Curcumin amends Ca2+ dysregulation in microglia by suppressing the activation of P2X7 receptor.

PMID: 

Mol Cell Biochem. 2020 Feb ;465(1-2):65-73. Epub 2020 Jan 1. PMID: 31894530

Abstract Title: 

Curcumin amends Cadysregulation in microglia by suppressing the activation of P2X7 receptor.

Abstract: 

Curcumin (Cur) is widely used as an anti-inflammation agent and has anti-depression potential. Neuroinflammation mediated by Cachannel activation is closely associated with the progression of post-stroke depression (PSD). In the current study, the role of P2X7 receptor (P2X7R) in the anti-PSD function of Cur was explored. Rats were subjected to middle cerebral artery occlusion (MCAO) surgery and chronic mild stress administration to induce PSD symptoms and then treated with Cur. The behaviors of rats were assessed with sucrose preference and forced swim tests. The accumulation of Caand the systemic inflammatory response in rats were detected. To determine the role of P2X7R in the anti-PSD function of curcumin, the PSD mice were further administrated with P2X7R agonist and antagonist. The administration of Cur attenuated behavior disorders associated with PSD. Moreover, the Caaccumulation and the inflammatory response associated with PSD were also blocked by Cur. Cur also inhibited the activation of Cachannel. The induced activity of P2X7R blocked the function of Cur by maintaining the symptoms of PSD in Cur-treated rats. Collectively, the anti-PSD function of Cur was dependent on the inhibition of P2X7R, which then deactivated Cachannel-mediated inflammatory response associated with PSD progression.

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Curcumin improved quality of life in liver cirrhotic patients.

PMID: 

Complement Ther Med. 2020 Mar ;49:102351. Epub 2020 Feb 19. PMID: 32147077

Abstract Title: 

Curcumin ameliorates health-related quality of life in patients with liver cirrhosis: A randomized, double-blind placebo-controlled trial.

Abstract: 

OBJECTIVES: Current study aimed to find the effects of curcumin on quality of life (QoL) in liver cirrhotic patients.DESIGN: In this randomized double-masked placebo-controlled trial, 70 cases with liver cirrhosis aged 20-70 years were randomly divided into two groups to receive 1000 mg/day curcumin (n = 35) or placebo (n = 35) for 12 weeks. The health-related QoL (HRQoL) was assessed by CLDQ, LDSI 2.0, and SF-36.RESULTS: Fifty-eight patients (28 in curcumin and 30 in placebo groups) finished the research. Compared with baseline, overall scores as well as most of CLDQ domains (e.g. Fatigue, Emotional Function, Worry, Abdominal Symptoms, and Systemic Symptoms) and the Physical and Mental health (Total) scores and most of SF-36 domains (e.g. Physical Functioning, Bodily Pain, Vitality, Social Functioning, and Mental Health) increased considerably (P 

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An experimental comparison of the effects of propolis, curcumin, and methylprednisolone on crush injuries of the sciatic nerve.

PMID: 

Ann Plast Surg. 2015 Jun ;74(6):684-92. PMID: 24317243

Abstract Title: 

An experimental comparison of the effects of propolis, curcumin, and methylprednisolone on crush injuries of the sciatic nerve.

Abstract: 

BACKGROUND: Propolis and curcumin have antioxidant, anti-inflammatory, immunomodulatory, and neuroprotective features. The goal of this study was to determine the effects of propolis and curcumin on nerve healing in rat sciatic nerve crush injuries and to compare these effects with results obtained using steroid treatment.METHODS: In the sham group, the right sciatic nerves of rats were dissected and exposed, and the skin was closed without any additional manipulation. In the control group (group C), after the right sciatic nerves of rats were exposed, crush damage was inflicted using a surgical clamp. In the control-methylprednisolone group, crush injuries were inflicted on sciatic nerves as in group C. After injury, 1-mg/kg methylprednisolone was administered daily for 6 days and was then tapered for 4 days. In the curcumin group, crush injuries were inflicted on sciatic nerves as in group C. Then, 100-mg/kg curcumin was given every day. In the propolis group, crush injuries were inflicted on sciatic nerves as in group C. Then, 200-mg/kg propolis was given every day. Rats were evaluated after 28 days using functional (walking track analysis and electrophysiological measurements), histomorphometric, electron microscopic, and muscle weight measurements.RESULTS: Compared to the control groups, the curcumin and propolis groups had better functional (walking track analysis and electrophysiological) results after experimental peripheral nerve crush injury.CONCLUSIONS: Curcumin and propolis, 2 traditional drugs, had a positive effect on nerve crush injuries. We are convinced that they can be used to support routine treatment in such nerve injuries.

