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.

Evaluation of oral nano-curcumin efficacy on respiratory function and quality of life in patients with bronchial non-atopic asthma: A randomized controlled trial.

Objective: Asthma is a common disease and curcumin has modest effect in inflammatory disorders. This study investigated the efficacy of nano-curcumin on asthma. Materials and Methods: In this double-blinded randomized clinical trial, 60 patients with non-atopic bronchial asthma were randomly stratified in two groups of intervention (N=30) and control (N=30) groups. Apart from their standard treatment, the intervention group received 40 mg nano-curcumin (soft gel) three times daily while the control group received placebo. During the 60-day study, patients were assessed using spirometry to measure Forced expiratory volume in first second (FEV1). Asthma control test (ACT) was completed every 30 days and asthma quality of life questionnaire (AQLQ) was completed at the first and end of the study. Results: Totally, 31 patients (51.7%) were male and the mean age was 51.45±12.58 years. FEV1 was improved but there was no significant difference between intervention and control groups. ACT and AQLQ domains scores significantly improved. However, it was not statistically different between control and intervention groups. Conclusion: Nano-curcumin at administered dosage had no additive effect on the standard treatment in asthmatic patients.

Nanocurcumin-Based Sugar-Free Formulation: Development and Impact on Diabetes and Oxidative Stress Reduction.

The objective of this study is the development of innovative nanocurcumin-based formulations designed for the treatment and prevention of oxidative stress and diabetes. Nanocurcumin was obtained through a micronization process and subsequently encapsulated within biopolymers derived from corn starch and fenugreek mucilage, achieving encapsulation rates of 75% and 85%, respectively. Subsequently, the encapsulated nanocurcumin was utilized in the formulation of sugar-free syrups based on Stevia rebaudiana Bertoni. The stability of the resulting formulations was assessed by monitoring particle size distribution and zeta potential over a 25-day period. Dynamic light scattering (DLS) revealed a particle size of 119.9 nm for the fenugreek mucilage-based syrup (CURF) and 117 nm for the corn starch-based syrup (CURA), with polydispersity indices PDIs of 0.509 and 0.495, respectively. The dissolution rates of the encapsulated nanocurcumin were significantly enhanced, showing a 67% improvement in CURA and a 70% enhancement in CURF compared with crude curcumin (12.82%). Both formulations demonstrated excellent antioxidant activity, as evidenced by polyphenol quantification using the 2.2-diphenyl 1-pycrilhydrazyl (DPPH) assay. In the evaluation of antidiabetic activity conducted on Wistar rats, a substantial reduction in fasting blood sugar levels from 392 to 187 mg/mL was observed. The antioxidant properties of CURF in reducing oxidative stress were clearly demonstrated by a macroscopic observation of the rats' livers, including their color and appearance.

Nanocurcumin prevents memory impairment, hippocampal apoptosis, Akt and CaMKII-α signaling disruption in the central STZ model of Alzheimer's disease in rat.

The central route of streptozotocin (STZ) administration has been introduced as a rat model of sporadic Alzheimer's disease (AD). Curcumin was suggested to possess possible neuroprotective effects, which may be profitable in AD. However, the low bioavailability of curcumin hinders its beneficial effects in clinical studies. Earlier studies suggested that a bovine serum albumin-based nanocurcumin, produces superior neuroprotective effects compared to natural curcumin. In the present study, the protective effect of nanocurcumin in rat model of central STZ induced memory impairment was assessed. In addition, due to the importance of the hippocampus in memory, the amounts of hippocampal active caspase-3, Akt, and CaMKII-α were evaluated. Adult male Wistar rats weighing 250-300 g were used. STZ (icv) was injected during days 1 and 3 (3 mg/kg in divided), and nanocurcumin or curcumin 50 mg/kg/oral gavage was administered daily during days 4-14. Morris water maze training was performed on days 15-17, and the retention memory test was achieved on the 18th day. Following memory assessment, the rats were sacrificed and the hippocampi were used to assess caspase-3 cleavage, Akt, and CaMKII-α signaling. The findings revealed that nanocurcumin ingestion (but not natural curcumin) in the dose of 50 mg/kg was capable to prevent the impairment of water maze learning and memory induced by central STZ. Molecular assessments indicated that STZ treatment increased the caspase-3 cleavage in the hippocampus while deactivating Akt and CaMKII-α. Nanocurcumin reduced caspase-3 cleavage to a non-significant level compared to control group and restored Akt and CaMKII-α within the hippocampus while natural curcumin exerted no significant effect. These findings might suggest that nanocurcumin can restore memory deficit, hippocampal apoptosis as well as Akt and CaMKII-α signaling disruption associated with brain insulin resistance.

