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The protective role of curcumin in cardiovascular diseases
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.
... 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 . ...
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.
... [11] Curcumin's antioxidant properties were found to reduce adriamycin-induced cardiotoxicity and may help prevent diabetic cardiovascular complications. [29] Curcumin also has an anti-thrombotic, anti-proliferative, and anti-inflammatory properties, and can lower serum cholesterol levels, all of which may protect against atherosclerosis. [29] In animal models, curcumin have been shown to reduce the development of cardiac hypertrophy and heart failure. ...
... [29] Curcumin also has an anti-thrombotic, anti-proliferative, and anti-inflammatory properties, and can lower serum cholesterol levels, all of which may protect against atherosclerosis. [29] In animal models, curcumin have been shown to reduce the development of cardiac hypertrophy and heart failure. [30] Curcumin post-cholecystectomy ...
Curcumin (diferuloylmethane) is a natural polyphenolic compound that targets multiple signaling molecules and helps in supporting health benefits as it aids in the management of oxidative and inflammatory conditions. However, curcumin by itself has poor absorption, rapid metabolism, and fast elimination, which makes its bioavailability very low. Therefore, curcumin is more active when combined with piperine to provide major health benefits. Several studies indicated that curcumin has powerful effects on post-surgical outcomes such as in ischemia-related surgeries, it improves postoperative pain and fatigue following laparoscopic cholecystectomy. Also, it is effective against traumatic brain injury outcomes through several molecular signaling pathways that include oxidative stress, inflammation, apoptosis, and autophagy. Finally, it has topical applications that improve granulation tissue formation, deposition of collagen, wound contraction, and remodeling of the tissue. In conclusion, curcumin has been shown to have strong antioxidant and anti-inflammatory effects that could result in improved post-surgical outcomes.
... Curcumin, a phenolic pigment responsible for the yellow color of the curry spice turmeric, inhibits lipid peroxidation through its free radical scavengers' role, increases intracellular level of glutathione, contributes to cholesterol homeostasis, and stabilizes cardiac cell membrane [104]. In animal models, the oral supplementation of curcumin proved to reduce doxorubicin toxicity in the heart, livers and kidneys [13]. ...
... Early detection of cardiac damage, proper early treatment and long-term follow-up are key strategies in the secondary prevention of the progressive cardiovascular alteration induced by antineoplastic drugs [113]. Indeed, an adequate screening combined with a prompt therapeutic management is a cost-effective strategy that leads to a reduction in the cumulative incidence of heart failure in childhood cancer survivors, and improves life quality and expectancy [104]. ...
Innovative therapeutic strategies in childhood cancer led to a significant reduction in cancer-related mortality. Cancer survivors are a growing fragile population, at risk of long-term side effects of cancer treatments, thus requiring customized clinical attention. Antineoplastic drugs have a wide toxicity profile that can limit their clinical usage and spoil patients’ life, even years after the end of treatment. The cardiovascular system is a well-known target of antineoplastic treatments, including anthracyclines, chest radiotherapy and new molecules, such as tyrosine kinase inhibitors. We investigated nutritional changes in children with cancer from the diagnosis to the end of treatment and dietary habits in cancer survivors. At diagnosis, children with cancer may present variable degrees of malnutrition, potentially affecting drug tolerability and prognosis. During cancer treatment, the usage of corticosteroids can lead to rapid weight gain, exposing children to overweight and obesity. Moreover, dietary habits and lifestyle often dramatically change in cancer survivors, who acquire sedentary behavior and weak adherence to dietary guidelines. Furthermore, we speculated on the role of nutrition in the primary prevention of cardiac damage, investigating the potential cardioprotective role of diet-derived compounds with antioxidative properties. Finally, we summarized practical advice to improve the dietary habits of cancer survivors and their families.
... 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]. ...
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]. ...
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.
... Additionally, VD9 was able to decrease CPK in patients who received VD9 along with standard care, which is a marker for cardiac injury that was found in hospitalized patients suggesting that patients with severe symptoms often have complications involving acute myocardial injury [90]. The mechanism of action of VD9 includes the protection of the cardiovascular system by baicalin, quercetin, luteolin, curcumin, and EGCG exerting prophylactic and therapeutic effects in cardiovascular disorders by providing beneficial effects in preventing cardiac dysfunction due to cardiac I/R injury as well as other cardiac pathologies thus playing the role of cardioprotection [91][92][93][94][95]. The animal studies investigated the effects of rutin and piperine suggested that rutin inhibits coronary heart disease in a porcine model [96] and piperine protected against cardiac fibrosis in mice [97] through extracellular signalregulated kinase (ERK) 1/2 and Akt signaling pathways. ...
... It also protects the heart against damage by preserving the integrity of the membrane. Studies have shown that the antioxidant effect of curcumin has a protective role on the heart and the 300 mg/kg dose applied has an antioxidant effect (Wongcharoen and Phrommintikul, 2009). ...
n present study, the effects of curcumin supplementation on oxidative stress and antioxidant defense system in heart tissue in adult rats were investigated. Sixteen rats (8-weeks-old) were selected and divided into two groups. The first group is the experimental group and these rats (n=8) were gavaged with curcumin, dissolved in corn oil, at a dose of 300 mg/kg per day for 28 days. The second group is the control group, rats in this group were given curcumin and equal amount of corn oil to eliminate the porter effect. Euthanasia was performed and total antioxidant capacity (TAS), total oxidant capacity (TOS), malondialdehyde (MDA) and glutathione (GSH) levels were analyzed from heart tissues. Curcumin supplementation resulted in significantly increased GSH levels(P0.05). The total antioxidant capacity (TAS) and total oxidant capacity (TOS) ratios were found to be statistically significant. In the other group supplemented with curcumin, MDA levels tended to decrease compared to the control group, and there was no statistically significant difference between the two groups. Curcumin supplementation protects the heart tissue against oxidative damage and strengthens the antioxidant defense system in adult rats.
