Article

The use of an anti-inflammatory supplement in patients with chronic kidney disease

Authors:
  • Waco Family Medicine Residency Program
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Abstract

Abstract Chronic kidney disease (CKD) is characterized by a continuous reduction in kidney function, increased inflammation, and reduced antioxidant capacity. The objective of this study was to assess the effects of a herbal supplement on systemic inflammation and antioxidant status in non-dialysis CKD patients. Sixteen patients with CKD (56.0±16.0 yrs, 171.4±11.9 cm, 99.3±20.2 kg) were randomly chosen to receive a herbal supplement composed of Curcuma longa and Boswellia serrata, or placebo. Plasma levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), glutathione peroxidase (GPx), and serum C-reactive protein (CRP) were measured at baseline and 8 weeks. Baseline data demonstrated elevated inflammation and low antioxidant levels. A significant time effect (p=0.03) and time x compliance interaction effect (p=0.04) were observed for IL-6. No significant differences were observed for any other variables. This study demonstrates that mild and moderate CKD is associated with chronic inflammation and low antioxidant activity. Systemic inflammation and impaired antioxidant status may be greater in CKD populations with multiple comorbidities. Curcumin and Boswellia serrata are safe and tolerable and helped to improve the levels of an inflammatory cytokine.

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... In total, ten clinical trials (which involved 523 patients) were incorporated into the metaanalysis (L. Alvarenga et al., 2020;Kabodan et al., 2018;Khajehdehi et al., 2011;Moreillon et al., 2013;Pakfetrat et al., 2014;Rodrigues et al., 2021;Samadian et al., 2017;Shafabakhsh et al., 2020;Vafadar-Afshar et al., 2021;Vafadar Afshar et al., 2020). From the selected trials, three studies investigated IL-6 (Kabodan et al., 2018;Moreillon et al., 2013;Vafadar-Afshar et al., 2021), eight studies involved hs-CRP (L. ...
... Alvarenga et al., 2020;Kabodan et al., 2018;Khajehdehi et al., 2011;Moreillon et al., 2013;Pakfetrat et al., 2014;Rodrigues et al., 2021;Samadian et al., 2017;Shafabakhsh et al., 2020;Vafadar-Afshar et al., 2021;Vafadar Afshar et al., 2020). From the selected trials, three studies investigated IL-6 (Kabodan et al., 2018;Moreillon et al., 2013;Vafadar-Afshar et al., 2021), eight studies involved hs-CRP (L. Alvarenga et al., 2020;Kabodan et al., 2018;Moreillon et al., 2013;Pakfetrat et al., 2014;Rodrigues et al., 2021;Samadian et al., 2017;Shafabakhsh et al., 2020;Vafadar Afshar et al., 2020) and four studies analyzed TNF-α (Khajehdehi et al., 2011;Moreillon et al., 2013;Pakfetrat et al., 2014; Vafadar-Afshar et al., 2021) ( Figure 1). ...
... From the selected trials, three studies investigated IL-6 (Kabodan et al., 2018;Moreillon et al., 2013;Vafadar-Afshar et al., 2021), eight studies involved hs-CRP (L. Alvarenga et al., 2020;Kabodan et al., 2018;Moreillon et al., 2013;Pakfetrat et al., 2014;Rodrigues et al., 2021;Samadian et al., 2017;Shafabakhsh et al., 2020;Vafadar Afshar et al., 2020) and four studies analyzed TNF-α (Khajehdehi et al., 2011;Moreillon et al., 2013;Pakfetrat et al., 2014; Vafadar-Afshar et al., 2021) ( Figure 1). ...
Article
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Objective: This study was designed to determine the association curcumin has on pro-inflammatory biomarkers in patients with chronic kidney disease (CKD (and in those receiving hemodialysis (HD). Materials and methods: This meta-analysis was undertaken following PRISMA guidelines. An extensive systematic review was undertaken until 10/11/2021 using PubMed, Web of Science (ISI), and Scopus databases. The standardized mean difference (SMD) and 95% confidence intervals (CI) were used to estimate the overall effect size of curcumin on serum high-sensitivity C-reactive protein (hs-CRP), and pro-inflammatory cytokines including interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) in patients with CKD and those receiving HD. Results: Overall, ten randomized controlled trials (RCTs) comprising 523 patients were incorporated into the systematic review and meta-analysis. The results showed that when compared with control groups, there was no significant effect observed linking curcumin and IL-6 (SMD = 0.24%, 95% CI = -0.14 to 0.62, p = 0.221), TNF-α (SMD = 0.11%, 95% CI = -0.19 to 0.40, p = 0.480) or hs-CRP (SMD = -0.17%, 95% CI = -0.36 to 0.03, p = 0.093). The analysis determined no publication bias related to the influence of curcumin on IL-6, TNF-α or acute phase reactant, hs-CRP. The Egger's and Begg's test results were not statistically significant (p˃0.20). Conclusion: In patients with CKD and those receiving HD, the use of curcumin supplementation has no statistically significant effect on the anti-inflammatory biomarkers reviewed in this study.
... Nineteen articles were selected for a full assessment, of which 12 records were appropriate ( Fig. 19.1). Thus, data extraction was performed on 12 articles [40][41][42][46][47][48][49][50][51][52][53][54]. The characteristics of each selected paper are shown in Table 19.1. ...
... The studies were published between 2011 and 2020 and comprised a total of 631 patients. Eight studies were conducted in Iran [40,42,47,48,[51][52][53][54], two in Mexico [46,50], one in Brazil [41], and one in the United States of America [49]. Six studies worked on hemodialysis patients [41,42,[50][51][52][53], three studies were conducted on CKD patients (with or without diabetes) [40,46,49], and one of these articles worked on contrastinduced nephropathy patients [40]. ...
... Eight studies were conducted in Iran [40,42,47,48,[51][52][53][54], two in Mexico [46,50], one in Brazil [41], and one in the United States of America [49]. Six studies worked on hemodialysis patients [41,42,[50][51][52][53], three studies were conducted on CKD patients (with or without diabetes) [40,46,49], and one of these articles worked on contrastinduced nephropathy patients [40]. One study was conducted on patients with overt type 2 diabetic nephropathy [47], one in patients with type 2 diabetes mellitus with overt albuminuria [54], and one in patients with relapsing or refractory biopsy- ...
Chapter
Chronic kidney disease (CKD) is one of the significant causes of morbidity and mortality worldwide, which could develop and progress to end-stage renal disease. Increased inflammation and reduced antioxidant capacity commonly occur in CKD and hemodialysis patients. Curcumin is a natural bioactive compound with antioxidant and anti-inflammatory properties. This systematic review was undertaken with the main aim of assessing the effects of curcumin/turmeric supplementation on renal diseases based on clinical trials. A comprehensive search was performed in PubMed/MEDLINE, Scopus, ISI Web of Science, and Google Scholar from inception up to April 6, 2020 to identify clinical trials assessing the effects of curcumin or turmeric alone, or in combination with other herbs or nutrients on renal diseases. Twelve studies met the eligibility criteria. These randomized controlled trials (RCTs) comprised 631 patients with either chronic kidney diseases (CKD), hemodialysis, diabetic proteinuria and nephropathy, and lupus nephritis. Curcumin/turmeric supplementation had favorable effects on renal diseases, particularly in terms of inflammation and oxidative stress. However, with the exception for proteinuria, their impact on clinical parameters, such as blood urea nitrogen, creatinine, glomerular filtration rate (GFR), and serum albumin, was weak and not significant. No serious adverse effects were reported following curcumin/turmeric supplementation. Within the limitations of this review, it can be concluded that curcumin/turmeric supplementation might have some beneficial effects on inflammatory and oxidative stress parameters of patients but no considerable positive impact on clinical outcomes of kidney diseases, apart from proteinuria.
... spices are considered natural plant products that have been used for their medicinal qualities that dates back centuries [17]. More recently, several of these spices, including turmeric, have been shown to reduce inflammation and improve other health outcomes present in chronic diseases such as arthritis, cardiovascular disease, diabetes, kidney disease and obesity [14,[18][19][20]. For instance, a crossover randomized controlled trial with overweight and obese males (n = 12) found that a high-fat, high carbohydrate meal containing 6 g of spice blend attenuated the inflammatory effects of the meal by reducing post-prandial il-1 [19]. ...
... the most active component of turmeric is curcumin, which makes up 2 to 5% of the spice and is considered the component that reduces inflammation [26]. the few clinical studies that have been conducted to determine the relationship between inflammation markers and curcumin have relied on supplements or orally administered curcumin [20,[27][28][29]. Results from these studies have shown that the bioavailability of dietary supplements may not be as high as the consumption of the food or spice directly through meals that include other components that can increase turmeric bioavailability [29,30]. ...
Article
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Background: Obesity is considered a low-grade chronically inflamed state that contributes to communicable chronic diseases. This inflammation may be modulated by consuming spices like turmeric daily. However, few studies have looked at the inclusion of spice within whole foods. Objective: The purpose of this feasibility pre/posttrial was to assess the influence of turmeric in a muffin on salivary IL-6 and CRP in adults who were obese. Methods: Participants consumed one, 60-gram muffin containing 3 g turmeric for 10 days. Participants provided a urinary sample at baseline, a 2-ml saliva sample, and a 30-day food frequency and spice consumption questionnaire at baseline and post-trial. A one-sample t-test was conducted using SAS v 9.4 with significance determined at p < 0.05. Results: A total of 14 participants, average BMI of 32.16 kg/m2 with 10 identifying as female, completed the trial after 5 dropped due to various reasons. The visit lengths and collection of data with participants adhering to the instructions were deemed a success. There was a significant decrease in salivary IL-6 (p = 0.03) but no statistical difference in salivary CRP (p = 0.46). Participants consumed fruits and vegetables at least once daily, chicken and eggs 5-6 times per week, and beef, pork, and fish at least once per week. Participants consumed chili pepper, garlic, cinnamon, cilantro, and ginger at least once per week. No changes were observed in dietary/spice habits during this trial. Conclusion: The feasibility pre/post study revealed that consumption of a muffin with turmeric reduced at least salivary IL-6 in 10 days. Modifications to the study design such as lengthier trial time to assess the impact of this muffin on CRP is necessary prior to implementing larger-scale randomized control trials.
... Biomarkers for oxidative stress were measured differently in the included studies: total antioxidant capacity (TAC); serum malondialdehyde (MDA) content; thiobarbituric acid reactive substances (TBARS); carbonyl values; oxygen radical absorbance capacity (ORAC); advanced oxidation products of protein (AOPP); 8-hydroxy-2'-deoxyguanosine (8-OHdG); Lucigenin-enhanced chemiluminescence (LucCL); formamidopyrimidine glycosylase (FPG); catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and superoxide dismutase (SOD) activities. Seven studies [12][13][14][15][16][17][18] were conducted in predialysis CKD patients. However, we further excluded one study because it used vitamin D as its primary intervention 17 . ...
... Three studies 18,42,43 included in this review discussed other antioxidant interventions, including the combination of curcumin and Boswellia serrata, fermentable fiber, and coenzyme Q10 (CoQ10). Moreillon et al 18 reported insignificant changes in serum IL-6, CRP, and TNF-α among patients receiving the combination of curcumin and B. serrata for eight weeks. ...
