Pharmaceuticals (Basel, Switzerland)最新文献_第8页

Anti-Itching and Anti-Inflammatory Effects of Kushenol F via the Inhibition of TSLP Production. 苦参酚F通过抑制TSLP产生的止痒和抗炎作用。

IF 4.6

Pharmaceuticals (Basel, Switzerland) Pub Date : 2022-10-31 DOI: 10.3390/ph15111347

Seongyea Jo, Eun-Yeung Gong, Wonbeak Yoo, Hyunji Choi, Dana Jung, Kyung Hee Noh, Seokho Kim, Sang-Hyun Kim, Hyeong-Kyu Lee

{"title":"Anti-Itching and Anti-Inflammatory Effects of Kushenol F via the Inhibition of TSLP Production.","authors":"Seongyea Jo, Eun-Yeung Gong, Wonbeak Yoo, Hyunji Choi, Dana Jung, Kyung Hee Noh, Seokho Kim, Sang-Hyun Kim, Hyeong-Kyu Lee","doi":"10.3390/ph15111347","DOIUrl":"https://doi.org/10.3390/ph15111347","url":null,"abstract":"Atopic dermatitis (AD) is a chronic inflammatory skin disease that results from eczema, itching, disrupted barrier function and aberrant cutaneous immune responses. The aim of the present study was to assess the efficacy of kushenol F as an effective treatment for AD via the suppression of thymic stromal lymphopoietin (TSLP) production. The results of the present study demonstrated that the clinical symptoms of AD were less severe and there was reduced ear thickening and scratching behavior in kushenol F-treated Dermatophagoides farinae extract (DFE)/1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD mice. Histopathological analysis demonstrated that kushenol F decreased the DFE/DNCB-induced infiltration of eosinophil and mast cells and TSLP protein expression levels. Furthermore, kushenol F-treated mice exhibited significantly lower concentrations of serum histamine, IgE and IgG2a compared with the DFE/DNCB-induced control mice. Kushenol F also significantly decreased phosphorylated NF-κB and IKK levels and the mRNA expression levels of IL-1β and IL-6 in cytokine combination-induced human keratinocytes. The results of the present study suggested that kushenol F may be a potential therapeutic candidate for the treatment of AD via reducing TSLP levels.","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40675921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In Vitro, Molecular Docking and In Silico ADME/Tox Studies of Emodin and Chrysophanol against Human Colorectal and Cervical Carcinoma. 大黄素和大黄酚抗人大肠癌和宫颈癌的体外分子对接和ADME/Tox研究。

IF 4.6

Pharmaceuticals (Basel, Switzerland) Pub Date : 2022-10-31 DOI: 10.3390/ph15111348

Wasim Ahmad, Mohammad Azam Ansari, Abdulrhman Alsayari, Dalia Almaghaslah, Shadma Wahab, Mohammad N Alomary, Qazi Mohammad Sajid Jamal, Firdos Alam Khan, Abuzer Ali, Prawez Alam, Abozer Y Elderdery

{"title":"In Vitro, Molecular Docking and In Silico ADME/Tox Studies of Emodin and Chrysophanol against Human Colorectal and Cervical Carcinoma.","authors":"Wasim Ahmad, Mohammad Azam Ansari, Abdulrhman Alsayari, Dalia Almaghaslah, Shadma Wahab, Mohammad N Alomary, Qazi Mohammad Sajid Jamal, Firdos Alam Khan, Abuzer Ali, Prawez Alam, Abozer Y Elderdery","doi":"10.3390/ph15111348","DOIUrl":"https://doi.org/10.3390/ph15111348","url":null,"abstract":"Anthraquinones (AQs) are present in foods, dietary supplements, pharmaceuticals, and traditional treatments and have a wide spectrum of pharmacological activities. In the search for anti-cancer drugs, AQ derivatives are an important class. In this study, anthraquinone aglycons chrysophanol (Chr), emodin (EM) and FDA-approved anticancer drug fluorouracil were analyzed by molecular docking studies against receptor molecules caspase-3, apoptosis regulator Bcl-2, TRAF2 and NCK-interacting protein kinase (TNIK) and cyclin-dependent protein kinase 2 (CDK2) as novel candidates for future anticancer therapeutic development. The ADMET SAR database was used to predict the toxicity profile and pharmacokinetics of the Chr and EM. Furthermore, in silico results were validated by the in vitro anticancer activity against HCT-116 and HeLa cell lines to determine the anticancer effect. According to the docking studies simulated by the docking program AutoDock Vina 4.0, Chr and EM had good binding energies against the target proteins. It has been observed that Chr and EM show stronger molecular interaction than that of the FDA-approved anticancer drug fluorouracil. In the in vitro results, Chr and EM demonstrated promising anticancer activity in HCT-116 and HeLa cells. These findings lay the groundwork for the potential use of Chr and EM in the treatment of human colorectal and cervical carcinomas.","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40675922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Andrographolide Promotes Uptake of Glucose and GLUT4 Transport through the PKC Pathway in L6 Cells. 穿心莲内酯通过PKC途径促进L6细胞的葡萄糖摄取和GLUT4运输。

