Clinical and Experimental Pharmacology and Physiology最新文献_第10页

Suppression of hypothalamic–pituitary–gonadal function by linzagolix in benign prostatic hyperplasia and polycystic ovary syndrome animal models 林扎哥利对良性前列腺增生及多囊卵巢综合征动物模型下丘脑-垂体-性腺功能的抑制作用

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-08-25 DOI: 10.1111/1440-1681.13817

Motohiro Tezuka, Saori Yonekubo-Awaka, Yasuaki Tamai, Kumi Tsuchioka, Kaoru Kobayashi, Yu Kuramochi, Satoshi Tatemichi, Tatsuya Nagasawa, Sumiyoshi Kiguchi

{"title":"Suppression of hypothalamic–pituitary–gonadal function by linzagolix in benign prostatic hyperplasia and polycystic ovary syndrome animal models","authors":"Motohiro Tezuka, Saori Yonekubo-Awaka, Yasuaki Tamai, Kumi Tsuchioka, Kaoru Kobayashi, Yu Kuramochi, Satoshi Tatemichi, Tatsuya Nagasawa, Sumiyoshi Kiguchi","doi":"10.1111/1440-1681.13817","DOIUrl":"10.1111/1440-1681.13817","url":null,"abstract":"The hypothalamic–pituitary–gonadal (HPG) axis is an important regulatory mechanism involved primarily in the development and regulation of the reproductive systems. The suppression of the HPG axis by gonadotropin-releasing hormone (GnRH) analogues is expected to be effective for the treatment of sex hormone-dependent diseases, such as endometriosis, uterine fibroid, prostate cancer, benign prostatic hyperplasia (BPH) and polycystic ovary syndrome (PCOS). Despite the established involvement of GnRH signalling in these disorders, the therapeutic efficacy of small molecular GnRH antagonists for BPH and PCOS has not been adequately evaluated in non-clinical studies. Therefore, the purpose of the present study was to evaluate the potential of linzagolix, a small molecular GnRH antagonist, as a potential new treatment option for BPH and PCOS. Dogs and rats exhibiting normal prostates and dogs diagnosed with prostatic hyperplasia were used to evaluate the effects of linzagolix in BPH. The effects of linzagolix were also examined in a rat model of PCOS induced by repeated administration of letrozole, an aromatase inhibitor. Linzagolix reduced serum luteinizing hormone and testosterone levels in male rats and normal or BPH model dogs and suppressed prostate weight without testosterone depletion, suggesting the existence of an optimal therapeutic testosterone level for BPH treatment. In a PCOS rat model, linzagolix improved both insulin resistance and ovarian dysfunction. Treatment with linzagolix decreased follicle-stimulating hormone levels, but did not alter serum luteinizing hormone and testosterone levels. These results indicate that linzagolix may provide a new treatment option for GnRH-related disorders, such as BPH and PCOS.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10071839","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

Evaluation of right atrium structure and function in a rat model of monocrotaline-induced pulmonary hypertension: Exploring the possible antiarrhythmic properties of amiodarone 大鼠肺动脉高压模型右心房结构和功能的评价:探讨胺碘酮可能的抗心律失常特性

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-08-23 DOI: 10.1111/1440-1681.13813

Jorge Lucas Teixeira-Fonseca, Julliane Vasconcelos Joviano-Santos, Fabiana da Silva Alcântara, Michael Ramon de Lima Conceição, Polyana Leal-Silva, Danilo Roman-Campos

{"title":"Evaluation of right atrium structure and function in a rat model of monocrotaline-induced pulmonary hypertension: Exploring the possible antiarrhythmic properties of amiodarone","authors":"Jorge Lucas Teixeira-Fonseca, Julliane Vasconcelos Joviano-Santos, Fabiana da Silva Alcântara, Michael Ramon de Lima Conceição, Polyana Leal-Silva, Danilo Roman-Campos","doi":"10.1111/1440-1681.13813","DOIUrl":"10.1111/1440-1681.13813","url":null,"abstract":"Atrial arrhythmias (AA) are common in pulmonary hypertension (PH) and are closely associated with poor clinical outcomes. One of the most studied models to investigate PH is the rat model of monocrotaline (MCT) induced PH (MCT-PH). To date, little is known about right atrium (RA) function in the MCT-PH model and the propensity of RA to develop arrhythmias. Therefore, the aim of the study was to evaluate the function of the RA of control (CTRL) and MCT treated rats, and the ability of amiodarone, a classical antiarrhythmic, to prevent the occurrence of AA in the RA in MCT-PH rats. RA function was studied in MCT-PH rats 20 days after a single subcutaneous injection of MCT 50 mg/kg. The histological results indicated the presence of RA and right ventricular hypertrophy. Surface electrocardiogram demonstrated increased P wave duration, PR wave duration and QT interval in MCT rats. RA from MCT rats were more susceptible to develop ex vivo burst pacing arrhythmias when compared to CTRL. Intriguingly, amiodarone in clinical relevant concentration was not able to prevent the occurrence arrhythmias in RA from MCT-PH animals. Hence, we conclude that the rat model of MCT-PH impairs RA structure and function, and acute exposure of RA to amiodarone in clinical relevant concentration is not able to attenuate the onset of arrhythmias in the ex vivo RA preparation.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10048770","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

