The synergistic effect of nanocurcumin and donepezil on Alzheimer's via PI3K/AKT/GSK-3ß pathway modulating.

Alzheimer's disease (AD) hallmarks include amyloid-ßeta (Aß) and tau proteins aggregates, neurite degeneration, microglial activation with cognitive impairment. Phosphatidylinositol-3-kinase/protein kinase B/Glycogen synthase kinase-3-beta (PI3K/AKT/GSK-3) pathway is essential for neuroprotection, cell survival and proliferation by blocking apoptosis. This study aimed to assess protective role of nanocurcumin (NCMN) as strong antioxidant and anti-inflammatory agent with elucidating its synergistic effects with Donepezil as acetylcholinesterase inhibitor on AD in rats via modulating PI3K/AKT/GSK-3ß pathway. The experiment was performed on 70 male Wistar albino rats divided into seven groups (control, NCMN, Donepezil, AD-model, Donepezil co-treatment, NCMN only co-treatment, and NCMN+Donepezil combined treatment). Behavioral and biochemical investigations as cholinesterase activity, oxidative stress (malondialdehyde, reduced glutathione, nitric oxide, superoxidedismutase, and catalase), tumor necrosis factor-alpha, Tau, ß-site amyloid precursor protein cleaving enzyme-1 (BACE-1), Phosphatase and tensin homolog (Pten), mitogen-activated protein kinase-1 (MAPK-1), Glycogen synthase kinase-3-beta (GSK-3ß) and toll-like receptor-4 were evaluated. Treatment with NCMN improved memory, locomotion, neuronal differentiation by activating PI3K/AKT/GSK-3ß pathway. These results were confirmed by histological studies in hippocampus.

Nanocurcumin attenuates pyroptosis and inflammation through inhibiting NF-κB/GSDMD signal in high altitude-associated acute liver injury.

Exposure to a hypobaric hypoxic environment at high altitudes can lead to liver injury, and mounting evidence indicates that pyroptosis and inflammation play important roles in liver injury. Curcumin (Cur) can inhibit pyroptosis and inflammation. Therefore, our purpose here was to clarify the mechanism underlying the protective effect of nanocurcumin (Ncur) and Cur in a rat model of high altitude-associated acute liver injury. Eighty healthy rats were selected and exposed to different altitudes (6000 or 7000 m) for 0, 24, 48, or 72 h. Fifty normal healthy rats were divided into normal control, high-altitude control, salidroside (40 mg/kg [Sal-40]), Cur (200 mg/kg [Cur-200]), and Ncur (25 mg/kg [Ncur-25]) groups and exposed to a high-altitude hypobaric hypoxic environment (48 h, 7000 m). Serum-liver enzyme activities (alanine transaminase, aspartate transaminase, and lactate dehydrogenase were detected and histopathology of liver injury was evaluated by hematoxylin and eosin staining, and inflammatory factors were detected in liver tissues by enzyme-linked immunosorbent assays. Pyroptosis-associated proteins (gasdermin D, gasdermin D N-terminal [GSDMD-N], pro-Caspase-1, and cleaved-Caspase-1 [cleaved-Casp1]) and inflammation-associated proteins (nuclear factor-κB [NF-κB], phospho-NF-κB [P-NF-κB], and high-mobility group protein B1 [HMGB1]) levels were analyzed by immunoblotting. Ncur and Cur inhibited increased serum-liver enzyme activities, alleviated liver injury in rats caused by high-altitude hypobaric hypoxic exposure, and downregulated inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-18, in rat liver tissues. The level of P-NF-κB, GSDMD-N, cleaved-Casp1, and HMGB1 in rat liver tissues increased significantly after high-altitude exposure. Ncur and Cur downregulated P-NF-κB, GSDMD-N, cleaved-Casp-1, and HMGB1. Ncur and Cur may inhibit inflammatory responses and pyroptosis in a rat model of high altitude-associated acute liver injury.

The effects of dietary Spirulina platensis or curcumin nanoparticles on performance, body chemical composition, blood biochemical, digestive enzyme, antioxidant and immune activities of Oreochromis niloticus fingerlings.

