ArticleLiterature Review

The protective role of curcumin in cardiovascular diseases

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Abstract

Curcumin (diferuloylmethane) is a polyphenol responsible for the yellow color of the curry spice turmeric. It has been used in a variety of diseases in traditional medicine. Modern scientific research has demonstrated its anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-thrombotic, and cardiovascular protective effects. In this review, we focused mainly on the effects of curcumin on the cardiovascular system. The antioxidant effects of curcumin have been shown to attenuate adriamycin-induced cardiotoxicity and may prevent diabetic cardiovascular complications. The anti-thrombotic, anti-proliferative, and anti-inflammatory effects of curcumin and the effect of curcumin in decreasing the serum cholesterol level may protect against the pathological changes occurring with atherosclerosis. The p300-HAT inhibitory effects of curcumin have been demonstrated to ameliorate the development of cardiac hypertrophy and heart failure in animal models. The inflammatory effects of curcumin may have the possibility of preventing atrial arrhythmias and the possible effect of curcumin for correcting the Ca(2+) homeostasis may play a role in the prevention of some ventricular arrhythmias. The preclinical studies from animal to clinical data in human are discussed.

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... In this model CUR caused heme oxygenase-1 activation (HO-1), [47] an enzyme that is important regulator in reducing the growth of vascular smooth muscle cells . [48] Induction of HO-1 results in a reduction in atherosclerotic lesions in the LDL receptor of knockout mice . [48] CUR is thought to induce HO-1 by activating the Nrf2-dependent antioxidant in various cells of the cardiovascular system (such as vascular endothelial cells, vascular smooth muscle cells, and human aortic smooth muscle cells) . ...
... [48] Induction of HO-1 results in a reduction in atherosclerotic lesions in the LDL receptor of knockout mice . [48] CUR is thought to induce HO-1 by activating the Nrf2-dependent antioxidant in various cells of the cardiovascular system (such as vascular endothelial cells, vascular smooth muscle cells, and human aortic smooth muscle cells) . [47][48][49] Hence, the anti-proliferative effect of CUR is significantly related to its ability to induce HO-1 . ...
... [48] CUR is thought to induce HO-1 by activating the Nrf2-dependent antioxidant in various cells of the cardiovascular system (such as vascular endothelial cells, vascular smooth muscle cells, and human aortic smooth muscle cells) . [47][48][49] Hence, the anti-proliferative effect of CUR is significantly related to its ability to induce HO-1 . [49] According to some in vitro studies, CUR caused inhibition of the platelet activating factor (PAF), and adenosine diphosphate-induced platelet aggregation . ...
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Cardiovascular diseases are the leading cause of death in the world and scientists pay a lot of attention to identify and reveal the mechanisms of their occurrence. Recently, the attention of scientists is focused increasingly on plant derivatives, such as flavonoids and polyphenols, due to their specific biological effects. One of these compounds is curcumin, which has many biological properties. Numerous studies have been performed to understand the molecular basis of the therapeutic properties of curcumin. As a result of these studies, there is considerable evidence to suggest that curcumin may affect signaling pathways associated with the cell growth, proliferation, survival, inflammation, and gene transcription. Antioxidant and anti-inflammatory mechanisms are the two basic mechanisms to which many of the effects of curcumin in various conditions are attributed. Many factors influence the development of heart disease, but one of the main culprits in their occurrence is the inflammatory process. According to recent research, curcumin is an ingredient that could be used in the prevention or treatment of cardiovascular disease. Also, some studies have shown that it has beneficial effects in preventing vascular damage and ischemia. Despite its beneficial and biological properties, it has been proven that curcumin has relatively low bioavailability and low stability in the human body, which limits its therapeutic application. In this regard, several attempts have been made to synthesize curcumin derivatives with improved bioavailability. In this paper, we review the potential and possibilities of using curcumin and its derivatives in the treatment of cardiovascular disease, which would significantly reduce the mortality rate in the population. Based on all of the above, it can be concluded that further studies of animal models and humans are needed to verify current knowledge about the application of curcumin and its derivatives in the treatment of cardiovascular diseases. In this way through these studies more reliable data will be generated concerning the effects of curcumin and its analogs on cellular and subcellular/molecular levels. Prospectively, we believe that this will ground the basis for further improved synthesis of curcumin-analogs, appropriate for the treatment of cardiovascular diseases.
... Moreover, the therapeutic effects of curcumin have been investigated in the treatment of CVD [10]. It seems that curcumin exerts its cardiovascular protective effects by its anti-inflammatory, antioxidant, antiproliferative, antilipidemic, and antithrombotic properties [11]. ...
... In recent decades, the health benefits and cardioprotective effects of curcumin and its nanorange formulations, namely nano-curcumin have been rigorously reported [9,11,37]. Some epidemiological surveys showed the positive effects of curcumin supplementation on the risk of different chronic diseases [38][39][40]. ...
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Background: Previous studies have indicated that curcumin supplementation may be beneficial for cardiometabolic health; however, current evidence regarding the effects of its nanorange formulations, popularly known as "nano-curcumin", remains unclear. This systematic review and meta-analysis aimed to determine the impact of nano-curcumin supplementation on risk factors for cardiovascular disease. Methods: PubMed, Scopus, Embase, and ISI web of science were systematically searched up to May 2021 using relevant keywords. All randomized controlled trials (RCTs) investigating the effects of nano-curcumin supplementation on cardiovascular disease risk factors were included. Meta-analysis was performed using random-effects models, and subgroup analysis was performed to explore variations by dose and baseline risk profiles. Results: According to the results of this study, nano-curcumin supplementation was associated with improvements in the glycemic profile by decreasing fasting blood glucose (FBG) (WMD: -18.14 mg/dL; 95% CI: -29.31 to -6.97; p = 0.001), insulin (WMD: -1.21 mg/dL; 95% CI: -1.43 to -1.00; p < 0.001), and HOMA-IR (WMD: -0.28 mg/dL; 95% CI: -0.33 to -0.23; p < 0.001). Interestingly, nano-curcumin supplementation resulted in increases in high-density lipoprotein (HDL) (WMD: 5.77 mg/dL; 95% CI: 2.90 to 8.64; p < 0.001). In terms of other lipid profile markers (triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL)), subgroup analyses showed that nano-curcumin supplementation had more favorable effects on lipid profiles in individuals with dyslipidemia at baseline. Nano-curcumin supplementation also showed favorable anti-inflammatory effects by decreasing C-reactive protein (CRP) (WMD: -1.29 mg/L; 95% CI: -2.15 to -0.44; p = 0.003) and interleukin-6 (IL-6) (WMD: -2.78 mg/dL; 95% CI: -3.76 to -1.79; p< 0.001). Moreover, our results showed the hypotensive effect of nano-curcumin, evidenced by a decrease in systolic blood pressure (SBP). Conclusions: In conclusion, our meta-analysis suggests that nano-curcumin supplementation may decline cardiovascular disease risk by improving glycemic and lipid profiles, inflammation, and SBP. Future large-scale investigations with longer durations are needed to expand on our findings.
... Curcumin, also known as diacetylmethane, belongs to a chemical class of polyphenols derived from the rhizomes of Curcuma longa L. (turmeric). It has garnered increasing attention in the past two decades because of its chemopreventive potential due to various bio-functional properties such as anti-oxidant, anti-in ammatory, and anti-cancer effects; genetic and epigenic modulatory effects[17]; safety and easy accessibility; and important roles in the prevention and treatment of various illnesses ranging from cancer to autoimmune [18], neurological[19], and cardiovascular diseases [20], and diabetes [21,22]. ...
... Recently, Curcumin has emerged as a potent anti-cancer agent that targets several biological pathways and processes in various cancers, including mutagenesis, cell cycle, oncogene expression, angiogenesis, metastasis, and cell death signaling such as apoptosis and autophagy without adverse effects on normal tissue [22]. Moreover, in combination with conventional anti-cancer therapies such as chemotherapy and radiation, Curcumin enhances e cacy by sensitizing cancer cells to their cytocidal effects and reduces treatment-associated side effects including cardio-, hepato-, nephro-and neuroprotective properties by balancing reactive oxygen species or in ammatory reactions [18][19][20][21][22][23]. In addition to its direct effects on cancer cells described above, emerging evidence has shed light on the immune-modulating effects of Curcumin that may play a role in its anti-tumor effects [23]. ...
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Background Despite recent advances in understanding the complex immunologic dysfunction in the tumor microenvironment (TME), fewer than 20% of patients with head and neck squamous cell carcinoma (HNSCC) respond to immune checkpoint blockade (ICB). Thus, it is important to understand how inhibitory IC receptors maintain the suppressed dysfunctional TME, and to develop more effective combination immunotherapy. This study evaluated the immune-modulating effects of Curcumin, which has well-established anti-cancer and chemopreventive properties, and its long-term safety as a phytochemical drug. Methods We carried out the western blot and small interfering RNA (siRNA) transfection assay to evaluate the effects of Curcumin on IC ligands and IC ligands function in HNSCC. Through T-cell cytotoxicity assay and measurements of cytokine secretion, we assessed the effects of combination of Curcumin with programmed death-ligand 1 (PD-L1) Ab on cancer cell killing. Flow cytometry were used to analyze the effects of Curcumin on the expression of programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain3 (TIM-3) on CD4, CD8 and Treg. Immunofluorescence, immunohistochemistry and western blot were used to detecte the cytokine (IFN-γ, Granzyme B), IC receptors (PD-1 and TIM-3) and its ligands (PD-L1, PD-L2, Galectin-9) in xenograft mouse model and 4-nitroquinoline-1-oxide (4-NQO) oral cancer model. Results We found that Curcumin decreased the expression of IC ligands such as PD-L1, PD-L2, and Galectin-9 in HNSCC, leading to regulation of epithelial-to-mesenchymal transition-associated tumor invasion. Curcumin also effectively restored the ability of CD8⁺ cytotoxic T cells to lyse cancer cells. To evaluate the effect of Curcumin on the TME further, the 4-NQO oral cancer model was used. Curcumin increased T-cell proliferation, tumor-infiltrating lymphocytes (TILs), and effector cytokines, and decreased the expression of PD-1, TIM-3, suppressive IC receptors and their ligands (PD-L1, PD-L2, and Galectin-9) in the TME, implying reinvigoration of the exhausted CD8⁺ T cells. In addition, Curcumin inhibited expression of CD4⁺CD25⁺FoxP3⁺ Treg cells as well as PD-1 and TIM-3. Conclusions These results show that Curcumin reinvigorates defective T cells via multiple (PD-1 and TIM-3) and multi-level (IC receptors and its ligands) IC axis suppression, thus providing a rationale to combine Curcumin with conventional targeted therapy or ICB as a multi-faceted approach for treating patients with HNSCC.