Berberine interacts with gut microbiota and its potential therapy for polycystic ovary syndrome 小檗碱与肠道菌群的相互作用及其对多囊卵巢综合征的潜在治疗

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-08-21 DOI: 10.1111/1440-1681.13814

Ting-Wei Zhu, Xue-Lian Li

引用次数: 0

Aucubin alleviates methotrexate-induced enteritis in rats by inducing autophagy Aucubin通过诱导自噬减轻甲氨蝶呤诱导的大鼠肠炎。

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-08-15 DOI: 10.1111/1440-1681.13810

Tongao Yang, Wuying Lang, Yun Zhao, Yahan Yang, Hongli Liu, Sufen Li, Xianglong Li, Shuangqi Zhang, Haihua Zhang

{"title":"Aucubin alleviates methotrexate-induced enteritis in rats by inducing autophagy","authors":"Tongao Yang, Wuying Lang, Yun Zhao, Yahan Yang, Hongli Liu, Sufen Li, Xianglong Li, Shuangqi Zhang, Haihua Zhang","doi":"10.1111/1440-1681.13810","DOIUrl":"10.1111/1440-1681.13810","url":null,"abstract":"One of the toxic side effects of methotrexate (MTX) is enteritis. Aucubin, an iridoid glycoside derived from traditional medicinal herbs, has been proven to have anti-inflammation, anti-apoptosis and anti-oxidation properties. This work explored the effect and mechanism of aucubin in treating MTX-induced enteritis in a rat model. Two doses of aucubin (5 and 10 mg/kg) were adopted for the assessment of its pharmacological activity. We observed that in rats with MTX-induced enteritis, the body weight and small intestinal weight decreased. The intestine barrier was injured, as reflected by pathological examinations and an increase in D-lactate and diamine oxidase concentration in serum. Intestinal inflammation was shown by the observation of macrophages in the intestine and the concentrations of inflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum. The NLR family pyrin domain containing 3 (NLRP3) inflammasome was shown to be activated by the enhancement of NLRP3, cleaved-caspase 1, IL-18 and IL-1β. Moreover, autophagy was reflected by transmission electron microscopy as slightly induced, along with changes in autophagy-related markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin1. Remarkably, aucubin treatment attenuated the MTX-induced disease activity index increase, intestinal damage, inflammatory response and NLRP3 inflammasome activation, but provoked autophagy. Rapamycin, an autophagy activator, showed similar therapeutic effects to aucubin on MTX-induced enteritis. However, 3-methyladenine, an autophagy inhibitor, reversed the protective effects of aucubin. These findings prompted the hypothesis that aucubin alleviates MTX-induced enteritis by aggravating autophagy. This study might provide evidence for further investigation on the therapeutic role of aucubin in MTX-resulted enteritis.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10061079","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

Ligustrazine and liguzinediol protect against doxorubicin-induced cardiomyocytes injury by inhibiting mitochondrial apoptosis and autophagy 川芎嗪和川芎二醇通过抑制线粒体凋亡和自噬来保护阿霉素诱导的心肌细胞损伤

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-08-13 DOI: 10.1111/1440-1681.13811