CONTEXT: Recently, prioritize has been given to using natural phytogenic or nano compounds as growth promoters and immunostimulants in fish diets as an alternative to antibiotics. AIMS: The main propose of this trial was to determine the impact of supplementing diets with spirulina or curcumin nanoparticles on the performance and health indicators of Nile tilapia fingerlings. METHODS: In a 56-day feeding trial, 180 tilapia fingerlings were assigned into three main groups, as follows: 1st, control group, 2nd, Spirulina platensis (SP; 5 g kg-1 diet) and 3rd, curcumin nanoparticles (CUR-NPs; 30 mg kg-1 diet). KEY RESULTS: Incorporating tilapia diets with SP or CUR-NPs significantly improved performance, body chemical analysis, blood biochemical and hematological indices, digestive enzyme activities, and antioxidant and immunostimulant features compared to the control. CONCLUSION: Fortified tilapia diets with CUR-NPs or SP efficiently boost the productivity and health of Nile tilapia fingerlings. IMPLICATIONS: The research introduces new practical solutions for applying safe feed additives as alternatives to antibiotics in tilapia farming.

Comparative effects of curcumin, nano curcumin and their combination on reproductive traits and spawning performance of red tilapia (Oreochromis Niloticus X O. Mossambicus).

Curcumin, the main polyphenol component of turmeric powder, has garnered increasing attention as an effective supplement in fish diets. A comparative trial was conducted to evaluate the impacts of dietary supplementation with different forms of curcumin (free, in combination, or nanoparticles) on hemato-biochemical parameters, reproductive capacity, and related gene expressions of red tilapia (Oreochromis niloticus x O. mossambicus) broodstock. Fish (n = 168) were fed an isonitrogenous (30% CP), isocaloric (18.72 MJ kg - 1) diet containing basal diet (Control), 60 mg kg-1 of either free curcumin (Cur), curcumin/nano-curcumin blend (Cur/NCur), or nano-curcumin (NCur) for 56 days. Red tilapia broodstock (155 ± 5.65 g) were stocked at a male: female ratio of 1:3. Blood samples and gonads were collected to assess hemato-biochemical parameters, reproductive capacity, and related gene expression at the end of the feeding trial. The results indicated that the values of hematological parameters (RBCs, WBCs, hemoglobin), total protein, albumin values, and reproductive hormones (T, LH, and FSH) were significantly increased, while liver function enzymes were decreased in the NCur group (P < 0.05). Reproductive performances (GSI, gonad maturation, total number of fry per female) were significantly improved in the NCur group compared with those in other groups (p < 0.05). The expression of reproductive genes (CYP19A1A, FSHR, LHR, FOXL2A, ESR1, ESR2A, and PGR) were significantly up-regulated in the gonads of fish fed NCur. Collectively, feeding red tilapia diets containing NCur led to noticeably better results followed by Cur/NCur blend, then free Cur compared to the control diet. These results indicate the superiority of NCur over its free or blended form, suggesting that a diet containing about 60 mg/kg of NCur is beneficial for enhancing hemato-biochemical parameters, improving reproductive performance, and enhancing the gonadal architecture of red tilapia.

Curcumin and its nano-formulations combined with exercise: From molecular mechanisms to clinic.

Curcumin is a strong substance derived from turmeric, a popular spice, renowned for its antioxidant and anti-inflammatory abilities. The study delved deeply into a thorough examination of various sources to evaluate the impact of both regular curcumin and nano-formulated curcumin on elements that impact physical performance, including muscular strain, discomfort, swelling, and oxidative tension. While engaging in exercise, the body experiences a rise in reactive oxygen species and inflammation. As a result, it is important to ensure a proper balance between internal and external sources of antioxidants to maintain stability in the skeletal muscle. Without this balance, there is a risk of muscle soreness, damage, and ultimately, a decline in exercise performance. Curcumin possesses the ability to enhance physical performance and reduce the symptoms of muscle fatigue and injury by virtue of its antioxidative and anti-inflammatory properties. Including curcumin supplements appears to have advantageous effects on various aspects of exercise, such as enhancing performance, assisting with recovery, lessening muscle damage and discomfort, and lowering levels of inflammation and oxidative stress. However, a thorough assessment is necessary to precisely gauge the healing advantages of curcumin in enhancing exercise ability and reducing recovery time.

