Pub Date : 2023-10-27DOI: 10.2174/0118715257259037231012182741
Pallavi Kumari, Shweta Dang
Introduction: The repurposing of drugs for their anticancer potential is gaining a lot of importance in drug discovery.
Aims: The present study aims to explore the potential of Simvastatin (SIM), a drug used in the treatment of high cholesterol, and thymoquinone (Nigella Sativa) (THY) for its anti-cancer activity on breast cancer cell lines. Thymoquinone is reported to have many potential medicinal properties exhibiting antioxidant, antiinflammatory, anti-cancer, and activities like tissue growth and division, hormone regulation, immune response and development, and cell signaling.
Methods: In this analysis, we explored the inhibitory effects of the combination of simvastatin ad thymoquinone on two breast cancer cell lines viz MCF-7 and MDA-MB-231 cells. The combined effect of simvastatin ad thymoquinone on cell viability, colony formation, cell migration, and orientation of more programmed cell death in vitro was studied. Cell cycle arrest in the G2/M phase was concomitant with the combined effect of SIM and THY persuading apoptosis and generating reactive oxygen species (ROS).
Results: The cell cycle arrest in combined treatment was 8.1% on MCF-7 cells and 3.8 % for MDA-MB-231 cells an increased apoptosis was observed when cells were treated in combination which was about 76.20% and 58.15 % respectively for MCF-7 and MDA-MB-231 cells.
Conclusion: It was concluded that the combined effect of simvastatin and thymoquinone stimulates apoptosis in breast cancer cells.
{"title":"Evaluation of Enhanced Cytotoxicity Effect of Repurposed Drug Simvastatin/ Thymoquinone Combination against Breast Cancer Cell Line.","authors":"Pallavi Kumari, Shweta Dang","doi":"10.2174/0118715257259037231012182741","DOIUrl":"https://doi.org/10.2174/0118715257259037231012182741","url":null,"abstract":"<p><strong>Introduction: </strong>The repurposing of drugs for their anticancer potential is gaining a lot of importance in drug discovery.</p><p><strong>Aims: </strong>The present study aims to explore the potential of Simvastatin (SIM), a drug used in the treatment of high cholesterol, and thymoquinone (Nigella Sativa) (THY) for its anti-cancer activity on breast cancer cell lines. Thymoquinone is reported to have many potential medicinal properties exhibiting antioxidant, antiinflammatory, anti-cancer, and activities like tissue growth and division, hormone regulation, immune response and development, and cell signaling.</p><p><strong>Methods: </strong>In this analysis, we explored the inhibitory effects of the combination of simvastatin ad thymoquinone on two breast cancer cell lines viz MCF-7 and MDA-MB-231 cells. The combined effect of simvastatin ad thymoquinone on cell viability, colony formation, cell migration, and orientation of more programmed cell death in vitro was studied. Cell cycle arrest in the G2/M phase was concomitant with the combined effect of SIM and THY persuading apoptosis and generating reactive oxygen species (ROS).</p><p><strong>Results: </strong>The cell cycle arrest in combined treatment was 8.1% on MCF-7 cells and 3.8 % for MDA-MB-231 cells an increased apoptosis was observed when cells were treated in combination which was about 76.20% and 58.15 % respectively for MCF-7 and MDA-MB-231 cells.</p><p><strong>Conclusion: </strong>It was concluded that the combined effect of simvastatin and thymoquinone stimulates apoptosis in breast cancer cells.</p>","PeriodicalId":93924,"journal":{"name":"Cardiovascular & hematological agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71430168","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}
Pub Date : 2023-10-27DOI: 10.2174/0118715257261643231018102928
Sakshi Tyagi, Shalini Mani
Diabetes is a series of metabolic disorders that can be categorized into three types depending on different aspects associated with age at onset, intensity of insulin resistance, and beta- cell dysfunction: Type 1 and 2 Diabetes, and Gestational Diabetes Mellitus. Type 2 Diabetes Mellitus (T2DM) has recently been found to account for more than 85% of diabetic cases. The current review intends to raise awareness among clinicians/researchers that combining vitamin D3 with metformin may pave the way for better T2DM treatment and management. An extensive literature survey was performed to analyze vitamin D's role in regulating insulin secretion, their action on the target cells and thus maintaining the normal glucose level. On the other side, the anti-hyperglycemic effect of metformin as well as its detailed mechanism of action was also studied. Interestingly both compounds are known to exhibit the antioxidant effect too. Literature supporting the correlation between diabetic phenotypes and deficiency of vitamin D was also explored further. To thoroughly understand the common/overlapping pathways responsible for the antidiabetic as well as antioxidant nature of metformin and vitamin D3, we compared their antihyperglycemic and antioxidant activities. With this background, we are proposing the hypothesis that it would be of great interest if these two compounds could work in synergy to better manage the condition of T2DM and associated disorders.