Naqi Lian, Jing Tong, Weijie Zhu, Qinghai Meng, Miao Jiang, Mianli Bian, Yu Li

{"title":"Ligustrazine and liguzinediol protect against doxorubicin-induced cardiomyocytes injury by inhibiting mitochondrial apoptosis and autophagy","authors":"Naqi Lian, Jing Tong, Weijie Zhu, Qinghai Meng, Miao Jiang, Mianli Bian, Yu Li","doi":"10.1111/1440-1681.13811","DOIUrl":"10.1111/1440-1681.13811","url":null,"abstract":"Preventing or treating heart failure (HF) by blocking cardiomyocyte apoptosis is an effective strategy that improves survival and reduces ventricular remodelling and dysfunction in the chronic stage. Autophagy is a mechanism that degrades intracellular components and compensates for energy deficiency, which is commonly observed in cardiomyocytes of failed hearts. Cardiomyocytes activated by doxorubicin (DOX) exhibit strong autophagy. This study aims to investigate the potential protective effect of ligustrazine and its derivative liguzinediol on regulating DOX-induced cardiomyocyte apoptosis and explore the use of the embryonic rat heart-derived myoblast cell line H9C2 for identifying novel treatments for HF. The results indicated that it has been demonstrated to reverse myocardial infarction remodelling in failed hearts by promoting autophagy in salvaged cardiomyocytes and anti-apoptosis of cardiomyocytes in granulation tissue. Our study suggests that ligustrazine and liguzinediol can be a promising agents and autophagy is potential pathway in the management of HF.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10362217","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

Intraoperative hemodynamics and risk of cardiac surgery-associated acute kidney injury: An observation study and a feasibility clinical trial 术中血流动力学与心脏手术相关急性肾损伤的风险:一项观察研究和可行性临床试验

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-08-07 DOI: 10.1111/1440-1681.13812

Khin M. Noe, Andrea Don, Andrew D. Cochrane, Michael Z. L. Zhu, Jennifer P. Ngo, Julian A. Smith, Amanda G. Thrift, Johnny Vogiatjis, Andrew Martin, Rinaldo Bellomo, James McMillan, Roger G. Evans

{"title":"Intraoperative hemodynamics and risk of cardiac surgery-associated acute kidney injury: An observation study and a feasibility clinical trial","authors":"Khin M. Noe, Andrea Don, Andrew D. Cochrane, Michael Z. L. Zhu, Jennifer P. Ngo, Julian A. Smith, Amanda G. Thrift, Johnny Vogiatjis, Andrew Martin, Rinaldo Bellomo, James McMillan, Roger G. Evans","doi":"10.1111/1440-1681.13812","DOIUrl":"10.1111/1440-1681.13812","url":null,"abstract":"Targeting greater pump flow and mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) could potentially alleviate renal hypoxia and reduce the risk of postoperative acute kidney injury (AKI). Therefore, in an observational study of 93 patients undergoing on-pump cardiac surgery, we tested whether intraoperative hemodynamic management differed between patients who did and did not develop AKI. Then, in 20 patients, we assessed the feasibility of a larger-scale trial in which patients would be randomized to greater than normal target pump flow and MAP, or usual care, during CPB. In the observational cohort, MAP during hypothermic CPB averaged 68.8 ± 8.0 mmHg (mean ± SD) in the 36 patients who developed AKI and 68.9 ± 6.3 mmHg in the 57 patients who did not (p = 0.98). Pump flow averaged 2.4 ± 0.2 L/min/m2 in both groups. In the feasibility clinical trial, compared with usual care, those randomized to increased target pump flow and MAP had greater mean pump flow (2.70 ± 0.23 vs. 2.42 ± 0.09 L/min/m2 during the period before rewarming) and systemic oxygen delivery (363 ± 60 vs. 281 ± 45 mL/min/m2). Target MAP ≥80 mmHg was achieved in 66.6% of patients in the intervention group but in only 27.3% of patients in the usual care group. Nevertheless, MAP during CPB did not differ significantly between the two groups. We conclude that little insight was gained from our observational study regarding the impact of variations in pump flow and MAP on the risk of AKI. However, a clinical trial to assess the effects of greater target pump flow and MAP on the risk of AKI appears feasible.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.13812","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10007826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Ginsenoside Rh4 inhibits the malignant progression of multiple myeloma and induces ferroptosis by regulating SIRT2 人参皂苷Rh4通过调节SIRT2抑制多发性骨髓瘤恶性进展，诱导铁下垂

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-07-15 DOI: 10.1111/1440-1681.13805