Article
Full-text available
Objective: This systematic review and meta-analysis aimed to address the effect of antioxidant supplementation on oxidative stress and proinflammatory biomarkers in patients with Chronic Kidney Disease (CKD). Materials and methods: Systematic literature searches from the date of inception up to September 16th, 2022, were performed on PubMed, SCOPUS, and the Cochrane Central Register of Controlled Trials using relevant keywords, i.e., "Chronic Kidney Disease" and "antioxidants", and "supplementation". All studies relevant to the selection criteria were included in the analysis, focusing on any type of oxidative stress and proinflammatory biomarkers. A meta-analysis of included literature was conducted if sufficient data was obtained. Results: This systematic review involved 32 published studies, with most having a Jadad score of ≥ 3 (65.6%). Only studies on antioxidants, i.e., polyphenols (n=5) and vitamin E (n=6) in curcumin/turmeric, were sufficient to be included in a meta-analysis. Curcumin/turmeric supplementation was found to significantly reduce the serum c-reative protein (CRP) [standardized mean difference (SMD) -0.5238 (95% CI: -1.0495, 0.0019); p = 0.05; I2 = 78%; p = 0.001]. Similarly, vitamin E supplementation was found to significantly reduce the serum CRP [SMD -0.37 (95% CI: -0.711, -0.029); p = 0.03; I2= 53%; p = 0.06] , but not serum interleukin-6 (IL-6) [SMD -0.26 (95% CI: -0.68, 0.16); p = 0.22; I2 = 43%; p = 0.17] and malondialdehyde (MDA) content [SMD -0.94 (95% CI: -1.92, 0.04); p = 0.06; I2= 87%; p = 0.0005]. Conclusions: Our review suggests that curcumin/turmeric and vitamin E supplements effectively lower serum CRP levels in CKD patients, particularly those undergoing chronic dialysis (CKD-5D). Higher scales of randomized controlled trials (RCTs) are still needed for other antioxidants due to inconclusive and contradicting results.
... These pathways are being hypothesized to produce convincing results in CKD. Fig. 2 depicted the different pathways for the renal defensive activity of curcumin (a), lowering in ROS (b), hinderance of NF-κB and Th1 cytokine in lymphocytes (c), diminished cyclooxygenase action in mesangial cells (d), threatened the TNFα-interceded (e), diminish in Peroxisome proliferator-activated receptor gamma decreased availability of lipopolysaccharide for use and (f), reduction of endoplasmic reticulum stress-induced apoptosis and MAPK gesticulating cascades (Moreillon et al., 2013;Ghosh et al., 2014;Guan et al., 2015;Afrin et al., 2017;de Almeida Alvarenga et al., 2018). ...
... Fig. 4 depicts the major problems encountered owing to the utilization of herbal therapy. The improper clinical designs, being one of the ubiquitous problems, pose the challenge such as a small sample size, which proceeds with pseudo presumptions about the outcome of studies (Moreillon et al., 2013;Ekor 2014). The other concerns encountered during the use of herbal therapy in CKD patients are unpredictable pharmacokinetics, herbal and physiological interactions, electrolytic imbalance and interaction with co-morbid conditions (Burrowes and Van Houten, 2005). ...
Article
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Background Due to the toxicity issues of synthetic compounds, herbal medicines are preferred in treating or curing many diseases in recent times. Because of limited treatment options for chronic kidney disease (CKD), the use of traditional herbal medication to alleviate urogenital problems is the alternate therapeutic selection. Purpose Here, we summarized the research outcomes for the use of herbal medicine in the treatment of CKD and hurdles in the way for further research. Methods A relevant literature based on combinations of keywords such as herbal medicines, Chinese herbal medicine, CKD, chronic renal failure, nephroprotection, renoprotection, vegetable-based diet, and plant-based diets was searched using Pub med, Google Scholar, and Science Direct databases. The original articles published from 2006 to 2021 were taken into consideration. The literature was evaluated by studying the abstract or full text, all irrelevant studies were ignored. Results About 54 studies were found to describe the utilization of herbal drugs in the treatment of CKD in both human and laboratory animals, 17 studies described the clinical application of about 13 medicinal plants used against CKD in humans and 37 studies demonstrated the beneficial use of 24 medicinal plants in animal models and in vitro studies for CKD treatment explaining possible mechanisms of their action. The herbal treatment displayed anti-inflammatory, antioxidant, chemopreventive, and immune-mediated properties. The anti-inflammatory action is well implicated via regulation of cyclooxygenase-2, signal transducer, and activation of transcription 3 and IκB kinase β pathways. These pathways are being hypothesized to produce convincing results in CKD. The CKD and gut microbiota is known to be closely related through inflammatory, renal, cardiovascular, and endocrine processes. The various concerns encountered during the use of herbal therapy in CKD are unpredictable pharmacokinetics, herbal and physiological interactions, electrolytic imbalance, and interaction with co-morbid conditions. The combined use of Chinese herbal medicine and Western medicine for the treatment of advanced-stage CKD was found to be effective in delaying dialysis initiation and reducing dialysis incidence. Conclusions A large number of medicinal plants have shown promising beneficial effects against several diseases including cancer, but only a handful of studies are available on CKD. Several studies explained the possible mechanisms of herbal medications in CKD for therapeutic use; however, the focussed molecular studies for identification of active components of medicinal herbs with their mechanism of action and safety standard are still awaited. The demand for well-designed clinical trials and rigorous pharmacological studies as well as a surge for combined use of herbal medicine and Western medicine for the treatment of CKD has been noticed. The nephrotoxicity issues of medicinal plants should not be ignored.
... Currently, some studies have shown the positive effects of curcumin supplementation in vivo models in animals and humans [23][24][25]. These studies demonstrated that curcumin positively regulates Nrf2 with a consequent increase in antioxidant enzymes and a reduction in inflammatory markers in CKD [23][24][25][26]. ...
... Currently, some studies have shown the positive effects of curcumin supplementation in vivo models in animals and humans [23][24][25]. These studies demonstrated that curcumin positively regulates Nrf2 with a consequent increase in antioxidant enzymes and a reduction in inflammatory markers in CKD [23][24][25][26]. Furthermore, curcumin was also efficient in improving intestinal architecture by increasing tight junction proteins and alkaline intestinal phosphatase (IAP), leading to lower intestinal permeability and better circulation of inflammatory factors in the systemic circulation [27]. ...
Article
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Background and objectives Recent studies have shed light on the potential role of curcumin in mitigating inflammation in patients with chronic kidney disease (CKD). This study aimed to evaluate the effects of curcumin supplementation on plasma levels of markers of inflammation and oxidative stress in patients with CKD undergoing hemodialysis (HD). Methods These are secondary exploratory analyses from a previous double-blind, randomized controlled pilot study registered under ClinicalTrials.gov Identifier no. NCT00123456. It included 28 hemodialysis patients from a previous study divided into two groups: curcumin group (receiving juice with 2.5 g of turmeric 3×/week for 12 weeks) and a control group. The TNF-α, IL-6 and Ox-LDL plasma levels were measured by sandwich enzyme immunoassays ELISA; lipid peroxidation was measured by the reaction between malondialdehyde (MDA) and thiobarbituric acid. Results After 12 weeks of supplementation with curcumin, the TNF-α plasma levels were significantly reduced [from 15.0 (8.23–73.3) to 6.17 (1.11–55.0) pg/mL, p = 0.01]. Conclusion 12 weeks of treatment with curcumin in HD patients resulted in a reduction in the biomarker of inflammation (TNF-α), confirming our previous hypothesis that curcumin has an anti-inflammatory effect.
... Clinical evidences support the role of curcumin in renoprotection [121]. Moreillon et al. in 2013 conducted a clinical trial on 16 patients with CKD and found that curcumin is able to reduce the inflammatory cytokines and improve renal functions. ...
... Moreillon et al. in 2013 conducted a clinical trial on 16 patients with CKD and found that curcumin is able to reduce the inflammatory cytokines and improve renal functions. This study showed a significant reduction of IL-6 in the treatment group and increase in the placebo group [121], which partially support anti-inflammatory effects of curcumin hypothesis. As impaired renal function partly results from adverse effects of persistent proteinuria, it is important to elucidate the effect of natural product such as dietary turmeric in ameliorating diabetic nephropathy and the renal lesions associated with it. ...
Article
The use of herb-based therapies is increasing over the past decades. These agents have been reported to provide many beneficial effects in many experimental and clinical studies. Curcumin is one of these agents which has potent pharmacological effects enabling it for the prevent and treatment of many diseases and pathologies such as renal disorders, hyperglycemia, oxidative stress, hypertension, and dyslipidemia. However, the exact molecular mechanisms mediating these renoprotective effects of curcumin are not well established. So, in the current study, we surveyed for possible renoprotective roles of curcumin and concluded how curcumin protects against renal injuries.
... The clinical data of high-quality CAM therapy is indeed scarce. Prescriptions and acupuncture have been studied in RCT grade [91,92], and the evidence of moxibustion belongs to meta-analysis grade [93]. However, most of the CAM therapy studies are still animal experiments. ...
... An RCT including patients with CKD revealed a significant decrease in plasma IL-6 following treatment with oral C. longa and B. serrata for 8 weeks compared with a placebo group; however, other variables such as TNF-α and CRP exhibited no significant differences. Moreillon et al. indicated that C. longa and B. serrata reduce IL-6 possibly through inhibition of the pathways of NF-κB and mitogen-activated protein kinase [91]. ...
Article
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Uremic toxins (UTs) are mainly produced by protein metabolized by the intestinal microbiota and converted in the liver or by mitochondria or other enzymes. The accumulation of UTs can damage the intestinal barrier integrity and cause vascular damage and progressive kidney damage. Together, these factors lead to metabolic imbalances, which in turn increase oxidative stress and inflammation and then produce uremia that affects many organs and causes diseases including renal fibrosis, vascular disease, and renal osteodystrophy. This article is based on the theory of the intestinal–renal axis, from bench to bedside, and it discusses nonextracorporeal therapies for UTs, which are classified into three categories: medication, diet and supplement therapy, and complementary and alternative medicine (CAM) and other therapies. The effects of medications such as AST-120 and meclofenamate are described. Diet and supplement therapies include plant-based diet, very low-protein diet, probiotics, prebiotics, synbiotics, and nutraceuticals. The research status of Chinese herbal medicine is discussed for CAM and other therapies. This review can provide some treatment recommendations for the reduction of UTs in patients with chronic kidney disease.
... Opioids are metabolized in the liver and their metabolites are excreted through the kidneys. This can be one of the possible reasons for the pathologic effects of opioids on the kidneys (Moreillon et al. 1975, Connolly et al. 2006. The kidneys play a major role in the excretion of morphine metabolites and only 10% dose of morphine is excreted unchanged in urine (Moreillon et al. 1975). ...
... This can be one of the possible reasons for the pathologic effects of opioids on the kidneys (Moreillon et al. 1975, Connolly et al. 2006. The kidneys play a major role in the excretion of morphine metabolites and only 10% dose of morphine is excreted unchanged in urine (Moreillon et al. 1975). Morphine is biotransformed in the liver and kidneys and can damage the kidneys and liver (Lock and Reed 1998). ...
Article
After cannabis, opiates are the world's second most widely abused illegal drug. Opium is the latex of unripe pods of Papaver somniferum (Opium poppy). Opium has been used traditionally for lowering blood lipids, and postpone cardiac diseases, as well as used for the treatment of diabetes and cancer. In eastern countries, the high prevalence of opium use could be attributed to high supply and conventional assumptions. Although, opium consumption reduced the levels of lipid profile and fasting blood sugar (FBS) in patients, while it also reduced left ventricle ejection fraction. Opium consumption increased inflammatory lung disease and risk of lung cancer as well as increased free radicals by activating lipid peroxidation. ARTICLE HISTORY
... The expression of pro-inflammatory cytokines and adhesion molecules (major mediators of inflammation) is stimulated by reactive oxygen species [69]. TNFα has been demonstrated to down-regulate peroxisome proliferator-activated receptor γ (PPARγ) by abolishing its strong, anti-inflammatory effects [70,71]. ...
... Moreover, it turned out to be safe for these patients. Moreillon et al. [69] assessed the impact of herbal supplement composed of Curcuma longa and Boswellia serrata on systemic inflammation and antioxidant status in non-dialysis CKD patients. They observed a marked reduction of inflammatory markers TNFα, IL-6, and C-reactive protein, but no impact on creatinine and blood urea nitrogen (BUN). ...
Article
Full-text available
Chronic kidney disease (CKD) is a worldwide health problem in which prevalence is constantly rising. The pathophysiology of CKD is complicated and has not been fully resolved. However, elevated oxidative stress is considered to play a vital role in the development of this disease. CKD is also thought to be an inflammatory disorder in which uremic toxins participate in the development of the inflammatory milieu. A healthy, balanced diet supports the maintenance of a good health status as it helps to reduce the risk of the development of chronic diseases, including chronic kidney disease, diabetes mellitus, and hypertension. Numerous studies have demonstrated that functional molecules and nutrients, including fatty acids and fiber as well as nutraceuticals such as curcumin, steviol glycosides, and resveratrol not only exert beneficial effects on pro-inflammatory and anti-inflammatory pathways but also on gut mucosa. Nutraceuticals have attracted great interest recently due to their potential favorable physiological effects on the human body and their safety. This review presents some nutraceuticals in which consumption could exert a beneficial impact on the development and progression of renal disease as well cardiovascular disease.