IF 4.6

Pharmaceuticals (Basel, Switzerland) Pub Date : 2022-10-31 DOI: 10.3390/ph15111346

Jingya Liao, Ziwei Yang, Yanhong Yao, Xinzhou Yang, Jinhua Shen, Ping Zhao

{"title":"Andrographolide Promotes Uptake of Glucose and GLUT4 Transport through the PKC Pathway in L6 Cells.","authors":"Jingya Liao, Ziwei Yang, Yanhong Yao, Xinzhou Yang, Jinhua Shen, Ping Zhao","doi":"10.3390/ph15111346","DOIUrl":"https://doi.org/10.3390/ph15111346","url":null,"abstract":"Glucose transporter 4 (GLUT4) is a membrane protein that regulates blood glucose balance and is closely related to type 2 diabetes. Andrographolide (AND) is a diterpene lactone extracted from herbal medicine Andrographis paniculata, which has a variety of biological activities. In this study, the antidiabetic effect of AND in L6 cells and its mechanism were investigated. The uptake of glucose of L6 cells was detected by a glucose assay kit. The expression of GLUT4 and phosphorylation of protein kinase B (PKB/Akt), AMP-dependent protein kinase (AMPK), and protein kinase C (PKC) were detected by Western blot. At the same time, the intracellular Ca2+ levels and GLUT4 translocation in myc-GLUT4-mOrange-L6 cells were detected by confocal laser scanning microscopy. The results showed that AND enhanced the uptake of glucose, GLUT4 expression and fusion with plasma membrane in L6 cells. Meanwhile, AND also significantly activated the phosphorylation of AMPK and PKC and increased the concentration of intracellular Ca2+. AND-induced GLUT4 expression was significantly inhibited by a PKC inhibitor (Gö6983). In addition, in the case of 0 mM extracellular Ca2+ and 0 mM extracellular Ca2+ + 10 μM BAPTA-AM (intracellular Ca2+ chelator), AND induced the translocation of GLUT4, and the uptake of glucose was significantly inhibited. Therefore, we concluded that AND promoted the expression of GLUT4 and its fusion with plasma membrane in L6 cells through PKC pathways in a Ca2+-dependent manner, thereby increasing the uptake of glucose.","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40675920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vasorelaxant Effects of Syzygium samarangense (Blume) Merr. and L.M.Perry Extract Are Mediated by NO/cGMP Pathway in Isolated Rat Thoracic Aorta. 马兰合欢的血管松弛作用。NO/cGMP通路对大鼠离体胸主动脉的调节作用。

IF 4.6

Pharmaceuticals (Basel, Switzerland) Pub Date : 2022-10-31 DOI: 10.3390/ph15111349

Noura A Hassan, Mohamed A O Abdelfattah, Yasmine M Mandour, Assem M El-Shazly, Mansour Sobeh, Mona F Mahmoud