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Immunomodulatory effects of nanocurcumin in arsenic-exposed rats.

PMID: 

Int Immunopharmacol. 2013 Sep ;17(1):65-70. Epub 2013 Jun 6. PMID: 23747587

Abstract Title: 

Immunomodulatory effects of nanocurcumin in arsenic-exposed rats.

Abstract: 

We evaluated whether the nanoformulation of curcumin could be more effective than free curcumin against arsenic-induced immune dysfunction in rats. Curcumin was encapsulated in polylactic-co-glycolic acid (PLGA). Nanocurcumin (CUR-NP) exhibited a spherical shape with the mean particle size of 130.8 nm. Rats were randomly divided into five groups of six each. Group I was kept as the control. In Group II, rats were exposed to sodium arsenite (25 ppm) daily through drinking water for 42 days. Groups III, IV and V were treated with arsenic as in Group II, however, they were administered with nanoparticle, curcumin (100 mg/kg bw) and CUR-NP (100 mg/kg bw), respectively, by oral gavage during the last 14 days of arsenic exposure. At term, serum and spleen were collected. Immune dysfunction was evaluated by assessing cellular and humoral immunities. Arsenic significantly decreased the splenic lymphocyte proliferation in response to the antigen — Keyhole Limpet Hemocyanin (KLH) and mitogen — concanavalin-A. Arsenic reduced both the delayed type hypersensitivity response and secondary antibody (IgG) response to KLH. It also reduced the lipopolysaccharide-stimulated nitric oxide production in splenic lymphocytes. Free curcumin and CUR-NP treatment significantly attenuated these arsenic-mediated effects. However, the magnitude of the effects indicates that CUR-NP has better ameliorative potential than free curcumin at the equivalent dose level.

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These findings offer curcumin as a new therapeutic agent with the potential of regulating astrocyte-mediated inflammatory diseases in the CNS.

PMID: 

Int Immunopharmacol. 2014 Sep ;22(1):230-5. Epub 2014 Jul 3. PMID: 24998635

Abstract Title: 

Study of curcumin immunomodulatory effects on reactive astrocyte cell function.

Abstract: 

Multiple sclerosis (MS) is considered an inflammatory and neurodegenerative disease of the central nervous system (CNS) which most often presents as relapsing-remitting episodes. Recent evidence suggests that activated astrocytes play a dual functional role in CNS inflammatory disorders such as MS. In this study, we tried to induce anti-inflammatory functions of astrocytes by curcumin. The effects of curcumin were examined on human a astrocyte cell line (U373-MG) induced by lipopolysaccharide (LPS) in vitro. Matrix metalloproteinase (MMP)-9 activity was assessed by gelatin zymography. Cytokine levels were evaluated by quantitative ELISA method and mRNA expression was measured by real-time PCR. We found that curcumin decreased the release of IL-6 and reduced MMP-9 enzyme activity. It down-regulated MCP-1 mRNA expression too. However, curcumin did not have significant effects on the expression of neurotrophin (NT)-3 and insulin-like growth factor (IGF)-1 mRNAs. Results suggest that curcumin might beneficially affect astrocyte population in CNS neuroinflammatory environment lean to anti-inflammatory response and help to components in respects of CNS repair. Our findings offer curcumin as a new therapeutic agent with the potential of regulating astrocyte-mediated inflammatory diseases in the CNS.

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Curcumin has strong antioxidant, with anti-inflammatory, immunomodulatory and analgesic properties.

PMID: 

Int J Pharm Investig. 2014 Jul ;4(3):138-41. PMID: 25126527

Abstract Title: 

Comparison of effectiveness of curcumin with triamcinolone acetonide in the gel form in treatment of minor recurrent aphthous stomatitis: A randomized clinical trial.