{"title":"Combined Administration of Metformin and Vitamin D: A Futuristic Approach for Management of Hyperglycemia.","authors":"Sakshi Tyagi, Shalini Mani","doi":"10.2174/0118715257261643231018102928","DOIUrl":"https://doi.org/10.2174/0118715257261643231018102928","url":null,"abstract":"<p><p>Diabetes is a series of metabolic disorders that can be categorized into three types depending on different aspects associated with age at onset, intensity of insulin resistance, and beta- cell dysfunction: Type 1 and 2 Diabetes, and Gestational Diabetes Mellitus. Type 2 Diabetes Mellitus (T2DM) has recently been found to account for more than 85% of diabetic cases. The current review intends to raise awareness among clinicians/researchers that combining vitamin D3 with metformin may pave the way for better T2DM treatment and management. An extensive literature survey was performed to analyze vitamin D's role in regulating insulin secretion, their action on the target cells and thus maintaining the normal glucose level. On the other side, the anti-hyperglycemic effect of metformin as well as its detailed mechanism of action was also studied. Interestingly both compounds are known to exhibit the antioxidant effect too. Literature supporting the correlation between diabetic phenotypes and deficiency of vitamin D was also explored further. To thoroughly understand the common/overlapping pathways responsible for the antidiabetic as well as antioxidant nature of metformin and vitamin D3, we compared their antihyperglycemic and antioxidant activities. With this background, we are proposing the hypothesis that it would be of great interest if these two compounds could work in synergy to better manage the condition of T2DM and associated disorders.</p>","PeriodicalId":93924,"journal":{"name":"Cardiovascular & hematological agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71490019","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}
Pub Date : 2023-10-23DOI: 10.2174/0118715257265832231009072953
Abhimanyu Chauhan, Chakresh Kumar Jain
In recent years, there has been increasing global concern about the rising prevalence and rapid progression of psychosomatic disorders (PD). This surge can be attributed to irregular biological conditions and the increasingly stressful lifestyles that individuals lead, ultimately resulting in functional impairments of vital organs. PD arises from intricate interactions involving the central nervous, endocrine, and immune systems. Notably, the hypothalamic-pituitaryadrenal (HPA) axis plays an essential role, as its dysregulation is influenced by prolonged stress and psychological distress. Consequently, stress hormones, including cortisol, exert detrimental effects on immunological function, inflammation, and homeostatic equilibrium. It emerges as physical symptoms influenced by psychological factors, such as persistent pain, gastrointestinal disturbances, or respiratory complications, and is pertinent to highlight that excessive and chronic stress, anxiety, or emotional distress may engender the onset or exacerbation of cardiovascular disorders, namely hypertension and heart disease. Although several therapeutic strategies have been proposed so far, the precise etiology of PD remains elusive due to the intricate nature of disease progression and the underlying modalities of action. This comprehensive review seeks to elucidate the diverse classifications of psychosomatic disorders, explicate their intricate mechanisms, and shed light on their impact on the human body, which may act as catalysts for the development of various other diseases. Additionally, it explores the inherent medico-clinical challenges posed by PD and also explores the cutting-edge technologies, tools, and data analytics pipelines that are being applied in the contemporary era to effectively analyze psychosomatic data.