... CUR is known to be a specific inhibitor of p300) [143], which regulates hypertrophy-responsive transcriptional factors and therefore presents a therapeutic agent for maladaptive hypertrophy of cardiomyocytes. This was demonstrated in several animal models of heart failure [141,142,144,145]. In combination with enalapril, CUR applied orally (50 mg/kg per day for 6 weeks) to rats after myocardial infarction enhanced LV fractional shortening (FS) and reduced cardiomyocyte diameter in the non-infarct area, as well as perivascular fibrosis [146]. ...
... [199,200]. The protective role of curcumin in CVDs is related to its antioxidant and anti-inflammatory properties associated with the chemotherapeutic effects and, in particular, the anti-thrombotic, and cardioprotective action [201,202]. The antioxidant effect of curcumin seems to be mediated by Nrf2, which interacts with antioxidant response elements by inducing the transcription of antioxidant enzymes, while, its anti-inflammatory properties are mediated by the activation of heme oxigenase (HO-1) [203]. ...
Article
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Cardiovascular diseases (CVDs), which include congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, and many other cardiac disorders, cause about 30% of deaths globally; representing one of the main health problems worldwide. Among CVDs, ischemic heart diseases (IHDs) are one of the major causes of morbidity and mortality in the world. The onset of IHDs is essentially due to an unbalance between the metabolic demands of the myocardium and its supply of oxygen and nutrients, coupled with a low regenerative capacity of the heart, which leads to great cardiomyocyte (CM) loss; promoting heart failure (HF) and myocardial infarction (MI). To date, the first strategy recommended to avoid IHDs is prevention in order to reduce the underlying risk factors. In the management of IHDs, traditional therapeutic options are widely used to improve symptoms, attenuate adverse cardiac remodeling, and reduce early mortality rate. However, there are no available treatments that aim to improve cardiac performance by replacing the irreversible damaged cardiomyocytes (CMs). Currently, heart transplantation is the only treatment being carried out for irreversibly damaged CMs. Hence, the discovery of new therapeutic options seems to be necessary. Interestingly, recent experimental evidence suggests that regenerative stem cell medicine could be a useful therapeutic approach to counteract cardiac damage and promote tissue regeneration. To this end, researchers are tasked with answering one main question: how can myocardial regeneration be stimulated? In this regard, natural compounds from plant extracts seem to play a particularly promising role. The present review will summarize the recent advances in our knowledge of stem cell therapy in the management of CVDs; focusing on the main properties and potential mechanisms of natural compounds in stimulating and activating stem cells for myocardial regeneration.
... In addition, Curcumin could be applied for cognitive therapy for the elderly [30]. In line with our results, a prior study indicated that Curcumin protected against cardiovascular diseases, such as atherosclerosis, through its anti-thrombotic and cardiovascular protective effects [31]. More importantly, a recent study detected that Curcumin attenuated lung injury resulting from ventilator in rats [32]. ...
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This study was intended to investigate the effect of Curcumin on acute pulmonary embolism (APE) via microRNA-21 (miR-21)/PTEN/NF-κB axis. APE model was induced on rats and administrated with Curcumin. Western blot analysis and RT-qPCR manifested the downregulation of Sp1, miR-21 and NF-κB, but the upregulation of PTEN in Curcumin-treated APE rats. Blood gas analysis, ELISA, and weighing of wet weight/dry weight (W/D) ratio indicated that Curcumin diminished mPAP and RVSP levels, W/D ratio, thrombus volume, and inflammatory factors in the lungs of APE rats. Further mechanical analysis was conducted by dual-luciferase reporter assays and ChIP assay, which showed that Sp1 increased miR-21 expression by binding to the miR-21 promoter, and that PTEN was targeted by miR-21. The APE rats were injected with adenovirus to evaluate the effect of Sp1, miR-21, or PTEN on lung injury and inflammation. It was observed that downregulation of miR-21 or Sp1, or upregulation of PTEN diminished mPAP and RVSP levels, W/D ratio, thrombus volume, and inflammatory factors in the lungs of APE rats. In summary, Curcumin decreased miR-21 expression by downregulating Sp1 to upregulate PTEN and to impair the NF-κB signaling pathway, thus suppressing lung injury and inflammation in APE rats.
... Also curcumin could significantly increase sodium nitroprusside SNPinduced vasodilatation in diabetes and could enhance smooth muscle cell relaxation when activated by NO donor. Regarding serum adiponectin level similar results was reported by Wongcharoen and Phrommintikul who showed that, curcmiun improve serum adiponectin level in hyperlipidemic rats as curcumin inhibits the independent mitogen activated protein kinase (MAPK) pathways which are the pathways activated by most inflammatory stimulation (26). ...
... Also curcumin could significantly increase sodium nitroprusside SNPinduced vasodilatation in diabetes and could enhance smooth muscle cell relaxation when activated by NO donor. Regarding serum adiponectin level similar results was reported by Wongcharoen and Phrommintikul who showed that, curcmiun improve serum adiponectin level in hyperlipidemic rats as curcumin inhibits the independent mitogen activated protein kinase (MAPK) pathways which are the pathways activated by most inflammatory stimulation (26). ...
... Although the mechanisms of biological fatty acid nitration remain incompletely characterized, recent studies reveal that during oleic acid nitration, vinyl nitro regioisomers represent a component that displays distinctive chemical reactivity and receptor-dependent signaling actions. Regarding serum adiponectin level similar results was reported by (Wongcharoen and Phrommintikul 2009), who showed that, curcmiun improve serum adiponectin level in hyperlipidemic rats as curcumin inhibits the independent mitogen activated protein kinase (MAPK) pathways which are the pathways activated by most inflammatory stimulation. Also, (Amitai et al., 2013), showed that, garlic improve serum adiponectin level in spontaneously hypertensive rats treated for 6 weeks with a daily dose of 80 mg/kg/day of garlic that is mediated via up-regulation of cellular glutathione levels in vascular endothelial cells and possibly preventing or remedying endothelial dysfunction. ...
... Also curcumin could significantly increase sodium nitroprusside SNPinduced vasodilatation in diabetes and could enhance smooth muscle cell relaxation when activated by NO donor. Regarding serum adiponectin level similar results was reported by Wongcharoen and Phrommintikul who showed that, curcmiun improve serum adiponectin level in hyperlipidemic rats as curcumin inhibits the independent mitogen activated protein kinase (MAPK) pathways which are the pathways activated by most inflammatory stimulation (26). ...
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This study was performed to investigate the effect of oral supplementation of curcumin, garlic extract and olive oil on lipid profile, nitric oxide, adiponectin, endothelin-1, blood glucose and some inflammatory markers in normal, diabetic and hyperlipidemic rats supplementing high fat and cholesterol-enriched diet. Forty female adult albino rats were divided into four equal groups of 10 rats each. Group (1): negative control received normal diet only, group (2): rats fed on normal diet and received curcumin orally, group (3): positive control received hyperlipidemic diet, group (4): rats fed on hyperlipidemic diet and received curcumin (350 mg/ 1 kg b.w.) orally. The obtained results revealed that, curcumin supplementations to hyperlipidemic rats showed a significant increase in serum HDL-cholesterol, nitric oxide, adiponectin and Endothelin-1 concentrations and significantly decrease in serum total cholesterol, triacylglycerols, LDL-cholesterol, Fasting blood glucose, Glycated Hemoglobin (HbA1C), high sensitive C-reactive protein and Interleukin-6 levels. These results suggest that, curcumin supplementations may have some benefits in patients suffering from dyslipidemia and diabetes.
... Curcumin's health benefits are well-documented, including anti-cancer, antiviral, antioxidant, anti-inflammatory, antimicrobial, hypoglycemic, to name a few [4,5]. These benefits are demonstrated as the therapeutic application of Curcumin in treating numerous diseases such as cancer, diabetes, neurological disorders, and cardiovascular diseases [6,7]. ...
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Cardiovascular diseases (CVDs) are one of the leading causes of the most considerable mortality globally, and it has been tried to find the molecular mechanisms and design new drugs that triggered the molecular target. Curcumin is the main ingredient of Curcuma longa (turmeric) that has been used in traditional medicine for treating several diseases for years. Numerous investigations have indicated the beneficial effect of Curcumin in modulating multiple signaling pathways involved in oxidative stress, inflammation, apoptosis, and proliferation. The cardiovascular protective effects of Curcumin against CVDs have been indicated in several studies. In the current review study, we provided novel information on Curcumin's protective effects against various CVDs and potential molecular signaling targets of Curcumin. Nonetheless, more studies should be performed to discover the exact molecular target of Curcumin against CVDs.
... Regarding serum adiponectin level similar results was reported by (Wongcharoen and Phrommintikul 2009), who showed that, curcmiun improve serum adiponectin level in hyperlipidemic rats as curcumin inhibits the independent mitogen activated protein kinase (MAPK) pathways which are the pathways activated by most inflammatory stimulation. ...