Nanocurcumin: A Promising Therapeutic Candidate for Experimental Trichinellosis.

In our pursuit of an alternative drug against Trichinella spiralis, we assessed the effectiveness of nanocurcumin in alleviating pathogenesis, parasitological factors, MMP-9 levels, and its expression in the enteral and parenteral phases of infection. The nanocurcumin particles, with a spherical shape and a size of 100 ± 20 nm, were used in the study. Eighty mice were divided into four groups: the control group, the untreated infected group, the nanocurcumin-treated group, and the albendazole-treated group. The nanocurcumin-treated group exhibited a statistically significant increase in the percentage of lymphocytes, along with a reduction in neutrophils, monocytes, and eosinophils compared to the untreated, infected group. Both the nanocurcumin (87.2 and 97.3%) and the albendazole-treated groups (99.8 and 98.2%) showed a significant reduction in the mean number of intestinal worms and encysted larvae, respectively. The treated groups exhibited normal intestinal villi, suppression of the inflammatory process, and fewer instances of degenerated larvae in the diaphragm and muscle compared to the untreated, infected group. Immunohistochemistry and ELISA analyses revealed a significant downregulation of MMP-9 levels in the intestines and muscles of the treated groups. Our data demonstrate that nanocurcumin contains highly versatile molecules capable of modulating biological activity against inflammation and its pathway markers.

Curcumin and nano-curcumin applications in psychiatric disorders.

Psychiatric disorders cause long-lasting disabilities across different age groups. While various medications are available for mental disorders, some patients do not fully benefit from them or experience treatment resistance. The pathogenesis of psychiatric disorders involves multiple mechanisms, including an increase in the inflammatory response. Targeting inflammatory mechanisms has shown promise as a therapeutic approach for these disorders. Curcumin, known for its anti-inflammatory properties and potential neuroprotective effects, has been the subject of studies investigating its potential as a treatment option for psychiatric disorders. This review comprehensively examines the potential therapeutic role of curcumin and its nanoformulations in psychiatric conditions, including major depressive disorder (MDD), bipolar disorder, schizophrenia, and anxiety disorders. There is lack of robust clinical trials across all the studied psychiatric disorders, particularly bipolar disorder and schizophrenia. More studies have focused on MDD. Studies on depression indicate that curcumin may be effective as an antidepressant agent, either alone or as an adjunct therapy. However, inconsistencies exist among study findings, highlighting the need for further research with improved blinding, optimized dosages, and treatment durations. Limited evidence supports the use of curcumin for bipolar disorder, making its therapeutic application challenging. Well-designed clinical trials are warranted to explore its potential therapeutic benefits. Exploring various formulations and delivery strategies, such as utilizing liposomes and nanoparticles, presents intriguing avenues for future research. More extensive clinical trials are needed to assess the efficacy of curcumin as a standalone or adjunctive treatment for psychiatric disorders, focusing on optimal dosages, formulations, and treatment durations.

Evaluating the possible genotoxicity of nanoaluminum incorporated in human vaccines and the potential protective role of nanocurcumin: an in vivo study.

For nearly 90 years, aluminum (Al) salts have been utilized as vaccination adjuvants. Nevertheless, there is a risk of adverse effects associated with the amount of nanoaluminum used in various national pediatric immunization regimens. This study aimed to investigate the possible genotoxic effects of nanoaluminum incorporated in human vaccines on the brains of newborn albino rats and whether nanocurcumin has a potential protective effect against this toxicity. Fifty newborn albino rats were randomly assigned to 5 groups, with 10 in each group. Groups 1 and 2 received "high" and "low" Al injections corresponding to either the American or Scandinavian pediatric immunization schedules, respectively, as opposed to the control rats (group 5) that received saline injections. Groups 3 and 4 received the same regimens as groups 1 and 2 in addition to oral nanocurcumin. The expression of both the cell breakdown gene tumor protein (P53) and the cell stress gene uncoupling protein 2 (UCP2) was significantly greater in groups 1 and 2 than in group 5. Groups 1 and 2 exhibited severe DNA fragmentation, which was observed as DNA laddering. Nanocurcumin significantly reduced the expression of the P53 and UCP2 genes in groups 3 and 4, with very low or undetectable DNA laddering in both groups. Vaccination with nanoaluminum adjuvants can cause genotoxic effects, which can be mediated by the inflammatory response and oxidative stress, and nanocurcumin can protect against these toxic effects through the modulation of oxidative stress regulators and gene expression.