Protective effect of nanocurcumin on acetaminophen-induced hepatic and renal toxicities in pigeons.

In this study, the effects of nanocurcumin on acetaminophen-induced acute hepatorenal toxicity in domestic pigeons (Columba livia) were investigated. Fifteen pigeons were randomly assigned into three groups. Group I was served as a negative control group and received tap water as a placebo. Pigeons in groups II and III were administered acetaminophen at the beginning of the experiment (hr 0). Group III was further treated with nanocurcumin, at 12 hr after acetaminophen administration, being continued every 12 hr for two days. The birds were observed for clinical signs of acute drug toxicity. Blood samples were collected from the pigeons at hr 0, 12, 24 and 48 of the experiment for biochemical analysis of the serum. The results showed that acetaminophen toxicity increased the serum levels of aspartate aminotransferase, alanine aminotransferase, urea and uric acid in the pigeons. Nanocurcumin treatment of acetaminophen intoxicated pigeons attenuated increases in biomarkers of the liver and kidney functions towards control levels. Also, the consumption of nanocurcumin minimized histopathological changes in the liver and kidney. A mortality of 60.00% was seen in the acetaminophen-induced toxicity group; while, none of the birds treated with nanocurcumin died. It can be concluded that nanocurcumin alleviates the acetaminophen-induced acute toxic liver and kidney damages, which can lead to pigeon mortality.

An overview of the efficacy of inhaled curcumin: a new mode of administration for an old molecule.

INTRODUCTION: Curcumin is a polyphenol with a variety of pharmacological actions. Despite its therapeutic effects and well-known safety profile, the utility of curcumin has been limited due to its deprived physical, chemical, and pharmacokinetic profile resulting from limited solubility, durability, prompt deterioration and pitiable systemic availability. Employment of an amalgamated framework integrating the potential advantages of a nanoscaffold alongside the beneficial traits of inhalational drug delivery system beautifully bringing down the restricting attributes of intended curative interventions and further assures its clinical success. AREAS COVERED: Current review discussed different application of inhalable nanocurcumin in different medical conditions. Lung diseases have been the prime field in which inhalable nanocurcumin had resulted in significant beneficial effects. Apart from this several lung protective potentials of the inhaled nanocurcumin have been discussed against severe pulmonary disorders such as pulmonary fibrosis, radiation pneumonitis and IUGR induced bronchopulmonary dysplasia. Also, application of the disclosed intervention in the clinical management of COVID-19 and Alzheimer's Disease has been discussed. EXPERT OPINION: In this portion, the potential of inhalable nanocurcumin in addressing various medical conditions along with ongoing advancements in nanoencapsulation techniques and the existing challenges in transitioning from pre-clinical models to clinical practice has been summarized.

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.

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 evaluation of the antibacterial activity of curcumin-coated gutta-percha versus nanocurcumin-coated gutta-percha against Escherichia coli: An in vitro study.

Introduction: Due to its biological and antibacterial qualities, many plants, including curcumin, are used as phytomedicines in dentistry. They are primarily used as intracanal medication in endodontics to prevent probable chemical side effects and also to address antimicrobial resistance. Curcumin nanoformulations have improved antibacterial activity and improved dispersion, making them the superior form of curcumin. The purpose of this study was to assess curcumin and nanocurcumin's antibacterial properties. As a gutta-percha coating, they are to be tested against Escherichia coli. Materials and Methods: The study employs the standard strain of E. coli, ATCC 25922. The antibacterial activity of gutta-percha cones against E. coli is assessed after coating them with suspensions of curcumin and nanocurcumin. Scanning electron microscopy is utilized to evaluate the coatings' continuity. Results: The gutta-percha cones that are untreated, coated with curcumin, and coated with nanocurcumin exhibit significantly different levels of antibacterial activity. There is statistically significant variation in their antibacterial activity. Conclusion: (1) Compared to curcumin-coated and untreated gutta-percha cones, those coated with nanocurcumin exhibit a stronger antibacterial activity. (2) Compared to uncoated gutta-percha cones, gutta-percha cones coated with curcumin exhibit more antibacterial action.