Qiuhua Ying, Jinjie Lou, Daibo Zheng

{"title":"Ginsenoside Rh4 inhibits the malignant progression of multiple myeloma and induces ferroptosis by regulating SIRT2","authors":"Qiuhua Ying, Jinjie Lou, Daibo Zheng","doi":"10.1111/1440-1681.13805","DOIUrl":"10.1111/1440-1681.13805","url":null,"abstract":"Multiple myeloma (MM) has a high mortality rate, and the exploration of therapeutic drugs for MM with low side effects is a hot topic at the moment. Ginsenoside Rh4 has been shown to inhibit tumour growth in many cancers. However, the role of ginsenoside Rh4 in MM and its reaction mechanism have not been reported so far. After the treatment with different concentrations of ginsenoside Rh4, the proliferation of NCI-H929 cells was detected by Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine staining. The cell apoptosis and cycle arrest were detected by flow cytometry and western blot. The thiobarbituric acid-reactive substances (TBARS) production was assessed with TBARS assay, whereas Fe2+ fluorescence assay was used for the measurement of Fe2+ level. The production of reactive oxygen species was evaluated with dichloro-dihydro-fluorescein diacetate staining, and western blot was applied for the estimation of ferroptosis-related proteins. The potential targets of ginsenoside Rh4 were predicted by molecular docking technology and verified by western blot. The transfection efficacy of overexpression-SIRT2 was examined with quantitative reverse transcription polymerase chain reaction and western blot. To figure out the detailed reaction mechanism between ginsenoside Rh4 and SIRT2 in MM, rescue experiments were conducted. We found that ginsenoside Rh4 inhibited cell proliferation, induced cell apoptosis, promoted cycle arrest and facilitated ferroptosis in MM. Moreover, ginsenoside Rh4 inhibited SIRT2 expression in MM cells. The overexpression of SIRT2 reversed the effects of ginsenoside Rh4 on cell proliferation, cell apoptosis, cycle arrest and ferroptosis in MM. Overall, ginsenoside Rh4 inhibited the malignant progression of MM and induced ferroptosis by regulating SIRT2.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10297214","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: 1

Role of the chloride channel blocker in the formation of filtering tract scars after glaucoma surgery in rats 氯通道阻滞剂在大鼠青光眼手术后滤过道瘢痕形成中的作用。

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-07-15 DOI: 10.1111/1440-1681.13803

Yujiao Jin, Weiyi Jin, Qiushuang Sun, Nan Li, Meiling Jiang, Yinfeng Liu, Lixia Sun

{"title":"Role of the chloride channel blocker in the formation of filtering tract scars after glaucoma surgery in rats","authors":"Yujiao Jin, Weiyi Jin, Qiushuang Sun, Nan Li, Meiling Jiang, Yinfeng Liu, Lixia Sun","doi":"10.1111/1440-1681.13803","DOIUrl":"10.1111/1440-1681.13803","url":null,"abstract":"Filtration surgery is commonly performed for glaucoma treatment to reduce intraocular pressure (IOP); however, scarring of the filtering bleb is the main cause of failure. In this study, we evaluated the effects of the chloride channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) on scar formation in filtering blebs. A glaucoma filtering surgery model was generated using Sprague–Dawley rats, divided into the control and NPPB groups receiving injections of different NPPB concentrations. The IOP of all rats decreased 1-day post-surgery and gradually increased afterward. However, IOP in rats from the NPPB groups recovered more slowly than that of the control group rats. In addition, the area and survival times of filtering blebs in rats from the NPPB groups were substantially larger and longer than those in the control group. Twenty-eight days after surgery, the protein and mRNA expression of collagen I, fibronectin and α-smooth muscle actin in the filtering area of rats from the NPPB groups were significantly lower than that in the control group rats. Collectively, our study demonstrates that NPPB inhibits filtering bleb scar formation, maintains filtering bleb morphology and prolongs filtering bleb survival time by inhibiting the differentiation of conjunctival fibroblasts and extracellular matrix synthesis.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.13803","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10152070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Esculentoside A ameliorates DNCB-induced atopic dermatitis by suppressing the ROS-NLRP3 axis via activating the Nrf2 pathway Esculentoside A通过激活Nrf2通路抑制ROS-NLRP3轴，改善dncb诱导的特应性皮炎

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-07-13 DOI: 10.1111/1440-1681.13809