{"title":"Vasorelaxant Effects of Syzygium samarangense (Blume) Merr. and L.M.Perry Extract Are Mediated by NO/cGMP Pathway in Isolated Rat Thoracic Aorta.","authors":"Noura A Hassan, Mohamed A O Abdelfattah, Yasmine M Mandour, Assem M El-Shazly, Mansour Sobeh, Mona F Mahmoud","doi":"10.3390/ph15111349","DOIUrl":"https://doi.org/10.3390/ph15111349","url":null,"abstract":"Syzygium samarangense (Blume) Merr. and L.M.Perry is utilized widely in traditional medicine. We have reported previously a wide array of pharmacological properties of its leaf extract, among them anti-inflammatory, antioxidant, hepatoprotective, antidiabetic, antiulcer, and antitrypanosomal activities. We also annotated its chemical composition using LC-MS/MS. Here, we continue our investigations and evaluate the vasorelaxant effects of the leaf extract on aortic rings isolated from rats and explore the possible underlying mechanisms. S. samarangense extract induced a concentration dependent relaxation of the phenylephrine-precontracted aorta in the rat model. However, this effect disappeared upon removing the functional endothelium. Pretreating the aortic tissues either with propranolol or NG-nitro-L-arginine methyl ester inhibited the relaxation induced by the extract; however, atropine did not affect the extract-induced vasodilation. Meanwhile, adenylate cyclase inhibitor, MDL; specific guanylate cyclase inhibitor, ODQ; high extracellular KCl; and indomethacin as cyclooxygenase inhibitor inhibited the extract-induced vasodilation. On the other hand, incubation of S. samarangense extract with aortae sections having their intact endothelium pre-constricted using phenylephrine or KCl in media free of Ca2+ showed no effect on the constriction of the aortae vessels induced by Ca2+. Taken together, the present study suggests that S. samarangense extract dilates isolated aortic rings via endothelium-dependent nitric oxide (NO)/cGMP signaling. The observed biological effects could be attributed to its rich secondary metabolites. The specific mechanisms of the active ingredients of S. samarangense extract await further investigations.","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40675923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Network Pharmacology of Ginseng (Part III): Antitumor Potential of a Fixed Combination of Red Ginseng and Red Sage as Determined by Transcriptomics. 人参网络药理学(三):用转录组学测定红参与丹参固定组合的抗肿瘤作用。

IF 4.6

Pharmaceuticals (Basel, Switzerland) Pub Date : 2022-10-30 DOI: 10.3390/ph15111345

Alexander Panossian, Sara Abdelfatah, Thomas Efferth

{"title":"Network Pharmacology of Ginseng (Part III): Antitumor Potential of a Fixed Combination of Red Ginseng and Red Sage as Determined by Transcriptomics.","authors":"Alexander Panossian, Sara Abdelfatah, Thomas Efferth","doi":"10.3390/ph15111345","DOIUrl":"https://doi.org/10.3390/ph15111345","url":null,"abstract":"Background: This study aimed to assess the effect of a fixed combination of Red Ginseng and Red Sage (RG-RS) on the gene expression of neuronal cells to evaluate the potential impacts on cellular functions and predict its relevance in the treatment of stress and aging-related diseases and disorders.Methods: Gene expression profiling was conducted by transcriptome-wide mRNA microarray analyses of murine HT22 hippocampal cell culture after treatment with RG-RS preparation. Ingenuity pathway analysis (IPA) was performed with datasets of significantly upregulated or downregulated genes and the expected effects on the physiological and cellular function and the diseases were identified.Results: RG-RS deregulates 1028 genes associated with cancer and 139 with metastasis, suggesting a predicted decrease in tumorigenesis, the proliferation of tumor cells, tumor growth, metastasis, and an increase in apoptosis and autophagy by their effects on the various signaling and metabolic pathways, including the inhibition of Warburg's aerobic glycolysis, estrogen-mediated S-phase entry signaling, osteoarthritis signaling, and the super-pathway of cholesterol biosynthesis.Conclusion: The results of this study provide evidence of the potential efficacy of the fixed combination of Red Ginseng (Panax ginseng C.A. Mey.) and Red Sage/Danshen (Salvia miltiorrhiza Bunge) in cancer. Further clinical and experimental studies are required to assess the efficacy and safety of RG-RS in preventing the progression of cancer, osteoarthritis, and other aging-related diseases.","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40675084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

The Role of Anthocyanin in Modulating Diabetic Cardiovascular Disease and Its Potential to Be Developed as a Nutraceutical. 花青素在糖尿病心血管疾病中的作用及其作为营养品开发的潜力。

IF 4.6

Pharmaceuticals (Basel, Switzerland) Pub Date : 2022-10-30 DOI: 10.3390/ph15111344

Syaifuzah Sapian, Izatus Shima Taib, Haliza Katas, Jalifah Latip, Satirah Zainalabidin, Zariyantey Abd Hamid, Nur Najmi Mohamad Anuar, Siti Balkis Budin