Nanocurcumin modulates Th17 cell responses in moderate and severe COPD patients.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory process in the airways that results in airflow obstruction. It is mainly linked to cigarette smoke exposure. Th17 cells have a role in the pathogenesis of COPD by secreting pro-inflammatory cytokines, which cause hyperinflammation and progression of the disease. This study aimed to assess the potential therapeutic effects of nanocurcumin on the Th17 cell frequency and its responses in moderate and severe COPD patients. This study included 20 patients with severe COPD hospitalized in an intensive care unit (ICU) and 20 patients with moderate COPD. Th17 cell frequency, Th17-related factors gene expression (RAR-related orphan receptor t (RORγt), IL-17, IL-21, IL-23, and granulocyte-macrophage colony-stimulating factor), and serum levels of Th17-related cytokines were assessed before and after treatment in both placebo and nanocurcumin-treated groups using flow cytometry, real-time PCR, and ELISA, respectively. According to our findings, in moderate and severe nanocurcumin-treated COPD patients, there was a substantial reduction in the frequency of Th17 cells, mRNA expression, and cytokines secretion level of Th17-related factors compared to the placebo group. Furthermore, after treatment, the metrics mentioned above were considerably lower in the nanocurcumin-treated group compared to before treatment. Nanocurcumin has been shown to decrease the number of Th17 cells and their related inflammatory cytokines in moderate and severe COPD patients. As a result, it might be used as an immune-modulatory agent to alleviate the patient's inflammatory state.

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.

Ameliorative anti-coagulant, anti-oxidative and anti-ferroptotic activities of nanocurcumin and donepezil on coagulation, oxidation and ferroptosis in Alzheimer's disease.

Alzheimer's disease (ad) is a neurological condition that worsens over time and is characterized by the buildup of amyloid (Aß) plaques in the brain parenchyma. Neuroprotection and cholinesterase inhibition have been the two primary techniques used in the creation of medications to date. In ad, a novel sort of programmed cell death known as ferroptosis takes place along with iron buildup, lipid peroxidation, and glutathione deficiency. The objective of the current investigation was to examine the neuroprotective and anti-ferroptotic role of nanocurcumin and Donepezil against model of aluminum chloride AlCl3 and D-galactose induced ad. The experiment was performed on 70 rats divided into (G1: control, G2: NCMN, G3: Donepezil, G4: ad-model, G5: Donepezil co-treatment, G6: NCMN co-treatment and G7: NCMN+Donepezil co-treatment). Hematological parameters and biochemical investigations as oxidative stress, liver function, kidney function, iron profile and plasma fibrinogen were evaluated. Treatment with Nanocurcumin alone or in combination with Donepezil improved oxidative stress, liver functions, and kidney functions, improve iron profile and decreased plasma fibrinogen.

Enhanced Drug Carriage Efficiency of Curcumin-Loaded PLGA Nanoparticles in Combating Diabetic Nephropathy via Mitigation of Renal Apoptosis.

Objectives: The Curcuma-derived diferuloylmethane compound CUR, loaded on Poly (lactide-co-glycolic) acid (PLGA) nanoparticles was utilized to combat DN-induced renal apoptosis by selectively targeting and modulating Bcl2. Methods: Upon in silico molecular docking and screening study CUR was selected as the core phytocompound for nanoparticle formulation. PLGA-nano-encapsulated-curcumin (NCUR) were synthesized following standard solvent displacement method. The NCUR were characterized for shape, size and other physico-chemical properties by Atomic Force Microscopy (AFM), Dynamic Light Scattering (DLS) and Fourier-Transform Infrared (FTIR) Spectroscopy studies. For in vivo validation of nephro-protective effects, Mus musculus were pre-treated with CUR at a dose of 50 mg/kg b.w. and NCUR at a dose of 25 mg/kg b.w. (dose 1), 12.5 mg/kg b.w (dose 2) followed by alloxan administration (100 mg/kg b.w) and serum glucose levels, histopathology and immunofluorescence study were conducted. Results: The in silico study revealed a strong affinity of CUR towards Bcl2 (dock score -10.94 Kcal/mol). The synthesized NCUR were of even shape, devoid of cracks and holes with mean size of ~80 nm having -7.53 mV zeta potential. Dose 1 efficiently improved serum glucose levels, tissue-specific expression of Bcl2 and reduced glomerular space and glomerular sclerosis in comparison to hyperglycaemic group. Conclusion: This study essentially validates the potential of NCUR to inhibit DN by reducing blood glucose level and mitigating glomerular apoptosis by selectively promoting Bcl2 protein expression in kidney tissue.

Evaluation of curcumin-based ophthalmic nano-emulsion on atropine-induced dry eye in mice.

Background: One of the most efficient treatments for dry eye syndrome (DES) is to use nanocarriers as a potential delivery system. We aim to evaluate curcumin in a nano emulsion formulation. Methods: A new formulation containing 5.5% curcuminoid was used. DLS, Zeta potential, TEM, and HPLC tests were performed to determine the size and morphology. First, 30 mice were selected as atropine-induced dry eye models. Next, 25 mice in 5 groups were treated with the nano emulsion at different doses, and corneal tissues were separated for evaluation. Results: The DLS test results were indicative of the particles' stability. Nano curcumin appeared to be thoroughly effective in all groups, with the highest dose showing the most similarity to the healthy control group. Conclusions: Curcumin-based nano emulsion eye drop is a promising candidate for DES management. However, further investigation is required to evaluate the possible risks in humans.