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This study was performed to investigate the effect of oral supplementation of curcumin, garlic extract and olive oil on lipid profile, nitric oxide, adiponectin, endothelin-1, blood glucose and some inflammatory markers in normal, diabetic and hyperlipidemic rats supplementing high fat and cholesterol-enriched diet. Forty female adult albino rats were divided into four equal groups of 10 rats each. Group (1): negative control received normal diet only, group (2): rats fed on normal diet and received curcumin orally, group (3): positive control received hyperlipidemic diet, group (4): rats fed on hyperlipidemic diet and received curcumin (350 mg/ 1 kg b.w.) orally. The obtained results revealed that, curcumin supplementations to hyperlipidemic rats showed a significant increase in serum HDL-cholesterol, nitric oxide, adiponectin and Endothelin-1 concentrations and significantly decrease in serum total cholesterol, triacylglycerols, LDL-cholesterol, Fasting blood glucose, Glycated Hemoglobin (HbA1C), high sensitive C-reactive protein and Interleukin-6 levels. These results suggest that, curcumin supplementations may have some benefits in patients suffering from dyslipidemia and diabetes. Rezumat Acest studiu a fost efectuat pentru a investiga efectul suplimentării orale de curcumin, extract de usturoi și ulei de măsline asupra profilul lipidic, oxidului nitric, adiponectinei, endotelinei-1, glicemiei și asupra unor marker inflamatori la șobolanii sănătoși, diabetici și cu hiperlipidemie prin completarea dietei cu un continut ridicat de grăsimi și colesterol. Patruzeci de femele adulte de șobolani albinoși au fost împărțiți în patru grupe egale a câte 10 șobolani fiecare. Grupul (1): control negativ cu dietă normală, grupul (2): șobolani hrăniți cu dieta normala si supliment oral de curcumin, grupul (3): control pozitiv cu dieta hiperlipedemica, grupul (4): șobolani hrăniți cu dietă hiperlipidemică și supliment de curcumin (350 mg / 1 kg greutate corporală) pe cale orală. Rezultatele obținute au relevat că suplimentul de curcumin la șobolanii hiperlipidemici a produs o crestere semnificativa a colesterolului HDL, oxidului nitric, adiponectinei și a concentrației de endotelina-1 și o reducere semnificativă a colesterolului total seric, triacilglicerolilor, colesterolului LDL, glucozei, hemoglobinei glicate (HbA1c) și a nivelurilor de proteina C reactiva de inalta sensibilitate si Interleukina-6. Aceste rezultate sugereaza că suplimentul de curcumin poate avea unele beneficii pentru pacientii care sufera de dislipidemie si diabet.
... The known risk factors for COVID-19 include age >60 years, diabetes (Zhang et al., 2013;Poolsup et al., 2019), hypertension (Leong, 2018), cardiac disease (Wongcharoen and Phrommintikul 2009), chronic lung disease (Venkatesan et al., 2007;Biswas and Rahman, 2008;Moriyuki et al., 2010), cerebrovascular disease (Ovbiagele, 2008), chronic kidney disease (Ghosh et al., 2014;de Almeida Alvarenga et al., 2018), immunosuppression (Sharma et al., 2007;Mollazadeh et al., 2019) and cancer (Ravindran et al., 2009). Curcumin is an effective adjuvant in the treatment of each of these conditions. ...
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Background: Coronavirus disease-2019 (COVID-19) has a wide range of pathophysiological effects. Curcumin, an active constituent of Curcuma longa (turmeric), has several properties, including anti-inflammatory, antioxidant, antiviral, anti-thrombotic, and anti-proliferative effects, which make it a promising candidate for the symptomatic treatment of COVID-19. Objective: We aimed to determine the effects of curcumin administered with piperine (to optimize absorption) on symptoms in patients with COVID-19 in a double-blind, randomized, controlled trial at a 30-bed dedicated COVID Health Center (DCHC) in Maharashtra, India. Methods: In addition to conventional COVID-19 treatment, patients in the control group received a dose of probiotics twice a day, and patients in the study group received curcumin (525 mg) with piperine (2.5 mg) in tablet form twice a day. The effects of curcumin/piperine treatment on primary and secondary outcomes were assessed for the duration of hospitalization. Results: Patients with mild, moderate, and severe symptoms who received curcumin/piperine treatment showed early symptomatic recovery (fever, cough, sore throat, and breathlessness), less deterioration, fewer red flag signs, better ability to maintain oxygen saturation above 94% on room air, and better clinical outcomes compared to patients of the control group. Furthermore, curcumin/piperine treatment appeared to reduce the duration of hospitalization in patients with moderate to severe symptoms, and fewer deaths were observed in the curcumin/piperine treatment group. Conclusions: Administration of oral curcumin with piperine as an adjuvant symptomatic therapy in COVID-19 treatment could substantially reduce morbidity and mortality, and ease the logistical and supply-related burdens on the healthcare system. Curcumin could be a safe and natural therapeutic option to prevent Post-Covid thromboembolic events. Clinicaltrials.gov identifier: CTRI/2020/05/025482
... Efficiency of curcumin in prevention and treatment of cardiovascular diseases has been well recognized in a series of experimental and clinical studies [112]. Anti-atherogenic effect of curcumin was confirmed in several in-vitro models. ...
Article
Background Chronic oxidative stress and inflammation are known to be among the leading causes of ageing. Therefore, dietary supplementation with bioactive phytochemicals having antioxidant and anti-inflammatory activities is currently regarded as a promising therapeutic strategy to combat ageing and associated pathological conditions. Methods Curcumin, a lipophilic polyphenol compound derived from the rhizome of the turmeric plant, is recognized as one of the most promising anti-ageing agents now. In this review, the research findings indicative of therapeutic potential of curcumin in combating age-related diseases are summarized and discussed. Results Evidence for antioxidant, immunomodulatory, anti-inflammatory, anti-microbial, cardio-protective, nephro-protective, hepato-protective, anti-neoplastic, anti-rheumatic and hypoglycaemic effects of curcumin has been provided in numerous in vitro and in vivo studies. One important challenge in its clinical application is poor bioavailability related to hydrophobic properties, low solubility and stability, and also quick systemic elimination due to intensive intestine-liver metabolism. Conclusions To overcome current limitations, innovative biotechnological strategies, such as the nanodelivery-based ones, are under active investigation now.
... The mechanism of cardioprotective effects of curcumin is unclear and multiple mechanisms have been proposed in this area including (1) curcumin prevents lipid peroxidation through free radicals scavenging, leading to a blocking of the lipid chain reaction. (2) Curcumin exerts membrane-stabilizing effect, which is supported by the fact that it could prevent the ECG changes induced by adriamycin [58]. ...
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Among the extensive public and scientific interest in the use of phytochemicals to prevent or treat human diseases in recent years, natural compounds have been highly investigated to elucidate their therapeutic effect on chronic human diseases including cancer, cardiovascular disease, and neurodegenerative disease. Curcumin, an active principle of the perennial herb Curcuma longa, has attracted an increasing research interest over the last half-century due to its diversity of molecular targets, including transcription factors, enzymes, protein kinases, growth factors, inflammatory cytokines, receptors, and it's interesting pharmacological activities. Despite that, the clinical effectiveness of the native curcumin is weak, owing to its low bioavailability and rapid metabolism. Preclinical data obtained from animal models and phase I clinical studies done in human volunteers confirmed a small amount of intestinal absorption, hepatic first pass effect, and some degree of intestinal metabolism, might explain its poor systemic availability when it is given via the oral route. During the last decade, researchers have attempted with new pharmaceutical methods such as nanoparticles, liposomes, micelles, solid dispersions, emulsions, and microspheres to improve the bioavailability of curcumin. As a result, a significant number of bioavailable curcumin-based formulations were introduced with a varying range of enhanced bioavailability. This manuscript critically reviews the available scientific evidence on the basic and clinical effects and molecular targets of curcumin. We also discuss its pharmacokinetic and problems for marketing curcumin as a drug.
... Each treatment was evaluated separately using a 2-point hedonic scale (yes/no). Using the acceptability and purchase intent questionnaire, consumers evaluated the beef stick product for acceptability, whether or not they would purchase the product and whether or not they would purchase the product if it claimed to contain turmeric which can promote health including preventing heart disease, Alzheimer's, cancer, and improve symptoms of depression and arthritis [15,16]. This includes a potent of anti- Table 4: Acceptability and purchase intent questionnaire (N = 58) of three levels of TP on beef stick products. ...
... Based on these findings, curcumin is expected to be effective for a range of diseases related to long-term inflammation, including cancer, cardiovascular disease, metabolic syndrome, Alzheimer's disease, osteoarthritis, and other common diseases and aging conditions. 3,4,9,10 Furthermore, curcumin can be a potent inhibitor of the production of inflammatory and catabolic mediators by chondrocytes. 9 As osteoarthritis and related osteoarticular conditions of the synovial joints are characterized by inflammation, curcumin's biological actions in joint tissues may facilitate the development of clinically safe, orally administered therapeutic agents for treating joint diseases. ...
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Background We previously developed a surface-controlled water-dispersible form of curcumin that we called Theracurmin ® . The area under the blood concentration-time curve (AUC) of Theracurmin in humans was 27-fold higher than that of curcumin powder. Previously, we reported on the anti-inflammatory effects of Theracurmin for knee osteoarthritis. Hypothesis/Purpose We determined the clinical effects of orally administered Theracurmin in patients with knee osteoarthritis over a 6-month period. Study Design Open prospective study. Methods Fifty patients Kellgren-Lawrence grade II, III, or IV knee osteoarthritis who were above 40 years old were enrolled in this clinical study. Theracurmin containing 180 mg/day of curcumin was administered orally every day for 6 months. To monitor for adverse events, blood biochemistry analyses were performed before and after 6 months of each intervention. The patients’ knee symptoms were evaluated at 0, 1, 2, 3, 4, 5, and 6 months based on the Japanese Knee Osteoarthritis Measure, the knee pain visual analog scale, and the knee scoring system of the Japanese Orthopedic Association. Results Five cases dropped out during the study, but no cases dropped out because of major problems. No major side effects were observed with Theracurmin treatment, including the blood biochemistry analysis results. The effective group included 34 cases (75.6%), while the not-effective group included 11 cases. Conclusion This study demonstrates the safety and good efficacy of Theracurmin for various types of knee osteoarthritis. Theracurmin shows great potential for the treatment of human knee osteoarthritis.
... 12 Since irregular inflammatory response plays a major role in the pathogenesis of many CVDs, especially atherosclerosis, the inhibition of inflammatory pathways may be one of the protective mechanisms of curcumin in the cardiovascular system. 13 Singh and Aggarwal were the first to show that curcumin suppresses the activation of nuclear factor (NF)-β from various inflammatory stimuli. 14 The suppression of this factor suppresses the expression of NF-α-dependent genes that mediate proliferation, invasion, and angiogenesis. ...
