J. Rajković, M. Perić, J. Stanišić, M. Gostimirovic, R. Novaković, V. Djokic, S. Tepavčević, J. Rakočević, M. Labudović-Borović, L. Gojković-Bukarica
Here we have shown for the first time altered expression of the vascular smooth muscle (VSM) KATP channel subunits in segments of the human internal mammary artery (HIMA) in patients with type-2 diabetes mellitus (T2DM). Functional properties of vascular KATP channels in the presence of T2DM, and the interaction between its subunits and endogenous ligands known to relax this vessel, were tested using the potassium (K) channels opener, pinacidil. HIMA is the most commonly used vascular graft in cardiac surgery. Previously it was shown that pinacidil relaxes HIMA segments through interaction with KATP (SUR2B/Kir6.1) vascular channels, but it is unknown whether pinacidil sensitivity is changed in the presence of T2DM, considering diabetes-induced vascular complications commonly seen in patients undergoing coronary artery bypass graft surgery (CABG). KATP subunits were detected in HIMA segments using Western blot and immunohistochemistry analyses. An organ bath system was used to interrogate endothelium-independent vasorelaxation caused by pinacidil. In pharmacological experiments, pinacidil was able to relax HIMA from patients with T2DM, with sensitivity comparable to our previous results. All three KATP subunits (SUR2B, Kir6.1 and Kir6.2) were observed in HIMA from patients with and without T2DM. There were no differences in the expression of the SUR2B subunit. The expression of the Kir6.1 subunit was lower in HIMA from T2DM patients. In the same group, the expression of the Kir6.2 subunit was higher. Therefore, KATP channels might not be the only method of pinacidil-induced dilatation of T2DM HIMA. T2DM may decrease the level of Kir6.1, a dominant subunit in VSM of HIMA, altering the interaction between pinacidil and those channels.
{"title":"Effect of Type-2 Diabetes Mellitus on the Expression and Function of Smooth Muscle ATP-Sensitive Potassium Channels in Human Internal Mammary Artery Grafts","authors":"J. Rajković, M. Perić, J. Stanišić, M. Gostimirovic, R. Novaković, V. Djokic, S. Tepavčević, J. Rakočević, M. Labudović-Borović, L. Gojković-Bukarica","doi":"10.3390/ph17070857","DOIUrl":"https://doi.org/10.3390/ph17070857","url":null,"abstract":"Here we have shown for the first time altered expression of the vascular smooth muscle (VSM) KATP channel subunits in segments of the human internal mammary artery (HIMA) in patients with type-2 diabetes mellitus (T2DM). Functional properties of vascular KATP channels in the presence of T2DM, and the interaction between its subunits and endogenous ligands known to relax this vessel, were tested using the potassium (K) channels opener, pinacidil. HIMA is the most commonly used vascular graft in cardiac surgery. Previously it was shown that pinacidil relaxes HIMA segments through interaction with KATP (SUR2B/Kir6.1) vascular channels, but it is unknown whether pinacidil sensitivity is changed in the presence of T2DM, considering diabetes-induced vascular complications commonly seen in patients undergoing coronary artery bypass graft surgery (CABG). KATP subunits were detected in HIMA segments using Western blot and immunohistochemistry analyses. An organ bath system was used to interrogate endothelium-independent vasorelaxation caused by pinacidil. In pharmacological experiments, pinacidil was able to relax HIMA from patients with T2DM, with sensitivity comparable to our previous results. All three KATP subunits (SUR2B, Kir6.1 and Kir6.2) were observed in HIMA from patients with and without T2DM. There were no differences in the expression of the SUR2B subunit. The expression of the Kir6.1 subunit was lower in HIMA from T2DM patients. In the same group, the expression of the Kir6.2 subunit was higher. Therefore, KATP channels might not be the only method of pinacidil-induced dilatation of T2DM HIMA. T2DM may decrease the level of Kir6.1, a dominant subunit in VSM of HIMA, altering the interaction between pinacidil and those channels.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":"19 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141699500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matheus de Lucca Thomaz, C. Vieira, J. A. Caris, M. P. Marques, A. Rocha, Tiago Antunes Paz, R. Rezende, V. Lanchote
This study aims to evaluate the impact of liver fibrosis stages of chronic infection with hepatitis C virus (HCV) on the in vivo activity of organic cation transporters (hepatic OCT1 and renal OCT2) using metformin (MET) as a probe drug. Participants allocated in Group 1 (n = 15, mild to moderate liver fibrosis) or 2 (n = 13, advanced liver fibrosis and cirrhosis) received a single MET 50 mg oral dose before direct-acting antiviral (DAA) drug treatment (Phase 1) and 30 days after achieving sustained virologic response (Phase 2). OCT1/2 activity (MET AUC0–24) was found to be reduced by 25% when comparing the two groups in Phase 2 (ratio 0.75 (0.61–0.93), p < 0.05) but not in Phase 1 (ratio 0.81 (0.66–0.98), p > 0.05). When Phases 1 and 2 were compared, no changes were detected in both Groups 1 (ratio 1.10 (0.97–1.24), p > 0.05) and 2 (ratio 1.03 (0.94–1.12), p > 0.05). So, this study shows a reduction of approximately 25% in the in vivo activity of OCT1/2 in participants with advanced liver fibrosis and cirrhosis after achieving sustained virologic response and highlights that OCT1/2 in vivo activity depends on the liver fibrosis stage of chronic HCV infection.