{"title":"Psychosomatic Disorder: The Current Implications and Challenges.","authors":"Abhimanyu Chauhan, Chakresh Kumar Jain","doi":"10.2174/0118715257265832231009072953","DOIUrl":"https://doi.org/10.2174/0118715257265832231009072953","url":null,"abstract":"<p><p>In recent years, there has been increasing global concern about the rising prevalence and rapid progression of psychosomatic disorders (PD). This surge can be attributed to irregular biological conditions and the increasingly stressful lifestyles that individuals lead, ultimately resulting in functional impairments of vital organs. PD arises from intricate interactions involving the central nervous, endocrine, and immune systems. Notably, the hypothalamic-pituitaryadrenal (HPA) axis plays an essential role, as its dysregulation is influenced by prolonged stress and psychological distress. Consequently, stress hormones, including cortisol, exert detrimental effects on immunological function, inflammation, and homeostatic equilibrium. It emerges as physical symptoms influenced by psychological factors, such as persistent pain, gastrointestinal disturbances, or respiratory complications, and is pertinent to highlight that excessive and chronic stress, anxiety, or emotional distress may engender the onset or exacerbation of cardiovascular disorders, namely hypertension and heart disease. Although several therapeutic strategies have been proposed so far, the precise etiology of PD remains elusive due to the intricate nature of disease progression and the underlying modalities of action. This comprehensive review seeks to elucidate the diverse classifications of psychosomatic disorders, explicate their intricate mechanisms, and shed light on their impact on the human body, which may act as catalysts for the development of various other diseases. Additionally, it explores the inherent medico-clinical challenges posed by PD and also explores the cutting-edge technologies, tools, and data analytics pipelines that are being applied in the contemporary era to effectively analyze psychosomatic data.</p>","PeriodicalId":93924,"journal":{"name":"Cardiovascular & hematological agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49695059","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}
The endoplasmic reticulum (ER) is a sub-cellular organelle that is responsible for the correct folding of proteins, lipid biosynthesis, calcium storage, and various post-translational modifications. In the disturbance of ER functioning, unfolded or misfolded proteins accumulate inside the ER lumen and initiate downstream signaling called unfolded protein response (UPR). The UPR signaling pathway is involved in lipolysis, triacylglycerol synthesis, lipogenesis, the mevalonate pathway, and low-density lipoprotein receptor recycling. ER stress also affects lipid metabolism by changing the levels of enzymes that are involved in the synthesis or modifications of lipids and causing lipotoxicity. Lipid metabolism and cardiac diseases are in close association as the deregulation of lipid metabolism leads to the development of various cardiovascular diseases (CVDs). Several studies have suggested that lipotoxicity is one of the important factors for cardiovascular disorders. In this review, we will discuss how ER stress affects lipid metabolism and their interplay in the development of cardiovascular disorders. Further, the current therapeutics available to target ER stress and lipid metabolism in various CVDs will be summarized.
{"title":"Lipotoxicity, ER Stress, and Cardiovascular Disease: Current Understanding and Future Directions.","authors":"Smriti Shreya, Md Jahangir Alam, Anupriya Anupriya, Saumya Jaiswal, Vibha Rani, Buddhi Prakash Jain","doi":"10.2174/0118715257262366230928051902","DOIUrl":"https://doi.org/10.2174/0118715257262366230928051902","url":null,"abstract":"<p><p>The endoplasmic reticulum (ER) is a sub-cellular organelle that is responsible for the correct folding of proteins, lipid biosynthesis, calcium storage, and various post-translational modifications. In the disturbance of ER functioning, unfolded or misfolded proteins accumulate inside the ER lumen and initiate downstream signaling called unfolded protein response (UPR). The UPR signaling pathway is involved in lipolysis, triacylglycerol synthesis, lipogenesis, the mevalonate pathway, and low-density lipoprotein receptor recycling. ER stress also affects lipid metabolism by changing the levels of enzymes that are involved in the synthesis or modifications of lipids and causing lipotoxicity. Lipid metabolism and cardiac diseases are in close association as the deregulation of lipid metabolism leads to the development of various cardiovascular diseases (CVDs). Several studies have suggested that lipotoxicity is one of the important factors for cardiovascular disorders. In this review, we will discuss how ER stress affects lipid metabolism and their interplay in the development of cardiovascular disorders. Further, the current therapeutics available to target ER stress and lipid metabolism in various CVDs will be summarized.</p>","PeriodicalId":93924,"journal":{"name":"Cardiovascular & hematological agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686260","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}
Pub Date : 2023-09-15DOI: 10.2174/1871525722666230915103747
Pankaj Kuamr Tripathi, Chakresh Kumar Jain
Background: Colorectal cancer is estimated to become the leading cause of cancer death worldwide. Since most of the available therapies affect vital organs such as heart and liver, herbal remedies as a substitute therapy have been reported in several evidence-based studies.
Objective: Medicinal plants exhibit a diverse range of bioactive elements known for their medicinal properties, such as anti-inflammatory, anticancer, antioxidant, and antimicrobial effects. Phytochemicals present in medicinal plants significantly trigger different signaling pathways, contributing to their therapeutic activities. This review covers a comprehensive summary of the therapeutic potential of an herbal diet in treating colorectal cancer and other ailments. Special attention will be given to exploring the interactions of medicinal plants with the microbiota and their associations with cancer pathways.