... In 2013, Moreillon et al. conducted a clinical trial involving 16 non-dialysis CKD patients [235]. CKD is characterized by increased inflammation and oxidative stress (OS). ...
... The patients in this study were administered with two capsules per day. Each capsule contained a herbal supplement containing C. longa and Boswellia serrata extract that was found to significantly reduce the levels of the inflammatory cytokine, IL-6 [235]. Following this, in 2017, Shelmadine and group evaluated the effect of this herbal supplement on eicosanoid Turmeric extract bcd 21 Safe; showed therapeutic response - [191] ( Continued ) derivatives in CKD patients not undergoing hemodialysis, and they found that this supplement had a significant impact on PGE2 levels in the treated group compared to placebo [236]. ...
Article
Introduction: Since ancient times, turmeric has been used in several folklore remedies against various ailments. The principle component of turmeric is curcumin and its efficacy has been advocated in in vitro, in vivo and clinical studies for different chronic diseases. However, some studies suggest that curcumin bioavailability is a major problem. Areas covered: This article discusses over 200 clinical studies with curcumin that have demonstrated pronounced protective role of this compound against cardiovascular diseases, inflammatory diseases, metabolic diseases, neurological diseases, skin diseases, liver diseases, various types of cancer, etc. The review also describes the combination of curcumin with many natural and synthetic compounds as well as various formulations of curcumin that have shown efficacy in multiple clinical studies. Expert opinion: The therapeutic potential of curcumin as demonstrated by clinical trials has overpowered the myth that poor bioavailability of curcumin poses a problem. Low curcumin bioavailabilty in certain studies has been addressed by using higher concentrations of curcumin within nontoxic limits. Moreover, curcumin in combination with other compounds or as formulations have shown enhanced bioavailability. Hence, bioavailability is not a problem in curcumin mediated treatment of chronic diseases. Therefore, this golden nutraceutical presents a safe, low-cost and effective treatment modality for different chronic diseases.
... Las mujeres presentan mayor cantidad de curcumina en plasma que los hombres, esto se le adjudica a la mayor actividad y expresión de la glicoproteína P (MDR1, multi-resistant protein) del transportador de eflujo hepático e isoformas de la glucuronosiltransferasas y sulfotransferasas involucradas en la biotransformación de curcumina. Otros factores son la grasa corporal, volumen sanguíneo y peso corporal, en mujeres estos parámetros son menores, por lo tanto hay menor volúmen de distribución (Moreillon et al. 2013;Schiborr et al. 2014). ...
Thesis
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Curcumin is the main bioactive component of Curcuma longa, this biomolecule has anti-inflammatory, antioxidant and nephroprotective properties. The main disadvantage of this molecule is its low bioavailability. The objective of this project was to evaluate the nephroprotective effect of curcumin by the synthesis of a nanocomposite of gold nanoparticles with curcumin, and evaluate the nephroprotective effect in a murine model of nephrotoxicity induced by gentamicin. This low bioavailability is due to its poor absorption, apparent rapid metabolism, inactivity of final metabolism products, rapid elimination, limited tissue distribution and a short half-life. One way to increase absorption, bioavailability and half-life in plasma is through the use of nanoparticle-based release systems. In this project, the nephroprotective effect of curcumin was evaluated by treatment-improvement with nanocomposite of gold nanoparticles with curcumin. We synthesize the nanocomposite by a green method, and characterize it with UV-vis, TEM and FTIR. Rats were randomly separated in 9 experimental groups with seven days-treatment, each group had 6 Wistar rats weighting between 220-250 g, group 1 healthy rats, group 2 native curcumin, group 3 gold nanoparticles, group 4 nanocomposite, group 5 rats with gentamicin-induced kidney damage (this model of nephrotoxicity will be used for groups 5, 6, 7, 8), group 6 + native curcumin, group 7 + gold nanoparticles, group 8 + nanocomposite, group 9 were pretreated rats for 7 days with nanocomposite, on day 8 gentamicin model was used + nanocomposite for 7 more days. The lethal dose 50 was determined for the nanocomposite. Serum renal biomarkers creatinine and BUN were measured. Histopathological study with hematoxylin-eosin stain was performed to detect changes in tubular necrosis, tubular dilatation, glomerulus structure, edema, infiltration of mononuclear cells and formation of hyaline drops in tubular cells. Our nanocomposite maintained normal levels of kidney function biomarkers.
... Several studies have shown the beneficial effects of turmeric and curcumin in treating renal disease. For example, a C. longa supplement improved the levels of the inflammatory cytokines and antioxidant capacity in CKD, suggesting the supplement may combat chronic inflammation [504][505][506][507] . ...
Article
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Turmeric (Curcuma longa) has been used for thousands of years for the prevention and treatment of various chronic diseases. Curcumin is just one of >200 ingredients in turmeric. Almost 7000 scientific papers on turmeric and almost 20,000 on curcumin have been published in PubMed. Scientific reports based on cell culture or animal studies are often not reproducible in humans. Therefore, human clinical trials are the best indicators for the prevention and treatment of a disease using a given agent/drug. Herein, we conducted an extensive literature survey on PubMed and Scopus following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The keywords "turmeric and clinical trials" and "curcumin and clinical trials" were considered for data mining. A total of 148 references were found to be relevant for the key term "turmeric and clinical trials", of which 70 were common in both PubMed and Scopus, 44 were unique to PubMed, and 34 were unique to Scopus. Similarly, for the search term "curcumin and clinical trials", 440 references were found to be relevant, of which 70 were unique to PubMed, 110 were unique to Scopus, and 260 were common to both databases. These studies show that the golden spice has enormous health and medicinal benefits for humans. This Review will extract and summarize the lessons learned about turmeric and curcumin in the prevention and treatment of chronic diseases based on clinical trials.
... 104 Curcumin and boswellic acids (as well as other constituents, such as maritime pine) were studied in combination for other indications in clinical trials in humans, including acute musculoskeletal pain, chronic kidney disease, benign thyroid nodules, diverticulitis, tendinopathy, and Gulf War syndrome. [107][108][109][110][111][112] In healthy adults with acute musculoskeletal pain, treatment with the combination of curcumin and boswellic acids or with acetaminophen for 7 days reduced pain intensity at a similar rate and to a similar level. 113 The only difference observed between the two groups was improved reduction in the affective domain of the McGill Pain Questionnaire in the curcumin and boswellic acids treatment group (8.57 ...
Article
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For several thousand years (~4000) Boswellia serrata and Curcuma longa have been used in Aryuvedic medicine for treatment of various illnesses, including asthma, peptic ulcers, and rheumatoid arthritis, all of which are mediated through pathways associated with inflammation and pain. Although the in vivo pharmacology of both these natural ingredients is difficult to study because of poor bioavailability, in vitro data suggest that both influence gene expression mediated through nuclear factor kappa B (NF-κB). Therefore, the activity of pathways associated with inflammation (including NF-κB and lipoxygenase- and cyclooxygenase-mediated reduction in leukotrienes/prostaglandins) and those involved in matrix degradation and apoptosis are reduced, resulting in a reduction in pain. Additive activity of boswellic acids and curcumin was observed in preclinical models and synergism was suggested in clinical trials for the management of osteoarthritis (OA) pain. Overall, studies of these natural ingredients, alone or in combination, revealed that these extracts relieved pain from OA and other inflammatory conditions. This may present an opportunity to improve patient care by offering alternatives for patients and physicians, and potentially reducing nonsteroidal anti-inflammatory or other pharmacologic agent use. Additional research is needed on the effects of curcumin on the microbiome and the influence of intestinal metabolism on the activity of curcuminoids to further enhance formulations to ensure sufficient anti-inflammatory and antinociceptive activity. This narrative review includes evidence from in vitro and preclinical studies, and clinical trials that have evaluated the mechanism of action, pharmacokinetics, efficacy, and safety of curcumin and boswellic acids individually and in combination for the management of OA pain.
... Some useful chemical agents applied in conventional medicine today are of Complimentary Contributor Copy botanical origin. Several herbs and combinations are currently used to manage kidney diseases (Moreillon et al., 2013;Yuan et al., 2016). ...
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Nanoparticle investigation is an interesting field of science. The powerfully sized- cognate characteristics of nanoparticles provide numerous possibilities for unexpected innovations. The performance of nanoparticles endure tremendous opportunity for pioneering high-tech application programs, but also stances excessive concerns to the researchers. At present, engineered nanoparticles uphold the outstanding potential in diversified fields of society such as the field of medicine, science, and industry without revealing its toxic implications. However, the growing production and utilization of engineered nanoparticles also arouse concern about inattentive exposure and the feasibility of detrimental effects on human wellness and biological complex. Thus, it is the most pressing need for examining the toxicity along with the application of such advantageous nanomaterial. Nanoparticles are atomic or molecular clusters with the size varying between 1 to 100 nm. Toxicity mechanisms of metal and metal oxide nanoparticles can transpire by various approaches like non-homeostasis impacts, oxidative stress, genotoxicity, implications, etc. Components that influence the metal and metal oxide nanoparticles are size, dissolution, and ways of exposure. This chapter will highlight an overview of metals and metal oxide nanoparticles and their toxic effects on living beings and biological systems.
... Some useful chemical agents applied in conventional medicine today are of Complimentary Contributor Copy botanical origin. Several herbs and combinations are currently used to manage kidney diseases (Moreillon et al., 2013;Yuan et al., 2016). ...
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Medicinal herbs are a rich source of therapeutic agents for the prevention and cure of diseases and ailments. They were used in folklore medicine in the treatment of toothache and strengthening of gums, anthelmintic, kidney diseases, analgesic, anti-inflammatory, hepatoprotective, antihyperglycaemic, antihyperglycaemic, and anticancer. There are many plants that have potential analgesic and anti-inflammatory activities and, many more plants are screened for the phyto-constituents having pain relief and anti- inflammatory properties to replace non-steroidal and opioid drugs, which have severe side effects. Different phyto-constituents like alkaloids, flavonoids, xanthone, coumarin, sterols, withaferin-A, andrographolide, etc., are proved effective as an analgesic and anti- inflammatory agents. Previous studies have contributed much to the understanding of the compound(s) responsible for the known anti-inflammatory and analgesic action. Drugs which are used presently for the management of pain and inflammatory conditions are either steroidal like corticosteroids or non-steroidal like aspirin. All of these drugs possess more or less side and toxic effects like renal failure, allergic reactions, hearing loss or they may increase the risk of hemorrhage by affecting platelet function. On the contrary, many medicines of plant origin had been used for ages without any adverse effects. It is therefore essential that efforts should be made to introduce new medicinal plants to develop more effective and cheaper drugs. Plants represent a large natural source of useful compounds that might serve as a source for the development of novel drugs. This chapter summarizes various medicinal plants and herbs with anti- inflammatory and analgesic properties that have been used by our ancestors to cure many of their ailments.
... CUR had no significant effect on kidney function test in the present study. Consistently, serum levels of urea and creatinine not differed significantly comparing the pre-and post-turmeric supplementation in two clinical trials among patients with type 2 diabetic nephropathy [68] and chronic kidney disease [69]. ...