Microbial fermentation-based synthesis of nano-curcumin suggesting the role of pullulan in nano-formulation.

Curcumin is a multitargeting nutraceutical with numerous health benefits, however, its efficacy is limited due to poor aqueous solubility and reduced bioavailability. While nano-formulation has emerged as an alternative to encounter such issues, it often involves use of toxic solvents. Microbial synthesis may be an innovative solution to address this lacuna. Present study, for the first time, reports exploitation of Aureobasidium pullulans RBF4A3 for production of nano-curcumin. For this purpose, Aureobasidium pullulans RBF4A3 was inoculated in YPD media along with curcumin (0.1 mg/mL) and incubated for 24 h, 48 h, and 72 h. Subsequently, residual sugar, biomass, EPS concentration, curcumin concentration, and curcumin nanoparticle size were measured. As a result, nano-curcumin with an average particle size of 31.63 nm and enhanced aqueous solubility was obtained after 72 h. Further, investigations suggested that pullulan, a reducing polysaccharide, played a significant role in curcumin nano-formulation. Pullulan-mediated nano-curcumin formulation, with an average particle size of 24 nm was achieved with conversion rate of around 59.19 %, suggesting improved aqueous solubility. Additionally, the anti-oxidant assay of the resulting nano-curcumin was around 53.7 % per µg. Moreover, kinetics and thermodynamic studies of pullulan-based nano-curcumin revealed that it followed first-order kinetics and was favored by elevated temperature for efficient bio-conversion. Also, various physico-chemical investigations like FT-IR, NMR, and XRD reveal that pullulan backbone remains intact while forming curcumin nanoparticle. This study may open up new avenues for synthesizing nano-polyphenols through a completely green and solvent free process with plausible diverse applications.

Effect of nanocurcumin on fertility in murine model of polycystic ovary syndrome.

The precise pathophysiology of polycystic ovary syndrome (PCOS) is not well-founded. In an attempt to fill this gap, the current study was executed to probe the effect of nanocurcumin (NCC) on ovarian tissue, in vitro fertilization (IVF) and pre-implantation embryo development in a mouse model of PCOS. Fifty adult female mice were randomly categorized into five equal groups including non-treated control and PCOS (receiving 0.20 mg estradiol valerate (EV) intra-peritoneally once a day for 21 days) as well as NCC12.50 + PCOS, NCC25 + PCOS and NCC50 + PCOS (receiving respectively 12.50, 25.00 and 50.00 mg kg-1 NCC daily along with EV injection through oral gavages for 21 days) groups. Subsequently, ovarian histo-architecture and total anti-oxidant capacity, and malonaldehyde and catalase levels as well as in vitro fertilizing potential, early embryonic development and serum testosterone concentration were analyzed. Results showed that NCC in a dose-dependent manner improved ovarian cyto-architectural organization and oxidant/anti-oxidant balance along with IVF rate and pre-implantation embryo development in PCOS mice. These findings revealed that NCC at the doses of 25.00 and 50.00 mg kg-1 could alleviate PCOS-linked reproductive disruptions in female mice.

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.

Immunoregulatory effects of nanocurcumin in inflammatory milieu: Focus on COVID-19.

The use of natural compounds, such as curcumin, to treat infections caused by bacteria, viruses, fungi, parasites, inflammatory diseases, and various types of cancer is an active and dynamic area of research. Curcumin has a long history of use in the food industry, and there is currently a growing interest in its therapeutic applications. Numerous clinical trials have consistently shown that curcumin, a polyphenolic compound, is safe and well-tolerated even at high doses. There is no toxicity limit. However, the clinical efficacy of curcumin has been limited by its constraints. However, scientific evidence indicates that the use of adjuvants and carriers, such as nanoparticles, exosomes, micelles, and liposomes, can help overcome this limitation. The properties, functions, and human benefits of using nanocurcumin are well-supported by scientific research. Recent evidence suggests that nanocurcumin may be a beneficial therapeutic modality due to its potential to decrease gene expression and secretion of specific inflammatory biomarkers involved in the cytokinestorm seen in severe COVID-19, as well as increase lymphocyte counts. Nanocurcumin has demonstrated the ability to improve clinical manifestations and modulate immune response and inflammation in various autoinflammatory diseases. Additionally, its efficacy, affordability, and safety make it a promising replacement for residual cancer cells after tumor removal. However, further studies are necessary to evaluate the safety and efficacy of nanocurcumin as a new therapeutic in clinical trials, including appropriate dosage, frequency, and duration.

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.