Sustainable, economical and rapid treatment of multiple lung diseases using therapeutic potential of curcumin nanoparticles.

The study was designed to prepare pure curcumin nanoparticles in rapid and simple way for target specific drug delivery to kill bacteria lying deep down within the alveoli of lungs via inhaler. Three different methods including evaporation precipitation of nanosuspension (ENP), solid dispersion (SD) and anti-solvent precipitation (ASP) were selected to prepare nanocurcumin in pure form in very simple way. This was done to compare their efficiency in terms of particle size obtained and water solubility and bacterial toxicity of as prepared curcumin nanoparticles. In this comparative study, curcumin NPs obtained from three different methods having particles size 65.3 nm, 98.7 nm and 47.4 nm respectively. The NPs were characterized using various techniques like SEM, XRD, UV-Visible and FTIR for their particle size determination and solubility evaluation. These particles were screened off against five bacterial strains causing lung diseases. AB3 prepared by ASP method, being smallest sized nanostructures, showed maximum solubility in water. These nanoparticles can be used as drug directly via inhaler to the target area without using any support or nano-carrier. In this way minimum dose formulation is required to target bacteria.

Current appraises of therapeutic applications of nanocurcumin: A novel drug delivery approach for biomaterials in dentistry.

Curcumin is a natural herb and polyphenol that is obtained from the medicinal plant Curcuma longa. It's anti-bacterial, anti-inflammatory, anti-cancer, anti-mutagenic, antioxidant and antifungal properties can be leveraged to treat a myriad of oral and systemic diseases. However, natural curcumin has weak solubility, limited bioavailability and undergoes rapid degradation, which severely limits its therapeutic potential. To overcome these drawbacks, nanocurcumin (nCur) formulations have been developed for improved biomaterial delivery and enhanced treatment outcomes. This novel biomaterial holds tremendous promise for the treatment of various oral diseases, the majority of which are caused by dental biofilm. These include dental caries, periodontal disease, root canal infection and peri-implant diseases, as well as other non-biofilm mediated oral diseases such as oral cancer and oral lichen planus. A number of in-vitro studies have demonstrated the antibacterial efficacy of nCur in various formulations against common oral pathogens such as S. mutans, P. gingivalis and E. faecalis, which are strongly associated with dental caries, periodontitis and root canal infection, respectively. In addition, some clinical studies were suggestive of the notion that nCur can indeed enhance the clinical outcomes of oral diseases such as periodontitis and oral lichen planus, but the level of evidence was very low due to the small number of studies and the methodological limitations of the available studies. The versatility of nCur to treat a diverse range of oral diseases augurs well for its future in dentistry, as reflected by rapid pace in which studies pertaining to this topic are published in the scientific literature. In order to keep abreast of the latest development of nCur in dentistry, this narrative review was undertaken. The aim of this narrative review is to provide a contemporaneous update of the chemistry, properties, mechanism of action, and scientific evidence behind the usage of nCur in dentistry.

Synergistic effects of dendrosomal nanocurcumin and oxaliplatin on oncogenic properties of ovarian cancer cell lines by down-expression of MMPs.