Article
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Background Vitamin D has an established role in female reproduction. There is also evidence for an association between vitamin D levels and menstrual problems such as premenstrual syndrome (PMS) and dysmenorrhea. Curcumin, is a bioactive polyphenol constituent of turmeric, that can potentially interact with vitamin D receptors and its molecular targets. This study evaluated the effects of curcumin on vitamin D levels in young women with PMS and dysmenorrhea. Methods In this randomized, triple-blind, placebo-controlled trial, women with PMS and dysmenorrhea were divided randomly into experimental and control groups to receive one capsule (500 mg of curcuminoid+ 5 mg piperine, or placebo) daily, from approximately 7 days before until 3 days after menstruation for three consecutive menstrual cycles. Serum vitamin D levels, renal function, and liver enzymes were also measured before and after intervention. Results A total of 76 subjects (38 in each group) were recruited into the trial. Curcumin significantly increased the median (IQR) serum levels of vitamin D [from 12.8 ng/ml (7.0–24.6) to 16.2 ng/ml (6.4–28.8); P = 0.045], compared with placebo [from 18.6 ng/ml (2.2–26.8) to 21.3 ng/ml (5.2–27.1); P = 0.17]. Serum levels of aspartate aminotransferase and direct bilirubin were reduced by the end of trial in the curcumin group (p < 0.05), but did not change significantly in the control group (p > 0.05). Finally, no significant differences in levels of fasting blood glucose were detected between curcumin and placebo groups. Conclusion Curcumin supplementation in women with PMS and dysmenorrhea led to a significant improvement of vitamin D, liver function enzyme test, but did not affect blood glucose. Trial registration The trial was registered on Iranian Registry of Clinical Trials registry (Trial ID: IRCT20191112045424N1 on 23 January 2020; available at https://www.irct.ir).
... Some useful chemical agents applied in conventional medicine today are of botanical origin. Several herbs and combinations are currently used to manage kidney diseases (Moreillon et al., 2013;Yuan et al., 2016). ...
Chapter
The kidney play essential biological roles necessary to maintain good health. The strategic physiological position of the kidney in metabolic processes expose it to the adverse effect of diseases emanating from other organs or systems. Abnormal metabolic processes as well as genetic defects can also induce injuries within the organ leading to kidney diseases that can progress to End Stage Renal Disease (ESRD). Prompt diagnoses and management are vital to reverse or slow the rate of progression and renal replacement therapy required for advanced stages to sustain life. This chapter is a review the biological roles of the kidneys in man, the diseases of the kidney, diagnostic parameters of kidney disease and nephroprotective mechanisms of phytochemicals in medicinal plants and natural drugs used by complementary and alternative medicine practitioners. Furthermore, factors militating against the application of herbal medicine in managing kidney diseases and some future perspectives are highlighted.
... Supplementation with C. longa and Boswellia serrata combination (824 mg purified turmeric extract, 95% curcuminoids, and 516 mg Boswellia serrata extract, 10% 3-acetyl-11-keto-β-boswellic acid) in patient with CKD, decreased serum level of IL-6, but did not modify the levels of C-reacive protein, TNF-α, and GPx compared to the placebo group [81]. ...
Chapter
Curcuma longa (C. longa) or turmeric is a plant with a long history of use in traditional medicine, especially for treatment of inflammatory conditions. Also, pharmacological effects such as antioxidant and anti-microbial properties were described for this plant. This chapter reports the latest knowledge on antiinflammatory, antioxidant and immunomodulatory effects of C. longa based on a literature survey using various databases and appropriate keywords until the end of July 2020. Various studies showed anti-inflammatory effects of C. longa, including decreased total white blood cells (WBC), neutrophils and eosinophils, as well as its effects on serum levels of inflammatory mediators such as phospholipase A2 (PLA2] and total protein in different inflammatory conditions. The anti-toxin effects of C. longa were also reported in several studies. The plant extracts decreased malondialdehyde and nitric oxide levels but increased thiol, superoxide dismutase, and catalase levels in oxidative stress conditions. Treatment with C. longa improved the levels of IgE, pro-inflammatory cytokines including interleukin (IL)-4, transforming growth factor beta (TGF-β) and IL-17 as well as anti-inflammatory cytokines such as interferon gamma (IFN-γ) and forkhead box P3 (FOXP3] and T helper cells 1 Th1/Th2 ratio in various conditions with disturbed immune balance. The reviewed papers showed anti-inflammatory, antioxidant and immunomodulatory effects of C. longa, indicating potential therapeutic property of the plant for treatment of inflammatory, oxidative and immune-dysregulation diseases.
... Some useful chemical agents applied in conventional medicine today are of Complimentary Contributor Copy botanical origin. Several herbs and combinations are currently used to manage kidney diseases (Moreillon et al., 2013;Yuan et al., 2016). ...
Chapter
Traditional medicine utilizing different herbal formulations has been an age old tradition being practiced in Indian context. This very regime quintessentially caters to the concept of Ayurveda Yoga Unani Siddha and Homeopathy (AYUSH). Ailments pertaining to Ear, Nose and Throat (ENT) have been mitigated by modern medicinal practices. Given this fact, emergence of antimicrobial resistance owing to unprecedented use of antibiotics has crippled the scenario of modern medicine. Being as one of the emerging challenges, a need of Complementary and Alternative Medicine (CAM) has arisen in recent times. For this to accomplish, ethano-botanical studies based at phyto-chemical interventions are envisaged. These studies are to identify and validate potential bio-active compounds which can be utilized either singly or in a formulation as potential bio-therapeutic agents possessing promising pharmacological activity for circumventing ENT disorders. An emerging concept of re-purposing of drugs and respective molecular docking patterns is a focal theme of recent research investigations. This concept has led to emergence of Active Pharmaceutical Ingredients (API) aimed to ward off ENT ailments (bacterial and fungal) without posing an occurrence of adverse affects. The chapter would highlight significance of ethano-botanical studies with special reference of medicinal plants of Sub-himalayan region, screening of bio-active compounds in obliterating common ENT ailments, patho-physiology of associated pathogens, and concept of re-purposing of drugs thus proving an impetus towards green and herbal medicine.
... It is released by activated eosinophils and macrophages but also by endothelial and epithelial cells. Furthermore, it is implicated in diseases, such as atherosclerosis, in an independent manner from its action on eosinophils [34][35][36][37], as well as in CKD [38]. ...
Article
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Vascular calcification (VC) is a risk factor for cardiovascular events and mortality in chronic kidney disease (CKD). Several components influence the occurrence of VC, among which inflammation. A novel uremic toxin, lanthionine, was shown to increase intracellular calcium in endothelial cells and may have a role in VC. A group of CKD patients was selected and divided into patients with a glomerular filtration rate (GFR) of <45 mL/min/1.73 m2 and ≥45 mL/min/1.73 m2. Total Calcium Score (TCS), based on the Agatston score, was assessed as circulating lanthionine and a panel of different cytokines. A hemodialysis patient group was also considered. Lanthionine was elevated in CKD patients, and levels increased significantly in hemodialysis patients with respect to the two CKD groups; in addition, lanthionine increased along with the increase in TCS, starting from one up to three. Interleukin IL-6, IL-8, and Eotaxin were significantly increased in patients with GFR < 45 mL/min/1.73 m2 with respect to those with GFR ≥ 45 mL/min/1.73 m2. IL-1b, IL-7, IL-8, IL-12, Eotaxin, and VEGF increased in calcified patients with respect to the non-calcified. IL-8 and Eotaxin were elevated both in the low GFR group and in the calcified group. We propose that lanthionine, but also IL-8 and Eotaxin, in particular, are a key feature of VC of CKD, with possible marker significance.
... Curcumin is the active ingredient and the main component of Curcuma longa that due to its specific structure and pharmacological effects such as; antimicrobial, antioxidant, inflammatory factors inhibitor, cell death induction and anti-carcinogen. In traditional medicine of some countries, such as Iran and India, it has been used to treat various diseases, especially respiratory, liver, gastrointestinal and for pain relief (Goel et al., 2010;Fallah et al., 2010;Moreillon et al., 2013;Anand et al., 2008). This compound by decreasing the expression of anti-apoptotic genes leads to increased expression of pro apoptotic proteins and targets the apoptotic pathway. ...
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Anaplastic thyroid carcinoma is highly invasive with a poor response to a treatment. In this study, curcumin bioavailability and its effects on apoptosis induction and selected genes expression of the human anaplastic thyroid carcinoma cell line (SW-1736) were examined. SW-1736 cells were incubated for 24 and 48 hours with different concentrations of curcumin 2.5, 5, 7.5 and 10 μM to examine bioavailability, and for 24, 48 and 72 hours with concentrations of 2.5, 5, 7.5, 10 μM and 2.5, 5 and 10 μM respectively to examine apoptosis and the expression of p53, PARP, p21 and Bcl-2 genes. Then, bioavailability was analyzed by MTS kit, apoptosis was analyzed by flow- cytometry using Annexin V-FITC/PI kit and the expression of p53, PARP, p21 and Bcl-2 genes were analyzed by Real Time PCR. ANOVA test and SPSS 16 software were used for statistical analysis. The results indicate that curcumin at the concentration of 7.5 μM has significantly decreased bioavailability in anaplastic thyroid cells in comparison with other treatments at both incubation periods. Induction of apoptosis with increasing concentration of curcumin in dose and time dependent manner increased in this cell line. Also, treatment with curcumin significantly decreased the expression of Bcl-2 gene and increased the expression of p53, PARP and p21 genes in some experimental groups compared to the control group. Curcumin inhibited the growth, proliferation and invasion of anaplastic thyroid cancer cells through altering the expression of the genes involved in the apoptosis process
... In animals, boswellia demonstrated neuroprotective and anti-inflammatory actions in a model of stroke [27] and significantly reduced levels of inflammatory mediators in a model of arthritis [28]. In patients with chronic kidney disease, boswellia reduced levels of IL-6 [29]. ...
Article
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This report is part of a larger study designed to rapidly and efficiently screen potential treatments for Gulf War Illness (GWI) by testing nine different botanicals. In this placebo-controlled, pseudo-randomized, crossover clinical trial of 20 men with GWI, we tested three botanical agents with putative peripheral and central anti-inflammatory actions: curcumin (Curcuma longa), boswellia (Boswellia serrata), and French maritime pine bark extract (Pinus pinaster). Participants completed 30 +/− 3 days of baseline symptom reports, followed by 30 +/− 3 days of placebo, 30 +/− 3 days of lower-dose botanical, and 30 +/− 3 days of higher-dose botanical. Participants then repeated the process with a new botanical until completing up to three botanical cycles. Data were analyzed using linear mixed models. Curcumin reduced GWI symptom severity significantly more than placebo at both the lower (p < 0.0001) and higher (p = 0.0003) dosages. Boswellia was not more effective than placebo at reducing GWI symptoms at either the lower (p = 0.726) or higher (p = 0.869) dosages. Maritime pine was not more effective than placebo at the lower dosage (p = 0.954) but was more effective than placebo at the higher dosage (p = 0.006). This study provides preliminary evidence that curcumin and maritime pine may help alleviate symptoms of GWI. As a screening study, a final determination of the efficacy of these compounds for all individuals with GWI cannot be made, and further studies will need to be conducted to determine strength and durability of effects, as well as optimal dosage. These results suggest that GWI may, at least in part, involve systemic inflammatory processes. This trial was registered on ClinicalTrials.gov (NCT02909686) on 13 September 2016.
... The pathophysiological mechanisms implied in these results consist in improvement of oxidative stress/antioxidant balance and consecutive inflammation, improvement of MMP-2 levels and histological aspect, and improvement of biomarkers of renal function. Different mechanisms regarding the beneficial effects of Curcumin on renal function were also reported: reducing pro-inflammatory cytokines (TNF-alpha, IL-6) [71], reducing growth factors synthesis (TGFβ, VEGF, and PDGF), which contribute to renal failure [72], xanthine oxidase blocking with oxidative stress attenuation [72]. Another important mechanism influenced by curcumin administration is represented by reducing NF-κB activation, which is correlated with the reduction of ROS and pro-inflammatory cytokine synthesis, influencing the pathophysiological loop between oxidative stress and overproduction of pro-inflammatory molecules with lesional consequences [73]. ...