... The prevention and management of cardiovascular diseases rely on dietary habits and lifestyle changes; studies on human and animal model for dietary supplements and food pattern in cardiovascular diseases showed the beneficial effects that are dependent on antioxidant and antiinflammatory properties with modulation in mitochondrial functions. Several studies have shown the potential role of the natural compounds from the medicinal plants, such as a yellow pigment phenolic compound, curcumin (diferuloylmethane) isolated from the herb C. longa (turmeric), in the management of many cardiovascular diseases (Aggarwal and Harikumar, 2009;Wongcharoen and Phrommintikul, 2009). Curcumin protects endothelium by generating HO-1 in bovine aortic endothelial cells (ECs) (Motterlini et al., 2000). ...
... Curcuma longa extracts, available as turmeric, contain curcumin, a bioactive polyphenolic yellow pigment having a wide range of pharmacologic activities, including antioxidant, and anti-inflammatory that are beneficial in maintaining cardiac health and is helpful in those cardiac ailments that involve blood vessel inflammation like atherosclerosis. Its mechanism of action mainly includes inhibition of the nuclear factor-kB (NF-kB) and subsequent reduction of inflammatory cytokines, alongside downregulation of inflammation proting pathways like Mitogen-Activated Protein Kinase (MAPK) (69,70). Beta vulgaris (Beetroot) extracts show high anti-inflammatory and antioxidant properties. ...
... Curcumin is the major curcuminoid extracted from Curcuma longa with well-known anti-inflammatory and insulin-sensitizing actions [119,120]. The chemical formula is C21H20O6, and the molecular mass is 368.38 units, and the compound has an intense yellow-orange colour and is insoluble in water. ...
Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even >50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.
... In many experimental and clinical studies, curcumin was also shown to be effective in combating cardiovascular diseases [82]. Some in vitro models demonstrated its anti-atherogenic effect. ...
... Adapted from Khatana et al. (2020Khatana et al. ( ). al., 2017Simental-Mendía et al., 2019). Curcumin decreases the aortic lipid lesions and inhibits development of atherosclerotic plaques (Wongcharoen and Phrommintikul 2009). Curcumin demonstrates antioxidant activity because the benzene rings in the structure of the Curcumin molecule eliminate reactive oxygen species (ROS) (Joe and Lokesh, 1994). ...
Atherosclerosis is the most frequent cause of death globally. Oxidized low-density lipoprotein (ox-LDL) has an essential role in the formation of atherosclerotic plaques and foamy macrophages. Ox-LDL increases the uptake of cholesterol by macrophages and is the major cause of blood flow disruption. Ox-LDL is produced during oxidative stress and treatment with antioxidants could inhibit the production and function of ox-LDL. Curcumin is a potent antioxidant and has a strong track record in the treatment of numerous diseases. Recent studies indicate that Curcumin exerts a lipid-lowering effect, and can modulate the formation of atherosclerotic plaque. The current review focuses upon the role of Curcumin in oxidation of LDL and foam cell formation in atherosclerotic lesions.
... Furthermore, curcumin has been investigated for its therapeutic effects in the treatment of cardiovascular disease [13]. A number of curcumin's cardiovascular protective effects can be attributed to its anti-inflammatory, antioxidant, antiproliferative, antilipidemic, and antithrombotic properties [14]. ...
Aims
Several meta-analyses exist supporting the beneficial effects of curcumin supplementation on lipid profile parameters; however, some studies' findings are inconsistent. Therefore, the current umbrella of meta-analysis of clinical trials was performed to evaluate the findings of multiple meta-analyses on the efficacy of curcumin on lipid profiles in adults.
Data synthesis
A comprehensive systematic search of PubMed/Medline, Scopus, Embase, Web of Science and Google Scholar were carried out up to May 2022 (in English only). Random-effects model was employed to conduct meta-analysis. The quality assessment of the selected meta-analyses was measured using a measurement tool to assess multiple systematic reviews (AMSTAR). From 101 articles returned in the literature search, 19 articles were met the qualified for inclusion in the umbrella meta-analysis. The results revealed that the curcumin supplementation was effective on reduction of total cholesterol (TC) (ES= -0.81 mg/dl; 95% CI: -1.39, -0.24, p= 0.006; I²= 68.8%, p<0.001), triglycerides (TG) (ES: -0.84 mg/dl, 95% CI: -1.42, -0.27, p= 0.004; I²=84.2 %, p<0.001), and low-density lipoprotein cholesterol (LDL-C) levels (ES: -0.49 mg/dl, 95%CI: -0.85, -0.13, p=0.007; I² = 51.9%, p= 0.004). Beyond that, Curcumin intake significantly increased high-density lipoprotein cholesterol (HDL-C) levels (ES: 1.34 mg/dl, 95% CI: 0.37, 2.31, p= 0.007; I²= 97.8%, p< 0.001).
Conclusion
Curcumin have ameliorating effects on TC, TG, LDL-c, and HDL-c levels. Overall, Curcumin could be recommended as an adjuvant anti-hyperlipidemic agent.
Registration number
PROSPERO, CRD42021289500.
... 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]. ...
Cardiovascular diseases (CVD) compromises a group of heart and blood vessels disorders with high impact on human health and wellbeing. Curcumin (CUR) have demonstrated beneficial effects on these group of diseases that represent a global burden with a prevalence that continues increasing progressively. Pre- and clinical studies have demonstrated the CUR effects in CVD through its anti-hypercholesterolemic and anti-atherosclerotic effects and its protective properties against cardiac ischemia and reperfusion. However, the CUR therapeutic limitation is its bioavailability. New CUR nanomedicine formulations are developed to solve this problem. The present article aims to discuss different studies and approaches looking into the promising role of nanotechnology-based drug delivery systems to deliver CUR and its derivatives in CVD treatment, with an emphasis on their formulation properties, experimental evidence, bioactivity, as well as challenges and opportunities in developing these systems.
... 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. ...
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]. ...
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). ...
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]. ...
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]. ...
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.
... 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]. ...
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.
... 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]. ...
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]. ...
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.
... 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). ...
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.
... 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. ...
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
... 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). ...
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. ...
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.