BACKGROUND: Contrary to the advantageous anticancer activities of curcumin (Cur), limited bioavailability and solubility hindered its efficacy. Here, nontoxic dendrosomal nano carrier with Cur was used to overcome these problems. Despite considerable antitumor properties of Oxaliplatin (Oxa), the limiting factors are drug resistance and adverse side-effects. The hypothesis of this study was to evaluate the possible synergism between dendrosomal nanocurcumin (DNC) and Oxa and these agents showed growth regulatory effects on SKOV3 and OVCAR3 cells. METHODS AND MATERIALS: In the present study, colony formation, wound healing motility, cell adhesion, transwell invasion and migration assay and cell cycle arrest with or without DNC, Oxa and Combination were defined. In addition to, real time PCR and Western blot were used to analyze AKT, PI3K, PKC, JNK, P38 and MMPs mRNAs and proteins expressions. Docking of MMP-2-Cur, MMP-2-DNC and MMP-2-Oxa was performed and the results of all three complexes were simulated by molecular dynamics. RESULTS: Our findings illustrated that DNC had the greatest effect on cell death as compared to the Cur alone. Moreover, the growth inhibitory effects (such as cell death correlated to apoptosis) were more intense if Oxa was added followed by DNC at 4 h interval. However, insignificant effects were observed upon simultaneous addition of these two agents in both cell lines. Besides, a combination of agents synergistically alters the relative expression of MMP-9. CONCLUSIONS: The docking results showed that His70 and Asp100 may play a key role at the MMP-2 binding site. The matrigel invasion as well as cell viability of ovarian cancer cell lines SKOV3 and OVCAR3 by DNC alone or in combination with Oxa was inhibited significantly. The inhibitory effects of these agents were due to the differential expression levels of MMP 2 and MMP 9 regulated by multiple downstream signaling cascades. From the molecular dynamic simulation studies, it was confirmed that DNC established a strong interaction with MMP-2.

The effectiveness of nano-curcumin on patients with COVID-19: A systematic review of clinical trials.

The main aim of the current study was to summarize the findings of available clinical studies to assess nano-curcumin's influence on COVID patients. A comprehensive online search was performed in Scopus, PubMed, ISI Web of Science, and Google Scholar until March 2022 to identify trials that investigated the effects of nano-curcumin in patients with COVID-19. Eight studies comprising 569 patients were included in this review. Compared with placebo, nano-curcumin had no significant effect on C-reactive protein (CRP) and high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). However, gene expression of IL-6 and gene expression as well as secretion of interleukin-1 beta (IL-1ß) significantly decreased following nano-curcumin intervention. Nano-curcumin had beneficial effects on fever, cough, chills, myalgia, and olfactory and taste disturbances. The duration of hospitalization and mortality rate were significantly lower in the nano-curcumin group compared with the control group. Lymphocyte count was significantly increased after curcumin supplementation. Nano-curcumin also had favorable effects on O2 saturation, sputum, chest pain, wheeze, and dyspnea in patients with COVID-19. No major adverse effects were reported in response to nano-curcumin supplementation. In summary, the results of this systematic review of clinical trials suggested that nano-curcumin supplementation has beneficial effects on inflammation, respiratory function, disease manifestations, and complications in patients with COVID-19 viral infection.

Promising clinical outcomes of nano-curcumin treatment as an adjunct therapy in hospitalized COVID-19 patients: A randomized, double-blinded, placebo-controlled trial.

Different immunomodulation strategies have been used to manage COVID-19 due to the complex immune-inflammatory processes involved in the pathogenesis of this infection. Curcumin with its powerful anti-inflammatory and antiviral properties could serve as a possible COVID-19 therapy. In this study, a randomized, double-blinded, placebo-controlled trial was performed to investigate the effectiveness and safety of nano-curcumin oral soft gels as a complementary therapy in moderate-severe COVID-19 patients. Hydroxychloroquine (HCQ) plus sofosbuvir was routinely administered to all 42 COVID-19 patients, who were randomly assigned to receive 140 mg of nano-curcumin or placebo for 14 days. CT scans of the chest were taken, and blood tests were run for all patients at time points of 0, 7, and 14 days. Our results indicated that C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels significantly decreased from baseline in the nano-curcumin-treated group on day 7. Furthermore, blood levels of D-dimer, CRP, serum ferritin, ESR, and inflammatory cytokines including IL-6, IL-8, and IL-10 decreased more significantly in the nano-curcumin-treated group after 14 days. Additionally, the nano-curcumin group showed significant improvements in chest CT scores, oxygen saturation levels, and hospitalization duration. Based on our data, oral administration of nano-curcumin may be regarded as a promising adjunct treatment for COVID-19 patients due to its ability to speed up chest clearance and recovery.

Curcumin nanoparticles: the topical antimycotic suspension treating oral candidiasis.