Article
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Background: Our study aimed to assess the efficiency of Curcumin nanoformulation (LCC) on experimental nephrotoxicity induced by Gentamicin in rats. Methods: Six groups of seven rats were used: C-(control group) received saline solution i.p. (i.p. = intraperitoneal), G-gentamicin (G, 80 mg/kg body weight (b.w.)), GCC1 and GCC2-with G and CC solution (single dose of 10 mg/kg b.w.-CC1, or 20 mg/kg b.w.-CC2), GLCC1 (10 mg/kg b.w.) and GLCC2 (20 mg/kg b.w.) with G and LCC administration. Oxidative stress parameters (NOx = nitric oxide, MDA = malondialdehyde, TOS = total oxidative stress), antioxidant parameters (CAT = catalase, TAC = total antioxidant capacity), matrix metalloproteinases (MMP-2 and MMP-9), and renal function parameters (creatinine, blood urea nitrogen, and urea) were measured. Kidneys histopathologic examination was made for each group. Results: Pretreatment with CC and LCC in both doses had significantly alleviating effects on assessed parameters (NOx, MDA, TOS, CAT, TAC, MMP-2, and -9) as compared with the untreated group (p < 0.006). Histopathological aspect and renal function were significantly improved in CC and LCC groups. Liposomal formulation (LCC) showed higher efficiency on all examined parameters compared to CC (p < 0.006). Conclusions: Our results demonstrated improving renal function and kidney cytoarchitecture, oxidative stress/antioxidant/balance, and MMPs plasma concentrations with better dose-related efficacity of LCC than CC.
... 218 Treatment with C. longa and Boswellia serrata combination (824 mg purified turmeric extract, 95% curcuminoids, and 516 mg B. serrata extract, 10% 3-acetyl-11-keto-β-boswellic acid) in a patient with CKD decreased serum level of IL-6 but did not modify levels of CRP, TNF-α, and GPx compared to placebo untreated group. 219 The anti-proliferative activities of the isolated compounds (three curcuminoids and two turmerones) from C. longa, in human cancer cell lines HepG2, MCF-7, and MDA-MB-231 inhibited proliferation of cancer cells dosedependently as well as inducing MDA-MB-231 cells apoptosis. Immunomodulatory effects of turmerones (alpha and aromatic) from C. longa in human PBMC showed activation of the caspase cascade indicated by decreased procaspases-3, -8, and -9 in alpha-turmerone treated cells. ...
Article
Curcuma longa (C. longa) or turmeric is a plant with a long history of use in traditional medicine, especially for treating inflammatory conditions C. longa and its main constituent, curcumin (CUR), showed various pharmacological effects such as antioxidant and anti-microbial properties. The updated knowledge of anti-inflammatory, antioxidant, and immunomodulatory effects of C. longa and CUR is provided in this review article. Pharmacological effects of C. longa, and CUR, including anti-inflammatory, antioxidant, and immunomodulatory properties, were searched using various databases and appropriate keywords until September 2020. Various studies showed anti-inflammatory effects of C. longa and CUR, including decreased white blood cell, neutrophil, and eosinophil numbers, and its protective effects on serum levels of inflammatory mediators such as phospholipase A2 and total protein in different inflammatory disorders. The antioxidant effects of C. longa and CUR were also reported in several studies. The plant extracts and CUR decreased malondialdehyde and nitric oxide levels but increased thiol, superoxide dismutase, and catalase levels in oxidative stress conditions. Treatment with C. longa and CUR also improved immunoglobulin E (Ig)E, pro-inflammatory cytokine interleukin 4 (IL)-4, transforming growth factor-beta, IL-17, interferon-gamma levels, and type 1/type 2 helper cells (Th1)/(Th2) ratio in conditions with disturbance in the immune system. Therefore C. longa and CUR showed anti-inflammatory, antioxidant, and immunomodulatory effects, indicating a potential therapeutic effect of the plant and its constituent, CUR, for treating of inflammatory, oxidative, and immune dysregulation disorders.
... A clinical study evaluating the effects of a combination of turmeric extract and Boswellia serrata as a treatment of patients with chronic kidney disease (CKD) has reported that the supplement is well tolerated by the patients and is safe to use. The treatment efficiently enhanced the J o u r n a l P r e -p r o o f inflammatory status of the patients via the downregulation of the inflammatory cytokine, IL-6 [435]. Moreover, regular intake of curcumin was found to impart anti-inflammatory effects in patients undergoing hemodialysis. ...
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Background Cytokine storm is the exaggerated immune response often observed in viral infections. It is also intimately linked with the progression of COVID-19 disease as well as associated complications and mortality. Therefore, targeting the cytokine storm might help in reducing COVID-19-associated health complications. The number of COVID-associated deaths (as of January 15, 2021; https://www.worldometers.info/coronavirus/) in the USA is high (1199/million) as compared to countries like India is low (110/million). Although the reason behind this is not clear, spices may have some role in explaining this difference. Spices and herbs are used in different traditional medicines, especially in countries such as India to treat various chronic diseases due to their potent antioxidant and anti-inflammatory properties. Aim To evaluate the literature available on the anti-inflammatory properties of some spices which might prove beneficial in the prevention and treatment of COVID-19 associated cytokine storm. Method A detailed literature search has been conducted on PubMed for collecting information pertaining to the COVID-19; the history, origin, key structural features, and mechanism of infection of SARS-CoV-2; the repurposed drugs in use for the management of COVID-19 and the anti-inflammatory role of spices to combat COVID-19 associated cytokine storm. Key findings The literature search resulted in numerous in vitro, in vivo and clinical trials that have reported the potency of spices to exert anti-inflammatory effects by regulating crucial molecular targets for inflammation. Significance As spices are derived from Mother Nature and are inexpensive, they are relatively safer to consume. Therefore, their anti-inflammatory property can be exploited to combat the cytokine storm in COVID-19 patients. This review thus focuses on the current knowledge on the role of spices for the treatment of COVID-19 through suppression of inflammation-linked cytokine storm.
... 26 Curcumin has been used as a therapeutic compound to treat a number of inflammatory disorders. 27,28 Abdolahi et al. showed that the administration of curcumin in combination with ω-3 fatty acids could reduce TNF-α gene expression in patients suffering from migraines, and that the two compounds appeared to work synergistically. 29 The findings of various studies indicated that high levels of pro-inflammatory cytokines increase mortality rate in the dialysis patients. ...
Article
Introduction: Serum levels of several pro-inflammatory cytokines are higher in hemodialysis patients compared to healthy people. Curcumin has been shown to be able to decrease cytokines levels in nonuremic subjects. Our goal was to evaluate the effect of nanocurcumin administration on cytokines levels in hemodialysis patients. Methods: The study was performed over a 3 months period on 54 hemodialysis patients who had been randomized to receive either nanocurcumin or placebo. Serum levels and gene expressions of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) were evaluated using enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR). Findings: Serum levels of IL-6 and TNF-α were similar in the two groups at baseline but were lower after 12 weeks of treatment with nanocurcumin compared to placebo (P = 0.024 for IL-6 and 0.02 for TNF). In the group given nanocurcumin, serum levels of both cytokines decreased substantially (P < 0.001 for each), whereas they were unchanged in the group given placebo. Gene expression for each cytokine in peripheral blood mononuclear cells (PBMCs) was reduced at 12 weeks vs. baseline in the group given nanocurcumin, and changes in gene expression correlated with changes in serum level for each of the two cytokines. Discussion: The results indicate that nanocurcumin supplementation reduces both serum levels and gene expression of IL-6 and TNF-α in hemodialysis patients. The feasibility and potential clinical benefits of nanocurcumin treatment to reduce inflammation in hemodialysis patients warrant further study.
... Regarding chronic kidney disease, it has been reported that curcumin is capable of decreasing inflammatory cytokine IL-6 (Moreillon et al. 2013). Moreover, it seems curcumin can improve endoscopic index as well as the clinical activity index in patients with ulcerative colitis (Hanai et al. 2006). ...
Chapter
Chapter 17 - Epilepsy is a life-shortening brain disorder that currently affects ~ 1% of the worldwide population. Despite the availability of several antiepileptic drugs (AEDs), severe side effects such as cognitive and affective disorders, teratogenicity, hepatotoxicity, among others, have been reported after chronic administration. Also, some patients remain refractory to the available AEDs. Such is the case of metabolic epilepsy. Hence, there is a current need for the discovery of novel active principles with minimal or no adverse side effects. Nature is an exciting source of potential drug candidates for the treatment of pharmacoresistant epilepsy (PRE) due to the highly diverse and complex chemical structures of bioactive vegetal compounds. In this context, the authors analyzed the rhizome powder of Curcuma longa, commonly known as turmeric. Until the authors’ study, the anticonvulsant properties of turmeric were exclusively attributed to its curcuminoids. For the first time, the authors revealed the anticonvulsant properties of turmeric oil and its main bisabolene sesquiterpenoids, ar-turmerone, α-, β-turmerone, and α-atlantone. Thus, the present chapter discusses the botanical aspects of turmeric, the chemical composition, and phytopharmacological aspects of turmeric, curcumin, and turmeric oil as well as the authors’ results obtained from the anticonvulsant activity characterization of turmeric oil and ar-turmerone. The authors’ findings support further characterization of the anticonvulsant properties of these active compounds and demonstrate the usefulness of the zebrafish and mouse models for searching novel AEDs. Also, the potential therapeutic application of turmeric oil and ar-turmerone for the treatment of metabolic epilepsy is discussed.
... Interleukin-6 is rapidly expressed in a highly transient manner during inflammation [37]. Curcumin may help to reduce the levels of the inflammatory cytokine IL-6 [38]. ...
... Owing to the lack of new synthetic antimicrobials to treat MDR Gram-negative infections, attention should be increasingly focused on natural compounds either as stand-alone or adjunctive therapies. Curcumin is a polyphenol mixture extracted from the yellow root of turmeric, which has several pharmacological effects including anti-inflammatory, anti-oxidant, anti-cancer, antidiabetic, anti-allergic, and antibacterial activity (15). Unfortunately, curcumin faces problems such as low solubility, chemical and biological instability. ...
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Background: Acinetobacter baumannii is one of the most important opportunistic and biofilms-forming microorganisms. Its biofilm structure provides an effective barrier against the antimicrobial penetration and increases the drug resistance of Acinetobacter baumannii by 1000× compared with plankton cells. However, nanoparticles have recently reported as suitable tools to prevent biofilm formation. Objectives: The aim of this study was to investigate the effect of curcumin nanoparticles on biofilm gene expression in Acinetobacter baumannii strains in vitro. Methods: Seventy clinical isolates of Acinetobacter baumannii were collected from different specimens and all specimens were diagnosed biochemically. Antibiotic resistance pattern was detected by disc diffusion method. Isolates of high biofilm producers were selected to investigate the effect of curcumin nanoparticles. The antibiofilm activity of curcumin nanoparticles was studied using Real-time PCR technique in the molecular level. Results: This bacterium showed high resistance to most antibiotics, except for polymyxin B. Twenty-five strains had high biofilm formation capacity. MIC for curcumin was 128 µg/mL in all 25 strains. The expression results showed that CsuE gene was downregulated to 0.31 fold in curcumin-treated samples compared to untreated samples. Conclusions: The study findings suggest that curcumin nanoparticles can be helpful as a candidate for inhibiting the formation of Acinetobacter biofilms.
... Mohammadi, Kayedpoor, Karimzadeh-Bardei, and Nabiuni (2017) found out that antiinflammatory and antioxidative impacts of curcumin in patients with polycystic ovary syndrome is related to its function of inhibiting the gene expression of tumor necrosis factor-α (TNF-α), and reducing the circulating levels of CRP and interleukin-6 (IL-6). In addition, anti-inflammatory effects of curcumin in patients diagnosed with metabolic syndrome have been demonstrated by others (Moreillon et al., 2013;Panahi et al., 2016). In a trial conducted on patients with tropical pancreatitis, curcumin ingestion at a dosage of 500 mg/day for 6 weeks significantly reduced malonyldialdehyde (MDA) concentrations and led to a significant increase in glutathione levels (Durgaprasad, Pai, Vasanthkumar, Alvres, & Namitha, 2005). ...