Tao Liu, Yuanmin He, Yongmei Liao

{"title":"Esculentoside A ameliorates DNCB-induced atopic dermatitis by suppressing the ROS-NLRP3 axis via activating the Nrf2 pathway","authors":"Tao Liu, Yuanmin He, Yongmei Liao","doi":"10.1111/1440-1681.13809","DOIUrl":"10.1111/1440-1681.13809","url":null,"abstract":"Atopic dermatitis (AD) is a chronic inflammatory skin condition with a high prevalence. Inflammation and oxidative stress are strongly associated with AD progression. Esculentoside A (EsA) inhibits inflammation and oxidative stress in various diseases. However, whether EsA mitigates AD by suppressing inflammation and oxidative stress remains unknown. A mouse model of AD was constructed by the induction of 1-chloro-2,4-dinitrochlorobenzene (DNCB). The mechanism of EsA and its effects on AD symptoms, pathology, inflammation and oxidative stress were investigated through histopathological staining, enzyme-linked immunosorbent assay, blood cells analysis, colorimetric measurement and western blot analysis. EsA improved the clinical symptoms and increased clinical skin scores in AD mice. Skin thickening of the epidermis and dermal tissues and the mast cell numbers in AD mice were reduced with the EsA treatment. EsA decreased the relative mRNA level of thymic stromal lymphopoietin, interleukin (IL)-4, IL-5 and IL-13; the serum concentrations of immunoglobulin E (IgE) and IL-6; and the numbers of white blood cells (WBC) and WBC subtypes, including basophil, lymphocytes, eosinophil, neutrophil and monocytes in DNCB-induced mice. DNCB caused higher levels of oxidative stress, which was reversed with the administration of EsA. Mechanically, EsA upregulated the expression of Nrf2 but downregulated the level of NLRP3 inflammasome in AD mice. The inhibitor of Nrf2 significantly recovered the EsA-induced changes in the NLRP3 inflammasome proteins in DNCB-treated mice. Therefore, EsA improved the clinical and pathological symptoms, inflammation and oxidative stress experienced by DNCB-induced mice and was involved in the inactivation of NLRP3 inflammasome by activating Nrf2.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10132280","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: 1

Diosmetin-7-O-β-D-glucopyranoside suppresses endothelial–mesenchymal transformation through endoplasmic reticulum stress in cardiac fibrosis 地奥美汀-7-O-β-D-吡喃葡糖苷通过内质网应激抑制心脏纤维化中的内皮间充质转化。

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2023-07-10 DOI: 10.1111/1440-1681.13802

Huahua Wang, Xiaoyu Zhang, Yangyang Liu, Yunyun Zhang, Yingyu Wang, Yunru Peng, Yongfang Ding

{"title":"Diosmetin-7-O-β-D-glucopyranoside suppresses endothelial–mesenchymal transformation through endoplasmic reticulum stress in cardiac fibrosis","authors":"Huahua Wang, Xiaoyu Zhang, Yangyang Liu, Yunyun Zhang, Yingyu Wang, Yunru Peng, Yongfang Ding","doi":"10.1111/1440-1681.13802","DOIUrl":"10.1111/1440-1681.13802","url":null,"abstract":"Diosmetin-7-O-β-D-glucopyranoside (Diosmetin-7-O-glucoside) is a natural flavonoid glycoside known to have a therapeutic application for cardiovascular diseases. Cardiac fibrosis is the main pathological change in the end stage of cardiovascular diseases. Endothelial-mesenchymal transformation (EndMT) induced by endoplasmic reticulum stress (ER stress) via Src pathways is involved in the process of cardiac fibrosis. However, it is unclear whether and how diosmetin-7-O-glucoside regulates EndMT and ER stress to treat cardiac fibrosis. In this study, molecular docking results showed that diosmetin-7-O-glucoside bound well to ER stress and Src pathway markers. Diosmetin-7-O-glucoside suppressed cardiac fibrosis induced by isoprenaline (ISO) and reduced the levels of EndMT, ER stress in mice heart. Primary cardiac microvascular endothelial cells (CMECs) were induced by transforming growth factor-β1 (TGF-β1) to perform EndMT. Diosmetin-7-O-glucoside could effectively regulate EndMT and diminish the accumulation of collagen I and collagen III. We also showed that the tube formation in CMECs was restored, and the capacity of migration was partially inhibited. Diosmetin-7-O-glucoside also ameliorated ER stress through the three unfolded protein response branches, as evidenced by organelle structure in transmission electron microscopy images and the expression of protein biomarkers like the glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP). Further analysis showed that diosmetin-7-O-glucoside could suppress the expression level of Src phosphorylation, then block EndMT with the maintenance of endothelial appearance and endothelial marker expression. These results suggested that the diosmetin-7-O-glucoside can regulate EndMT through ER stress, at least in part via Src-dependent pathways.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10205033","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: 1