to BAY 60–2770, a soluble guanylate cyclase activator 猪冠状动脉和静脉对可溶性鸟苷酸环化酶激活剂 BAY 60-2770 的不同敏感性

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-11-14 DOI: 10.1016/j.jphs.2024.11.002

Masashi Tawa, Keisuke Nakagawa, Mamoru Ohkita

{"title":"Different sensitivities of porcine coronary arteries and veins to BAY 60–2770, a soluble guanylate cyclase activator","authors":"Masashi Tawa, Keisuke Nakagawa, Mamoru Ohkita","doi":"10.1016/j.jphs.2024.11.002","DOIUrl":"10.1016/j.jphs.2024.11.002","url":null,"abstract":"<div><div>Nitric oxide (NO)-donor drugs, which stimulate reduced form of soluble guanylate cyclase (sGC), have different efficacy to the arteries and veins. This study examined whether sGC activators, which activate oxidized/apo sGC, also have arteriovenous selectivity similar to that of NO-donor drugs. The mechanical responses of the isolated blood vessels were assessed using the organ chamber technique and protein expression was verified using western blotting. BAY 60–2770 (sGC activator) caused concentration-dependent relaxation in both porcine coronary arteries and veins, with the response being slightly more pronounced in the arteries. In contrast, sodium nitroprusside (NO-donor drug)-induced relaxation of the arteries was slightly weaker than that of the veins. Vasorelaxant responses to 8-Br-cGMP (cGMP analog) did not differ between the arteries and veins. In the presence of ODQ (heme oxidant), the heterogeneities in the responses to BAY 60–2770 and sodium nitroprusside between the arteries and veins disappeared. The sGC expression in the arteries did not differ from that in the veins. These findings suggest that sGC activators, in contrast to NO-donor drugs, have greater effects on the arteries than on the veins. This may be due to differences in the balance of sGC forms expressed in the arteries and veins.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 1","pages":"Pages 1-7"},"PeriodicalIF":3.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142697758","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

Rehmannioside A promotes the osteoblastic differentiation of MC3T3-E1 cells via the PI3K/AKT signaling pathway and inhibits glucocorticoid-induced bone loss in vivo 地黄甙 A 通过 PI3K/AKT 信号通路促进 MC3T3-E1 细胞的成骨细胞分化并抑制糖皮质激素诱导的体内骨质流失

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-11-06 DOI: 10.1016/j.jphs.2024.11.001

Haisheng Huang , Fang Ji , Guobin Qi , Yuting Cao , Xuecheng He , Hao Wang , Zengxin Jiang

{"title":"Rehmannioside A promotes the osteoblastic differentiation of MC3T3-E1 cells via the PI3K/AKT signaling pathway and inhibits glucocorticoid-induced bone loss in vivo","authors":"Haisheng Huang , Fang Ji , Guobin Qi , Yuting Cao , Xuecheng He , Hao Wang , Zengxin Jiang","doi":"10.1016/j.jphs.2024.11.001","DOIUrl":"10.1016/j.jphs.2024.11.001","url":null,"abstract":"<div><div>Glucocorticoid-induced osteoporosis (GIOP) is a widespread disease characterized by low bone density. There remains a lack of effective means for osteoporosis. Rehmannioside A (ReA), an iridoid glycoside, exhibits various pharmacological activities. This study aimed to explore the role and mechanism of ReA in osteogenic differentiation of osteoblasts. Cell viability, reactive oxygen species (ROS) generation, and cell apoptosis were assessed using corresponding assay kits. Real-time quantitative polymerase chain reaction, Western blotting, and alkaline phosphatase (ALP) staining were performed to evaluate the osteogenic differentiation of MC3T3-E1 cells. Alizarin red S staining was used to assess the mineralization of MC3T3-E1 cells. Protein expression associated with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was analyzed using Western blotting. Micro-computed tomography, histopathological, and immunohistochemical analyses were performed to determine the therapeutic effect of ReA on GIOP <em>in vivo</em>.The results showed that ReA promoted the osteogenic differentiation of MC3T3-E1 cells by regulating the PI3K/AKT signaling pathway and protected mice against glucocorticoid-induced bone loss by promoting osteoblast-mediated bone formation <em>in vivo</em>. The findings of the current study revealed that ReA is a potential therapeutic agent for osteoporosis.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 4","pages":"Pages 247-257"},"PeriodicalIF":3.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142663088","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

Targeting TMEM16A ion channels suppresses airway hyperreactivity, inflammation, and remodeling in an experimental Guinea pig asthma model 在实验性几内亚猪哮喘模型中，靶向 TMEM16A 离子通道可抑制气道过度反应、炎症和重塑

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-10-28 DOI: 10.1016/j.jphs.2024.10.004

Jozef Mažerik , Eduard Gondáš , Matúš Dohál , Lukáš Smieško , Marta Jošková , Soňa Fraňová , Martina Šutovská