Article
Besides other benefits, curcumin is getting more recognized for its antioxidant and anti‐inflammatory properties, highlighting the importance of curcumin application for chronic disease prevention. This systematic review and meta‐analysis of randomized controlled trials (RCTs) was conducted to assess the influence of curcumin‐containing supplements on biomarkers of inflammation and oxidative stress. MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched till January 2018 for eligible studies. The selected studies were evaluated for their quality using the Cochrane risk of bias tool and relevant data were extracted from included studies. Data were pooled using the inverse variance method and expressed as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Fifteen RCTs were included in the final analysis. The meta‐analysis indicated that curcumin supplementation significantly decreased interleukin 6 (IL‐6) (SMD −2.08; 95% CI [−3.90, −0.25]; p = 0.02), high‐sensitivity C‐reactive protein (hs‐CRP) (SMD −0.65; 95% CI [−1.20, −0.10], p = 0.02), and malondialdehyde (MDA) concentrations (SMD −3.14; 95% CI [‐4.76, −1.53], p < 0.001). Though, curcumin supplementation had no significant effect on tumor necrosis factor‐alpha (SMD −1.62; 95% CI [−3.60, 0.36]; p = 0.10) and superoxide dismutase levels (SMD 0.34; 95% CI [−1.06, 1.74], p = 0.63). Overall, this meta‐analysis suggests that taking curcumin‐containing supplements may exert anti‐inflammatory and antioxidant properties through a significant reduction in IL‐6, hs‐CRP, and MDA levels.
... [20,21] Specifically, 1,8-cineole (eucalyptol), 1-octanol, L-menthol, 3-cyclohexen-1-ol, octanoic acid, thymol, and carvacrol were reported as the chief active components in B. sacra water extract. [22] To the best of our knowledge, only two studies in the literature, Mahmoud et al. [23] and Moreillon et al., [24] were concerned with studying the effect of frankincense extract on kidney diseases, but these studies used lipophilic portion. Hence, our study aims to evaluate the efficacy of the aqueous extract of frankincense on chronic adenine-induced renal failure in the rat model. ...
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Background: Chronic renal failure (CRF) treatment through kidney transplantation or dialysis is restricted because of economic and medical resources deficiency. Thus, demand for using dietary supplements that can delete or ameliorate uremia or even to delay the need for dialysis is rising. Objectives: This study is the first one conducted to evaluate the efficacy of frankincense aqueous extract on CRF induced by adenine in rats. Materials and Methods: Forty male Sprague‑Dawley rats were divided into four equal groups: control, frankincense, adenine, and frankincense + adenine. Kidney function tests, liver function tests, minerals’ levels, antioxidant status, and histopathological alterations were investigated. Results: Results showed significant increases in relative kidney weight, serum level of urea, creatinine, blood urea nitrogen (BUN), uric acid, phosphorous, cholesterol, total bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in adenine group, as well as significant decreases in body weight, calcium, total protein, and albumin. Significant elevation was also demonstrated in lipid peroxidation marker associated with depletion in activities of superoxide dismutase (SOD) and catalase in tissues of kidney and liver. In addition, there were marked histopathological changes of kidney and liver. Conclusion: Study results demonstrated that co‑administration of frankincense aqueous extract with adenine is an effective way to reduce the signs of adenine‑induced CRF and have returned them to almost completely normal levels.
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Pharmaceutical drugs are chemical compounds that are designed to prevent, diagnose, and treat a specific disorder. Nutraceuticals are products that come from food sources which help in aiding physiological benefits and preventing various diseases. Nutraceuticals have major benefits over pharmaceuticals. These include no adverse effects, being economically affordable, ease of access to the public, multiple therapeutic effects, and increasing the health value by improving the medical condition. Many foods and drugs that classify as nutraceuticals offer health and medical benefits to the consumer. These include dietary supplements, probiotics, vitamins, and medicinal foods. While offering multiple health benefits, many of these nutraceuticals also offer some protection against chronic diseases. These include vitamin C, which has been studied to increase the manageability of various conditions including the more recent pandemic of SARS-CoV-2 infection and reduce the risk of Alzheimer’s disease. These nutraceuticals have also been proven to aid in the treatment of numerous cancers by strengthening the immune system while undergoing chemotherapy. While evidence shows a beneficial effect of these nutraceuticals on human health and disease, dietary supplements are not reviewed and approved by FDA instead FDA issues regulations about ingredients, labeling, registration, etc., and it is the industry’s responsibility to comply with these regulations. Further, there are many clinical trials for the consumption of nutraceuticals. Examples are the use of resveratrol, omega-3, alpha-lipoic acid, curcumin, coenzyme Q10, and l-arginine. This review summarizes the current treatment strategies and clinical trials of nutraceuticals in various conditions with focus on CNS disorders emphasizing its therapeutic value in AD. We believe this information will assist industries and R & D sectors interested in developing nutraceuticals for the treatment of various diseases, as well as patients who suffer from chronic diseases.
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Background: Chronic kidney disease (CKD) is a significant risk factor for cardiovascular disease (CVD) and death. Increased oxidative stress in people with CKD has been implicated as a potential causative factor. Antioxidant therapy decreases oxidative stress and may consequently reduce cardiovascular morbidity and death in people with CKD. This is an update of a Cochrane review first published in 2012. Objectives: To examine the benefits and harms of antioxidant therapy on death and cardiovascular and kidney endpoints in adults with CKD stages 3 to 5, patients undergoing dialysis, and kidney transplant recipients. Search methods: We searched the Cochrane Kidney and Transplant Register of Studies until 15 November 2022 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. Selection criteria: We included all randomised controlled trials investigating the use of antioxidants, compared with placebo, usual or standard care, no treatment, or other antioxidants, for adults with CKD on cardiovascular and kidney endpoints. Data collection and analysis: Titles and abstracts were screened independently by two authors who also performed data extraction using standardised forms. Results were pooled using random effects models and expressed as risk ratios (RR) or mean difference (MD) with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results: We included 95 studies (10,468 randomised patients) that evaluated antioxidant therapy in adults with non-dialysis-dependent CKD (31 studies, 5342 patients), dialysis-dependent CKD (41 studies, 3444 patients) and kidney transplant recipients (21 studies, 1529 patients). Two studies enrolled dialysis and non-dialysis patients (153 patients). Twenty-one studies assessed the effects of vitamin antioxidants, and 74 assessed the effects of non-vitamin antioxidants. Overall, the quality of included studies was moderate to low or very low due to unclear or high risk of bias for randomisation, allocation concealment, blinding, and loss to follow-up. Compared with placebo, usual care, or no treatment, antioxidant therapy may have little or no effect on cardiovascular death (8 studies, 3813 patients: RR 0.94, 95% CI 0.64 to 1.40; I² = 33%; low certainty of evidence) and probably has little to no effect on death (any cause) (45 studies, 7530 patients: RR 0.95, 95% CI 0.82 to 1.11; I² = 0%; moderate certainty of evidence), CVD (16 studies, 4768 patients: RR 0.79, 95% CI 0.63 to 0.99; I² = 23%; moderate certainty of evidence), or loss of kidney transplant (graft loss) (11 studies, 1053 patients: RR 0.88, 95% CI 0.67 to 1.17; I² = 0%; moderate certainty of evidence). Compared with placebo, usual care, or no treatment, antioxidants had little to no effect on the slope of urinary albumin/creatinine ratio (change in UACR) (7 studies, 1286 patients: MD -0.04 mg/mmol, 95% CI -0.55 to 0.47; I² = 37%; very low certainty of evidence) but the evidence is very uncertain. Antioxidants probably reduced the progression to kidney failure (10 studies, 3201 patients: RR 0.65, 95% CI 0.41 to 1.02; I² = 41%; moderate certainty of evidence), may improve the slope of estimated glomerular filtration rate (change in eGFR) (28 studies, 4128 patients: MD 3.65 mL/min/1.73 m², 95% CI 2.81 to 4.50; I² = 99%; low certainty of evidence), but had uncertain effects on the slope of serum creatinine (change in SCr) (16 studies, 3180 patients: MD -13.35 µmol/L, 95% CI -23.49 to -3.23; I² = 98%; very low certainty of evidence). Possible safety concerns are an observed increase in the risk of infection (14 studies, 3697 patients: RR 1.30, 95% CI 1.14 to 1.50; I² = 3%; moderate certainty of evidence) and heart failure (6 studies, 3733 patients: RR 1.40, 95% CI 1.11 to 1.75; I² = 0; moderate certainty of evidence) among antioxidant users. Results of studies with a low risk of bias or longer follow-ups generally were comparable to the main analyses. Authors' conclusions: We found no evidence that antioxidants reduced death or improved kidney transplant outcomes or proteinuria in patients with CKD. Antioxidants likely reduce cardiovascular events and progression to kidney failure and may improve kidney function. Possible concerns are an increased risk of infections and heart failure among antioxidant users. However, most studies were of suboptimal quality and had limited follow-up, and few included people undergoing dialysis or kidney transplant recipients. Furthermore, the large heterogeneity in interventions hampers drawing conclusions on the efficacy and safety of individual agents.
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Guggul, also known as bdellium in India, is a flowering plant that produces oleoresin and is a member of the Burseraceae family. This plant is mostly found in rocky areas of the world This plant has numerous therapeutic advantages. It is a treasure trove of chemical components i.e. lignans, triterpenoids, amino acids, sesquiterpenoids steroids, and flavonoids. This plant leaves, roots and stem extracts are being using in medicine for different diseases. It cure for the skin diseases, anti-inflammatory, anti-cancer, against microbial activity, ulcers, snake bites, stomach pain, healing of wounds and relaxing of the muscles.
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Curcumin, a natural polyphenol, derived from Curcuma longa L. is extensively studied by various researchers across the globe and has established its immense potential in the management of several disorders at clinical level. The underlying mechanism of curcumin involves regulation of various molecular targets, namely, inflammatory cytokines, transcription factor, apoptotic genes, growth factors, oxidative stress biomarkers, and protein kinases. In clinical trials, curcumin as an adjuvant has significantly boost‐up the efficacy of many proven drugs in the management of arthritis, neurodegenerative disorder, oral infection, and gastrointestinal disorders. Moreover, clinical studies have suggested curcumin as an appropriate candidate for the prevention and/or management of various cancers via regulation of signaling molecules including NF‐kB, cytokines, C‐reactive protein, prostaglandin E2, Nrf2, HO‐1, ALT, AST, kinases, and blood profiles. This article highlights plethora of clinical trials that have been conducted on curcumin and its derivatives in the management of several ailments. Besides, it provides recent updates to the investigators for conducting future research to fulfill the current gaps to expedite the curcumin utility in clinical subjects bearing different pathological states.
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Chronic kidney disease (CKD) is a health problem that is constantly growing. This disease presents a diverse symptomatology that implies complex therapeutic management. One of its characteristic symptoms is dyslipidemia, which becomes a risk factor for developing cardiovascular diseases and increases the mortality of CKD patients. Various drugs, particularly those used for dyslipidemia, consumed in the course of CKD lead to side effects that delay the patient’s recovery. Therefore, it is necessary to implement new therapies with natural compounds, such as curcuminoids (derived from the Curcuma longa plant), which can cushion the damage caused by the excessive use of medications. This manuscript aims to review the current evidence on the use of curcuminoids on dyslipidemia in CKD and CKD-induced cardiovascular disease (CVD). We first described oxidative stress, inflammation, fibrosis, and metabolic reprogramming as factors that induce dyslipidemia in CKD and their association with CVD development. We proposed the potential use of curcuminoids in CKD and their utilization in clinics to treat CKD-dyslipidemia.
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The kidney is susceptible to hypoxia and ischemia. Experimental studies and clinical trials showed the protective effects of antioxidants and its nephroprotective effects improving kidney function. This chapter highlights the potential role of synthetic drugs and pharmacological agents isolated from natural compounds used as antioxidants in renal disease treatment, revealed in vitro, in vivo, and clinical trial studies. In vitro, several synthetic agents obtained from natural products, as well as nephroprotective drugs, act mainly decreasing oxidative stress. In vivo, some compounds showed antioxidant and anti-inflammatory activities improving renal function. In clinical studies, a few antioxidants substances showed protective or preventive effects, while others one did not have success in kidney diseases.