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Background: Coronary artery disease (CAD) is the most common type of cardiovascular disease. Increasing the expression and activity of matrix metalloproteinases (MMPs) facilitates vascular remodeling and cardiovascular complications. Curcumin (the active ingredient of turmeric) is a potent natural anti-inflammatory agent, with cardiovascular protective effects. The present study was a clinical trial for investigating the effects of curcumin on activity and gene expression of MMP-2 and MMP-9 in patients with CAD. Methods: In this study, 70 patients with CAD (with 40%-50% stenosis) were randomly divided into two groups of curcumin (80 mg nanomicelle per day) and placebo. The intervention lasted 3 months. The activity levels of MMP-2 and MMP-9 in serum samples of patients were measured using gelatin zymography assay before and after the intervention. MMP-2 and MMP-9 gene expression in peripheral blood mononuclear cells (PBMCs) was also analyzed using real-time polymerase chain reaction (PCR). Statistical significance was set at P < 0.0500. Results: After 3 months of medication, the expression of MMP-9 produced by PBMCs significantly decreased in the curcumin group (0.811 ± 0.25) in comparison with the placebo group (2.23 ± 0.94) (P < 0.0001). Furthermore, the zymographic analysis showed that the administration of curcumin significantly inhibited the activity levels of MMP-2 (12469.7 ± 5308.64 pixels) and MMP-9 (14007.2 ± 5371.67 pixels) in comparison with that in patients receiving placebo (MMP-2: 17613.8 ± 5250.68 pixels; MMP-9: 20010.1 ± 3259.37 pixels) (P < 0.0500). Conclusion: Our results show that curcumin can significantly reduce the expression and activity of MMP-2 and MMP-9. Because of the anti-inflammatory effects of curcumin, this compound can be considered as a new strategy for the prevention of cardiovascular events.
... Several studies of animals and humans have evaluated the role of curcumin, a polyphenol from turmeric, and have shown positive health benefits, including modulation of vascular smooth muscle cell proliferation and improvement in fasting lipid panels. 67 In a meta-analysis of randomized controlled trials, use of turmeric and curcumin significantly reduced serum low-density lipoprotein cholesterol and triglyceride levels, although serum highdensity lipoprotein cholesterol levels were not statistically different in comparison to a control group. 68 Biases in this meta-analysis include nonuniform use of curcumin and/or Sedation: There is historical use for this substance in Ayurvedic medicine, but no data Bioflavonoid 39,40 Preoperative BP: Various doses of different flavonoids have been shown to decrease SBP and/or DBP; the decrease in BP was not consistent Postdonation Drug-drug interactions: Shown to be significant inhibitors of Pgp Black cohosh 41 Preoperative BP: In vitro vasodilation in rats has been shown Boswellia 42 Postdonation Drug-drug interactions: These extracts have been shown be mild to potent inhibitors of a number of CYP enzymes Cherry fruit 43,44 Preoperative BP: 20 women and 17 men aged 65-80 y randomly assigned to 480 mL of tart cherry juice for 12 wk or a control drink: treatment group had a larger reduction in SBP than control (P = 0.04) Postdonation ...
Article
Dietary supplement use is high among United States adults, with the intention by users to promote overall health and wellness. Kidney donors, who are selected based on their overall good health and wellness, can have high utilization rates of dietary supplements. We provide a framework for evaluation of living kidney donors and use of dietary supplements. In this review, dietary supplements will include any orally administered dietary or complementary nutritional products, but excluding micronutrients (vitamins and minerals), food, and cannabis. Use of dietary supplements can influence metabolic parameters that mask future risk for chronic illness such as diabetes and hypertension. Dietary supplements can also alter bleeding risk, anesthesia and analgesic efficacy and safety in a perioperative period. Finally, post-donation monitoring of kidney function and risk of supplement-related nephrotoxicity should be part of a kidney donor educational process. For practitioners evaluating a potential kidney donor, we provide a list of the most commonly used herbal supplements and the effects on evaluation in a pre-donation, peri-operative donation, and post-operative donation phase. Finally, we provide recommendations for best practices for integration into a comprehensive care plan for kidney donors during all stages of evaluation. We recommend avoidance of dietary supplements in a kidney donor population, although there is a paucity of data that identifies true harm. Rather, associations, known mechanisms of action, and common sense suggest that we avoid use in this population.
... Historically, China and India have used turmeric in traditional medicine to treat sickness and disease (Wongcharoen and Phrommintikul 2009). Additionally, turmeric has been used for culinary, cosmetic, and fabric-dying purposes for more than 2000 years (Ammon and Wahl 1991). ...
Article
Intense exercise, especially involving eccentric contractions, causes muscle damage concomitant with increased reactive oxygen species (ROS), which can lead to increased fatigue and decrements in physical performance. Additionally, inflammatory cytokines and advanced glycation end-products (AGEs) are produced as a result of eccentric exercise and may further lead to decreased exercise performance. Nutritional interventions may provide an avenue to respond to and reduce the symptoms associated with muscle damage. Of recent interest, curcumin, the main constituent in the spice turmeric, has been the focus of various studies considering post-exercise recovery. Curcumin has potent anti-oxidant and anti-inflammatory properties and can reduce the accumulation of AGEs. This review considers the current evidence for curcumin to impact muscle recovery following exercise to improve performance and the potential mechanisms of action. To date, clinical studies have considered the potential role of curcumin to reduce muscular damage following treadmill running (downhill and flat), conventional walking/running, cycling (acute and chronic), single-leg jumping (downhill), and eccentric muscular fitness exercises of the upper and lower body (single- and double-leg). Studies have been conducted in sedentary to highly active men and women, both young and old, with supplementation duration lasting from a single, acute dose to daily dosages for three months. Various curcumin-based interventions have improved self-perceived measures of pain and tenderness, reduced evidence of muscle damage, ameliorated inflammatory markers, increased markers of antioxidant capacity, diminished markers of oxidative stress, reduced markers of AGEs, and attenuated loss in mean power of single-leg sprints. However, these findings have not been consistently reported.
... Curcuminoids are a mixture of curcumin, demethoxycurcumin and bisdemethoxycurcumin. In recent years curcumin has attracted significant attention due to its health-promoting effects, such as protection against cancer, heart diseases (Wongcharoen and Phrommintikul, 2009) and other chronic human disorders (Mantzorou et al., 2018). Moreover, curcumin has also been used as a natural replacement for synthetic food colourants (Ismail and Sakr, 2016) and is an integral part of religious ceremonies (Chattopadhyay et al., 2004). ...
Article
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Turmeric, the golden spice belonging to the family Zingiberaceae, is enriched with biologically active curcuminoids composed of curcumin, demethoxycurcumin and bisdemethoxycurcumin. Curcuminoids are phenylpropanoid derivatives, and the biosynthetic pathway is controlled by several transcription factors (TFs). bHLH, WD40 and MYB TFs are the most important TFs regulating phenylpropanoid biosynthesis in plants. Through comparative transcriptome analysis of high and low curcumin germplasm accessions, 20 TFs belonging to the classes bHLH, WD 40, NAC, WRKY and bZIP, which showed differential expression with respect to curcumin, were identified. Among these, two bHLH and one WD40 TFs showed maximum comparative fold change and negative correlation vis-a-vis curcumin content in quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The results of comparative transcriptome and qRT-PCR analyses were in congruence, indicating their putative role as negative regulators.
... 16 Recent studies demonstrated that curcumin has several biological and pharmacological effects, 17 including antioxidant, antiinflammation, 18 anticarcinogenic, 19 hepatoprotective, thrombosuppressive, 20 antiarthritic 21 and modulation of multiple signalling pathways. 14 Furthermore, it is a natural remedy for the prevention and treatment of many disorders 17 such as skin disease, 22 chronic kidney disease, 23,24 diabetes, 25 allergy, 26 asthma, 27 cardiovascular diseases, 28 neurodegenerative diseases, 29 pancreatitis 30 and inflammatory bowel disease and RA. 31 Besides this, because of the side effects of drugs and the tendency of patients to use natural remedies, the effectiveness of curcumin on RA has been investigated in many studies. However, to our best knowledge, no study has still reviewed existing literature. ...
Article
Background Curcumin is a natural polyphenol and the main compound from the rhizome of Turmeric (Curcuma longa) and other Curcuma species. It has been widely used for different medical purposes, such as improvement of pain and inflammatory conditions in various diseases. Purpose This systematic review was aimed to assess all studies regarding the efficacy of the pure form of curcumin (unformulated curcumin) on rheumatoid arthritis (RA). Methods The comprehensive search of the literature was done until September 2020 on the MEDLINE, Embase, Scopus, and Web of Knowledge databases. Out of 2079 initial records, 51 articles (13 in vitro and 37 animal and one human) were met our inclusion criteria. Results Most studies have shown the curative effects of curcumin on clinical and inflammatory parameters of RA and reported different mechanisms; inhibition of mitogen‐activated protein kinase family (MAPK), extracellular signal‐regulated protein kinase (ERK1/2), activator protein‐1 (AP‐1), and nuclear factor kappa B (NF‐kB) are the main mechanisms associated with the anti‐inflammatory function of curcumin in RA. The results of the only human study showed that curcumin significantly improved morning stiffness, walking time, and joint swelling. Conclusion In conclusion, curcumin seems to be useful and it is recommended that more human studies be performed to approve the cellular and animal results and determine the effective and optimal doses of curcumin on RA patients.
... Furthermore, other experimental studies have revealed a therapeutic effect of curcuminoids supplementation on clinical outcomes of experimental animals with TBI through improving the neurological functions, reducing the size of lesions related to brain injury and brain levels of malondialdehyde (MDA), alleviating brain edema and finally decreasing the mortality rate (Wu, Ying, Schubert, & Gomez-Pinilla, 2011). Although certain underlying mechanisms for the significant effects of curcumin supplementation on the APPACHEII T A B L E 4 Comparisons of energy and protein intake of the patients with TBI who received either curcuminoids supplements or placebo during the study score are unclear, curcuminoids may beneficially affect components of the APPACHEII scale including white blood cell (WBC) count (Kamarudin, Othman, Mohd Ramli, Md Isa, & Das, 2012), heart rate (Wongcharoen & Phrommintikul, 2009), respiratory rate (Panahi, Ghanei, Bashiri, Hajihashemi, & Sahebkar, 2015) and serum creatinine (Exner et al., 2004). In this regards, curcuminoids may reduce WBCs count through suppression of cell infiltration and expression of adhesion molecules on the surface of monocytes as well as inhibition of production of inflammatory biomarkers such as IL-6 and TNF-α (Kamarudin et al., 2012). ...