{"title":"Liver Fibrosis Stages Affect Organic Cation Transporter 1/2 Activities in Hepatitis C Virus-Infected Patients","authors":"Matheus de Lucca Thomaz, C. Vieira, J. A. Caris, M. P. Marques, A. Rocha, Tiago Antunes Paz, R. Rezende, V. Lanchote","doi":"10.3390/ph17070865","DOIUrl":"https://doi.org/10.3390/ph17070865","url":null,"abstract":"This study aims to evaluate the impact of liver fibrosis stages of chronic infection with hepatitis C virus (HCV) on the in vivo activity of organic cation transporters (hepatic OCT1 and renal OCT2) using metformin (MET) as a probe drug. Participants allocated in Group 1 (n = 15, mild to moderate liver fibrosis) or 2 (n = 13, advanced liver fibrosis and cirrhosis) received a single MET 50 mg oral dose before direct-acting antiviral (DAA) drug treatment (Phase 1) and 30 days after achieving sustained virologic response (Phase 2). OCT1/2 activity (MET AUC0–24) was found to be reduced by 25% when comparing the two groups in Phase 2 (ratio 0.75 (0.61–0.93), p < 0.05) but not in Phase 1 (ratio 0.81 (0.66–0.98), p > 0.05). When Phases 1 and 2 were compared, no changes were detected in both Groups 1 (ratio 1.10 (0.97–1.24), p > 0.05) and 2 (ratio 1.03 (0.94–1.12), p > 0.05). So, this study shows a reduction of approximately 25% in the in vivo activity of OCT1/2 in participants with advanced liver fibrosis and cirrhosis after achieving sustained virologic response and highlights that OCT1/2 in vivo activity depends on the liver fibrosis stage of chronic HCV infection.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":"15 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141715461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. C. da Silveira, Fernanda da Silva Platner, L. B. da Rosa, Matheus L. C. Silva, K. S. da Silva, N. M. T. de Oliveira, E. Moffa, K. F. Silva, L. Lima-Neto, Daniele Maria-Ferreira, L. M. Cordeiro, M. B. Gois, Elizabeth S Fernandes
The biological activities of plant-derived soluble dietary fibres (SDFs) have been widely investigated. Pectin from yellow passion fruit (YPF-peSDF) peels was suggested as a protective macromolecule in ulcers and colitis due to its antioxidant and anti-inflammatory properties. Sepsis has high mortality and morbidity and is characterised by inflammatory and oxidative stress imbalances. Evidence suggests that pectins may aid sepsis treatment; however, the effects of YPF-peSDF on sepsis remain unclear. Herein, polymicrobial sepsis was induced by cecal-ligation and puncture in mice treated with YPF-peSDF (1 and 10 mg/kg; gavage). YPF-peSDF accelerated mortality, reaching 100% in 24 h. Inflammation was present in the colons and small intestines (SI) of both vehicle- and fibre-treated mice. Although crypt depth and width, and villus height were preserved in the SI of septic mice administered YPF-peSDF, they exhibited exacerbated muscle layer atrophy and mucosa and submucosa hypertrophy, along with shortened enterocytes. Larger crypts and shorter enterocytes were noted in their colons in comparison with vehicle-controls. YPF-peSDF also reduced inflammatory cell numbers and exacerbated IL-6 levels in peritoneal lavage fluid (PELF) samples. YPF-peSDF modulated SI but not colon cytokines. Lipoperoxidation and antioxidant capacity levels were attenuated in PELF samples. Overall, in contrast to previous evidence, YPF-peSDF worsened polymicrobial sepsis outcomes in mice.