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Background Chronic kidney disease (CKD) and end-stage renal diseases, has high global morbidity and mortality. Objective We aimed to investigate the antioxidant and anti-inflammatory properties of curcumin and its impact on kidney biochemical parameters associated with kidney disease among CKD and hemodialysis (HD) patients. Methods The intended keywords were used in the literature search. Clinical trial studies from the very beginning to December 25th, 2021, indexed in the Institute for Scientific Information (ISI), Scopus, and PubMed databases were included in the review. Records with no accessible full texts, non-English language articles, and studies that were not related to the study aim were excluded. The agreement for exclusion required all authors to concur. Finally, after reviewing all available literature, 27 articles were included in this systematic review. Results Curcumin supplementation increased antioxidant capacity by improving catalase (CAT) activity, free radical scavenging activity, and, nuclear factor erythroid 2–related factor 2 (Nrf2). It also reduced hs-CRP, IL-6, and, TNF-a levels in patients with CKD and HD patients. Different results were reported regarding the effect of curcumin on kidney-related biochemical parameters. But mostly the results showed that there are no significant changes were seen in glomerular filtration (GFR), albumin (Alb), serum creatinine (sCr), proteinuria (PRO), and blood urea nitrogen (BUN) in these patients. Conclusion Although it seems curcumin improved antioxidant capacity and decreased inflammatory cytokines in CKD and HD patients, it did not affect renal biochemical parameters. More clinical studies with larger sample sizes appear to be needed.
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Objectives An evaluation the effects of curcumin on inflammatory markers and lipid profiles among patients with chronic kidney diseases (CKD). Methods The electronic databases such as PubMed, and Scopus were searched systematically up until 12 December 2021. To evaluate the quality of the included studies, the Cochrane risk-of-bias tool for randomized trials was utilized. Likewise, data pooling was performed using a random effects model, also called a variance components model. Also, the findings were calculated as weighted mean difference (WMD) with a 95% confidence interval (CI). Results In the end, this meta-analysis comprised a total number of nine studies. Curcumin intake significantly reduced total cholesterol (TC) (WMD=−13.77 mg/dL; 95% CI, −26.77, −0.77; p=0.04) and tumor necrosis factor alpha (TNF-α) (WMD=−18.87 pg/mL; 95% CI, −28.36, −9.38; p<0.001) compared with controls. The results did not confirm the significant effect of curcumin intake on triglyceride (TG) (WMD=−6.37 mg/dL; 95% CI, −26.59, 13.85; p=0.54), low-density lipoproteins (LDL-C) (WMD=−5.65 mg/dL; 95% CI, −20.81, 9.50; p=0.46), high-density lipoprotein (HDL-C) (WMD=0.16 mg/dL; 95% CI, −2.55, 2.88; p=0.91), and C-reactive protein (CRP) (WMD=−0.13 mg/L; 95% CI, −3.25, 3.30; p=0.93). Conclusions Our study showed that curcumin significantly impacts TC and TNF levels in CKD patients.
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In this study, spinel ferrite nanocarriers Ca1–xMnxFe2O4 (0 < x < 1) were fabricated by thermal treatment at 873 K. Different techniques were used to study of structural characteristics and physical properties of ferrite nanocarriers in various concentrations. The highest drug loading was in the x = 0.4 sample and the lowest was observed in the x = 0.6 and x = 0.8 samples. The rapid initial release of Quercetin (Que) occurred at both pH values (5.5 and 7.4), which may be due to the diffusion of Que bound to the surface of nanocarriers (NCs). Although each nanocarrier had its release behavior, with decreased pH from 7.4 to 5.5, the values of Que release percentage increased and x = 0.8 and x = 0.6 samples showed the highest release percentage in both media. The cytotoxicity of NCs and Que-loaded on NCs against HEK 293-T human cells was investigated using the MTT assay. Mild cellular activity of x = 0, x = 0.2, and x = 0.4 NCs may have resulted from Que phenoxyl radicals. The cell viability of cancer cells was examined using the MTT method that was different for each sample at different concentrations, the proliferation of MCF-7 cells was prevented in a dose-dependent manner up by increasing the concentration to 60 µg/ml. The percent hemolytic activity of NCs was also determined by hemolysis assay, but no significant hemolytic activity was observed.
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The last decade has seen an unprecedented rise in the prevalence of chronic diseases worldwide. Different mono-targeted approaches have been devised to treat these multigenic diseases, still most of them suffer from limited success due to the off-target debilitating side effects and their inability to target multiple pathways. Hence a safe, efficacious, and multi-targeted approach is the need for the hour to circumvent these challenging chronic diseases. Curcumin, a natural compound extracted from the rhizomes of Curcuma longa, has been under intense scrutiny for its wide medicinal and biological properties. Curcumin is known to manifest antibacterial, antiinflammatory, antioxidant, antifungal, antineoplastic, antifungal, and proapoptotic effects. A plethora of literature has already established the immense promise of curcuminoids in the treatment and clinical management of various chronic diseases like cancer, cardiovascular, metabolic, neurological, inflammatory, and infectious diseases. To date, more than 230 clinical trials have opened investigations to understand the pharmacological aspects of curcumin in human systems. Still, further randomized clinical studies in different ethnic populations warrant its transition to a marketed drug. This review summarizes the results from different clinical trials of curcumin-based therapeutics in the prevention and treatment of various chronic diseases.
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Renal damage can result from of a variety of insults, including exposure to nephrotoxins, chronic illness, and acute conditions. During wound healing, macrophages infiltrate injured kidney tissue to clear damaged cells and regulate reparative responses, while resident fibroblasts deposit extracellular matrix to promote healing. However, these reparative processes are often dysregulated, especially during severe and chronic insults, resulting in tissue inflammation and fibrosis, and ultimately, long-term disease. Therefore, kidney inflammation and fibrosis present barriers to repair after renal injury. In addition, regenerative capacity is determined by nicotinamide adenine dinucleotide (NAD⁺) production and consumption. This chapter is a review of natural products and their mechanisms of action that may provide benefit in renal regeneration, with specific focus on compounds that target inflammation and fibrosis, and that promote NAD⁺ supply.
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Inflammation and oxidative stress are the main pathological processes that accompany ischemic injury of kidneys and other organs. Based on this, these factors are often chosen as a target for treatment of acute kidney injury (AKI) in a variety of experimental and clinical studies. Note, that since these two components are closely interrelated during AKI development, substances that treat one of the processes often affect the other. The review considers several groups of promising nephroprotectors that have both anti-inflammatory and antioxidant effects. For example, many antioxidants, such as vitamins, polyphenolic compounds, and mitochondria-targeted antioxidants, not only reduce production of the reactive oxygen species in the cell but also modulate activity of the immune cells. On the other hand, immunosuppressors and non-steroidal anti-inflammatory drugs that primarily affect inflammation also reduce oxidative stress under some conditions. Another group of therapeutics is represented by hormones, such as estrogens and melatonin, which significantly reduce severity of the kidney damage through modulation of both these processes. We conclude that drugs with combined anti-inflammatory and antioxidant capacities are the most promising agents for the treatment of acute ischemic kidney injury.
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Turmeric belongs to the family Zingiberaceae and is a yellow spice of high economic importance due to its medicinal value. Cultivated in tropical and sub-tropical regions around the world, it is used extensively as a colouring, flavouring and preserving agent. In recent years, several drugs derived from natural products have been developed and current drug research is actively investigating the possible therapeutic roles of many Ayurvedic medicines, most notable among those being examined is turmeric. The wide range of pharmacological activities attributed to turmeric come mainly from curcuminoids and two related compounds, demethoxycurcumin and bisdemethoxycurcumin. This comprehensive book brings together the research carried out on constituents obtained from turmeric and highlights their chemical and biological activities. Comprising 17 chapters, each written by experts in their respective field and curated by authorities, it will be invaluable to all those who are involved in the production, processing, marketing, and the use of turmeric. Appealing to researchers and professionals in natural products, nutraceuticals and food chemists, this book is exposing some of the myths and showing areas for possible future use.
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Curcumin is a natural compound derived from the spice, turmeric, that has been extensively reported for its efficacy in controlling or treatment of several inflammatory diseases. There is a growing body of literature that recognizes the anti-inflammatory effects of curcumin in the immune system. On the other hand, the role of inflammatory signaling pathways has been highlighted in the pathogenesis of several inflammatory diseases, and signaling molecules involved in these pathways are considered as valuable targets for new treatment approaches. We aimed to provide a comprehensive overview of the modulatory effects of curcumin on inflammatory signaling pathways which leads to inhibition of inflammation in different types of immune cells and animal models. In this comprehensive review, we elaborate on how curcumin can effectively inhibit multiple signaling molecules involved in inflammation including NF-κB, JAKs/STATs, MAPKs, β-catenin, and Notch-1.
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Turmeric dietary supplement sales, which accounted for US$69 million in spending in 2016, have been increasing exponentially in the USA, making this one of the most popular botanical supplements sold in the USA. Herbal supplement use, which is generally regarded as safe by consumers, is not usually reported to healthcare providers. We reported here on a case of autoimmune hepatitis, occurring in a 71-year-old woman taking turmeric dietary supplements for the maintenance of cardiovascular health, which resolved rapidly following discontinuation of the turmeric supplements. Of particular note, turmeric use was not documented in the patient’s medical records and the potential causative role of the turmeric supplementation was ultimately identified by the patient rather than the healthcare providers. To our knowledge, this is the first documented report of turmeric supplement-induced autoimmune hepatitis.
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A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990. To document trends in alternative medicine use in the United States between 1990 and 1997. Nationally representative random household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997, respectively. A total of 1539 adults in 1991 and 2055 in 1997. Prevalence, estimated costs, and disclosure of alternative therapies to physicians. Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8% in 1990 to 42.1% in 1997 (P < or = .001). The therapies increasing the most included herbal medicine, massage, megavitamins, self-help groups, folk remedies, energy healing, and homeopathy. The probability of users visiting an alternative medicine practitioner increased from 36.3% to 46.3% (P = .002). In both surveys alternative therapies were used most frequently for chronic conditions, including back problems, anxiety, depression, and headaches. There was no significant change in disclosure rates between the 2 survey years; 39.8% of alternative therapies were disclosed to physicians in 1990 vs 38.5% in 1997. The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 (64.0%) and 1997 (58.3%) (P=.36). Extrapolations to the US population suggest a 47.3% increase in total visits to alternative medicine practitioners, from 427 million in 1990 to 629 million in 1997, thereby exceeding total visits to all US primary care physicians. An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and/or high-dose vitamins (18.4% of all prescription users). Estimated expenditures for alternative medicine professional services increased 45.2% between 1990 and 1997 and were conservatively estimated at $21.2 billion in 1997, with at least $12.2 billion paid out-of-pocket. This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations. Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $27.0 billion, which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services. Alternative medicine use and expenditures increased substantially between 1990 and 1997, attributable primarily to an increase in the proportion of the population seeking alternative therapies, rather than increased visits per patient.
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5-Loxin is a novel Boswellia serrata extract enriched with 30% 3-O-acetyl-11-keto-beta-boswellic acid (AKBA), which exhibits potential anti-inflammatory properties by inhibiting the 5-lipoxygenase enzyme. A 90-day, double-blind, randomized, placebo-controlled study was conducted to evaluate the efficacy and safety of 5-Loxin in the treatment of osteoarthritis (OA) of the knee. Seventy-five OA patients were included in the study. The patients received either 100 mg (n = 25) or 250 mg (n = 25) of 5-Loxin daily or a placebo (n = 25) for 90 days. Each patient was evaluated for pain and physical functions by using the standard tools (visual analog scale, Lequesne's Functional Index, and Western Ontario and McMaster Universities Osteoarthritis Index) at the baseline (day 0), and at days 7, 30, 60 and 90. Additionally, the cartilage degrading enzyme matrix metalloproteinase-3 was also evaluated in synovial fluid from OA patients. Measurement of a battery of biochemical parameters in serum and haematological parameters, and urine analysis were performed to evaluate the safety of 5-Loxin in OA patients. Seventy patients completed the study. At the end of the study, both doses of 5-Loxin conferred clinically and statistically significant improvements in pain scores and physical function scores in OA patients. Interestingly, significant improvements in pain score and functional ability were recorded in the treatment group supplemented with 250 mg 5-Loxin as early as 7 days after the start of treatment. Corroborating the improvements in pain scores in treatment groups, we also noted significant reduction in synovial fluid matrix metalloproteinase-3. In comparison with placebo, the safety parameters were almost unchanged in the treatment groups. 5-Loxin reduces pain and improves physical functioning significantly in OA patients; and it is safe for human consumption. 5-Loxin may exert its beneficial effects by controlling inflammatory responses through reducing proinflammatory modulators, and it may improve joint health by reducing the enzymatic degradation of cartilage in OA patients. (Clinical trial registration number: ISRCTN05212803.).