Conclusion: A medicinal plant rich in bioactive compounds is a therapeutic option for colorectal cancer and potent cardioprotective and hepatoprotective agents. These bioactive compounds have demonstrated the ability to impede the growth of cancerous cells and trigger apoptosis. Our findings suggest that pomegranate, garlic, soybean, olive, green tea, papaya, and grapes are potential medicinal plants for combating cancer and related side effects. Bioactive compounds can modulate the gut microbiota's metabolism, and short-chain fatty acid production shows cardioprotective effects and reduces the risk of colorectal cancer. Hence, it can be stated that the interaction between a medicinal plant-rich diet and the gut microbiota plays a crucial role in preventing colorectal cancer and cardiac arrest.
{"title":"Medicinal Plant-Rich Diet: A Potential Therapeutic Role in Colorectal Cancer.","authors":"Pankaj Kuamr Tripathi, Chakresh Kumar Jain","doi":"10.2174/1871525722666230915103747","DOIUrl":"https://doi.org/10.2174/1871525722666230915103747","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer is estimated to become the leading cause of cancer death worldwide. Since most of the available therapies affect vital organs such as heart and liver, herbal remedies as a substitute therapy have been reported in several evidence-based studies.</p><p><strong>Objective: </strong>Medicinal plants exhibit a diverse range of bioactive elements known for their medicinal properties, such as anti-inflammatory, anticancer, antioxidant, and antimicrobial effects. Phytochemicals present in medicinal plants significantly trigger different signaling pathways, contributing to their therapeutic activities. This review covers a comprehensive summary of the therapeutic potential of an herbal diet in treating colorectal cancer and other ailments. Special attention will be given to exploring the interactions of medicinal plants with the microbiota and their associations with cancer pathways.</p><p><strong>Conclusion: </strong>A medicinal plant rich in bioactive compounds is a therapeutic option for colorectal cancer and potent cardioprotective and hepatoprotective agents. These bioactive compounds have demonstrated the ability to impede the growth of cancerous cells and trigger apoptosis. Our findings suggest that pomegranate, garlic, soybean, olive, green tea, papaya, and grapes are potential medicinal plants for combating cancer and related side effects. Bioactive compounds can modulate the gut microbiota's metabolism, and short-chain fatty acid production shows cardioprotective effects and reduces the risk of colorectal cancer. Hence, it can be stated that the interaction between a medicinal plant-rich diet and the gut microbiota plays a crucial role in preventing colorectal cancer and cardiac arrest.</p>","PeriodicalId":93924,"journal":{"name":"Cardiovascular & hematological agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41168726","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}
Valeria Hirschler, M Esteban, C González, C Molinari, L Castano
Background: Studies in adults show that central obesity increases the likelihood of Type 2 diabetes (T2DM).
Objective: To determine the association between waist circumference (WC) and non-traditional risk factors such as magnesium (Mg), phosphorus, and uric acid in indigenous children living at high altitudes.
Methods: A total of 354 (166 M) indigenous school children, aged 9.6 + 2.3 years, were enrolled in a cross-sectional study in November 2011. Central obesity was defined as WC > 90th percentile according to age and sex. Low Mg and phosphorus levels were defined as serum Mg <1.8 mg/dL and phosphorus <2.4 mg/dL . Hyperuricemia was defined as serum uric acid > 7 mg/dL.
Results: The prevalence of central obesity was 6.8% (24/354). None of the children had hyperuricemia or low P levels. HypoMg was identified in 21.7% (57/263). There was a significant association between WC (z-score) and Mg (r-015), uric acid (r0.28), phosphorus (r-0.30), HOMA-IR (r0.49), Triglycerides (r0.24), and HDL-C (r0.24). However, calcium, sodium, and potassium were not significantly associated with WC. As z-WC quartiles increased Mg and phosphorus levels significantly decreased, whereas uric acid levels increased. Multiple linear regression analysis showed that z-WC was associated significantly and directly with uric acid (B0.31), triglycerides (B0.004), and HOMA-IR (B0.35); and inversely with Mg (B-0.83) and phosphorus (B-0.25), adjusted for confounding variables (R2 0.34).
Conclusion: Our results indicate that central obesity was significantly and inversely associated with Mg and phosphorus and directly with uric acid in indigenous school children. Supplementation with Mg and/or phosphorus could prevent future cardiovascular disease. Prospective and randomized studies should be performed to confirm these findings.