{"title":"Oral Treatment with the Pectin Fibre Obtained from Yellow Passion Fruit Peels Worsens Sepsis Outcome in Mice by Affecting the Intestinal Barrier","authors":"B. C. da Silveira, Fernanda da Silva Platner, L. B. da Rosa, Matheus L. C. Silva, K. S. da Silva, N. M. T. de Oliveira, E. Moffa, K. F. Silva, L. Lima-Neto, Daniele Maria-Ferreira, L. M. Cordeiro, M. B. Gois, Elizabeth S Fernandes","doi":"10.3390/ph17070863","DOIUrl":"https://doi.org/10.3390/ph17070863","url":null,"abstract":"The biological activities of plant-derived soluble dietary fibres (SDFs) have been widely investigated. Pectin from yellow passion fruit (YPF-peSDF) peels was suggested as a protective macromolecule in ulcers and colitis due to its antioxidant and anti-inflammatory properties. Sepsis has high mortality and morbidity and is characterised by inflammatory and oxidative stress imbalances. Evidence suggests that pectins may aid sepsis treatment; however, the effects of YPF-peSDF on sepsis remain unclear. Herein, polymicrobial sepsis was induced by cecal-ligation and puncture in mice treated with YPF-peSDF (1 and 10 mg/kg; gavage). YPF-peSDF accelerated mortality, reaching 100% in 24 h. Inflammation was present in the colons and small intestines (SI) of both vehicle- and fibre-treated mice. Although crypt depth and width, and villus height were preserved in the SI of septic mice administered YPF-peSDF, they exhibited exacerbated muscle layer atrophy and mucosa and submucosa hypertrophy, along with shortened enterocytes. Larger crypts and shorter enterocytes were noted in their colons in comparison with vehicle-controls. YPF-peSDF also reduced inflammatory cell numbers and exacerbated IL-6 levels in peritoneal lavage fluid (PELF) samples. YPF-peSDF modulated SI but not colon cytokines. Lipoperoxidation and antioxidant capacity levels were attenuated in PELF samples. Overall, in contrast to previous evidence, YPF-peSDF worsened polymicrobial sepsis outcomes in mice.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141702291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jussara de Jesus Simão, Andressa de Sousa Bispo, V. Plata, Lucia Armelin-Correa, M. I. Alonso-Vale
This study investigated the effects of fish oil (FO) treatment, particularly enriched with eicosapentaenoic acid (EPA), on obesity induced by a high-fat diet (HFD) in mice. The investigation focused on elucidating the impact of FO on epigenetic modifications in white adipose tissue (WAT) and the involvement of adipose-derived stem cells (ASCs). C57BL/6j mice were divided into two groups: control diet and HFD for 16 weeks. In the last 8 weeks, the HFD group was subdivided into HFD and HFD + FO (treated with FO). WAT was removed for RNA and protein extraction, while ASCs were isolated, cultured, and treated with leptin. All samples were analyzed using functional genomics tools, including PCR-array, RT-PCR, and Western Blot assays. Mice receiving an HFD displayed increased body mass, fat accumulation, and altered gene expression associated with WAT inflammation and dysfunction. FO supplementation attenuated these effects, a potential protective role against HFD-induced obesity. Analysis of H3K27 revealed HFD-induced changes in histone, which were partially reversed by FO treatment. This study further explored leptin signaling in ASCs, suggesting a potential mechanism for ASC dysfunction in the obesity-rich leptin environment of WAT. Overall, FO supplementation demonstrated efficacy in mitigating HFD-induced obesity, influencing epigenetic and molecular pathways, and shedding light on the role of ASCs and leptin signaling in WAT dysfunction associated with obesity.
{"title":"Fish Oil Supplementation Mitigates High-Fat Diet-Induced Obesity: Exploring Epigenetic Modulation and Genes Associated with Adipose Tissue Dysfunction in Mice","authors":"Jussara de Jesus Simão, Andressa de Sousa Bispo, V. Plata, Lucia Armelin-Correa, M. I. Alonso-Vale","doi":"10.3390/ph17070861","DOIUrl":"https://doi.org/10.3390/ph17070861","url":null,"abstract":"This study investigated the effects of fish oil (FO) treatment, particularly enriched with eicosapentaenoic acid (EPA), on obesity induced by a high-fat diet (HFD) in mice. The investigation focused on elucidating the impact of FO on epigenetic modifications in white adipose tissue (WAT) and the involvement of adipose-derived stem cells (ASCs). C57BL/6j mice were divided into two groups: control diet and HFD for 16 weeks. In the last 8 weeks, the HFD group was subdivided into HFD and HFD + FO (treated with FO). WAT was removed for RNA and protein extraction, while ASCs were isolated, cultured, and treated with leptin. All samples were analyzed using functional genomics tools, including PCR-array, RT-PCR, and Western Blot assays. Mice receiving an HFD displayed increased body mass, fat accumulation, and altered gene expression associated with WAT inflammation and dysfunction. FO supplementation attenuated these effects, a potential protective role against HFD-induced obesity. Analysis of H3K27 revealed HFD-induced changes in histone, which were partially reversed by FO treatment. This study further explored leptin signaling in ASCs, suggesting a potential mechanism for ASC dysfunction in the obesity-rich leptin environment of WAT. Overall, FO supplementation demonstrated efficacy in mitigating HFD-induced obesity, influencing epigenetic and molecular pathways, and shedding light on the role of ASCs and leptin signaling in WAT dysfunction associated with obesity.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":"243 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141712343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luz V. Arroyo-Cruz, Sebastián Sagardía-González, Kurt Miller, Taotao Ling, Fatima Rivas, Michelle M. Martínez-Montemayor
Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 expression. It is known for its high malignancy, invasiveness, and propensity for metastasis, resulting in a poor prognosis due to the absence of beneficial therapeutic targets. Natural products derived from mushrooms have gained significant attention in neoplastic therapy due to their potential medicinal properties. The therapeutic potential of Ganoderma lucidum in breast cancer has been highlighted by our group, suggesting its use as an adjuvant treatment. The present study aims to assess the potential antineoplastic capacity of two Caribbean native Ganoderma species found in Puerto Rico, Ganoderma multiplicatum (G. multiplicatum) and Ganoderma martinicense (G. martinicense). Antiproliferative studies were conducted via cell viability assays after cultivation, harvesting, and fractionation of both species. The obtained results indicate that most of the fractions show some cytotoxicity against all cell lines, but 33% of the fractions (F1, F2, F7, F12) display selectivity towards cancer cell models. We demonstrate for the first time that native Ganoderma species can generate metabolites with anti-TNBC properties. Future avenues will focus on structure elucidation of the most active fractions of these Ganoderma extracts.