{"title":"The Role of Anthocyanin in Modulating Diabetic Cardiovascular Disease and Its Potential to Be Developed as a Nutraceutical.","authors":"Syaifuzah Sapian, Izatus Shima Taib, Haliza Katas, Jalifah Latip, Satirah Zainalabidin, Zariyantey Abd Hamid, Nur Najmi Mohamad Anuar, Siti Balkis Budin","doi":"10.3390/ph15111344","DOIUrl":"https://doi.org/10.3390/ph15111344","url":null,"abstract":"Cardiovascular disease (CVD) is directly linked to diabetes mellitus (DM), and its morbidity and mortality are rising at an alarming rate. Individuals with DM experience significantly worse clinical outcomes due to heart failure as a CVD consequence than non-diabetic patients. Hyperglycemia is the main culprit that triggers the activation of oxidative damage, inflammation, fibrosis, and apoptosis pathways that aggravate diabetic CVD progression. In recent years, the development of phytochemical-based nutraceutical products for diabetic treatment has risen due to their therapeutic properties. Anthocyanin, which can be found in various types of plants, has been proposed for preventing and treating various diseases, and has elicited excellent antioxidative, anti-inflammation, anti-fibrosis, and anti-apoptosis effects. In preclinical and clinical studies, plants rich in anthocyanin have been reported to attenuate diabetic CVD. Therefore, the development of anthocyanin as a nutraceutical in managing diabetic CVD is in demand. In this review, we unveil the role of anthocyanin in modulating diabetic CVD, and its potential to be developed as a nutraceutical for a therapeutic strategy in managing CVD associated with DM.","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40675083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Central Composite Design Implemented Azilsartan Medoxomil Loaded Nanoemulsion to Improve Its Aqueous Solubility and Intestinal Permeability: In Vitro and Ex Vivo Evaluation. 中心复合设计实现阿齐沙坦-美多索米纳米乳提高其水溶性和肠道渗透性:体外和离体评价。

IF 4.6

Pharmaceuticals (Basel, Switzerland) Pub Date : 2022-10-29 DOI: 10.3390/ph15111343

Girish Kumar, Tarun Virmani, Kamla Pathak, Omkulthom Al Kamaly, Asmaa Saleh

{"title":"Central Composite Design Implemented Azilsartan Medoxomil Loaded Nanoemulsion to Improve Its Aqueous Solubility and Intestinal Permeability: In Vitro and Ex Vivo Evaluation.","authors":"Girish Kumar, Tarun Virmani, Kamla Pathak, Omkulthom Al Kamaly, Asmaa Saleh","doi":"10.3390/ph15111343","DOIUrl":"https://doi.org/10.3390/ph15111343","url":null,"abstract":"The present research attempted to design and develop a nanoemulsion formulation of azilsartan medoxomil to improve its aqueous solubility and intestinal permeability. Based on the solubility profile, ethyl oleate, tween 80, and Transcutol P were selected as the oil phase, surfactant, and co-surfactant, respectively. Central composite design (CCD) suggested an optimized azilsartan medoxomil- nanoemulsion formulation (optimized AZL-NE formulation) with 1.25% oil, 15.73% Smix, and 90 s ultrasonication time; it was found to have the droplet size, percentage transmittance, and % cumulative drug release (%CDR) of 71.5 nm, 93.46 ± 1.13%, and 90.14 ± 0.94%, respectively. Furthermore, it exhibited a 0.141 polydispersity index, 34.05 mV zeta potential, a 1.413 ± 0.03 refractive index, 6.68 ± 0.22 pH, 28.17 ± 0.52 cps viscosity, and a 96.98 ± 0.94% percentage drug content. Transmission electron microscopy (TEM) assessed the nano-sized spherical shape, and a differential scanning calorimeter (DSC) assessed the solubilization of the drug in the optimized formulation. The %CDR was 1.71 times higher and the % cumulative drug permeation was 2.1 times higher for the optimized AZL-NE formulation than for the drug suspension through an intestinal segment of a rat, which was also supported by confocal laser scanning microscopy (CLSM) studies. Thus, the nanoemulsion formulation of azilsartan medoxomil ensured the enhancement of the drug availability in the body.","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40675081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Combined Effects of Methyldopa and Baicalein or Scutellaria baicalensis Roots Extract on Blood Pressure, Heart Rate, and Expression of Inflammatory and Vascular Disease-Related Factors in Spontaneously Hypertensive Pregnant Rats. 甲基多巴与黄芩苷或黄芩根提取物联合对自发性高血压妊娠大鼠血压、心率及炎症及血管疾病相关因子表达的影响