Golden plant (Turmeric) has succulent, religious views with numerous pharmaceutical values. Due to its pharmaceutical values, it has been a research center for long years. Many bioactive compounds like curcuminoid, identified in turmeric, are rich in therapeutics. In the last 10 years, research interests have concentrated on bioactive curcuminoid compounds (curcumin, demethoxy curcumin, and bisdemethoxy curcumin). Lipophilic polyphenol, curcumin ((1E,6E)-(1,7-bis-(4-hydroxy-3-methoxyphenyl)-hepta-1,6-diene-3,5-dione;4-hydroxynaphthalene-1,2-dione)), was found to have maximum amounts in Curcuma longa as curcuminoids. In recent studies, it has been found to play a very effective role against diseases such as cancer, biotic, inflammatory, and aging. The present study summarizes the pharmaceutical usages of turmeric with distinct reference to its polyphenolic compound curcumin.Keywords
Curcuma longa
NutraceuticalPhytochemistryCurcuminoidsPharmaceutical and disease
Ageing is the multifaceted reduction in physiological function of all living organisms. Several characteristics of ageing have been identified, including epigenetic dysregulation. Epigenetic dysregulation is receiving a lot of attention right now as a key component in ageing and age-related neurodegenerative diseases including Alzheimer’s, Parkinson’s and Huntington’s disease, where it may influence interactions between genetic and environmental risk factors. Life expectancy diversity is influenced by epigenetic factors such as DNA methylation and histone modifications. Histone variations, changes in chromatin accessibility, histone and heterochromatin loss, aberrant histone modifications and unregulated miRNA expression are all epigenetic alterations that contribute to ageing and ageing-related diseases. Oxidative stress, which is caused by the build-up of reactive oxygen species (ROS), can cause lipid, protein, nucleic acid and organelle damage, resulting in an unbalanced homeostasis and the induction of cellular senescence, which is one of the key processes driving ageing. The senescent-associated phenotype includes chronic, pro-inflammatory signals which cause risk in developing ageing-related disorders (ARDs). Researchers have discovered that anti-ageing bioactive components have promising anti-ageing properties in vitro, in animals and in humans. Recent research has revealed that bioactive compounds have distinct modes of action, enhanced effectiveness and reduced toxicity. Hence, this bioactive compound has the ability to suppress the ROS formation and can be investigated as therapeutics interventions in ARDs.KeywordsAgeingEpigenetic dysregulationOxidative stressAgeing-related disordersBioactive compounds
It is well known that there are no efficacious prevention and treatment strategies available for OSF. However, accumulating line of evidence suggests that turmeric and the yellow colored compound isolated from the spice, curcumin have significant potential in the management of this disease. Curcumin is known to inhibit the cytokine storm induced by areca nut and prevent fibrosis of the oral cavity. Various studies have shown that curcumin could inhibit the symptoms related to this disease, such as burning sensation, and improve mouth opening, and tongue protrusion through the modulation of various biochemical processes and molecules. Curcumin was found to modulate multiple hallmarks of several fibrosis disorders characterized by cytokine storm, oxidative stress, collagen synthesis, and expression of matrix metalloproteinases. As curcumin is a safe and affordable agent, it has remarkable potential in the prevention and treatment of OSF.KeywordsOral submucous fibrosis (OSF)TurmericCurcuminInflammationFibrosis
Chronic kidney disease (CKD) affects a huge portion of the world’s population and frequently leads to cardiovascular diseases (CVDs). It might be because of common risk factors between chronic kidney disease and cardiovascular diseases. Renal dysfunction caused by chronic kidney disease creates oxidative stress which in turn leads to cardiovascular diseases. Oxidative stress causes endothelial dysfunction and inflammation in heart which results in atherosclerosis. It ends in clogging of veins and arteries that causes cardiac stroke and myocardial infarction. To develop an innovative therapeutic approach and new drugs to treat these diseases, it is important to understand the pathophysiological mechanism behind the CKD and CVDs and their interrelationship. Natural phytoconstituents of plants such as polyphenolic compounds are well known for their medicinal value. Polyphenols are plant secondary metabolites with immense antioxidant properties, which can protect from free radical damage. Nowadays, polyphenols are generating a lot of buzz in the scientific community because of their potential health benefits especially in the case of heart and kidney diseases. This review provides a detailed account of the pathophysiological link between CKD and CVDs and the pharmacological potential of polyphenols and their nanoformulations in promoting cardiovascular and renal health.
Metabolic syndrome is characterized by multiple metabolic disorders. Several studies indicated that curcumin plus piperine could affect lipids profiles in various diseases. The present meta‐analysis aims to assess the effect of curcumin plus piperine on lipid profiles in patients with MetS and associated disorders using a systematic review and meta‐analysis of randomized controlled trials. Trials were searched by several electronic databases up to May 2022. The Comprehensive Meta‐Analysis (CMA) version3 software carried out this systematic review and meta‐analysis. Random‐effects model and the inverse variance method were used to conduct the meta‐analysis. We evaluated the publication bias and heterogeneity of all eligible studies. In addition, subgroup analyses and sensitivity assessments were performed to assess potential sources of heterogeneity. The combined results by the random‐effects model demonstrated that curcumin plus piperine significantly decreased total cholesterol and LDL‐C in patients suffering from metabolic syndrome. In comparison, the results of the overall effect size did not show any significant change in triglyceride concentrations. Our results were robust in sensitivity analysis and were not dependent on the dose of curcumin, the dose of piperine, and the duration of treatment. Our results showed that co‐administration of piperine and curcumin supplementation improves the lipid profile in metabolic syndrome. However, further long‐term RCTs are required to ascertain their clinical benefit.
The concept that aging is a disease and the rise in the elderly population all over the world have increased the need for drugs to intervene the aging and age-induced impairments. Bioactives derived from plants have shown the possibility to be utilized as potential natural remedies against many age-related complications, such as cancer, cardiovascular diseases, neurodisorders, and diabetes to enhance life as well as healthspans. However, drug discovery and development based on these active molecules face serious challenges due to the lack of complete scientific information, their possible interactions with other drugs/molecules, low bioavailability, improper stability, undermined safety/toxicity, and reduced number of new drug approvals coupled with extortionate rising investment. The present chapter deals with the procedures and challenges associated with plant-based drugs against aging.