{"title":"Selective Antineoplastic Potential of Fractionated Caribbean Native Ganoderma Species Extracts on Triple-Negative Breast Cancer Cells","authors":"Luz V. Arroyo-Cruz, Sebastián Sagardía-González, Kurt Miller, Taotao Ling, Fatima Rivas, Michelle M. Martínez-Montemayor","doi":"10.3390/ph17070864","DOIUrl":"https://doi.org/10.3390/ph17070864","url":null,"abstract":"Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 expression. It is known for its high malignancy, invasiveness, and propensity for metastasis, resulting in a poor prognosis due to the absence of beneficial therapeutic targets. Natural products derived from mushrooms have gained significant attention in neoplastic therapy due to their potential medicinal properties. The therapeutic potential of Ganoderma lucidum in breast cancer has been highlighted by our group, suggesting its use as an adjuvant treatment. The present study aims to assess the potential antineoplastic capacity of two Caribbean native Ganoderma species found in Puerto Rico, Ganoderma multiplicatum (G. multiplicatum) and Ganoderma martinicense (G. martinicense). Antiproliferative studies were conducted via cell viability assays after cultivation, harvesting, and fractionation of both species. The obtained results indicate that most of the fractions show some cytotoxicity against all cell lines, but 33% of the fractions (F1, F2, F7, F12) display selectivity towards cancer cell models. We demonstrate for the first time that native Ganoderma species can generate metabolites with anti-TNBC properties. Future avenues will focus on structure elucidation of the most active fractions of these Ganoderma extracts.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":"12 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141714064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nadia Hadi, A. Drioiche, El Moumen Bouchra, Soukayna Baammi, Abdelaaty Abdelaziz Shahat, I. Tagnaout, Mohamed Radi, Fidaous Remok, A. Bouzoubaa, T. Zair
Anethum graveolens is an aromatic plant traditionally used as an antispasmodic and carminative. The objective of this study is to analyze the chemical composition of the essential oils and extracts obtained from seeds gathered in Errachidia, southern Morocco. Additionally, the antioxidant and antimicrobial properties of these oils and extracts will be evaluated. GC-MS analysis of the EO isolated by hydrodistillation revealed that its main compounds were E-anethole (38.13%), estragole (29.32%), fenchone (17.21%), and α-pinene (7.37%). The phenolic components were extracted using the methods of decoction and Soxhlet. The assay of the phenolic compounds showed that A. graveolens seeds contained considerable amounts of polyphenols, flavonoids, and condensed tannins, with variable levels depending on the extract analyzed. HPLC/UV-ESI-MS analyses performed on the decoction revealed a structural diversity of the molecules present in this extract, the most important of which were umbelliferone (12.35%), 3-hydroxyflavone (11.23%), rosmanol (8.95%), biotin (8.36%), emmotin H (4.91%), and coumarin (4.21%). The antioxidant activity, as determined by three techniques (DPPH•, FRAP, and CAT), demonstrated that the essential oils (EOs) and extracts had a potent capacity to counteract detrimental free radicals, control the generation of reactive oxygen species, and mitigate oxidative damages. The antimicrobial activity of the Eos and extracts was carried out in a liquid medium against five strains (E. cloacae, K. pneumoniae, E. coli, S. aureus, and S. epidermidis) and four candidiasis (C. albicans, C. dubliniensis, C. tropicalis, and C. parapsilosis) and Aspergillus niger. The results showed the effectiveness of the EOs compared to the aqueous, ethanolic, and decoction extracts against most of the microorganisms tested. In addition, the ethanolic extract showed antifungal activity that was distinguished from that of the other extracts. The antimicrobial efficacy of the essential oils under study can primarily be attributed to the synergistic interactions among its three principal constituents (E-anethole, estragole, and fenchone). Furthermore, molecular docking and molecular dynamics simulation results reveal significant interactions and stability between the selected bioactive compounds and different target proteins involved in antimicrobial and antioxidant activities. Compounds like 3-hydroxyflavone, emmotin H, trans-caftaric acid, methyl rosmarinate, 1-caffeoyl-beta-D-glucose, and kaempferol exhibited better binding energies with the explored proteins, indicating their potential as antimicrobial and antioxidant agents. Finally, our findings emphasize the significance of A. graveolens seeds as a promising reservoir of advantageous health compounds that can serve as organic substitutes for the presently employed synthetic preservatives.