{"title":"Association between waist circumference and magnesium and uric acid in indigenous Argentinean children living at high altitude.","authors":"Valeria Hirschler, M Esteban, C González, C Molinari, L Castano","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Studies in adults show that central obesity increases the likelihood of Type 2 diabetes (T2DM).</p><p><strong>Objective: </strong>To determine the association between waist circumference (WC) and non-traditional risk factors such as magnesium (Mg), phosphorus, and uric acid in indigenous children living at high altitudes.</p><p><strong>Methods: </strong>A total of 354 (166 M) indigenous school children, aged 9.6 + 2.3 years, were enrolled in a cross-sectional study in November 2011. Central obesity was defined as WC > 90th percentile according to age and sex. Low Mg and phosphorus levels were defined as serum Mg <1.8 mg/dL and phosphorus <2.4 mg/dL . Hyperuricemia was defined as serum uric acid > 7 mg/dL.</p><p><strong>Results: </strong>The prevalence of central obesity was 6.8% (24/354). None of the children had hyperuricemia or low P levels. HypoMg was identified in 21.7% (57/263). There was a significant association between WC (z-score) and Mg (r-015), uric acid (r0.28), phosphorus (r-0.30), HOMA-IR (r0.49), Triglycerides (r0.24), and HDL-C (r0.24). However, calcium, sodium, and potassium were not significantly associated with WC. As z-WC quartiles increased Mg and phosphorus levels significantly decreased, whereas uric acid levels increased. Multiple linear regression analysis showed that z-WC was associated significantly and directly with uric acid (B0.31), triglycerides (B0.004), and HOMA-IR (B0.35); and inversely with Mg (B-0.83) and phosphorus (B-0.25), adjusted for confounding variables (R2 0.34).</p><p><strong>Conclusion: </strong>Our results indicate that central obesity was significantly and inversely associated with Mg and phosphorus and directly with uric acid in indigenous school children. Supplementation with Mg and/or phosphorus could prevent future cardiovascular disease. Prospective and randomized studies should be performed to confirm these findings.</p>","PeriodicalId":93924,"journal":{"name":"Cardiovascular & hematological agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975014","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}
This study aims to evaluate the underlying mechanism of action involved in the hypotensive effect of Chamaemulum nobile L. (Cn) aqueous extract and in anesthetized Wistar rats. Lyophilized aqueous extract was administered in the jugular vein, arterial blood pressure and heart rate were measured in the carotide artery over 120 min of injection throughout an invasive direct blood pressure measuring procedure. Intravenous bolus injection of aqueous Cn extract at the doses of 50, 100 and 200 mg/kg produced a dose dependent reduction in arterial blood pressure and heart rate (p<0.001). Specific receptor antagonists (Phentolamine, Terazosin and Atropine) and pharmacological agents (N(omega)-Nitro-L-Arginine Methyl Ester and Captopril) were used for determining the underlying mechanism involved in the hypotensive effect of Cn. Only Phentolamine treatment (2 mg/kg) reduced significantly the hypotensive effect of aqueous Cn extract at a dose of 200 mg/kg. Intravenous perfusion of aqueous Cn extract caused a significant reduction of arterial blood pressure (p<0.01) and reduced the hypertensive effect of intravenous injection of norepinephrine at a dose of 1 µg/kg. We conclude that aqueous Cn extract exhibits a hypotensive effect which may be probably due to an alpha adrenergic receptor blockade mechanism.