Phytotherapeutics is widely used nowadays as an alternative to the current antifungal drugs to reduce their side effects. Curcumin, with its wide therapeutic array as antioxidant and anti-inflammatory agent, is one of the natural compounds that ha..s an antifungal effect, especially when being used at nanoscale to increase its bioavailability. Our research aimed to evaluate clinically and microbiologically the effect of using topical nanocurcumin suspension to treat oral candidiasis. After 4 days from induction of oral candidiasis (baseline), we randomly divided 39 female BALB/c mice into three groups of 13 animals; nanocurcumin, nystatin, and sham groups. All animals in nanocurcumin and nystatin groups received topical treatment twice daily for 10 days. Then, we performed clinical and microbiological evaluations at baseline, day 5, and day 10. By the end of treatment, our results revealed that nanocurcumin promoted a significant reduction in the number of candida colonies. There was no statistically significant difference neither clinically nor microbiologically between nanocurcumin and nystatin groups. In conclusion, nanocurcumin has a good antifungal effect as nystatin, however, its therapeutic efficacy takes a longer time to appear than nystatin. The enhanced bioavailability of curcumin at the nanoscale qualifies this nano-herb as a promising alternative therapy for oral candidiasis, evading nystatin-associated morbidity.

Protective effects of nanocurcumin against stress-induced deterioration in the intestine.

The therapeutic activities of curcumin have long been investigated in some chronic and inflammatory diseases. This study was designed to investigate the protective effects of nanocurcumin on intestinal barrier function, apoptosis, and oxidative stress in rats exposed to traffic noise. Forty rats were divided into four groups: two traffic noise-exposed groups of animals that received either vehicle (NOISE) or nanocurcumin (NCUR + NOISE) and two control groups that either remained intact (CON) or received nanocurcumin (NCUR). Nanocurcumin injection (15 mg/Kg/ip) and traffic noise exposure were administered daily for two weeks. The relative protein expression of intestinal tight junctions, occludin, and ZO-1 and Bax/Bcl-2 ratio was measured to evaluate barrier integrity and apoptosis in intestinal samples, respectively. Plasma D-lactate concentration was examined as a criterion of intestinal permeability. Corticosterone, superoxide dismutase (SOD) activity, glutathione (GSH), total antioxidant capacity (TAC), and nitrite were measured in serum. The noise exposure increased Bax/Bcl-2 ratio, corticosterone, and oxidative stress in the NOISE animals. Nanocurcumin treatment improved the Bax/Bcl-2 ratio and reduced corticosterone and oxidative stress in the NCUR + NOISE animals. The expression of tight junction proteins was decreased while the concentration of D-lactate was increased in the NOISE animals. Nanocurcumin did not efficiently impact the expression of tight junction proteins and the D-lactate level in the NCUR + NOISE group. Nanocurcumin administration displayed antioxidant and anti-apoptotic roles in the noise-exposed rats, however, it did not affect the intestinal barrier integrity. We concluded that reduced apoptosis in the intestine might be related to the antioxidant activity of nanocurcumin and its modulatory effects on the HPA axis in the nanocurcumin-treated animals.

Ameliorative effect of nanocurcumin and Saccharomyces cell wall alone and in combination against aflatoxicosis in broilers.

BACKGROUND: The adverse effect of aflatoxin in broilers is well known. However, dietary supplementation of Saccharomyces cell wall and/or Nanocurcumin may decrease the negative effect of aflatoxin B1 because of the bio-adsorbing feature of the functional ingredients in Yeast Cell Wall and the detoxification effect of curcumin nanoparticles. The goal of this study was to see how Saccharomyces cell wall/Nanocurcumin alone or in combination with the aflatoxin-contaminated diet ameliorated the toxic effects of aflatoxin B1 on broiler development, blood and serum parameters, carcass traits, histology, immune histochemistry, liver gene expression, and aflatoxin residue in the liver and muscle tissue of broilers for 35 days. Moreover, the withdrawal time of aflatoxin was measured after feeding the aflatoxicated group an aflatoxin-free diet. Broiler chicks one day old were distributed into five groups according to Saccharomyces cell wall and/or nanocurcumin with aflatoxin supplementation. The G1 group was given a formulated diet without any supplements. The G2 group was supplemented with aflatoxin (0.25 mg/kg diet) in the formulated diet. The G3 group was supplemented with aflatoxin (0.25 mg/kg diet) and Saccharomyces cell wall (1 kg/ton diet) in the formulated diet. The G4 group was supplemented with aflatoxin (0.25 mg/kg diet) and nanocurcumin (400 mg/kg) in the formulated diet. The G5 group was supplemented with aflatoxin (0.25 mg/kg diet) and Saccharomyces cell wall (1 kg/ton diet) in combination with nanocurcumin (200 mg/kg) in the formulated diet. RESULTS: According to the results of this study, aflatoxin supplementation had a detrimental impact on the growth performance, blood and serum parameters, carcass traits, and aflatoxin residue in the liver and muscle tissue of broilers. In addition, aflatoxin supplementation led to a liver injury that was indicated by serum biochemistry and pathological lesions in the liver tissue. Moreover, the shortening of villi length in aflatoxicated birds resulted in a decrease in both the crypt depth ratio and the villi length ratio. The expression of CYP1A1 and Nrf2 genes in the liver tissue increased and decreased, respectively, in the aflatoxicated group. In addition, the aflatoxin residue was significantly (P ≤ 0.05) decreased in the liver tissue of the aflatoxicated group after 2 weeks from the end of the experiment. CONCLUSION: Saccharomyces cell wall alone or with nanocurcumin attenuated these negative effects and anomalies and improved all of the above-mentioned metrics.