{"title":"Phytochemical Analysis and Evaluation of Antioxidant and Antimicrobial Properties of Essential Oils and Seed Extracts of Anethum graveolens from Southern Morocco: In Vitro and In Silico Approach for a Natural Alternative to Synthetic Preservatives","authors":"Nadia Hadi, A. Drioiche, El Moumen Bouchra, Soukayna Baammi, Abdelaaty Abdelaziz Shahat, I. Tagnaout, Mohamed Radi, Fidaous Remok, A. Bouzoubaa, T. Zair","doi":"10.3390/ph17070862","DOIUrl":"https://doi.org/10.3390/ph17070862","url":null,"abstract":"Anethum graveolens is an aromatic plant traditionally used as an antispasmodic and carminative. The objective of this study is to analyze the chemical composition of the essential oils and extracts obtained from seeds gathered in Errachidia, southern Morocco. Additionally, the antioxidant and antimicrobial properties of these oils and extracts will be evaluated. GC-MS analysis of the EO isolated by hydrodistillation revealed that its main compounds were E-anethole (38.13%), estragole (29.32%), fenchone (17.21%), and α-pinene (7.37%). The phenolic components were extracted using the methods of decoction and Soxhlet. The assay of the phenolic compounds showed that A. graveolens seeds contained considerable amounts of polyphenols, flavonoids, and condensed tannins, with variable levels depending on the extract analyzed. HPLC/UV-ESI-MS analyses performed on the decoction revealed a structural diversity of the molecules present in this extract, the most important of which were umbelliferone (12.35%), 3-hydroxyflavone (11.23%), rosmanol (8.95%), biotin (8.36%), emmotin H (4.91%), and coumarin (4.21%). The antioxidant activity, as determined by three techniques (DPPH•, FRAP, and CAT), demonstrated that the essential oils (EOs) and extracts had a potent capacity to counteract detrimental free radicals, control the generation of reactive oxygen species, and mitigate oxidative damages. The antimicrobial activity of the Eos and extracts was carried out in a liquid medium against five strains (E. cloacae, K. pneumoniae, E. coli, S. aureus, and S. epidermidis) and four candidiasis (C. albicans, C. dubliniensis, C. tropicalis, and C. parapsilosis) and Aspergillus niger. The results showed the effectiveness of the EOs compared to the aqueous, ethanolic, and decoction extracts against most of the microorganisms tested. In addition, the ethanolic extract showed antifungal activity that was distinguished from that of the other extracts. The antimicrobial efficacy of the essential oils under study can primarily be attributed to the synergistic interactions among its three principal constituents (E-anethole, estragole, and fenchone). Furthermore, molecular docking and molecular dynamics simulation results reveal significant interactions and stability between the selected bioactive compounds and different target proteins involved in antimicrobial and antioxidant activities. Compounds like 3-hydroxyflavone, emmotin H, trans-caftaric acid, methyl rosmarinate, 1-caffeoyl-beta-D-glucose, and kaempferol exhibited better binding energies with the explored proteins, indicating their potential as antimicrobial and antioxidant agents. Finally, our findings emphasize the significance of A. graveolens seeds as a promising reservoir of advantageous health compounds that can serve as organic substitutes for the presently employed synthetic preservatives.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":"4 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141698506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stanislava Ivanova, Zoya Dzhakova, Radiana Staynova, K. Ivanov
Species belonging to the genus Salvia, Lamiaceae, have been deeply involved in the folk medicine of different nations since ancient times. Lilac sage, or Salvia verticillata L. (S. verticillata) is a less studied species from the genus. However, it seems to have a prominent potential for the future drug discovery strategies of novel phytopharmaceuticals. This review aims to summarise the data on the biological activity and the phytochemical profile of extracts and essential oils derived from S. verticillata. This review is based on data from 57 in vitro and in vivo studies. The chemical profile of S. verticillata includes different synergic compounds like phenolic acids, flavonoids, terpenes, and salvianolic acids. Although some small amounts of salvianolic acid B were found in S. verticillata extracts, the major compound among the salvianolic acids is salvianolic acid C, a compound associated with the potential for improving liver fibrosis, cardio- and hepatoprotection, and the inhibition of SARS-CoV-2 infection. The cannabinoid type 2 receptor agonist β-caryophyllene is one of the major compounds in S. verticillata essential oils. It is a compound with a prominent potential in regenerative medicine, neurology, immunology, and other medical fields. The in vivo and the in vitro studies, regarding S. verticillata highlighted good antioxidant potential, anti-inflammatory, antibacterial, and antifungal activity. S.verticillata was also reported as a potential source of drug candidates for the treatment of neurodegenerative diseases such as Alzheimer’s disease, because of the inhibitory activity on the acetylcholinesterase. However, the number of studies in this direction is limited.