Cardiac arrhythmias, characterized by an irregular heartbeat, are associated with high mortality and morbidity. Because of the narrow therapeutic window of antiarrhythmic drugs (AADs), the management of arrhythmia is still challenging. Therefore, searching for new safe, and effective therapeutic options is unavoidable. In this study, the antiarrhythmic effects of medicinal plants and their active constituents were systematically reviewed to introduce some possible candidates for mechanism-based targeting of cardiac arrhythmias. PubMed, Embase, and Cochrane library were searched from inception to June 2021 to find the plant extracts, phytochemicals, and multi-component herbal preparations with antiarrhythmic activities. From 7337 identified results, 57 original studies consisting of 49 preclinical and eight clinical studies were finally included. Three plant extracts, eight multi-component herbal preparations, and 26 phytochemicals were found to have antiarrhythmic effects mostly mediated by affecting K+ channels, followed by modulating Ca2+ channels, upstream target pathways, Nav channels, gap junction channels, and autonomic receptors. The most investigated medicinal plants were Rhodiola crenulata and Vitis vinifera. Resveratrol, Oxymatrine, and Curcumin were the most studied phytochemicals found to have multiple mechanisms of antiarrhythmic action. This review emphasized the importance of research on the cardioprotective effect of medicinal plants and their bioactive compounds to guide the future development of new AADs. The most prevalent limitation of the studies was their unqualified methodology. Thus, future well-designed experimental and clinical studies are necessary to provide more reliable evidence.
Bu araştırmanın amacı Mardin yöresinde en çok yetiştirilen Adana 99, Ceyhan 99, Segittario ve Dinç ekmeklik buğday çeşitlerinin fiziksel, teknolojik ve fiziko-kimyasal kalite özelliklerini incelemek-tir. Buğday örnekleri Tarım İşletmeleri Genel Müdürlüğü’nden temin edilmiştir. Analizlerden önce tüm buğday çeşitleri içindeki yabancı maddeler, taş, toprak, kırık ve bozuk taneler ayıklanmak suretiyle te-mizlenmiştir. Sonuçlar, ekmeklik buğday çeşitleri arasında, bin tane ağırlığı (g/g k.m), hektolitre ağırlığı (kg/hl), tane boyutu (uzunluk (mm), genişlik (mm), kalınlık (mm), eşdeğer çap (mm)), küresellik, Hun-ter renk (L *, a * ve b *) değerleri gibi fiziksel özellikler açısından önemli farklılıklar olduğu ve bu farkların istatistiksel (P≤0.05) olarak anlamlı olduğu bulunmuştur. Ayrıca kuru ağırlık (g/100 tane), yaş ağırlık (g/100 tane), su alma kapasitesi (g/tane), su alma indeksi (%), kuru hacim (ml), ıslak hacim (ml), şişme kapasitesi (ml/tane) ve şişme indeksi (%) gibi teknolojik kalite özellikleri bakımından bu çeşitler arasında istatistiksel olarak anlamlı farklar bulunmuştur (P≤0.05). Fiziko-kimyasal kalite özellikleri (nem (%), yaş glüten (%), gluten indeksi (%), Zeleny sedimantasyon (ml) ve gecikmeli sedimantasyon (ml)) bakımından da buğday çeşitleri arasında önemli farkla bulunmuş ve bu farkların istatistiksel (P≤0.05) olarak anlamlı olduğu tespit edilmiştir. Ekmeklik buğday çeşitleri arasındaki tespit edilen ka-lite karakteristiklerindeki bu farklılıklar un sanayisinde ve ekmek yapımındaki işlemler açısından önemli olabilir. Bu sektörlerdeki işletmecilere bir kılavuz olabilir.
Overproduction of reactive oxygen species (ROS) regulating many physiological functions is implicated in the pathogenesis of various inflammatory diseases. The aging processes are linked with inflammation and oxidative stress in various systems of the body. Supplementation of antioxidants can help fight aging and pathological environments associated with it. Extracts derived from plants with antioxidant activity and food grade in nature can be promising ingredients for supplements. Many potent bioactive phytochemicals like quercetin, resveratrol, naringenin, catechins, and curcumin can modulate cellular damages arising due to free radicals. The lower stability, solubility, and bioavailability limit the therapeutic effects of these bioactive compounds. Recent application of nanotechnology for the delivery of plant‐derived antioxidants extends enhanced bioavailability and better efficacy in therapeutic applications. Antioxidant nanotherapies aid with superior ROS‐scavenging activities and steady anti‐oxidative effect through better pharmacokinetics, solubility, stability, prolonged half‐life, improved tissue targeting, and diminished side effects. This chapter aims to summarize the recent developments in nano‐delivery of phytoantioxidants for inflammatory disorders associated with oxidative stress.
Human adipose tissue is involved in fat storage and also plays a role in the immune response. Curcumin (CUR), a natural polyphenol is suggested to supress adipocyte differentiation in the early stage by inhibiting secretion of some regulators and the inflammatory cytokines and by activating the secretion of antiinflammatory cytokines. Our aim in this research was to examine the molecular pathways of the inhibitory effects of different doses of curcumin (0.5 µM, 5 µM, 10 µM, 20 µM, 50 µM) on the preadipocyte-adipocyte differentiation and the anti-inflammatory effect of curcumin for preventing adipocyte related oxidative and inflammatory status. Differentiation of cells was performed using Oil red O, mRNA expression levels of adiponectin, CCAAT/enhancer binding proteinα (C/EBPα), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), leptin, Nuclear Factor kappa B1 (NFκB1), peroxisome proliferator-activated receptor gamma (PPARγ), sirtuin-1 (SIRT-1), tumor necrosis factor-α (TNF-α), transient receptor potential vanilloid receptor1 (TRPV1), uncoupling protein2 (UCP2), vasculer endothelial growth factor-A (VEGF-A), vascular endothelial growth factor receptor I (VEGF-RI), VEGF-RII were evaluated in preadipocytes and adipocytes. Curcumin suppressed the differentiation of preadipocyte to adipocytes, decreased the release of proinflammatory cytokines, but it did this by regulating C/EBPα and PPARγ gene expressions outside the NF-κB pathway. Curcumin effectively suppressed adipogenic transcription factors and also adipocyte differentiation at all doses between 0.5–50 µM, but showed its anti-inflammatory effect especially in the application of curcumin of 50 µM.
Endothelial dysfunction is an early hallmark of cardiovascular diseases (CVDs). Monotherapies are limited due to the complex, multifactorial pathways. The multi-component and multi-targeted approach of natural products have the potential to manage CVDs.