Abstract: 

INTRODUCTION: Recurrent aphthous stomatitis (RAS) is an unfortunately most common disease occurring in oral cavity. Although the lesion is usually self-limited, its painful presentation, high frequency of occurrence, and multifactorial etiology leads to significant morbidity. So, an efficient therapeutic strategy is needed to provide relief to the patients.AIM: To assess and compare the efficacy of Curcumin with Triamcinolone acetonide in the gel form in treatment of minor RAS.MATERIALS AND METHODS: As a randomized clinical trial, 60 patients of either sex with clinically diagnosed RAS were randomly divided into 2 groups-Curcumin gel group (Group I) and Triamcinolone Acetonide gel group (Group II). Patients in either group were asked to apply the gel three times a day on each ulcer. Assessment of efficacy of gel was done on the basis of time required for regression in pain, size, and number of the ulcers.RESULTS: The results showed significant difference in size, pain, number, and duration of ulcers in Group I and Group II within a period of 7 days. However, no significant difference was noted in both the groups in the treatment of RAS. To evaluate the efficacy, Mann-Whitney U test was used and statistical analysis was done using Statistical Package for the Social Sciences (SPSS) 19 software.CONCLUSION: Curcumin has strong antioxidant, with anti-inflammatory, immunomodulatory and analgesic properties, which according to the results obtained from the present study, can be used as an effective alternative to steroids in treatment of RAS.

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Curcumin loaded solid lipid nanoparticles ameliorate adjuvant-induced arthritis.

PMID: 

Eur J Pain. 2015 Aug ;19(7):940-52. Epub 2014 Nov 17. PMID: 25400173

Abstract Title: 

Curcumin loaded solid lipid nanoparticles ameliorate adjuvant-induced arthritis in rats.

Abstract: 

BACKGROUND: Rheumatoid arthritis (RA), a chronic and systemic inflammation, results in destruction of joints and cartilages. Effectiveness of curcumin has been established in a wide variety of inflammatory disorders, but its utility as a therapeutic agent is limited by its poor absorption, rapid metabolism and fast systemic elimination. To apprehend these limitations, we propose to use highly bioavailable curcumin loaded solid lipid nanoparticles (C-SLNs) for the treatment of RA.METHODS: In the present study, the protective effect of curcumin and its SLNs was evaluated in complete Freund's adjuvant (CFA)-induced arthritis in rats.RESULTS: Arthritic rats exhibited marked decrease in paw withdrawal threshold in Randall-Selitto and von Frey hair test along with decreased reaction time in hot plate. Arthritic rats also showed significant joint hyperalgesia, joint stiffness and increased paw volume along with marked decrease in mobility score. Arthritic rats showed a significant increase in blood leukocyte count, oxidative-nitrosative stress, tumour necrosis factor-α, C-reactive protein, cyclic citrullinated peptide antibody levels and radiological alterations in tibiotarsal joint. C-SLN administration (10 and 30 mg/kg), when compared with free curcumin (10 and 30 mg/kg), significantly and dose dependently ameliorated various symptoms of arthritis in rats, improved biochemical markers and preserved radiological alterations in joints of arthritic rats.CONCLUSIONS: The current findings suggest the protective potential of curcumin-SLNs in ameliorating CFA-induced arthritis in rats through attenuation of oxido-inflammatory and immunomodulatory cascade. Further, the results emphasize that SLNs are a novel approach to deliver curcumin into the inflamed joints and improve its biopharmaceutical performance.

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The study demonstrated that curcumin was a potent protective compound against the nicotine-induced stress.

PMID: 

Mol Biol Rep. 2015 Dec ;42(12):1623-37. Epub 2015 Nov 11. PMID: 26559197

Abstract Title: 

Curcumin protects against nicotine-induced stress during protein malnutrition in female rat through immunomodulation with cellular amelioration.