自古以来，丹参属（唇形科）植物一直是各国民间医药的重要组成部分。丁香鼠尾草（Salvia verticillata L., S. verticillata）是该属中研究较少的一个品种。然而，它在未来新型植物药的药物发现战略中似乎具有突出的潜力。本综述旨在总结从 S. verticillata 提取物和精油中提取的生物活性和植物化学成分。本综述基于 57 项体外和体内研究的数据。S. verticillata 的化学成分包括不同的协同化合物，如酚酸、类黄酮、萜烯和丹酚酸。虽然在 S. verticillata 提取物中发现了少量丹酚酸 B，但丹酚酸中的主要化合物是丹酚酸 C，这种化合物具有改善肝纤维化、保护心血管和肝脏以及抑制 SARS-CoV-2 感染的潜力。大麻素 2 型受体激动剂 β-石竹烯是 S. verticillata 精油中的主要化合物之一。它是一种在再生医学、神经学、免疫学和其他医学领域具有突出潜力的化合物。关于 S. verticillata 的体内和体外研究都强调了其良好的抗氧化潜力、抗炎、抗菌和抗真菌活性。据报道，由于 S.verticillata 具有抑制乙酰胆碱酯酶的活性，因此也是治疗神经退行性疾病（如阿尔茨海默氏症）的潜在候选药物来源。然而，这方面的研究数量有限。
{"title":"Salvia verticillata (L.)—Biological Activity, Chemical Profile, and Future Perspectives","authors":"Stanislava Ivanova, Zoya Dzhakova, Radiana Staynova, K. Ivanov","doi":"10.3390/ph17070859","DOIUrl":"https://doi.org/10.3390/ph17070859","url":null,"abstract":"Species belonging to the genus Salvia, Lamiaceae, have been deeply involved in the folk medicine of different nations since ancient times. Lilac sage, or Salvia verticillata L. (S. verticillata) is a less studied species from the genus. However, it seems to have a prominent potential for the future drug discovery strategies of novel phytopharmaceuticals. This review aims to summarise the data on the biological activity and the phytochemical profile of extracts and essential oils derived from S. verticillata. This review is based on data from 57 in vitro and in vivo studies. The chemical profile of S. verticillata includes different synergic compounds like phenolic acids, flavonoids, terpenes, and salvianolic acids. Although some small amounts of salvianolic acid B were found in S. verticillata extracts, the major compound among the salvianolic acids is salvianolic acid C, a compound associated with the potential for improving liver fibrosis, cardio- and hepatoprotection, and the inhibition of SARS-CoV-2 infection. The cannabinoid type 2 receptor agonist β-caryophyllene is one of the major compounds in S. verticillata essential oils. It is a compound with a prominent potential in regenerative medicine, neurology, immunology, and other medical fields. The in vivo and the in vitro studies, regarding S. verticillata highlighted good antioxidant potential, anti-inflammatory, antibacterial, and antifungal activity. S.verticillata was also reported as a potential source of drug candidates for the treatment of neurodegenerative diseases such as Alzheimer’s disease, because of the inhibitory activity on the acetylcholinesterase. However, the number of studies in this direction is limited.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":"75 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141694535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Magdalena Kotańska, M. Zadrożna, M. Kubacka, Kamil Mika, Katarzyna Szczepańska, Barbara Nowak, Alessio Alesci, Anthea Miller, E. R. Lauriano, Katarzyna Kieć-Kononowicz
Background: Numerous studies highlight the critical role that neural histamine plays in feeding behavior, which is controlled by central histamine H3 and H1 receptors. This is the fundamental motivation for the increased interest in creating histamine H3 receptor antagonists as anti-obesity medications. On the other hand, multiple other neurotransmitter systems have been identified as pharmacotherapeutic targets for obesity, including sigma-2 receptor systems. Interestingly, in our previous studies in the rat excessive eating model, we demonstrated a significant reduction in the development of obesity using dual histamine H3/sigma-2 receptor ligands. Moreover, we showed that compound KSK-94 (structural analog of Abbott’s A-331440) reduced the number of calories consumed, and thus acted as an anorectic compound. Therefore, in this study, we extended the previous research and studied the influence of KSK-94 on adipose tissue collected from animals from our previous experiment. Methods: Visceral adipose tissue was collected from four groups of rats (standard diet + vehicle, palatable diet + vehicle, palatable diet + KSK-94, and palatable diet + bupropion/naltrexone) and subjected to biochemical, histopathological, and immunohistochemical studies. Results: The obtained results clearly indicate that compound KSK-94 prevented the hypertrophy and inflammation of visceral adipose tissue, normalized the levels of leptin, resistin and saved the total reduction capacity of adipose tissue, being more effective than bupropion/naltrexon in these aspects. Moreover, KSK-94 may induce browning of visceral white adipose tissue. Conclusion: Our study suggests that dual compounds with a receptor profile like KSK-94, i.e., targeting histamine H3 receptor and, to a lesser extent, sigma-2 receptor, could be attractive therapeutic options for patients at risk of developing obesity or with obesity and some metabolic disorders. However, more studies are required to determine its safety profile and the exact mechanism of action of KSK-94.