This review aims to provide a comprehensive insight into the synergistic mechanism of natural product combinations in protecting the endothelium against various cardiovascular risk factors.
Databases (PubMed, MEDLINE and EMBASE) and Google Scholar were searched, and studies in English published between January 2000 and February 2022 were collated. Clinical and pre-clinical studies of natural product combinations with or without pharmaceutical medicines, compared with monotherapy and/or proposing the underlying mechanism in protecting endothelial function, were included.
Four clinical studies demonstrated that natural product combinations or natural product-pharmaceutical combinations improved endothelial function. This was associated with multi-targeted effects or improved absorption of the active substances in the body. Seventeen preclinical studies showed that natural product combinations produced synergistic (demonstrated by combination index or Bliss independence model) or enhanced effects in protecting the endothelium against hyperlipidemia, hypertension, diabetes mellitus, platelet activation, oxidative stress and hyperhomocysteinemia. The molecular targets included reactive oxygen species, Nrf2-HO-1, p38MAPK, P13K/Akt and NF-κB.
Thus, the current available evidence of natural product combinations in targeting endothelial dysfunction is predominantly from preclinical studies. These have demonstrated synergistic/enhanced pharmacological activities and proposed associated mechanisms. However, evidence from larger, well-designed clinical trials remains weak. More cohesion is required between preclinical and clinical data to support natural product combinations in preventing or slowing the progression of CVDs.
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.
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.
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.
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.
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.
High altitude exposure leads to compromised physical performance with considerable weight loss. The major stressor at high altitude is hypobaric hypoxia which leads to disturbance in redox homeostasis. Oxidative stress is a well-known trigger for many high altitude illnesses and regulates several key signaling pathways under stressful conditions. Altered redox homeostasis is considered the prime culprit of high altitude linked skeletal muscle atrophy. Hypobaric hypoxia disturbs redox homeostasis through increased RONS production and compromised antioxidant system. Increased RONS disturbs the cellular homeostasis via multiple ways such as inflammation generation, altered protein anabolic pathways, redox remodeling of RyR1 that contributed to dysregulated calcium homeostasis, enhanced protein degradation pathways via activation calcium-regulated protein, calpain, and apoptosis. Ultimately, all the cellular signaling pathways aggregately result in skeletal muscle atrophy. Dietary supplementation of phytochemicals could become a safe and effective intervention to ameliorate skeletal muscle atrophy and enhance the physical performance of the personnel who are staying at high altitude regions. The present evidence-based review explores few dietary supplementations which regulate several signaling mechanisms and ameliorate hypobaric hypoxia induced muscle atrophy and enhances physical performance. However, a clinical research trial is required to establish proof-of-concept.
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.
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.
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.
“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.
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.
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.
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.
Curcumin (diferuloylmethane), a yellow substance from the root of the plant Curcuma longa Linn., has been demonstrated to inhibit carcinogenesis of murine skin, stomach, intestine and liver. However, the toxicology, pharmacokinetics and biologically effective dose of curcumin in humans have not been reported. This prospective phase-I study evaluated these issues of curcumin in patients with one of the following five high-risk conditions: 1) recently resected urinary bladder cancer; 2) arsenic Bowen's disease of the skin; 3) uterine cervical intraepithelial neoplasm (CIN); 4) oral leucoplakia; and 5) intestinal metaplasia of the stomach. Curcumin was taken orally for 3 months. Biopsy of the lesion sites was done immediately before and 3 months after starting curcumin treament. The starting dose was 500 mg/day. If no toxicity > or = grade II was noted in at least 3 successive patients, the dose was then escalated to another level in the order of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day. The concentration of curcumin in serum and urine was determined by high pressure liquid chromatography (HPLC). A total of 25 patients were enrolled in this study. There was no treatment-related toxicity up to 8,000 mg/day. Beyond 8,000 mg/day, the bulky volume of the drug was unacceptable to the patients. The serum concentration of curcumin usually peaked at 1 to 2 hours after oral intake of crucumin and gradually declined within 12 hours. The average peak serum concentrations after taking 4,000 mg, 6,000 mg and 8,000 mg of curcumin were 0.51 +/- 0.11 microM, 0.63 +/- 0.06 microM and 1.77 +/- 1.87 microM, respectively. Urinary excretion of curcumin was undetectable. One of 4 patients with CIN and 1 of 7 patients with oral leucoplakia proceeded to develop frank malignancies in spite of curcumin treatment. In contrast, histologic improvement of precancerous lesions was seen in 1 out of 2 patients with recently resected bladder cancer, 2 out of 7 patients of oral leucoplakia, 1 out of 6 patients of intestinal metaplasia of the stomach, I out of 4 patients with CIN and 2 out of 6 patients with Bowen's disease. In conclusion, this study demonstrated that curcumin is not toxic to humans up to 8,000 mg/day when taken by mouth for 3 months. Our results also suggest a biologic effect of curcumin in the chemoprevention of cancer.
Ca2+ transport by sarcoplasmic reticulum (SR) ATPase occurs with an optimal coupling ratio of 2 Ca2+ per ATP in pre-steady state. However, slippage of the pump and lower coupling ratios are observed in steady state. Slippage
depends on the presence of high Ca2+ in the lumen of SR vesicles and high nucleotide in the medium. Thereby, Ca2+and/or nucleotide-bound phosphoenzyme intermediates accumulate and undergo uncoupled cleavage, before vectorial translocation
of bound Ca2+ in the forward direction of the cycle or before productive reversal to ATP synthesis. Transport efficiency and coupling ratios
are improved by reduction of nucleotide concentration in the presence of ATP regenerating systems and/or complexation of luminal
Ca2+ with phosphate or oxalate. Curcumin (1–5 μm) lowers the concentration of phosphate or oxalate required to reduce slippage of the Ca2+ pump. Thereby, under appropriate conditions, curcumin favors kinetic flow, completion of productive cycles, and improvement
of coupling ratios. The findings obtained with isolated SR vesicles suggest that slippage is an important phenomenon under
prevailing conditions of muscle fibersin situ. Ca2+ transport and its slippage can be improved by curcumin in cardiac as well as in skeletal SR, raising the possibility of pharmacological
interventions to correct defective Ca2+ homeostasis. Higher curcumin concentrations (5–30 μm), however, inhibit overall ATPase activity and Ca2+ transport by interfering with phosphoenzyme formation with ATP or Pi.