Abstract: 

Nicotine aggravates many chronic inflammatory disorders in females under the protein-malnourished conditions because women are more susceptible to nicotine-induced diseases due to their low innate immunity. Although curcumin have been found to obliterate the nicotine-induced disorders through its anti-nicotinic activity under the protein-malnourished condition, the exact mechanism of protective action of curcumin is still unclear. Female Wister rats maintained under the normal and protein-restricted diets in two separate groups were injected with the effective dose of nicotine-tartrate (2.5 mg/kg body weight/day, subcutaneously) and supplemented with the effective dose of curcumin (80 mg/kg body weight/day, orally) for 21 days. The morphology of red blood cells (RBCs), molecular docking, lipid profile and activities of antioxidant enzymes in tissues, cytokines profiling (T helper cell type 1; and T helper cell type 2), mRNA and protein expression of cytokines, transcription factors (activator protein 1), regulatory molecule (P(53)), growth factors (Granulocyte-macrophage colony-stimulating factor; Transforming growth factor beta) were determined to establish the mechanism ofactions of curcumin against the nicotine-mediated stress in the protein-malnourished rats. This study revealed that curcumin bound to the Histidine 87 residues of haemoglobin with a greater binding affinity and significantly protected the RBCs against nicotine-induced damage. Furthermore, the nicotine-mediated disruption of Th1/Th2 balance through upregulation and downregulation of different factors was effectively restored by curcumin under the protein-malnourished conditions. The study demonstrated that curcumin was a potent protective compound against the nicotine-induced stress and offereda probable biochemical and immunomodulatory mechanism of protective action of curcumin.

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This study suggests that 25-hydroxyvitamin D treatment may relieve the offspring’s MetS.

PMID: 

Front Pharmacol. 2020 ;11:97. Epub 2020 Feb 28. PMID: 32184720

Abstract Title: 

Maternal 25-Hydroxyvitamin D Deficiency Promoted Metabolic Syndrome and Downregulated Nrf2/CBR1 Pathway in Offspring.

Abstract: 

Metabolic syndrome is a disorder of energy use and storage, which is characterized by central obesity, dyslipidemia, and raised blood pressure and blood sugar levels. Maternal 25-hydroxyvitamin D deficiency is known to cause metabolic changes, chronic disease, and increased adiposity in adulthood. However, the underlying mechanism of induced metabolic syndrome (MetS) in the offspring in vitamin D deficient pregnant mothers remains unclear. We identified that maternal 25-hydroxyvitamin D deficiency enhances oxidative stress, which leads to the development of MetS in the mother and her offspring. Further, immunohistochemical, Western blotting, and qRT-PCR analyses revealed that maternal 25-hydroxyvitamin D deficiency inhibited the activation of the Nrf2/carbonyl reductase 1 (CBR1) pathwayin maternal placenta, liver, and pancreas, as well as the offspring's liver and pancreas. Further analyses uncovered that application of 25-hydroxyvitamin D activated the Nrf2/CBR1 pathway, relieving the oxidative stress in BRL cells, suggesting that 25-hydroxyvitamin D regulates oxidative stress in offspring and induces the activation of the Nrf2/CBR1 pathway. Taken together, our study finds that maternal 25-hydroxyvitamin D deficiency is likely to result in offspring's MetS probablyabnormal nutrition transformation across placenta. Depression of the Nrf2/CBR1 pathway in both mothers and their offspring is one of the causes of oxidative stress leading to MetS. This study suggests that 25-hydroxyvitamin D treatment may relieve the offspring's MetS.

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Effects of vitamin D supplementation on depression and some involved neurotransmitters.

PMID: 

J Affect Disord. 2020 May 15 ;269:28-35. Epub 2020 Mar 13. PMID: 32217340

Abstract Title: 

Effects of vitamin D supplementation on depression and some involved neurotransmitters.

Abstract: 

BACKGROUND: Low vitamin D levels are associated with a dysregulated hypothalamic-pituitary-adrenal (HPA) axis and depression but a causal relationship has not been established. This study aimed to evaluate the effects of vitamin D supplementation on depression severity, serum 25(OH)D, and some neurotransmitters in patients with mild to moderate depression.METHODS: An 8-week double-blind randomized clinical trial was conducted on 56 subjects with mild to moderate depression, aged 43.0 ± 1.15yrs. The patients were randomly allocated into two groups: intervention (50,000 IU cholecalciferol/2wks) and control (placebo). Biochemical parameters (serum 25(OH)D, iPTH, oxytocin and platelet serotonin), and depression severity (Beck Depression Inventory-II (BDI-II)) were initially and finally assessed.RESULTS: Following intervention, significant changes were observed in the intervention group compared to the controls: 25(OH)D concentrations increased (+40.83±28.57 vs. +5.14±23.44 nmol/L, P

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