Article
Experimental studies have suggested the beneficial effects of curcuminoids as natural polyphenols against traumatic brain injury (TBI). The aim of this study was to investigate the effects of supplementation with curcuminoids on inflammatory and oxidative stress biomarkers, clinical outcomes and nutritional status in critically ill patients with TBI. A total of 62 ICU‐admitted adult patients with TBI were randomly allocated to receive either a daily dose of 500 mg curcuminoids or matched placebo via enteral nutrition for 7 consecutive days based on stratified block randomization by age and sex. Inflammatory and oxidative stress as well as clinical outcomes and nutritional status of the patients were measured at baseline and at the end of the study. There were no overall group effects regarding to all dependent variables. Compared with baseline, serum levels of IL‐6, TNF‐α, MCP‐1 and CRP were significantly reduced in patients receiving curcuminoids (p < .05) without any significant changes in placebo group; however, changes in the activities of GPx and SOD in serum were not significant between two groups. Moreover, APACHEII and NUTRIC score were significantly improved following curcuminoids consumption in comparison with placebo (p < .05). The findings of this study suggest that short‐term supplementation with curcuminoids may have beneficial effects on inflammation, clinical outcomes and nutritional status of critically ill patients with TBI.
... Roflumilast can also suppress the secretion of inflammatory factors and attenuate cardiomyocyte inflammation by upregulating SIRT1 [92]. In addition, curcumin ameliorate DOX-mediated cardiac hypertrophy through the disruption of the p300-HAT activity [93]. NLRP3, a modulator of the innate immune system, is activated in response to danger signals caused by diseases and infections and has been implicated in DOX-induced cardiotoxicity [94]. ...
Article
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As a potent chemotherapeutic agent, doxorubicin (DOX) is widely used for the treatment of a variety of cancers However, its clinical utility is limited by dose-dependent cardiotoxicity, and pathogenesis has traditionally been attributed to the formation of reactive oxygen species (ROS). Accordingly, the prevention of DOX-induced cardiotoxicity is an indispensable goal to optimize therapeutic regimens and reduce morbidity. Acetylation is an emerging and important epigenetic modification regulated by histone deacetylases (HDACs) and histone acetyltransferases (HATs). Despite extensive studies of the molecular basis and biological functions of acetylation, the application of acetylation as a therapeutic target for cardiotoxicity is in the initial stage, and further studies are required to clarify the complex acetylation network and improve the clinical management of cardiotoxicity. In this review, we summarize the pivotal functions of HDACs and HATs in DOX-induced oxidative stress, the underlying mechanisms, the contributions of noncoding RNAs (ncRNAs) and exercise-mediated deacetylases to cardiotoxicity. Furthermore, we describe research progress related to several important SIRT activators and HDAC inhibitors with potential clinical value for chemotherapy and cardiotoxicity. Collectively, a comprehensive understanding of specific roles and recent developments of acetylation in doxorubicin-induced cardiotoxicity will provide a basis for improved treatment outcomes in cancer and cardiovascular diseases.
... On the basis of these findings, curcumin is expected to be effective for multiple diseases related to chronic inflammation, including cancer, cardiovascular disease, metabolic syndrome, Alzheimer's disease, osteoarthritis, and other common diseases and aging conditions. 1,2,7,8 Furthermore, curcumin can act as a potent inhibitor of the production of inflammatory and catabolic mediators by chondrocytes. 7 Because osteoarthritis and related osteoarticular conditions of the synovial joints are characterized by inflammation, the biological effects of curcumin in joint tissues may facilitate the development of clinically safe, orally administered therapeutic agents for treating joint diseases. ...
Article
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Purpose The purpose of this study was to determine the clinical and chondroprotective efficacy and safety of orally administered Theracurmin in patients who underwent mosaicplasty for knee chondral or osteochondral diseases over 12 months of treatment. Methods We enrolled 50 patients, older than 20 years of age, who underwent mosaicplasty for their knee joint diseases. Theracurmin at 180 mg of curcumin per day or placebo was administered orally every day for 12 months. Because 7 patients dropped out of the study, 43 patients were examined; they included 14 men and 29 women and 24 right and 19 left knees. The mean operative age was 59.5 years (range, 24-84 years). We evaluated the Japanese Orthopaedic Association knee osteoarthritis score (JOA), visual analog scale (VAS), and Japanese Knee Osteoarthritis Measure (JKOM) as clinical symptoms; T2 mapping values using magnetic resonance imaging as an indication of the chondroprotective effect; and blood concentration of curcumin at 0, 3, 6, and 12 months after the operations. We performed intraoperative acoustic evaluation of articular cartilage as a measure of chondroprotective effect during the operations and second-look arthroscopy. Results The JOA, VAS and JKOM at 3, 6, and 12 months were significantly better than those during the preoperative period. However, the values of JOA, VAS and JKOM and T2 mapping were not significantly different between the Theracurmin and placebo groups. The blood concentration of curcumin in the Theracurmin group was significantly higher than that in the placebo group at 3, 6, and 12 months after the operations. Cartilage stiffness and surface roughness were significantly better in the Theracurmin group than in the placebo group at second-look arthroscopy. Conclusion The oral administration of Theracurmin for 1 year demonstrated significantly better chondroprotective effects and no worse clinical effects and adverse events than the placebo.
... Curcumin not only upregulates the sirtuin pathway but also activates the Nrf2-ARE pathway [282]. There is increasing evidence of a potential role of curcumin in protection from CVDs [283,284]. The effects of curcumin are mediated by various molecular targets, including ERK, MAPK p38, Janus Kinase 2 (JAK2)/STAT3, AMPK/UCP2, Akt/Nrf2, JNK, MCP-1, ICAM-1 and IL-8 [189,285,286]. ...
Article
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Ageing, in a natural way, leads to the gradual worsening of the functional capacity of all systems and, eventually, to death. This process is strongly associated with higher metabolic and oxidative stress, low-grade inflammation, accumulation of DNA mutations and increased levels of related damage. Detrimental changes that accumulate in body cells and tissues with time raise the vulnerability to environmental challenges and enhance the risk of major chronic diseases and mortality. There are several theses concerning the mechanisms of ageing: genetic, free radical telomerase, mitochondrial decline, metabolic damage, cellular senescence, neuroendocrine theory, Hay-flick limit and membrane theories, cellular death as well as the accumulation of toxic and non-toxic garbage. Moreover, ageing is associated with structural changes within the myocardium, cardiac conduction system, the endocardium as well as the vasculature. With time, the cardiac structures lose elasticity, and fibrotic changes occur in the heart valves. Ageing is also associated with a higher risk of atherosclerosis. The results of studies suggest that some natural compounds may slow down this process and protect against age-related diseases. Animal studies imply that some of them may prolong the lifespan; however, this trend is not so obvious in humans.
... In case of mutant BRCA1-AURKA complex, the best docked natural metabolite namely, dihydrocurcumin, a curcumin derivative obtained from curcuma longa plant, has been reported for its anti-cancerous, antioxidant and anti-inflammatory properties in breast, lung, colorectal and hepatocellular carcinoma (Nagahama et al., 2016;Venkatesan, 1998). Curcumin and its derivatives have been reported to reduce adriamycin-induced cardiotoxicity through its antioxidant role (Wongcharoen & Phrommintikul, 2009). There are several reports for curcumin and its derivative having a prominent role against many cardiovascular diseases like myocardial infarction, cardiac hypertrophy, atherosclerosis and heart failure (Cookson et al., 2014;Li et al., 2020). ...
Article
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Breast cancer type 1 susceptibility protein (BRCA1) plays an important role in maintaining genome stability and is known to interact with several proteins involved in cellular pathways, gene transcription regulation and DNA damage response. More than 40% of inherited breast cancer cases are due to BRCA1 mutation. It is also a prognostic marker in non-small cell lung cancer patients as well as a gatekeeper of cardiac function. Interaction of mutant BRCA1 with other proteins is known to disrupt the tumor suppression mechanism. Two directly interacting proteins with BRCA1 namely, DNA repair protein RAD51 (RAD51) and Aurora kinase A (AURKA), known to regulate homologous recombination (HR) and G/M cell cycle transition, respectively, form protein complex with both wild and mutant BRCA1. To analyze the interactions, protein–protein complexes were generated for each pair of proteins. In order to combat the cardiotoxic effects of cancer drugs, pharmacokinetically screened natural metabolites derived from plant, marine and bacterial sources and along with FDA-approved cancer drugs as control, were subjected to molecular docking. Piperoleine B and dihydrocircumin were the best docked natural metabolites in both RAD51 and AURKA complexes, respectively. Molecular dynamics simulation (MDS) analysis and binding free energy calculations for the best docked natural metabolite and drug for both the mutant BRCA1 complexes suggested better stability for the natural metabolites piperolein B and dihydrocurcumin as compared to drug. Thus, both natural metabolites could be further analyzed for their role against the cardiotoxic effects of cancer drugs through wet lab experiments. Communicated by Ramaswamy H. Sarma
... As an additional mechanism, CUR fixes lysosomal membranes and reduces the function of lysosomal acid hydrolases, thus preventing the aberrant deposition of different connective tissue components in aging endothelium. A similar upgrade in endothelial function was also observed in postmenopausal women after eight weeks of treatment [88], whereas in elderly with diabetes and cardiomyopathy, CUR mitigated hypertrophy in the aging heart via suppression of p300, the global transcription activator [89]. Beneficial effects of CUR on vascular aging also concern the development of age-related macular degeneration (AMD), one of the most important causes of blindness in elderly [90,91]. ...