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.
Curcumin (diferuloylmethane) is a polyphenol derived from the plant Curcuma longa, commonly called turmeric. Extensive research over the last 50 years has indicated this polyphenol can both prevent and treat cancer. The anticancer potential of curcumin stems from its ability to suppress proliferation of a wide variety of tumor cells, down-regulate transcription factors NF-kappa B, AP-1 and Egr-1; down-regulate the expression of COX2, LOX, NOS, MMP-9, uPA, TNF, chemokines, cell surface adhesion molecules and cyclin D1; down-regulate growth factor receptors (such as EGFR and HER2); and inhibit the activity of c-Jun N-terminal kinase, protein tyrosine kinases and protein serine/threonine kinases. In several systems, curcumin has been described as a potent antioxidant and anti-inflammatory agent. Evidence has also been presented to suggest that curcumin can suppress tumor initiation, promotion and metastasis. Pharmacologically, curcumin has been found to be safe. Human clinical trials indicated no dose-limiting toxicity when administered at doses up to 10 g/day. All of these studies suggest that curcumin has enormous potential in the prevention and therapy of cancer. The current review describes in detail the data supporting these studies.
A variety of stresses on the heart initiate a number of subcellular signaling pathways, which finally reach the nuclei of cardiac myocytes and cause myocyte hypertrophy with heart failure. However, common nuclear pathways that lead to this state are unknown. A zinc finger protein, GATA-4, is one of the transcription factors that mediate changes in gene expression during myocardial-cell hypertrophy. p300 not only acts as a transcriptional coactivator of GATA-4, but also possesses an intrinsic histone acetyltransferase activity. In primary cardiac myocytes derived from neonatal rats, we show that stimulation with phenylephrine increased an acetylated form of GATA-4 and its DNA-binding activity, as well as expression of p300. A dominant-negative mutant of p300 suppressed phenylephrine-induced nuclear acetylation, activation of GATA-4-dependent endothelin-1 promoters, and hypertrophic responses, such as increase in cell size and sarcomere organization. In sharp contrast to the activation of cardiac MEK-1, which phosphorylates GATA-4 and causes compensated hypertrophy in vivo, p300-mediated acetylation of mouse cardiac nuclear proteins, including GATA-4, results in marked eccentric dilatation and systolic dysfunction. These findings suggest that p300-mediated nuclear acetylation plays a critical role in the development of myocyte hypertrophy and represents a pathway that leads to decompensated heart failure.
Diabetic cardiomyopathy is responsible for substantial morbidity and mortality in the diabetic population. Increased oxidative stress has been associated with the pathogenesis of chronic diabetic complications including cardiomyopathy. Multiple biochemical mechanisms have been proposed to increase oxidative stress in diabetes. The present study was aimed at elucidating the role of a potent oxidative and cellular stress-responsive system, the heme oxygenase (HO) system, in the heart in diabetes. Streptozotocin-induced diabetic rats were treated with a potent inhibitor of HO system, tin protoporphyrin IX (SnPPIX, 50 micromol/kg/d), and were compared with untreated diabetic and non-diabetic animals. All treatments began at the onset of diabetes, 48 h after injection of streptozotocin along with the confirmation of hyperglycemia. Animals were euthanized after 1 week and 1 month of treatment, and heart tissues were harvested. Frozen tissues were subjected to HO-1 and HO-2 mRNA expression by real-time RT-PCR and HO activity determination. Paraffin-embedded tissue sections were used for immunohistochemical analysis of HO-1 and HO-2. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) stain, a sensitive and specific marker of DNA damage, was preformed to assess damage induced by oxidative stress. In addition, tissue sections were subjected to histochemical analysis for iron. We further examined non-diabetic animals treated with a direct HO agonist, hemin (50 mg/kg/d). A possible relationship between the HO and the nitric oxide (NO) pathways was also considered by studying the mRNA levels of endothelial nitric oxide synthase (NOS) and inducible NOS, and by measuring the amount of NOS products. Our results demonstrate no significant alterations of the HO system following 1 week of diabetes. However, 1 month of diabetes caused increased oxidative stress as demonstrated by higher levels of 8-OHdG-positive cardiomyocytes (80% positive as compared to 11.25% in controls), in association with increased HO isozyme mRNA (2.7-fold increase as compared to controls) and protein expression, and augmented HO activity (759.3 as compared to 312.3 pmol BR/h/mg protein in controls). Diabetic rats further demonstrated increased number of cardiomyocytes with stainable iron. SnPPIX treatment resulted in reduced number of 8-OHdG-positive cardiomyocytes (19.5% as compared to 80% in diabetics) in parallel with reduced HO activity (569.7 as compared to 759.3 pmol BR/h/mg protein in diabetics). Non-diabetic rats treated with HO-agonist hemin exhibited abnormalities similar to diabetic rats. Our results provide the first direct demonstration that diabetes-induced oxidative stress in the heart is, in part, due to upregulated HO expression and activity. These results provide evidence of pro-oxidant activity of HO in the heart in diabetes, which could be mediated by increased redox-active iron.
Curcumin, a natural compound used as a food additive, has been shown to have anti-inflammatory and antioxidant properties in cell culture and animal studies. A pure curcumin preparation was administered in an open label study to five patients with ulcerative proctitis and five with Crohn's disease. All proctitis patients improved, with reductions in concomitant medications in four, and four of five Crohn's disease patients had lowered CDAI scores and sedimentation rates. This encouraging pilot study suggests the need for double-blind placebo-controlled follow-up studies.
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.
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.