{"title":"The Effect of KSK-94, a Dual Histamine H3 and Sigma-2 Receptor Ligand, on Adipose Tissue in a Rat Model of Developing Obesity","authors":"Magdalena Kotańska, M. Zadrożna, M. Kubacka, Kamil Mika, Katarzyna Szczepańska, Barbara Nowak, Alessio Alesci, Anthea Miller, E. R. Lauriano, Katarzyna Kieć-Kononowicz","doi":"10.3390/ph17070858","DOIUrl":"https://doi.org/10.3390/ph17070858","url":null,"abstract":"Background: Numerous studies highlight the critical role that neural histamine plays in feeding behavior, which is controlled by central histamine H3 and H1 receptors. This is the fundamental motivation for the increased interest in creating histamine H3 receptor antagonists as anti-obesity medications. On the other hand, multiple other neurotransmitter systems have been identified as pharmacotherapeutic targets for obesity, including sigma-2 receptor systems. Interestingly, in our previous studies in the rat excessive eating model, we demonstrated a significant reduction in the development of obesity using dual histamine H3/sigma-2 receptor ligands. Moreover, we showed that compound KSK-94 (structural analog of Abbott’s A-331440) reduced the number of calories consumed, and thus acted as an anorectic compound. Therefore, in this study, we extended the previous research and studied the influence of KSK-94 on adipose tissue collected from animals from our previous experiment. Methods: Visceral adipose tissue was collected from four groups of rats (standard diet + vehicle, palatable diet + vehicle, palatable diet + KSK-94, and palatable diet + bupropion/naltrexone) and subjected to biochemical, histopathological, and immunohistochemical studies. Results: The obtained results clearly indicate that compound KSK-94 prevented the hypertrophy and inflammation of visceral adipose tissue, normalized the levels of leptin, resistin and saved the total reduction capacity of adipose tissue, being more effective than bupropion/naltrexon in these aspects. Moreover, KSK-94 may induce browning of visceral white adipose tissue. Conclusion: Our study suggests that dual compounds with a receptor profile like KSK-94, i.e., targeting histamine H3 receptor and, to a lesser extent, sigma-2 receptor, could be attractive therapeutic options for patients at risk of developing obesity or with obesity and some metabolic disorders. However, more studies are required to determine its safety profile and the exact mechanism of action of KSK-94.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":"91 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141714489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Pepe, M. Di Nicola, Fabrizio Cocciolillo, S. Chiappini, G. Martinotti, M. Calcagni, G. Sani
New Psychoactive Substances (NPS) are modifying the drug scenario worldwide and have become a public health concern because of their toxicological profiles and their harmful physical/psychological effects. 3-Methoxy-Phencyclidine (3-MeO-PCP), a non-competitive antagonist of glutamate N-methyl-D-aspartate (NMDA) receptors, belongs to the phencyclidine-like subfamily of arylcyclohexylamines and has gained attention for its toxic, sometimes fatal, effects. Despite several cases of intoxication and death reported in the literature, little is known about substance-induced psychotic disorders (SIP) and potential cognitive impairment following 3-MeO-PCP intake. This literature review aimed to summarize available evidence about 3-MeO-PCP mechanisms of action and physical and psychotropic effects and to spread preliminary findings about persistent psychotic symptoms and impaired cognitive functioning. Additionally, the case of an SIP is reported in a 29-year-old man with small oral intakes of 3-MeO-PCP over two weeks until a high dose ingestion. Psychometric and neuropsychological assessment and brain [18F]-fluorodeoxyglucose positron emission tomography integrated with computed tomography were used to support clinical description. Identifying and addressing the characteristic clinical features and neural substrates of NPS-induced psychoses might help clinicians with a more precise differentiation from other psychotic disorders. Although further studies are required, phenotyping the cognitive profile of NPS users might provide targets for tailored therapeutic approaches.