IF 4.6

Pharmaceuticals (Basel, Switzerland) Pub Date : 2022-10-29 DOI: 10.3390/ph15111342

Michał Szulc, Radosław Kujawski, Przemysław Ł Mikołajczak, Anna Bogacz, Marlena Wolek, Aleksandra Górska, Kamila Czora-Poczwardowska, Marcin Ożarowski, Agnieszka Gryszczyńska, Justyna Baraniak, Małgorzata Kania-Dobrowolska, Artur Adamczak, Ewa Iwańczyk-Skalska, Paweł P Jagodziński, Bogusław Czerny, Adam Kamiński, Izabela Uzar, Agnieszka Seremak-Mrozikiewicz

{"title":"Combined Effects of Methyldopa and Baicalein or Scutellaria baicalensis Roots Extract on Blood Pressure, Heart Rate, and Expression of Inflammatory and Vascular Disease-Related Factors in Spontaneously Hypertensive Pregnant Rats.","authors":"Michał Szulc, Radosław Kujawski, Przemysław Ł Mikołajczak, Anna Bogacz, Marlena Wolek, Aleksandra Górska, Kamila Czora-Poczwardowska, Marcin Ożarowski, Agnieszka Gryszczyńska, Justyna Baraniak, Małgorzata Kania-Dobrowolska, Artur Adamczak, Ewa Iwańczyk-Skalska, Paweł P Jagodziński, Bogusław Czerny, Adam Kamiński, Izabela Uzar, Agnieszka Seremak-Mrozikiewicz","doi":"10.3390/ph15111342","DOIUrl":"https://doi.org/10.3390/ph15111342","url":null,"abstract":"The aim of the study was to investigate the effect of baicalein or Scutellaria baicalensis root extract interaction with methyldopa in pregnant spontaneously hypertensive rats (SHR) at the pharmacodynamic, molecular, and biochemical levels. The rats, after confirming pregnancy, received baicalein (200 mg/kg/day, p.o.) and extract (1000 mg/kg/day, p.o.), in combination with methyldopa (400 mg/kg/day; p.o.), for 14 consecutive days, 1 h before blood pressure and heart rate measurements. In the heart and placenta from mothers after giving birth to their offspring, mRNA expression of factors related to inflammatory processes (TNF-α, Il-1β, IL-6) and vascular diseases (TGF-β, HIF-1α, VEGF, PlGF) was measured. Levels of markers of oxidative stress (superoxide dismutase and malondialdehyde) in the placenta and indicators of myocardial damage (troponin cTnC and cTnI, creatine kinase, myoglobin, and lactate dehydrogenase) in the heart were also assessed. Baicalein co-administered with methyldopa was associated with reduced blood pressure, especially during the first three days. The interactions were more pronounced for such factors as TGF-β, HIF-1α, VEGF, and PlGF than TNF-α, Il-1β, and IL-6. Combined application of baicalein and extract with methyldopa may be of value in the development of a new antihypertensive medication intended for patients suffering from preeclampsia or pregnancy-induced hypertension.","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40675082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

In Vivo Treatment with a Standardized Green Tea Extract Restores Cardiomyocyte Contractility in Diabetic Rats by Improving Mitochondrial Function through SIRT1 Activation. 标准绿茶提取物在体内通过SIRT1激活改善线粒体功能，恢复糖尿病大鼠心肌细胞收缩能力。

IF 4.6

Pharmaceuticals (Basel, Switzerland) Pub Date : 2022-10-28 DOI: 10.3390/ph15111337

Rocchina Vilella, Simona Izzo, Valeria Naponelli, Monia Savi, Leonardo Bocchi, Cristina Dallabona, Maria Carla Gerra, Donatella Stilli, Saverio Bettuzzi