Hypertrophy of mammalian cardiac muscle is mediated, in part, by angiotensin II through an angiotensin II type1a receptor (AT1aR)-dependent mechanism. To understand how the level of AT1aRs is altered in this pathological state, we studied the expression of an injected AT1aR promoter-luciferase reporter gene in adult rat hearts subjected to an acute pressure overload by aortic coarctation. This
model was validated by demonstrating that coarctation increased expression of the α-skeletal actin promoter 1.7-fold whereas
the α-myosin heavy chain promoter was unaffected. Pressure overload increased expression from the AT1aR promoter by 1.6-fold compared with controls. Mutations introduced into consensus binding sites for AP-1 or GATA transcription
factors abolished the pressure overload response but had no effect on AT1aR promoter activity in control animals. In extracts from coarcted hearts, but not from control hearts, a Fos-JunB-JunD complex
and GATA-4 were detected in association with the AP-1 and GATA sites, respectively. These results establish that the AT1aR promoter is active in cardiac muscle and its expression is induced by pressure overload, and suggest that this response
is mediated, in part, by a functional interaction between AP-1 and GATA-4 transcription factors.
JID: 8200291; 2008/11/17 [received]; 2008/11/17 [accepted]; 2008/11/28 [aheadofprint]; ppublish
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.
The effect of curcumin administration in reducing the serum levels of cholesterol and lipid peroxides was studied in ten healthy human volunteers, receiving 500 mg of curcumin per day for 7 days. A significant decrease in the level of serum lipid peroxides (33%), increase in HDL Cholesterol (29%), and a decrease in total serum cholesterol (11.63%) were noted. As curcumin reduced serum lipid peroxides and serum cholesterol, the study of curcumin as a chemopreventive substance against arterial diseases is suggested.
The effects of curcumin, an anti-inflammatory agent from Curcuma longa, on the proliferation of blood mononuclear cells and vascular smooth muscle cells were studied. Proliferative responses were determined from the uptake of tritiated thymidine. In human peripheral blood mononuclear cells, curcumin dose dependently inhibited the responses to phytohemagglutinin and mixed lymphocyte reaction at the dose ranges of 10(-6) to 3 x 10(-5) and 3 x 10(-6) to 3 x 10(-5) M, respectively. Curcumin (10(-6) to 10(-4) M) dose dependently inhibited the proliferation of rabbit vascular smooth muscle cells stimulated by fetal calf serum. Curcumin had a greater inhibitory effect on platelet-derived growth factor-stimulated proliferation than on serum-stimulated proliferation. Cinnamic acid, coumaric acid and ferulic acid were much less effective than curcumin as inhibitors of serum-induced smooth muscle cell proliferation, suggesting that the cinnamic acid and ferulic acid moieties alone are not sufficient for activity, and that the characteristics of the diferuloylmethane molecule itself are necessary for activity. Curcumin may be useful as a new template for the development of better remedies for the prevention of the pathological changes of atherosclerosis and restenosis.
Doxorubicin (Adriamycin) and the related anthracycline antibiotic daunorubicin play a central part in cancer therapy because of their efficacy in the treatment of hematologic cancers (both acute leukemias and lymphomas), as well as carcinomas of the breast, lung, and thyroid and bone and soft-tissue sarcomas.1 Furthermore, these drugs are widely used in both adults and children in treatment regimens aimed at the cure of neoplasms as well as at palliation. The discovery more than 20 years ago that therapy with anthracyclines could produce irreversible and possibly life-threatening cardiac injury has led to limitations on the use of these drugs in . . .
The changes in the activities of certain lysosomal hydrolases, viz., beta-glucuronidase, beta-N-acetylglucosaminidase, beta-galactosidase, beta-glucosidase, alpha-glucosidase, alpha-galactosidase, alpha-mannosidase, cathepsin B, cathepsin D, and collagenolytic cathepsin, in serum and heart of rats subject to myocardial infarction with isoproterenol, were studied during the periods of peak infarction and recovery. The activities of all the enzymes assayed exhibited a significant increase both in serum and in heart at peak infarction stage and these levels returned to normal during the stage of recovery and repair. The infiltration of inflammatory cells at the infarct regions and the altered lysosomal fragility are probably responsible for the increased activity of the enzymes studied. This may also bring about the catabolism of connective tissue constituents as reported in literature.
Myocardial extracellular matrix is organized into a complex arrangement of intercellular and pericellular fibres and fibrils that serves as a supporting framework for contracting cells. Recent evidence suggests that changes in ventricular shape and function occurring after ischaemic injury may be related to alterations of this matrix. In this report we describe the rapid and extensive loss of collagen in myocardial infarction produced by ligating the left anterior descending coronary artery of the rat for 1-3 h. The total collagen content in the myocardial infarct zones after 1, 2 and 3 h of ligation was 75 +/- 8%, 65 +/- 7% and 50 +/- 10% respectively (mean +/- S.D.) of that of either the non-infarcted tissue controls or of the same regions in sex- and age-matched normal left ventricles. A marked decrease also occurred in the residual collagens which were not extractable with 6 M-guanidine hydrochloride, suggesting that rapid degradation of insoluble collagen fibres may also occur. The decreased collagen content in the 3 h myocardial infarct coincided with the appearance of several enzyme activities. Collagenase, other neutral proteinase and presumed lysosomal serine proteinase activities were increased by 3, 3 and 2 times the control values respectively. These results suggest that the increased activities of collagenase and other neutral proteinases may be responsible for the rapid degradation of extracellular matrix collagen in myocardial infarct.
The antineoplastic drug doxorubicin is capable of generating a variety of free radical species in subcellular systems and this capacity has been considered critical for its antitumor action. However, for most tumor cell lines this mechanism of cytotoxicity does not appear to play a major role. Free radical-independent cytotoxicity mechanisms, taking place in the nuclear compartment of the cell, may more likely be involved in the antitumor effect of doxorubicin.
A new model for evaluating nonsteroidal anti-inflammatory drugs (NSAIDs) is described. In this model of postoperative inflammation, the anti-inflammatory activity of curcumin (diferuloyl methane) was investigated in comparison with phenylbutazone and placebo. Phenylbutazone and curcumin produced a better anti-inflammatory response than placebo.
The changes in the concentration of total hexose, fucose and sialic acid were studied in the heart at peak period of infarction (1 1/2 - 2 1/2 days after first injection of isoproterenol) and stages of recovery in isoproterenol-induced myocardial infarction in rats. Carbohydrate components increased at the peak period of infarction and remained elevated during the stages of recovery. Serum protein-bound hexose, fucose and sialic acid also increased at the peak period and slowly decreased during stages of recovery. The activities of β-N-acetyl glucosaminidase, β-fucosidase and β-glucosidase increased in the heart at the peak period, while in the serum only β-fucosidase increased.