Article
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Aging is characterized by a progressive inability to maintain homeostasis, self-repair, renewal, performance, and fitness of different tissues throughout the lifespan. Senescence is occurring following enormous intracellular or extracellular stress stimuli. Cellular senescence serves as an antiproliferative process that causes permanent cell cycle arrest and restricts the lifespan. Senescent cells are characterized by terminal cell cycle arrest, enlarged lysosome, and DNA double-strand breaks as well as lipofuscin granularity, senescence-associated heterochromatin foci, and activation of DNA damage response. Curcumin, a hydrophobic polyphenol, is a bioactive chemical constituent of the rhizomes of Curcuma longa Linn (turmeric), which has been extensively used for the alleviation of various human disorders. In addition to its pleiotropic effects, curcumin has been suggested to have antiaging features. In this review, we summarized the therapeutic potential of curcumin in the prevention and delaying of the aging process.
... Turmeric derives its unique benefits predominantly from the component curcumin (diferulomethane), a polyphenol responsible for turmeric's yellow color [73]. The mechanism of curcumin-mediated CV risk modification includes decreasing oxidative stress by scavenging reactive oxygen species (ROS) and providing a protective role in the pathogenesis of atherosclerosis [74,75]. ...
Article
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Purpose of Review The prevalence of cardiovascular disease despite good medical therapy is on the rise, driven by risk factors such as hypertension, diabetes, hypercholesterolemia, and obesity. As healthcare providers, we must seek to better advise patients on preventative strategies through lifestyle changes. Recent Findings Guideline recommendations have been published by professional societies on the prevention of heart disease through lifestyle changes; however, limited education and experience with these lifestyle-modifying methods hinders appropriate counseling and treatment of patients. Summary Robust data support the use of lifestyle medicine to reduce cardiovascular morbidity and risk. These include, a more plant-based whole food diet, regular exercise, stress relief, connectedness, and other lifestyle approaches. This review will help further the understanding of the front-line clinician in cardiovascular prevention.
... Curcumin is stated to enable HO-1 expression by actuating Nrf2-dependent antioxidant response element. It is also stated that curcumin suppress TNF-a in vascular and aortic smooth muscle cells; and that it increases p21 expression through HO-1 (Pae et al., 2007;Wongcharoen and Phrommintikul, 2009). Curcumin treatment on animals has been determined to decrease ischemia through activation of JAK2/STAT3 signal pathway (Duan et al., 2012). ...
... Curcumin is the main active ingredient in turmeric with several proven health benefits [26][27][28][29][30][31]. It has been shown that this natural bioactive compound has several unique properties such as anti-tumor, anti-inflammatory, antioxidant, antithrombotic, chemosensitizing and chemopreventive, neuroprotective and cardioprotective, lipid-modifying, analgesic, and antirheumatic activities [22,[32][33][34][35][36]. ...
Chapter
Chronic kidney disease (CKD) is one of the significant causes of morbidity and mortality worldwide, which could develop and progress to end-stage renal disease. Increased inflammation and reduced antioxidant capacity commonly occur in CKD and hemodialysis patients. Curcumin is a natural bioactive compound with antioxidant and anti-inflammatory properties. This systematic review was undertaken with the main aim of assessing the effects of curcumin/turmeric supplementation on renal diseases based on clinical trials. A comprehensive search was performed in PubMed/MEDLINE, Scopus, ISI Web of Science, and Google Scholar from inception up to April 6, 2020 to identify clinical trials assessing the effects of curcumin or turmeric alone, or in combination with other herbs or nutrients on renal diseases. Twelve studies met the eligibility criteria. These randomized controlled trials (RCTs) comprised 631 patients with either chronic kidney diseases (CKD), hemodialysis, diabetic proteinuria and nephropathy, and lupus nephritis. Curcumin/turmeric supplementation had favorable effects on renal diseases, particularly in terms of inflammation and oxidative stress. However, with the exception for proteinuria, their impact on clinical parameters, such as blood urea nitrogen, creatinine, glomerular filtration rate (GFR), and serum albumin, was weak and not significant. No serious adverse effects were reported following curcumin/turmeric supplementation. Within the limitations of this review, it can be concluded that curcumin/turmeric supplementation might have some beneficial effects on inflammatory and oxidative stress parameters of patients but no considerable positive impact on clinical outcomes of kidney diseases, apart from proteinuria.
... Curcumin is a primary component of turmeric with several proven health benefits and is considered as a safe natural agent for both prevention and treatment of several diseases [13][14][15][16][17][18][19]. It has been shown that this active compound of turmeric has several unique properties such as antitumour, anti-inflammatory, antioxidant, antithrombotic, chemosensitising and chemopreventive, anti-atherosclerotic and cardioprotective, lipid-modifying, antibacterial, antifungal, antiviral, analgesic, antidepressant and antirheumatic activities [20][21][22][23][24]. Evidence suggests that curcumin has anticancer activity [25][26][27][28][29] and, based on preclinical studies, it might be used to downregulate gene expression in prostate cancer cells [30][31][32]. ...
Chapter
Prostate cancer is one of the significant causes of morbidity and mortality worldwide. Benign prostatic hyperplasia is another condition of the prostate which, like prostate cancer, is more common among ageing men and is linked to inflammation. In this study, a systematic review was undertaken to estimate the effect of turmeric or curcumin supplementation on prostate diseases. A comprehensive search was conducted in PubMed, Scopus, ISI Web of Science and Google Scholar up to 15 April 2020 to identify clinical trials assessing the effects of curcumin/turmeric alone or in combination with other herbs on prostate diseases. This led to the identification of 11 records comprising 745 patients who met the eligibility criteria. Eight studies were conducted on patients with prostate cancer, and three were on other diseases of the prostate. Although outcomes across the studies were heterogeneous, in some studies curcumin/turmeric supplementation had some favourable effects. This included beneficial effects on the levels of prostate-specific antigen (PSA) (2/6 studies), quality of life (1/2 studies), as well as on oxidative stress markers, feelings of incomplete bladder emptying, urination frequency, intermittency, urgency, weak stream, straining and nocturia. Curcumin/turmeric supplementation had no significant adverse effects among patients. This study demonstrated that turmeric or curcumin supplementation might have beneficial effects on some parameters related to prostate diseases, but it should be noted that some studies showed no effect. Therefore, further studies using curcumin-related compounds, particularly in highly bioavailable forms, are needed to assess the impact of curcumin on prostate conditions.
Book
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Economic importance of plants includes the study of the relationship between people (individuals and cultures) and plants. It intersects many fields including established disciplines such as agronomy, anthropology, archaeology, chemistry, economics, ethnobotany, ethnology, forestry, genetic resources, geography, geology, horticulture, medicine, microbiology, nutrition, pharmacognosy, and pharmacology. This link between botany and anthropology explores the ways humans use plants for food, medicines, and commerce. This Book offers a systematic approach to the wide variety of published materials on the use of plants. Economic plants are defined as being useful either directly, as in food, or indirectly, as products we use or that enhance the environment. Plants are essential to life on earth; they produce the oxygen we breathe through photosynthesis and provide much of the food we eat. Some species provide medicines and promote healing, others are used for insect control or to conserve water. Plants with dense root systems prevent soil erosion and those with brightly colored flowers attract pollinators. Plants have been used to control body functions and fertility, to poison, and to make clothing, paper, and rubber. The guide includes references to materials on food plants, fiber plants, dye plants, edible plants, medicinal plants, oilseed plants, as well as plants used in ceremonies, cultivated for commercial purposes, or used as shelter.
Chapter
Noncommunicable diseases (NCDs) are one of the major public health concerns globally. Most of the NCDs including insulin resistance, metabolic syndrome, type 2 diabetes mellitus, fatty liver disease, and coronary heart disease are related to obesity and are called obesity-related NCDs (OR-NCDs). However, adipocytes can reduce OR-NCDs by secreting adiponectin. Adiponectin has an inverse relationship with body fat. Obese people have impairment in differentiating pre-adipocytes to adipocytes, the process facilitated by adiponectin. Adiponectin directly increases insulin sensitivity and reduces obesity-related insulin resistance by down-regulating hepatic glucose production and increasing fatty acid (FA) oxidation in skeletal muscle. Considering the various beneficial effects of adiponectin on health, increasing adiponectin might be a promising approach to prevent and treat OR-NCDs. Recent studies have shown that nutraceuticals and medicinal compounds isolated from plants could prevent and treat various diseases, particularly cardiovascular diseases (CVDs), diabetes mellitus, obesity, and non-alcoholic fatty liver disease. However, to our knowledge, the effect of these natural products, including herbal supplements and functional foods on adiponectin, has not yet been fully reviewed. The main aim of this review is to summarize the effects of nutraceuticals and herbal bioactive compounds on plasma adiponectin concentrations based on clinical studies. It can be concluded that medicinal plants, and herbal bioactive compounds, particularly curcumin, anthocyanins, resveratrol, soy, walnut, and dihydromyricetin can be used as adjunct or complementary therapeutic agents to increase plasma adiponectin, which could potentially prevent and treat NCDs.
Article
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Curcumin, belongs to the curcuminoid family, is a natural phenolic compound, presenting low bioavailability and pleiotropic activity. Since ancient times, curcumin has been in use as food spices and folk remedy to treat cough, cold, cuts and wounds, and skin diseases. Preclinical and clinical studies have indicated that curcumin acts a promising therapeutic agent in the management of a wide array of health issues, viz., hyperlipidemia, metabolic syndrome, anxiety, arthritis, cancer and inflammatory diseases. Owing to its enormous potential, recent research has been focused on the synthesis of curcumin and its analogues for the management of metabolic disorders. In the current scenario, hypertension is considered as a key risk factor due to its involvement in various pathogeneses. Mechanistically, curcumin and its analogues like hexahydrocurcumin, tetrahydrocurcumin, etc. have been reported to elicit anti-hypertensive effect through diverse signalling pathways, viz., pathway mediated by Nrf2-ARE, NF-kB, NO/cGMP/PDE5/MMPs, RAAS/ACE, HAT/HDAC, G0/G1/apoptosis, CYP3A4, UCP2/PARP, VEGF/STAT/AXL/tyrosine kinase and TGF-β/Smad-mediated pathways. Thus, the present review has been aimed to highlight different molecular pathways involved in the amelioration of hypertension and associated conditions.