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Chronic kidney disease (CKD) is a major public health problem that often goes unrecognized until late-stage disease. In the United States, nearly 20 million people have CKD, and this number is likely to grow as the population ages and the prevalence of diabetes and hypertension rises. With $28 billion currently spent on end-stage renal disease care in the United States and with the rapidly expanding dialysis population, it is essential to actively address this epidemic, both by reducing the number of patients who reach kidney failure and by decreasing morbidity and mortality among those with early-stage CKD. To review the burden of CKD and its comorbidities on patients, physicians, and payers and discuss the potential benefits to individual patients and society of identifying and treating earlier stages of CKD. Major steps in dealing with the CKD epidemic are (1) identifying individuals at risk for and with earlier stages of CKD, (2) initiating therapies to slow progression of kidney disease, and (3) treating comorbid conditions associated with CKD, including cardiovascular disease and anemia.
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Human esophageal epithelial cells play a key role in esophageal inflammation in response to acidic pH during gastroesophageal reflux disease (GERD), increasing secretion of IL-6 and IL-8. The mechanisms underlying IL-6 and IL-8 expression and secretion in esophageal epithelial cells after acid stimulation are not well characterized. We investigated the role of PKC, MAPK, and NF-kappaB signaling pathways and transcriptional regulation of IL-6 and IL-8 expression in HET-1A cells exposed to acid. Exposure of HET-1A cells to pH 4.5 induced NF-kappaB activity and enhanced IL-6 and IL-8 secretion and mRNA and protein expression. Acid stimulation of HET-1A cells also resulted in activation of MAPKs and PKC (alpha and epsilon). Curcumin, as well as inhibitors of NF-kappaB (SN-50), PKC (chelerythrine), and p44/42 MAPK (PD-098059) abolished the acid-induced expression of IL-6 and IL-8. The JNK inhibitor SP-600125 blocked expression/secretion of IL-6 but only partially attenuated IL-8 expression. The p38 MAPK inhibitor SB-203580 did not inhibit IL-6 expression but exerted a stronger inhibitory effect on IL-8 expression. Together, these data demonstrate that 1) acid is a potent inducer of IL-6 and IL-8 production in HET-1A cells; 2) MAPK and PKC signaling play a key regulatory role in acid-mediated IL-6 and IL-8 expression via NF-kappaB activation; and 3) the anti-inflammatory plant compound curcumin inhibits esophageal activation in response to acid. Thus IL-6 and IL-8 expression by acid may contribute to the pathobiology of mucosal injury in GERD, and inhibition of the NF-kappaB/proinflammatory cytokine pathways may emerge as important therapeutic targets for treatment of esophageal inflammation.
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Adherence to the Mediterranean diet (Med-Diet) is associated with a reduced risk of cardiovascular disease (CVD). However, the molecular mechanisms involved are not fully understood. The objective was to compare the effects of 2 Med-Diets with those of a low-fat diet on immune cell activation and soluble inflammatory biomarkers related to atherogenesis in subjects at high risk of CVD. In a controlled study, we randomly assigned 112 older subjects with diabetes or > or =3 CVD risk factors to 3 dietary intervention groups: Med-Diet with supplemental virgin olive oil (VOO), Med-Diet with supplemental nuts, and low-fat diet. Changes from baseline in cellular and serum inflammatory biomarkers were assessed at 3 mo. One hundred six participants (43% women; average age: 68 y) completed the study. At 3 mo, monocyte expression of CD49d, an adhesion molecule crucial for leukocyte homing, and of CD40, a proinflammatory ligand, decreased (P < 0.05) after both Med-Diets but not after the low-fat diet. Serum interleukin-6 and soluble intercellular adhesion molecule-1, inflammatory mediators crucial in firm adhesion of leukocytes to endothelial surfaces, decreased (P < 0.05) in both Med-Diet groups. Soluble vascular cellular adhesion molecule-1 and C-reactive protein decreased only after the Med-Diet with VOO (P < 0.05), whereas interleukin-6, soluble vascular cellular adhesion molecule-1, and soluble intercellular adhesion molecule-1 increased (P < 0.05) after the low-fat diet. Med-Diets supplemented with VOO or nuts down-regulate cellular and circulating inflammatory biomarkers related to atherogenesis in subjects at high risk of CVD. The results support the recommendation of the Med-Diet as a useful tool against CVD.
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We studied three children with chronic gastrointestinal disease who had been on intravenous hyperalimentation for periods of time ranging from 4 to 23 months. Each child was found to have low plasma and red blood cell glutathione peroxidase activity. This was associated, in the two children tested, with a marked deficiency of serum selenium. Their plasma glutathione peroxidase levels ranged between 4 and 24% of normal and their red blood cell levels ranged between 4 and 14% of normal. The intravenous alimentation was then supplemented with sodium selenite (240 micrograms Se/d). Within 4-5 weeks, the plasma glutathione peroxidase activity returned to normal. Red cell glutathione peroxidase activity remained essentially unchanged for 4-6 weeks, after which it increased over the following 3-4 months. Red cells were separated by density on a continuous Percoll-diatrizoate gradient. In normal individuals, the specific activity of glutathione peroxidase did not differ across the gradient despite a 2.5-fold difference in the specific activity of pyruvate kinase. When studied initially, glutathione peroxidase activity from the deficient patients did not change across the gradient. As the red cell enzyme activity increased with selenium repletion, the highest specific activity was initially found at the top of the gradient (youngest cells). After 3-4 months of supplementation, the specific activity became equal across the gradient. Thus, with selenium repletion, there is a rapid increase in plasma glutathione peroxidase activity, a 4-6 week lag prior to an increase in red cell enzyme activity, and the increase in red cell activity is due to newly synthesized red cells made in the presence of selenium.
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Although the medical determinants of mortality in patients with end-stage renal disease (ESRD) treated with hemodialysis (HD) are well appreciated, the contribution of immunologic parameters to survival in such patients is unclear, especially when variations in age, medical comorbidity and nutrition are controlled. In addition, although dysregulation of cytokine metabolism has been appreciated in patients with ESRD, the association of these parameters with outcomes has not been established. Recently, the type of dialyzer used in patients' treatment has been associated with survival, but the mechanisms underlying these findings, including their immune effects, have not been established. We conducted a prospective, cross-sectional, observational multicenter study of urban HD patients to determine the contribution of immunological factors to patient survival. We hypothesized increased proinflammatory cytokines would be associated with increased mortality, and that improved immune function would be associated with survival. Patients were assessed using demographic and anthropometric indices, Kt/V, protein catabolic rate (PCR) and immunologic variables including circulating cytokine [interleukin (IL)-1, IL-2, IL-4, IL-5, IL-6, IL-12, IL-13 and tumor necrosis factor (TNF)-alpha] levels, total hemolytic complement activity (CH50), and T cell number and function. A severity index, previously demonstrated to be a mortality marker, was used to grade medical comorbidity. A Cox proportional hazards model, controlling for patients' age, severity index, level of serum albumin concentration, dialyzer type and dialysis site was used to asses relative survival risk. Two hundred and thirty patients entered the study. The mean (+/- SD) age of the population was 54.4 +/- 14.2 years, mean serum albumin concentration was 3.86 +/- 0.47 g/dl, mean PCR was 1.1 +/- 0.28 g/kg/day, and mean Kt/V 1.2 +/- 0.3. Patients' serum albumin concentration was correlated with levels of Kt/V and PCR, and their circulating IL-13 and TNF-alpha levels, but negatively with their circulating IL-2 levels, T-cell number and T-cell antigen recall function. T-cell antigen recall function correlated negatively with PCR, but not Kt/V. There was no correlation of any other immune parameter and medical or demographic factor. Immune parameters, were all highly intercorrelated. Mean level of circulating cytokines in HD patients were in all cases greater than those of a normal control group. There were few differences in medical risk factors or immune parameters between patients treated with different types of dialyzers. After an almost three-year mean follow-up period, increased IL-1, TNF-alpha, IL-6, and IL-13 levels were significantly associated with increased relative mortality risk, while higher levels of IL-2, IL-4, IL-5, IL-12, T-cell number and function, and CH50 were associated with improved survival. The difference in survival between patients treated with unmodified cellulose dialyzers and modified or synthetic dialyzers approached the level of statistical significance, but there were no differences in levels of circulating cytokines between these two groups. Higher levels of circulating proinflammatory cytokines are associated with mortality, while immune parameters reflecting improved T-cell function are associated with survival in ESRD patients treated with HD, independent of other medical risk factors. These factors may serve as markers for outcome. The mechanism underlying the relationship of immune function and survival, and the effect of interventions to normalize immune function in HD patients should be studied.
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Inflammation, an independent cardiovascular disease risk factor is common in patients with chronic kidney disease. Suppressors of cytokine signaling (SOCS) are induced by cytokines in a variety of cells and modulate inflammatory responses. We hypothesized that in chronic kidney disease, SOCS expression in peripheral blood mononuclear cells is increased, and related to inflammation and renal function. We also tested correlations between SOCS expression and biomarkers and risk factors of cardiovascular disease. Whether monocytes and lymphocytes differentially respond to interleukin-6 (IL-6) was tested ex vivo.
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The aim of this study was to investigate the pro-oxidant and proinflammatory biomarkers and their relationship with dimethylarginines (DMAs) in patients at various stages of chronic kidney disease (CKD). We studied 114 CKD patients, 36 were hemodialyzed, 41 peritoneal dialyzed and 37 nondialyzed (early stage) CKD patients. The control group consisted of 31 healthy subjects. Plasma levels of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), L-arginine, nitric oxide (NO) and proinflammatory cytokines (TNF-alpha and IL-6) were determined, and their relationships with the degree of disease were evaluated. Both DMAs were at high levels in all CKD patients, whereas arginine concentrations were low in patients undergoing dialysis. Elevated TNF-alpha and IL-6 in CKD patients were indicative of ongoing chronic inflammatory state. A significant positive correlation between SDMA and creatinine suggests that plasma SDMA level may be an index for renal function.
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TNF-alpha and NF-kappaB play important roles in the development of inflammation in chronic renal failure (CRF). In hepatic cells, curcumin is shown to antagonize TNF-alpha-elicited NF-kappaB activation. In this study, we hypothesized that if inflammation plays a key role in renal failure then curcumin should be effective in improving CRF. The effectiveness of curcumin was compared with enalapril, a compound known to ameliorate human and experimental CRF. Investigation was conducted in Sprague-Dawley rats where CRF was induced by 5/6 nephrectomy (Nx). The Nx animals were divided into untreated (Nx), curcumin-treated (curcumin), and enalapril-treated (enalapril) groups. Sham-operated animals served as a control. Renal dysfunction in the Nx group, as evidenced by elevated blood urea nitrogen, plasma creatinine, proteinuria, segmental sclerosis, and tubular dilatation, was significantly reduced by curcumin and enalapril treatment. However, only enalapril significantly improved blood pressure. Compared with the control, the Nx animals had significantly higher plasma and kidney TNF-alpha, which was associated with NF-kappaB activation and macrophage infiltration in the kidney. These changes were effectively antagonized by curcumin and enalapril treatment. The decline in the anti-inflammatory peroxisome proliferator-activated receptor gamma (PPARgamma) seen in Nx animals was also counteracted by curcumin and enalapril. Studies in mesangial cells were carried out to further establish that the anti-inflammatory effect of curcumin in vivo was mediated essentially by antagonizing TNF-alpha. Curcumin dose dependently antagonized the TNF-alpha-mediated decrease in PPARgamma and blocked transactivation of NF-kappaB and repression of PPARgamma, indicating that the anti-inflamatory property of curcumin may be responsible for alleviating CRF in Nx animals.