Nanocurcumin as an adjuvant in killed Toxoplasma gondii vaccine formulation: An experience in BALB/c mice.

Toxoplasma gondii (T. gondii) remains as one of the controversial infections in the world. T. gondii is an important obligate intracellular protozoan parasite in the immune-deficient patients and pregnant women, sometimes leading to death and abortion, respectively. Herein, the adjuvant activity of nanocurcumin was assessed in the T. gondii killed vaccine model in BALB/c mice. In this study, 144 BALB/c mice were included in 8 groups and administered with different regimens of the vaccine; vac+30, 20 mg/kg of curcumin and nanocurcumin, vac + Freund's adjuvant, killed vac, vac + Alum adjuvant, and PBS via the subcutaneous route of immunization for three times with two-week intervals. Two weeks after the last immunization, the splenocytes' culture supernatant was evaluated for IL-4, IFN-γ, IL-2 and TNF-α cytokines and IFN-γ/IL-4, IFN-γ/TNF-α, and IL-2/IL-4 cytokine ratios using commercial ELISA kits. Specific total IgG antibodies, IgG1, and IgG2a were assessed with an optimized ELISA. Then the survival rate was determined 10 days after the experimental challenge. The results showed that the vaccine formulation in nanocurcumin at 20 mg/kg significantly increases IFN-γ cytokine and IFN-γ/IL4, IFN-γ/TNFα, and IL-2/IL4 ratios versus the vaccine formulated in curcumin, killed vaccine, and PBS group. In addition, specific total IgG antibody response showed that the vaccine formulated in nanocurcumin was more potent than that formulated in curcumin in the induction of humoral immune responses. Furthermore, results from the experimental challenge showed that nanocurcumin at a dose of 20 mg/kg could promote the life span of mice approximately by 12% versus the killed vaccine group. The present study showed that nanocurcumin in the vaccine formulation not only is more bioactive than curcumin in the modulation of cellular and humoral immune responses, but also provides more protectivity rate in the vaccinated mice on the killed T. gondii vaccine model. It seems that nanocurcumin can be used as an immunomodulator in vaccine formulation or as part of a complex adjuvant.

Effect of nanocurcumin supplementation on the severity of symptoms and length of hospital stay in patients with COVID-19: A randomized double-blind placebo-controlled trial.

It has been more than a year since the outbreak of COVID-19, and it is still the most critical issue of the healthcare system. Discovering effective strategies to treat infected patients is necessary to decrease the mortality rate. This study aimed to determine the effects of nanocurcumin on the severity of symptoms and length of hospital stay (LOS) in COVID-19 patients. Forty-eight COVID-19 patients were randomly assigned into nanocurcumin (n = 24) and placebo (n = 24) groups receiving 160 mg/day nanocurcumin or placebo capsules for 6 days. Mean differences of O2 saturation were significantly higher in patients who received nanocurcumin supplements (p = 0.02). Also, nanocurcumin treatment significantly reduced the scores of domains 3 and 4 and the total score of Wisconsin Upper Respiratory System Survey (WURSS-24), indicating milder symptoms in the treatment group (p = 0.01, 0.03, and 0.01 respectively). Besides, the LOS in curcumin groups was lower than in the placebo group, although the difference was not statistically significant (6.31 ± 5.26 vs. 8.87 ± 8.12 days; p = 0.416). CBC/differentiate, hs-CRP level and the pulmonary involvement in CT scan were not different between the two groups. As nanocurcumin can be effective in increasing O2 saturation and reducing the severity of symptoms in COVID-19 patients, it could probably be used as a complementary agent to accelerate the recovery of patients.