Article
Significance: The prevalence of obesity and cardiometabolic phenotypes is alarmingly increasing across the globe and associates with atherosclerotic vascular complications and high mortality. Although multifactorial interventions, vascular residual risk remains high in this patient population, suggesting the need for breakthrough therapies. The mechanisms underpinning obesity-related vascular disease remain elusive and represent an intense area of investigation. Recent advances: Epigenetic modifications - defined as environmentally-induced chemical changes of DNA and histones which do not affect DNA sequence - are emerging as a potent modulator of gene transcription in the vasculature and might significantly contribute to the development of obesity-induced endothelial dysfunction. DNA methylation and histone posttranslational modifications cooperate to build complex epigenetic signals altering transcriptional networks implicated in redox homeostasis, mitochondrial function, vascular inflammation and perivascular fat homeostasis in patients with cardiometabolic disturbances. Critical issues: Deciphering the epigenetic landscape in the vasculature is extremely challenging due to the complexity of epigenetic signals and their function in regulating transcription. An overview of the most important epigenetic pathways is required to identify potential molecular targets to treat or prevent obesity-related endothelial dysfunction and atherosclerotic disease. This would enable the employment of precision medicine approaches in this setting. Future directions: Current and future research efforts in this field entail a better definition of the vascular epigenome in obese patients as well as the unveiling of novel, cell-specific chromatin-modifying drugs able to erase specific epigenetic signals responsible for maladaptive transcriptional alterations and vascular dysfunction in obese patients.
Article
Obesity has become a major health problem that has rapidly prevailed over the past several decades worldwide. Curcumin, a natural polyphenolic compound present in turmeric, has been shown to have a protective effect on against obesity and metabolic diseases. However, its underlying mechanism remains largely unknown. Here, we show that the administration of curcumin significantly prevents HFD-induced obesity and decreases the fat mass of the subcutaneous inguinal WAT (iWAT) and visceral epididymal WAT (eWAT) in mice. Mechanistically, curcumin inhibits adipogenesis by reducing the expression of AlkB homolog 5 (ALKHB5), an m6 A demethylase, which leads to higher m6 A-modified TNF receptor-associated factor 4 (TRAF4) mRNA. TRAF4 mRNA with higher m6 A level is recognized and bound by YTHDF1, leading to enhanced translation of TRAF4. TRAF4, acting as an E3 RING ubiquitin ligase, promotes degradation of adipocyte differentiation regulator PPARγ by a ubiquitin-proteasome pathway thereby inhibiting adipogenesis. Thus, m6 A-dependent TRAF4 expression upregulation by ALKBH5 and YTHDF1 contributes to curcumin-induced obesity prevention. Our findings provide mechanistic insights into how m6 A is involved in the anti-obesity effect of curcumin.
Article
Background Curcumin, a polyphenol derived from Curcuma longa, has some adverse effects on heart; however, its toxic effects on cardiac cells are poorly understood.Objective To evaluate the toxicity of curcumin on H9c2 rat cardiomyoblasts. To this, H9c2 cells were exposed to different concentrations of curcumin and proliferation, viability, cell cycle, oxidative stress, mitochondrial membrane potential (ΔΨm), death and autophagy were evaluated.ResultsCurcumin caused concentration-dependent inhibition of H9c2 cells proliferation and viability. A higher sub-G1 population was observed in cells treated with curcumin, which was related with phosphatidylserine translocation and increase of activated caspase-9, indicating apoptotic death. Curcumin induced oxidative stress and decreased ΔΨm causing mitochondrial dysfunction. Additionally, it promoted autophagy, revealed by higher LC3B and beclin-1 protein expression and mitophagy.Conclusion Curcumin exhibited toxic effects in cardiac cells and further studies are required to validate its therapeutic potential and use as anti-inflammatory and anti-oxidant agent in the cardiovascular system.Graphic abstract
Article
Aortic dissection (AD) is a life-threatening disease featured by the dissection of intimal layer and the formation of a blood-filled false lumen within the aortic wall. Recent studies revealed that the formation and progression of AD lesions is closely related to vascular inflammation and macrophage infiltration. However, the potential efficacy of anti-inflammatory therapy on the prevention and treatment of AD has not been extensively investigated. Herein, we proposed a biomimetic anti-inflammatory liposome (PM/TN-CCLP) co-loaded with curcumin and celecoxib (CC), modified with cell-penetrating TAT-NBD fusion peptide (TN), and further camouflaged by isolated macrophage plasma membrane (PM), as a potential nanotherapy for AD. In vitro results showed that PM/TN-CCLP exhibited low cytotoxicity and elevated cellular uptake by inflammatory macrophages, and prominently inhibited the transendothelial migration, inflammatory responses and ROS generation of macrophages. Moreover, the PM/TN-CCLP treatment significantly prevented the H2O2-induced smooth muscle cell apoptosis. In vivo experiments were performed on the acute and chronic AD mouse models, respectively. The results verified the elevated accumulation of PM-camouflaged liposome at the aorta lesions. Further, the anti-inflammatory liposomes, especially PM/TN-CCLP, could reduce the rupture rate of dissection, prevent the loss of elastic fibers, and reduce MMP-9 expression as well as macrophage infiltration in the aortic lesions. Notably, as compared with free drugs and TN-CCLP, the PM/TN-CCLP treatment displayed the longest survival period along with the minimal aortic injury on both acute and chronic AD mice. Taken together, the present study suggested that the macrophage-biomimetic anti-inflammatory nanotherapy would be a promising strategy for the prevention and therapy of aortic dissection.
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Background: Despite recent advances in understanding the complex immunologic dysfunction in the tumor microenvironment (TME), fewer than 20% of patients with head and neck squamous cell carcinoma (HNSCC) respond to immune checkpoint blockade (ICB). Thus, it is important to understand how inhibitory IC receptors maintain the suppressed dysfunctional TME, and to develop more effective combination immunotherapy. This study evaluated the immune-modulating effects of Curcumin, which has well-established anti-cancer and chemopreventive properties, and its long-term safety as a phytochemical drug. Methods: We carried out the western blot and small interfering RNA (siRNA) transfection assay to evaluate the effects of Curcumin on IC ligands and IC ligands function in HNSCC. Through T-cell cytotoxicity assay and measurements of cytokine secretion, we assessed the effects of combination of Curcumin with programmed death-ligand 1 (PD-L1) Ab on cancer cell killing. Flow cytometry were used to analyze the effects of Curcumin on the expression of programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain3 (TIM-3) on CD4, CD8 and Treg. Immunofluorescence, immunohistochemistry and western blot were used to detecte the cytokine (IFN-γ, Granzyme B), IC receptors (PD-1 and TIM-3) and its ligands (PD-L1, PD-L2, Galectin-9) in xenograft mouse model and 4-nitroquinoline-1-oxide (4-NQO) oral cancer model. Results: We found that Curcumin decreased the expression of IC ligands such as PD-L1, PD-L2, and Galectin-9 in HNSCC, leading to regulation of epithelial-to-mesenchymal transition-associated tumor invasion. Curcumin also effectively restored the ability of CD8+ cytotoxic T cells to lyse cancer cells. To evaluate the effect of Curcumin on the TME further, the 4-NQO oral cancer model was used. Curcumin increased T-cell proliferation, tumor-infiltrating lymphocytes (TILs), and effector cytokines, and decreased the expression of PD-1, TIM-3, suppressive IC receptors and their ligands (PD-L1, PD-L2, and Galectin-9) in the TME, implying reinvigoration of the exhausted CD8+ T cells. In addition, Curcumin inhibited expression of CD4+CD25+FoxP3+ Treg cells as well as PD-1 and TIM-3. Conclusions: These results show that Curcumin reinvigorates defective T cells via multiple (PD-1 and TIM-3) and multi-level (IC receptors and its ligands) IC axis suppression, thus providing a rationale to combine Curcumin with conventional targeted therapy or ICB as a multi-faceted approach for treating patients with HNSCC.
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Curcumin exerts therapeutic effects in heart disease, but has limited bioavailability. Extracellular vesicles (EVs) have gained attention as nanovehicles; however, the poor targeting ability of systemically administered EVs still remains a crucial issue. Herein, we generated heart-targeted EVs (CTP-EVs) by functionalizing EVs surface with cardiac targeting peptide (CTP) using genetic modification of EVs-secreting cells, and further loaded curcumin into CTP-EVs (CTP-EVs-Cur). Consequently, CTP-EVs were able to specifically deliver curcumin to the heart. In addition, curcumin-loaded CTP-EVs possess improved bioavailability, and are fully functional with a high cardioprotective efficiency. Moreover, we loaded miR-144-3p in CTP-EVs-Cur following validation of miR-144-3p as a major contributor in curcumin-mediated therapeutic effects. The simultaneous packing of curcumin and miR-144-3p in CTP-EVs not only retains the active heart-targeting ability but also achieves enhanced cardioprotective effects both in vitro and in vivo, indicating the possibility of combining and sustaining their therapeutic potential by simultaneously loading in CTP-EVs. Therefore, CTP-EVs could be a potential and effective strategy for the delivery of therapeutic molecules, thereby providing a promising nanomedicine for MI therapy.