{"title":"Targeting TMEM16A ion channels suppresses airway hyperreactivity, inflammation, and remodeling in an experimental Guinea pig asthma model","authors":"Jozef Mažerik , Eduard Gondáš , Matúš Dohál , Lukáš Smieško , Marta Jošková , Soňa Fraňová , Martina Šutovská","doi":"10.1016/j.jphs.2024.10.004","DOIUrl":"10.1016/j.jphs.2024.10.004","url":null,"abstract":"<div><div>Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness, inflammation, and remodeling. Calcium (Ca<sup>2+</sup>)-activated chloride (Cl<sup>−</sup>) channels, such as TMEM16A, are inferred to be involved in asthma. Therefore, the present study investigated the therapeutic potential of TMEM16A inhibition in a guinea pig model of ovalbumin (OVA)-induced allergic asthma. Guinea pigs were treated with a specific blocker, CaCCinh-A01 (10 μM), administered via inhalation. A significant reduction in cough reflex sensitivity and specific airway resistance was observed in animals treated with CaCCinh-A01, highlighting its potential to improve airway function. Despite a reduction in ciliary beating frequency (CBF), CaCCinh-A01 reduced airway mucus viscosity by decreasing the production of mucin-5AC (MUC5AC). The nonspecific reduction in the Th1/Th2 cytokine spectrum following CaCCinh-A01 treatment indicated the suppression of airway inflammation. Additionally, markers associated with airway remodeling were diminished, suggesting that CaCCinh-A01 may counteract structural changes in airway tissues. Therefore, inhibition appears to mitigate the pathological aspects of asthma, including airway hyperresponsiveness, inflammation, and remodeling. However, further studies are required to comprehensively evaluate the potential of TMEM16A as a therapeutic target for asthma.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 4","pages":"Pages 239-246"},"PeriodicalIF":3.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142552112","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

Glucosylceramide synthase inhibitor ameliorates chronic inflammatory pain 葡萄糖酰胺合成酶抑制剂可改善慢性炎症性疼痛

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-10-15 DOI: 10.1016/j.jphs.2024.10.003

Shun Watanabe , Misa Oyama , Takashi Iwai , Mitsuo Tanabe

引用次数: 0

Analgesic effect of Keishinieppiittokajutsubu on low barometric pressure-induced pain response in arthritic model rats Keishinieppiittokajutsubu 对低气压引起的关节炎模型大鼠疼痛反应的镇痛效果

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-10-09 DOI: 10.1016/j.jphs.2024.10.002

Yuki Kurauchi , Kana Inoue , Tomoka Kawakami , Manami Ueda , Tomoko Yamaguchi , Junji Akaki , Masahiko Komorisono , Hiroshi Katsuki

引用次数: 0

TND1128, a 5-deazaflavin derivative with auto-redox ability, facilitates polarization of mitochondrial membrane potential (ΔΨm) and on-demand ATP synthesis in mice brain slices TND1128是一种具有自动氧化还原能力的5-去氮黄素衍生物，可促进小鼠脑切片线粒体膜电位（ΔΨm）的极化和按需合成 ATP

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2024-10-09 DOI: 10.1016/j.jphs.2024.10.001

Nanae Takahashi , Tomohisa Nagamatsu , Norio Akaike , Yoshihisa Kudo

{"title":"TND1128, a 5-deazaflavin derivative with auto-redox ability, facilitates polarization of mitochondrial membrane potential (ΔΨm) and on-demand ATP synthesis in mice brain slices","authors":"Nanae Takahashi , Tomohisa Nagamatsu , Norio Akaike , Yoshihisa Kudo","doi":"10.1016/j.jphs.2024.10.001","DOIUrl":"10.1016/j.jphs.2024.10.001","url":null,"abstract":"<div><div>TND1128, a 5-deazaflavin derivative, is a drug with self-redox ability. We examined the effect of TND1128 on the level of mitochondrial membrane potential (ΔΨ<sub>m</sub>), which is the most critical motive power for the biosynthesis of ATP. We prepared brain slices from mice pretreated with TND1128 (0.1–10 mg/kg, intraperitoneally) and detected ΔΨ<sub>m</sub> level with JC-1, a fluorescence ΔΨ<sub>m</sub> indicator. We further examined the depolarization of ΔΨ<sub>m</sub> under 5-min exposure to 25 mM KCl-ACSF (25K-ACSF), which activated neuronal voltage-dependent Ca<sup>2+</sup> channels. We evaluated the effect of TND1128 by using the inverse number of the ΔΨ<sub>m</sub> value as the ATP synthesis index (ASI). The level of ΔΨ<sub>m</sub> increased significantly by 24-h pretreatment with TND1128 (10 mg/kg), and significantly higher depolarization of the ΔΨ<sub>m</sub> was observed with 25K-ACSF exposure than in non-treated control. We found a significant decrease in 25K-ACSF induced [Ca<sup>2+</sup>]<sub>c</sub> and [Ca<sup>2+</sup>]<sub>m</sub> levels in the TND1128-pretreated preparations. We confirmed the dose and time-dependent facilitatory effects of TND1128 on the ASI. This study suggested that TND1128 could be incorporated into the TCA cycle and electron transfer chains to facilitate the polarization of ΔΨ<sub>m</sub> and activate on-demand ATP synthesis. TND1128 might rescue neurons in various brain diseases caused by energy defects. (198)</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"156 4","pages":"Pages 218-229"},"PeriodicalIF":3.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432368","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