{"title":"3-Methoxy-Phencyclidine Induced Psychotic Disorder: A Literature Review and an 18F-FDG PET/CT Case Report","authors":"M. Pepe, M. Di Nicola, Fabrizio Cocciolillo, S. Chiappini, G. Martinotti, M. Calcagni, G. Sani","doi":"10.3390/ph17040452","DOIUrl":"https://doi.org/10.3390/ph17040452","url":null,"abstract":"New Psychoactive Substances (NPS) are modifying the drug scenario worldwide and have become a public health concern because of their toxicological profiles and their harmful physical/psychological effects. 3-Methoxy-Phencyclidine (3-MeO-PCP), a non-competitive antagonist of glutamate N-methyl-D-aspartate (NMDA) receptors, belongs to the phencyclidine-like subfamily of arylcyclohexylamines and has gained attention for its toxic, sometimes fatal, effects. Despite several cases of intoxication and death reported in the literature, little is known about substance-induced psychotic disorders (SIP) and potential cognitive impairment following 3-MeO-PCP intake. This literature review aimed to summarize available evidence about 3-MeO-PCP mechanisms of action and physical and psychotropic effects and to spread preliminary findings about persistent psychotic symptoms and impaired cognitive functioning. Additionally, the case of an SIP is reported in a 29-year-old man with small oral intakes of 3-MeO-PCP over two weeks until a high dose ingestion. Psychometric and neuropsychological assessment and brain [18F]-fluorodeoxyglucose positron emission tomography integrated with computed tomography were used to support clinical description. Identifying and addressing the characteristic clinical features and neural substrates of NPS-induced psychoses might help clinicians with a more precise differentiation from other psychotic disorders. Although further studies are required, phenotyping the cognitive profile of NPS users might provide targets for tailored therapeutic approaches.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":"39 49","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140357664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vincenzo Russo, Nicola Napolitano, Antonia Ascrizzi, Silvia Leonardi, Filomena Pisacane, P. Di Micco, E. Imbalzano, F. C. Sasso, A. D’Andrea, A. Caturano, A. Mauriello
Background: Cardiovascular disease is a global health concern and reducing plasma LDL-C levels is a major goal in cardiovascular prevention. Our study aimed to evaluate the effectiveness of a nutraceutical formulation including leucoselect® phytosome®, red yeast rice, policosanol and folic acid on LDL-c levels in patients at low cardiovascular risk with dyslipidemia. Materials and Methods: We prospectively enrolled all consecutive patients with dyslipidemia at low cardiovascular risk who were unresponsive to diet and physical activity. Clinical assessments and laboratory analyses, encompassing lipid profile, hepatic function, and CPK levels, were performed at baseline prior to initiating treatment and repeated at the 12-week mark following administration of the study nutraceutical. Results: Sixty (60) consecutive patients (mean age 48.02 ± 10.1 years; 60% male) were included. At the 12-week follow-up, a statistically significant reduction in Total Cholesterol (13.1%) and LDL-c serum level (20.4%) was observed. Hepatic and muscular function remain stable over the time. The adherence to therapy was 99% and the persistence was maximum. Conclusions: The nutraceutical formulation including leucoselect® phytosome® red yeast rice, policosanol and folic acid significantly reduced the LDL-c plasma levels, consistent with previous research showing that the bioactive component in red yeast rice—lovastatin—is effective in addressing problems with lipid metabolism. Importantly, it was safe and well-tolerated among patients with dyslipidemia in a real-world setting.
{"title":"The Lipid-Lowering Efficacy of a Nutraceutical Combination Including Leucoselect Phytosome, Red Yeast Rice, Policosanol and Folic Acid in Dyslipidaemia Patients: Real-World Insights","authors":"Vincenzo Russo, Nicola Napolitano, Antonia Ascrizzi, Silvia Leonardi, Filomena Pisacane, P. Di Micco, E. Imbalzano, F. C. Sasso, A. D’Andrea, A. Caturano, A. Mauriello","doi":"10.3390/ph17040447","DOIUrl":"https://doi.org/10.3390/ph17040447","url":null,"abstract":"Background: Cardiovascular disease is a global health concern and reducing plasma LDL-C levels is a major goal in cardiovascular prevention. Our study aimed to evaluate the effectiveness of a nutraceutical formulation including leucoselect® phytosome®, red yeast rice, policosanol and folic acid on LDL-c levels in patients at low cardiovascular risk with dyslipidemia. Materials and Methods: We prospectively enrolled all consecutive patients with dyslipidemia at low cardiovascular risk who were unresponsive to diet and physical activity. Clinical assessments and laboratory analyses, encompassing lipid profile, hepatic function, and CPK levels, were performed at baseline prior to initiating treatment and repeated at the 12-week mark following administration of the study nutraceutical. Results: Sixty (60) consecutive patients (mean age 48.02 ± 10.1 years; 60% male) were included. At the 12-week follow-up, a statistically significant reduction in Total Cholesterol (13.1%) and LDL-c serum level (20.4%) was observed. Hepatic and muscular function remain stable over the time. The adherence to therapy was 99% and the persistence was maximum. Conclusions: The nutraceutical formulation including leucoselect® phytosome® red yeast rice, policosanol and folic acid significantly reduced the LDL-c plasma levels, consistent with previous research showing that the bioactive component in red yeast rice—lovastatin—is effective in addressing problems with lipid metabolism. Importantly, it was safe and well-tolerated among patients with dyslipidemia in a real-world setting.","PeriodicalId":509865,"journal":{"name":"Pharmaceuticals","volume":"50 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140361518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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