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ÖZ: Bitkisel ürünler insanlık tarihi boyunca çeşitli amaçlarla kullanılmıştır. Bu ürünlerin çoğu, ilaçların keşfi ve tasarımında yararlanılabilecek farmakolojik veya biyolojik aktiviteye sahiptir. Zerdeçal, zencefil ailesinin bir üyesi Kurkuma longa bitkisinden elde edilmiştir. Zerdeçal, Hint ayurvedik tıbbında ve Unani geleneksel tıbbında en az 2500 yıldır sindirim ve karaciğer hastalıkları, deri enfeksiyonları ve artrit tedavisinde kullanılmaktadır. İlk kez 1815'te Vogel ve Pelletier tarafından zerdeçaldan izole edilmiş olan kürküminin 1870'de saf ve kristal formu, 1910'da ise diferuloilmetan yapısı bulunmuştur. Zerdeçalın 100 gramında; 390 kcal, toplam 10 g yağ, 3 g doymuş yağ, 0 mg kolesterol, 0.2 g kalsiyum, 0.26 g fosfor, 10 mg sodyum, 2500 mg potasyum, 47.5 mg demir, 0.9 mg tiamin, 0.19 mg riboflavin, 4.8 mg niasin, 50 mg askorbik asit, toplam 69.9 g karbonhidrat, 21 g diyet lifi, 3 g şeker ve 8 g protein bulunmaktadır. Zerdeçaldaki ana biyoaktif bileşen olan kürkümin, antioksidan, anti-inflamatuar, anti-bakteriyel ve anti-aterosklerotik özelliklere sahiptir. Bu özellikleri zerdeçalı, Alzheimer, kanser, kardiyovasküler hastalıklar, diyabet, obezite ve depresyon gibi pek çok hastalığın tedavisinde ilgi çekici kılmıştır. Bu derlemede zerdeçalın genel sağlık üzerine etkilerinin irdelenmesi amaçlanmıştır. ABSTRACT Herbal products have been used for various purposes throughout human history. Many of these products have pharmacological or biological activity that can be utilized in the discovery and design of drugs. Turmeric is derived from the Curcuma longa plant, a member of the ginger family. Turmeric has been used in Indian Ayurvedic medicine and Unani traditional medicine for at least 2500 years to treat digestive and liver diseases, skin infections and arthritis. Curcumin, which was first isolated from turmeric by Vogel and Pelletier in 1815, was found in its pure and crystalline form in 1870 and its diferuloylmethane structure in 1910. In 100 grams of turmeric; 390 kcal, 10 g total fat, 3 g saturated fat, 0 mg cholesterol, 0.2 g calcium, 0.26 g phosphorus, 10 mg sodium, 2500 mg potassium, 47.5 mg iron, 0.9 mg thiamine, 0.19 mg riboflavin, 4.8 mg niacin, 50 mg ascorbic acid, a total of 69.9 g carbohydrates, 21 g dietary fiber, 3 g sugar and 8 g protein. Curcumin, the main bioactive ingredient in turmeric, has antioxidant, anti-inflammatory, anti-bacterial and anti-atherosclerotic properties. These properties have made turmeric interesting in the treatment of many diseases such as Alzheimer's, cancer, cardiovascular diseases, diabetes, obesity and depression. In this review, it is aimed to examine the effects of turmeric on general health.
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“Fetal” gene transcription, including activation of the skeletal α-actin (SkA) promoter, is provoked in cardiac myocytes by mechanical stress and trophic ligands. Induction of the promoter by transforming growth factor β or norepinephrine requires serum response factor (SRF) and TEF-1; expression is inhibited by YY1. We and others postulated that immediate-early transcription factors might couple trophic signals to this fetal program. However, multiple Fos/Jun proteins exist, and the exact relationship between control by Fos/Jun versus SRF, TEF-1, and YY1 is unexplained. We therefore co-transfected ventricular myocytes with Fos, Jun, or JunB, and SkA reporter genes. SkA transcription was augmented by Jun, Fos/Jun, Fos/JunB, and Jun/JunB; Fos and JunB alone were neutral or inhibitory. Mutation of the SRF site, SRE1, impaired activation by Jun; YY1, TEF-1, and Sp1 sites were dispensable. SRE1 conferred Jun activation to a heterologous promoter, as did the c-fos SRE. Deletions of DNA binding, dimerization, or trans-activation domains of Jun and SRF abolished activation by Jun and synergy with SRF. Neither direct binding of Fos/Jun to SREs, nor physical interaction between Fos/Jun and SRF, was detected in mobility-shift assays. Thus, AP-1 factors activate a hypertrophy-associated gene via SRF, without detectable binding to the promoter or to SRF.
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To determine the influence of cardiac ischemia on the activity and subcellular localization of lysosomal cathepsin D, anesthetized rabbits were subjected to ligation of the circumflex coronary artery. Total enzyme activity remained unchanged throughout the 2-h ischemic period, but the subcellular distribution of cathepsin D, as analyzed by biochemical and immunohistochemical techniques, was altered dramatically. A marked increase in nonsedimentable (i.e., 40,000-g supernate) activity developed by 30-45 min and increased further by 2 h. Simultaneously, the immunofluorescent localization of cathepsin D was also changed significantly. Within 30-60 min after occlusion, the fine, particulate staining observed in control myocytes was replaced by bright fluorescent patches composed of large granules. Many of these structures displayed prominent halos of diffuse fluorescent staining in the neighboring myocytic cytoplasm, apparently outside lysosomes per se. After 2 h, when nonsedimentable activity was maximally elevated, most of the fluorescent particles had disappeared completely. During this same interim there was no detectable change in the distribution of lysosomal cathepsin D within interstitial cells. These results are consistent with the hypothesis that an early feature of cardiac ischemia is the release of cathepsin D from myocytic lysosomes into the cytosol of damaged cells.
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p300/CBP transcriptional co-activator proteins play a central role in co-ordinating and integrating multiple signal-dependent events with the transcription apparatus, allowing the appropriate level of gene activity to occur in response to diverse physiological cues that influence, for example, proliferation, differentiation and apoptosis. p300/CBP activity can be under aberrant control in human disease, particularly in cancer, which may inactivate a p300/CBP tumour-suppressor-like activity. The transcription regulating-properties of p300 and CBP appear to be exerted through multiple mechanisms. They act as protein bridges, thereby connecting different sequence-specific transcription factors to the transcription apparatus. Providing a protein scaffold upon which to build a multicomponent transcriptional regulatory complex is likely to be an important feature of p300/CBP control. Another key property is the presence of histone acetyltransferase (HAT) activity, which endows p300/CBP with the capacity to influence chromatin activity by modulating nucleosomal histones. Other proteins, including the p53 tumour suppressor, are targets for acetylation by p300/CBP. With the current intense level of research activity, p300/CBP will continue to be in the limelight and, we can be confident, yield new and important information on fundamental processes involved in transcriptional control.
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Curcumin, an important inhibitor of carcinogenesis, is an inhibitor of the ATPase activity of the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum (SR). Inhibition by curcumin is structurally specific, requiring the presence of a pair of -OH groups at the 4-position of the rings. Inhibition is not competitive with ATP. Unexpectedly, addition of curcumin to SR vesicles leads to an increase in the rate of accumulation of Ca(2+), unlike other inhibitors of the Ca(2+)-ATPase that result in a reduced rate of accumulation. An increase in the rate of accumulation of Ca(2+) is seen in the presence of phosphate ion, which lowers the concentration of free Ca(2+) within the lumen of the SR, showing that the effect is not passive leak across the SR membrane. Rather, simulations suggest that the effect is to reduce the rate of slippage on the ATPase, a process in which a Ca(2+)-bound, phosphorylated intermediate releases its bound Ca(2+) on the cytoplasmic rather than on the lumenal side of the membrane. The structural specificity of the effects of curcumin on ATPase activity and on Ca(2+) accumulation is the same, and the apparent dissociation constants for the two effects are similar, suggesting that the two effects of curcumin could follow from binding to a single site on the ATPase.
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Cardiac hypertrophy is the heart's response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress. While hypertrophy can eventually normalize wall tension, it is associated with an unfavorable outcome and threatens affected patients with sudden death or progression to overt heart failure. Accumulating evidence from studies in human patients and animal models suggests that in most instances hypertrophy is not a compensatory response to the change in mechanical load, but rather is a maladaptive process. Accordingly, modulation of myocardial growth without adversely affecting contractile function is increasingly recognized as a potentially auspicious approach in the prevention and treatment of heart failure. In this review, we summarize recent insights into hypertrophic signaling and consider several novel antihypertrophic strategies.
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Cardiovascular complications account for significant morbidity and mortality in the diabetic population. Diabetic cardiomyopathy, a prominent cardiovascular complication, has been recognized as a microvascular disease that may lead to heart failure. Pathogenesis of diabetic cardiomyopathy involves vascular endothelial cell dysfunction, as well as myocyte necrosis. Clinical trials have identified hyperglycemia as the key determinant in the development of chronic diabetic complications. Sustained hyperglycemia induces several biochemical changes including increased non-enzymatic glycation, sorbitol-myoinositol-mediated changes, redox potential alterations, and protein kinase C (PKC) activation, all of which have been implicated in diabetic cardiomyopathy. Other contributing metabolic abnormalities may include defective glucose transport, increased myocyte fatty acid uptake, and dysmetabolism. These biochemical changes manifest as hemodynamic alterations and structural changes that include capillary basement membrane (BM) thickening, interstitial fibrosis, and myocyte hypertrophy and necrosis. Diabetes-mediated biochemical anomalies show cross-interaction and complex interplay culminating in the activation of several intracellular signaling molecules. Studies in both animal and human diabetes have shown alteration of several factors including vasoactive molecules that may be instrumental in mediating structural and functional deficits at both the early and the late stages of the disease. In this review, we will highlight some of the important vascular changes leading to diabetic cardiomyopathy and discuss the emerging potential therapeutic interventions.
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JID: 8200291; 2008/11/17 [received]; 2008/11/17 [accepted]; 2008/11/28 [aheadofprint]; ppublish
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Principles of Ethical Publishing in the International Journal of Cardiology: 1. That the corresponding author has the approval of all other listed authors for the submission and publication of all versions of the manuscript. 2. That all people who have a right to be recognised as authors have been included on the list of authors and everyone listed as an author has made an independent material contribution to the manuscript.3. That the work submitted in the manuscript is original and has not been published elsewhere and is not presently under consideration of publication by any other journal. The oral or poster presentation of parts of the work and its publishing as a single page abstract does not count as prior publication for this purpose. 4. That the material in the manuscript has been acquired according to modern ethical standards and does not contain material copied from anyone else without their written permission.5. That all material which derives from prior work, including from the same authors, is properly attributed to the prior publication by proper citation.6. That the manuscript will be maintained on the servers of the Journal and held to be a valid publication by the Journal only as long as all statements in these principles remain true.7. That if any of the statements above ceases to be true the authors have a duty to notify the journal as soon as possible so that the manuscript can be withdrawn.
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