{"title":"Pharmacological evidence of α-adrenergic receptors in the hypotensive effect of Chamaemulum nobile L.","authors":"M Hebi, M Ajebli, N A Zeggwagh, M Eddouks","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This study aims to evaluate the underlying mechanism of action involved in the hypotensive effect of Chamaemulum nobile L. (Cn) aqueous extract and in anesthetized Wistar rats. Lyophilized aqueous extract was administered in the jugular vein, arterial blood pressure and heart rate were measured in the carotide artery over 120 min of injection throughout an invasive direct blood pressure measuring procedure. Intravenous bolus injection of aqueous Cn extract at the doses of 50, 100 and 200 mg/kg produced a dose dependent reduction in arterial blood pressure and heart rate (p<0.001). Specific receptor antagonists (Phentolamine, Terazosin and Atropine) and pharmacological agents (N(omega)-Nitro-L-Arginine Methyl Ester and Captopril) were used for determining the underlying mechanism involved in the hypotensive effect of Cn. Only Phentolamine treatment (2 mg/kg) reduced significantly the hypotensive effect of aqueous Cn extract at a dose of 200 mg/kg. Intravenous perfusion of aqueous Cn extract caused a significant reduction of arterial blood pressure (p<0.01) and reduced the hypertensive effect of intravenous injection of norepinephrine at a dose of 1 µg/kg. We conclude that aqueous Cn extract exhibits a hypotensive effect which may be probably due to an alpha adrenergic receptor blockade mechanism.</p>","PeriodicalId":93924,"journal":{"name":"Cardiovascular & hematological agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975016","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}
Ana Rita Santos Estrela, Frederico Cerveira, Bárbara Regadas Correia, Ana Reis, Margarida Fardilha, Pedro Domingues, Rita Ferreira, M Rosário M Domingues
Hypovitaminosis D is a worldwide clinical problem, affecting populations in numerous ways. Several factors seem to affect vitamin D metabolism, including the suggestion that therapy with the lipid lowering HMG-CoA inhibitors might modulate vitamin D levels. However, the relationship between statins intake and serum levels of vitamin D is still controversial. The present work aimed to add new insights on the association between statins therapy, and more specifically the generation of statins, and the lipid profile in a population of 106 subjects treated with these HMG-CoA inhibitors. Data showed that despite a higher prevalence of hipovitaminosis D in subjects treated with statins, there is no association between statin generation, total and LDL cholesterol and vitamin D levels. Moreover, second generation statins, the most common treatment of hypercholesterolemia in the studied population, promoted the remodelling of serum fatty acids that was characterized by the increase of arachidonic acid (AA) relative levels without affecting eicosapentaenoic acid (EPA) levels. Among statin treated subjects, vitamin D levels did not affect serum fatty acid profile. The statin-related increased ratio AA/EPA suggests a pro- inflammatory status, whose long-term impact should be better clarified in the future.
维生素 D 不足是一个世界性的临床问题,以多种方式影响着人群。影响维生素 D 代谢的因素似乎有很多,其中包括降血脂药物 HMG-CoA 抑制剂可能会调节维生素 D 水平。然而,他汀类药物摄入量与血清维生素 D 水平之间的关系仍存在争议。本研究旨在为他汀类药物治疗(更具体地说是他汀类药物的产生)与使用这些 HMG-CoA 抑制剂的 106 名受试者的血脂状况之间的关系提供新的见解。数据显示,尽管他汀类药物治疗受试者髋部维生素 D 的患病率较高,但他汀类药物的产生、总胆固醇和低密度脂蛋白胆固醇与维生素 D 水平之间并无关联。此外,第二代他汀类药物是研究人群中最常见的治疗高胆固醇血症的药物,它促进了血清脂肪酸的重塑,其特点是花生四烯酸(AA)相对水平增加,而不影响二十碳五烯酸(EPA)水平。在接受他汀类药物治疗的受试者中,维生素 D 水平不会影响血清脂肪酸谱。与他汀类药物相关的 AA/EPA 比率升高表明,他汀类药物会促进炎症状态,其长期影响应在未来得到更好的阐明。
{"title":"New Insights on the Impact of Statin Therapy in the Susceptibility to Hypovitaminosis D Through Serum Lipidome Profiling.","authors":"Ana Rita Santos Estrela, Frederico Cerveira, Bárbara Regadas Correia, Ana Reis, Margarida Fardilha, Pedro Domingues, Rita Ferreira, M Rosário M Domingues","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hypovitaminosis D is a worldwide clinical problem, affecting populations in numerous ways. Several factors seem to affect vitamin D metabolism, including the suggestion that therapy with the lipid lowering HMG-CoA inhibitors might modulate vitamin D levels. However, the relationship between statins intake and serum levels of vitamin D is still controversial. The present work aimed to add new insights on the association between statins therapy, and more specifically the generation of statins, and the lipid profile in a population of 106 subjects treated with these HMG-CoA inhibitors. Data showed that despite a higher prevalence of hipovitaminosis D in subjects treated with statins, there is no association between statin generation, total and LDL cholesterol and vitamin D levels. Moreover, second generation statins, the most common treatment of hypercholesterolemia in the studied population, promoted the remodelling of serum fatty acids that was characterized by the increase of arachidonic acid (AA) relative levels without affecting eicosapentaenoic acid (EPA) levels. Among statin treated subjects, vitamin D levels did not affect serum fatty acid profile. The statin-related increased ratio AA/EPA suggests a pro- inflammatory status, whose long-term impact should be better clarified in the future.</p>","PeriodicalId":93924,"journal":{"name":"Cardiovascular & hematological agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975015","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}