Nanocurcumin formulation: a possible therapeutic agent for post COVID inflammatory syndrome.

Over the last twenty months, the attention of the world has been focusing on managing the unprecedented and devastating wave of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) and mitigating its impacts. Recent findings indicated that high levels of pro-inflammatory cytokines are leading cause of poor prognosis in severely ill COVID-19 patients. Presently, the multiple variants and highly contagious nature of virus makes challenge humongous. The shortage and vaccine hesitancy also prompted to develop antiviral therapeutic agents to manage this pandemic. Nanocurcumin has potential antiviral activities and also beneficial in post COVID inflammatory complications. We have developed nanocurcumin based formulation using pyrroloquinoline quinone (PQQ) which protects cardio-pulmonary function and mitochondrial homeostasis in hypobaric hypoxia induced right ventricular hypertrophy in animal model and human ventricular cardiomyocytes. Nanocurcumin based formulation (NCF) with improved bioavailability, has proven several holistic therapeutic effects including myocardial protection, and prevents edema formation, anti-inflammatory and antioxidant properties, maintaining metabolic and mitochondrial homeostasis under hypoxic condition. The post COVID-inflammatory syndrome also reported to cause impaired heart function, lung injuries and increased C-reactive protein level in severely ill patients. Thus, we speculate that NCF could be a new treatment option to manage post COVID-19 inflammatory syndrome.

Effects of nanocurcumin supplementation on T-helper 17 cells inflammatory response in patients with Behcet's disease: a randomized controlled trial.

OBJECTIVE: Present research was performed to assess the effects of nanocurcumin supplementation on T-helper 17 (Th17) cells inflammatory response in patients with Behcet's disease (BD). METHODS: In this randomized double-blind, placebo-controlled trial, 36 BD subjects were randomly placed into two groups to take 80 mg/day nanocurcumin or placebo for eight weeks. Disease activity, frequency of Th17 cells and expression of related parameters including retinoic acid-related orphan receptor γ (RORγt) transcription factor messenger RNA (mRNA), related microRNAs (miRNAs) such as miRNA-155, miRNA-181, and miRNA-326 as well as proinflammatory cytokines including interleukin (IL)-17 and IL-23 were evaluated. RESULTS: Thirty-two patients (17 in the nanocurcumin and 15 in the placebo groups) completed the trial. Number of Th17 cells decreased significantly in the nanocurcumin group compared to baseline (p = .012) and placebo (p = .047). Moreover, RORγt, IL-17, IL-23, miRNA-155, miRNA-181, and miRNA-326 mRNA expression decreased significantly in the nanocurcumin group compared with baseline (p = .004, p = .009, p < .001, p < .001, p < .001, p < .001, respectively) and placebo (p = .002, p = .021, p = .006, p = .035, p < .001, p = .017, respectively). Significant reductions in IL-17 and IL-23 were seen in nanocurcumin group compared with baseline (p = .017 and p = .015) and placebo (p = .047 and p = .048, respectively). Significant reduction in disease activity was observed in nanocurcumin group compared with placebo group (p = .035). CONCLUSION: Nanocurcumin supplementation had favorable effects in improving inflammatory factors and disease activity in BD patients. Additional studies are warranted to suggest nanocurcumin as a safe complementary therapy in BD.HighlightsNanocurcumin supplementation decreased Th17 cells frequency significantly compared with baseline and placebo group.Nanocurcumin supplementation decreased mRNA expression of RORγt, IL-17, IL-23, miRNA-155, miRNA-181, and miRNA-326 significantly compared to baseline and placebo group.Nanocurcumin supplementation decreased cell supernatant IL-17 and IL-23 significantly compared to baseline and placebo group.Nanocurcumin supplementation decreased disease activity significantly compared to placebo group.