L-Arginine-derived nitric oxide (NO) and its derivatives, such as peroxynitrite and nitrogen dioxide, play a role in inflammation and also possibly in the multistage process of carcinogenesis. We investigated the effect of various non-steroidal anti-inflammatory agents and related compounds on the induction of NO synthase (NOS) in RAW 264.7 macrophages activated with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Low concentrations of curcumin, a potent anti-tumour agent having anti-inflammatory and anti-oxidant properties, inhibited NO production, as measured by the amount of nitrite released into the culture medium in 24 h (IC50 = 6 microM). NOS activity in soluble extracts of macrophages activated for 6-24 h in the presence of curcumin (10 microM) was significantly lower than that of macrophages activated without curcumin. Northern-blot and immunoblotting analyses demonstrated that significantly reduced levels of the mRNA and 130-kDa protein of inducible NOS were expressed in macrophages activated with curcumin, compared to those without curcumin. Inhibition of NOS induction was maximal when curcumin was added together with LPS and IFN-gamma and decreased progressively as the interval between curcumin and LPS/IFN-gamma was increased to 18 h.
Nitric oxide (NO), which accounts for the biological activity of endothelium-derived relaxing factor, is now thought to play a variety of roles in the nervous system and in immunologic reactions. NO is synthesized from L-arginine by nitric oxide synthase (NOS). There are three isoforms of NOS; type I (neuronal), type II (inducible), and type III (endothelial). The fundamental structure of the three isoforms, which contain calmodulin-, FMN-, FAD-, and NADPH-binding domains, is the same. Calmodulin is already bound to inducible NOS without requiring Ca2+, while the others are Ca2+/calmodulin-dependent. Endothelial NOS is bound to membranes by N-myristoylation, while the other isoforms are soluble. The human endothelial NOS gene has been cloned. It has several highly repetitive regions which could provide potential sites for DNA polymorphism. It might be of interest to examine the relationship between such polymorphism and cardiovascular disorders.
A single intravenous injection of doxorubicin (DOX, 30 mg/kg body weight) caused a significant rise in the content of lipid peroxidation products in hearts of mice. The concentration of conjugated dienes (CD) and malondialdehyde (MDA) found 24 h after injection of DOX increased about 1.8- and 2.4-fold and reached values of 11.31 +/- 2.24 A233/g and 3.72 +/- 0.40 mumol/g, respectively. The same dose of 4'-epi-doxorubicin (EPI), a less cardiotoxic epimer of DOX, increased only the heart level of MDA. Both antracyclines were not able to induce increased formation of CD in murine liver and lungs. Ambroxol, an expectorant drug which possesses the ability to scavenge hydroxyl radicals, injected intravenously (70 mg/kg) 30 min prior to DOX, completely abolished the rise in heart content of CD and MDA. The heart levels of CD and MDA in animals treated with ambroxol and DOX were 3 and 2.7 times lower than those observed in mice treated with water and DOX, respectively. Ambroxol had no effect on DOX- and EPI-induced formation of MDA in the lungs. Our results indicate that (1) DOX is a more powerful inductor lipid peroxidation in the heart than EPI; and (2) ambroxol may be useful in preventing lipid peroxidation in the heart caused by DOX.
The effect of curcumin on lysosomal hydrolases in serum and heart was studied by determining the activities of beta-glucuronidase, beta-N-acetylglucosaminidase, cathepsin B, cathepsin D, and acid phosphatase. Rats treated with isoproterenol (30 mg/100 g body weight) showed a significant increase in serum lysosomal hydrolase activities, which were found to decrease after curcumin treatment. Isoproterenol administration to rats resulted in decreased stability of the membranes, which was reflected by the lowered activity of cathepsin D in mitochondrial, lysosomal, and microsomal fractions. Curcumin treatment returned the activity levels almost to normal, showing that curcumin restored the normal function of the membrane. Histopathological studies of the infarcted rat heart also showed a decreased degree of necrosis after curcumin treatment.
The effect of curcumin on the biochemical changes induced by isoproterenol (ISO) administration in rats was examined. ISO (300 mg Kg-1 administered subcutaneously twice at an interval of 24 h) caused a decrease in body weight and an increase in heart weight, water content as well as in the levels of serum marker enzymes viz creatine kinase (CK), lactate dehydrogenase (LDH) and LDH1 isozyme. It also produced electrocardiographic changes such as increased heart rate, reduced R amplitude and ST elevation. Curcumin at a concentration of 200 mg.Kg-1, when administered orally, showed a decrease in serum enzyme levels and the electrocardiographic changes got restored towards normalcy. Myocardial infarction was accompanied by the disintegration of membrane polyunsaturated fatty acids expressed by increase of thiobarbituric acid reactive substance (TBARS), a measure of lipid peroxides and by the impairment of natural scavenging, characterized by the decrease in the levels of superoxide dismutase, catalase, glutathione peroxidase, ceruloplasmin, alpha tocopherol, reduced glutathione (GSH) and ascorbic acid. The oral pretreatment with curcumin two days before and during ISO administration decreased the effect of lipid peroxidation. It was shown to have a membrane stabilizing action by inhibiting the release of beta-glucuronidase from nuclei, mitochondria, lysosome and microsome. Curcumin pre- and co-treatment decreased the severity of pathological changes and thus, could have a protective effect against the damage caused by myocardial infarction (MI).
External load plays a critical role in determining muscle mass and its phenotype in cardiac myocytes. Cardiac myocytes have the ability to sense mechanical stretch and convert it into intracellular growth signals, which lead to hypertrophy. Mechanical stretch of cardiac myocytes in vitro causes activation of multiple second messenger systems that are very similar to growth factor-induced cell signaling systems. Stretch of neonatal rat cardiac myocytes stimulates a rapid secretion of angiotensin II which, together with other growth factors, mediates stretch-induced hypertrophic responses in vitro. In this review, various cell signaling mechanisms initiated by mechanical stress on cardiac myocytes are summarized with emphasis on potential mechanosensing mechanisms and the relationship between mechanical loading and the cardiac renin-angiotensin system.