{"title":"In Vivo Treatment with a Standardized Green Tea Extract Restores Cardiomyocyte Contractility in Diabetic Rats by Improving Mitochondrial Function through SIRT1 Activation.","authors":"Rocchina Vilella, Simona Izzo, Valeria Naponelli, Monia Savi, Leonardo Bocchi, Cristina Dallabona, Maria Carla Gerra, Donatella Stilli, Saverio Bettuzzi","doi":"10.3390/ph15111337","DOIUrl":"https://doi.org/10.3390/ph15111337","url":null,"abstract":"Background. Green tea catechins are known to promote mitochondrial function, and to modulate gene expression and signalling pathways that are altered in the diabetic heart. We thus evaluated the effectiveness of the in vivo administration of a standardized green tea extract (GTE) in restoring cardiac performance, in a rat model of early streptozotocin-induced diabetes, with a focus on the underlying mechanisms. Methods. Twenty-five male adult Wistar rats were studied: the control (n = 9), untreated diabetic animals (n = 7) and diabetic rats subjected to daily GTE administration for 28 days (n = 9). Isolated ventricular cardiomyocytes were used for ex vivo measurements of cell mechanics and calcium transients, and molecular assays, including the analysis of functional protein and specific miRNA expression. Results. GTE treatment induced an almost complete recovery of cardiomyocyte contractility that was markedly impaired in the diabetic cells, by preserving mitochondrial function and energy availability, and modulating the expression of the sarcoplasmic reticulum calcium ATPase and phospholamban. Increased Sirtuin 1 (SIRT1) expression and activity substantially contributed to the observed cardioprotective effects. Conclusions. The data supported the hypothesis that green tea dietary polyphenols, by targeting SIRT1, can constitute an adjuvant strategy for counteracting the initial damage of the diabetic heart, before the occurrence of diabetic cardiomyopathy.","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40675077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Benzylisoquinoline Alkaloids from the Stems of Limacia scandens and Their Potential as Autophagy Inhibitors. 椴树茎中的苯基异喹啉类生物碱及其作为自噬抑制剂的潜力。

IF 4.6

Pharmaceuticals (Basel, Switzerland) Pub Date : 2022-10-28 DOI: 10.3390/ph15111332

Hee-Ju Lee, Eun-Jin Park, Byeol Ryu, Hyo-Moon Cho, Duc-Trong Nghiem, Ha-Thanh-Tung Pham, Cheol-Ho Pan, Won-Keun Oh

{"title":"Benzylisoquinoline Alkaloids from the Stems of Limacia scandens and Their Potential as Autophagy Inhibitors.","authors":"Hee-Ju Lee, Eun-Jin Park, Byeol Ryu, Hyo-Moon Cho, Duc-Trong Nghiem, Ha-Thanh-Tung Pham, Cheol-Ho Pan, Won-Keun Oh","doi":"10.3390/ph15111332","DOIUrl":"https://doi.org/10.3390/ph15111332","url":null,"abstract":"Limacia scandens is traditionally used to treat depression and affective disorders in Malaysia. The chemical compositions have been reported to include bisbenzylisoquinoline and aporphine-type alkaloids in the genus Limacia Lour., but studies on the components of L. scandens have rarely been reported. Therefore, this study was conducted to determine new benzylisoquinoline alkaloid derivatives with autophagy regulation activity from this plant. Bioactivity-guided isolation was applied to various column chromatography methods using RP-18, Sephadex LH-20 open column chromatography, and preparative HPLC. The chemical structures of the isolated compounds were elucidated through spectroscopic data analysis, including NMR, HR-ESI-MS, and ECD data. In addition, isolated compounds were tested for autophagy-regulating activity in HEK293 cells expressing GFP-L3. Three new dimeric benzylisoquinoline alkaloids (1-3), one new 4-hydroxybenzoic acid-conjugated benzylisoquinoline alkaloid (4), and six known compounds (5-10) were isolated from the stems of L. scandens. All compounds (1-10) were screened for autophagy regulation in HEK293 cells stably expressing the GFP-LC3 plasmid. Among the isolated compounds, 1, 2, and 4 showed autophagic regulation activity that blocked the process of combining autophagosomes and lysosomes. They also inhibit the protein degradation process from the autolysosome as inhibitors of autophagy. Novel benzylisoquinoline alkaloids from L. scandens showed potent potency for the inhibition of autophagic flux. This study provides potential candidates for developing natural autophagy inhibitors for disease prevention and treatment.","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40477772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1