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PMID: 

Endocr Metab Immune Disord Drug Targets. 2019 ;19(3):247-258. PMID: 30488803

Abstract Title: 

Molecular Mechanisms of Curcumin in Neuroinflammatory Disorders: A Mini Review of Current Evidences.

Abstract: 

OBJECTIVE: Neuroinflammatory disease is a general term used to denote the progressive loss of neuronal function or structure. Many neuroinflammatory diseases, including Alzheimer's, Parkinson's, and multiple sclerosis (MS), occur due to neuroinflammation. Neuroinflammation increases nuclear factor-κB (NF-κB) levels, cyclooxygenase-2 enzymes and inducible nitric oxide synthase, resulting in the release of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). It could also lead to cellular deterioration and symptoms of neuroinflammatory diseases. Recent studies have suggested that curcumin (the active ingredient in turmeric) could alleviate the process of neuroinflammatory disease. Thus, the present mini-review was conducted to summarize studies regarding cellular and molecular targets of curcumin relevant to neuroinflammatory disorders.
METHODS: A literature search strategy was conducted for all English-language literature. Studies that assessed the various properties of curcuminoids in respect of neuroinflammatory disorders were included in this review.
RESULTS: The studies have suggested that curcuminoids have significant anti- neuroinflammatory, antioxidant and neuroprotective properties that could attenuate the development and symptom of neuroinflammatory disorders. Curcumin can alleviate neurodegeneration and neuroinflammation through multiple mechanisms, by reducing inflammatory mediators (such as TNF-α, IL-1β, nitric oxide and NF-κB gene expression), and affect mitochondrial dynamics and even epigenetic changes.
CONCLUSION: It is a promising subject of study in the prevention and management of the neuroinflammatory disease. However, controlled, randomized clinical trials are needed to fully evaluate its clinical potential.

PMID: 

Food Chem Toxicol. 2019 Feb ;124:182-191. Epub 2018 Dec 5. PMID: 30529260

Abstract Title: 

Mechanistic insights of hepatoprotective effects of curcumin: Therapeutic updates and future prospects.

Abstract: 

The liver is the most essential organ of the body performing vital functions. Hepatic disorders affect the physiological and biochemical functions of the body. These disorders include hepatitis B, hepatitis C, alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), liver cirrhosis, hepatic failure and hepatocellular carcinoma (HCC). Drugs related hepatotoxicity is one of the major challenges facing by clinicians as it is a leading cause of liver failure. During post-marketing surveillance studies, detection and reporting of drug-induced hepatotoxicity may lead to drug withdrawal or warnings. Several mechanisms are involved in hepatotoxicity such as cell membrane disruption, initiating an immune response, alteration of cellular pathways of drug metabolism, accumulation of reactive oxygen species (ROS), lipid peroxidation and cell death. Curcumin, the active ingredient of turmeric and exhibits therapeutic potential for the treatment of diabetes, cardiovascular disorders and various types of cancers. Curcumin is strong anti-oxidant and anti-inflammatory effects and thus it possesses hepatoprotective properties. Despite its low bioavailability, its hepatoprotective effects have been studied in various protocols of hepatotoxicity including acetaminophen, alcohol, lindane, carbon tetrachloride (CCL), diethylnitrosamine and heavy metals induced hepatotoxicities. This report reviews the hepatoprotective effects of curcumin with a focus on its mechanistic insights in various hepatotoxic protocols.

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PMID: 

J Cell Physiol. 2019 08 ;234(8):12237-12248. Epub 2018 Dec 10. PMID: 30536381

Abstract Title: 

Curcumin as a therapeutic candidate for multiple sclerosis: Molecular mechanisms and targets.

Abstract: 

Multiple sclerosis (MS) is a disease that has shown a considerable increase in prevalence in recent centuries. Current knowledge about its etiology is incomplete, and therefore it cannot be managed optimally utilizing targeted therapeutic regimens at each stage of the disease. MS progresses in different stages, beginning with a cascade of inflammation. The pivotal spark to initiate this cascade seems to be the migration of Th17 into the central nervous system across the blood-brain barrier (BBB) through the disrupted tight junctions. Coupling of interleukin (IL)-17 and IL-22 to their receptors in the BBB layer facilitates this migration. Subsequently, axon degeneration and the various manifestations of nerve-muscle disorders appear. Curcumin, a major component of turmeric, is derived from Curcuma longa, which belongs to the Zingiberaceae family. Numerous properties of curcumin have been identified recently, some of which can be effective in the treatment of MS, particularly the anti-inflammatory properties via inhibition of secretion of proinflammatory cytokines. In this paper, we will review the various properties and key effects of curcumin for the treatment of MS.

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PMID: 

Endocr Metab Immune Disord Drug Targets. 2019 ;19(6):874-884. PMID: 30760195

Abstract Title: 

The Neuromodulatory Effects ofω-3 Fatty Acids and Nano-Curcumin on the COX-2/ iNOS Network in Migraines: A Clinical Trial Study from Gene Expression to Clinical Symptoms.

Abstract: 

BACKGROUND: Migraine is a common neuroinflammatory disorder characterized by recurrent attacks of pain. Human and experimental models of migraine studies have demonstrated the role played by COX-2/ iNOS in migraine's neuroinflammatory pathogenesis. COX-2 and iNOS are closely linked and both contribute to inflammation and neurogenic pain in the central nervous system. Omega- 3 fatty acids and curcumin, an active polyphenol of turmeric, have anti-inflammatory and neuroprotective effects through several mechanisms, including the suppression of COX-2 and iNOS gene expression, as well as their serum levels. The aim of the present study is to evaluate the nutrigenomic effects ofω-3 fatty acids, nano-curcumin, and a combination of the two, on neuroinflammation and clinical symptoms in migraine patients.METHODS: This study reports the results of a clinical trial over a 2-month period, involving 74 episodic migraine patients who receivedω-3 fatty acids, nano-curcumin, a combination of them, or a placebo. At the start and end of the study, the expression of COX-2/iNOS (in peripheral mononuclear blood cells isolated from patients) and COX-2/iNOS serum levels were measured, using real-time PCR and ELISA respectively. The frequency, severity and duration of pain attacks were also recorded.RESULTS: The results of the present trial showed thatω-3 fatty acids and nano-curcumin can reinforce each other's effects in the downregulation of COX-2/iNOS mRNA, as well as reduce their serum levels. In addition, the combination of ω-3 and nano-curcumin significantly reduced the frequency, severity and duration of headaches (P

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PMID: 

Neurotox Res. 2019 Jul ;36(1):12-26. Epub 2019 Apr 4. PMID: 30949950

Abstract Title: 

Effects of Curcumin on Microglial Cells.

Abstract: 

Microglia are innate immune system cells which reside in the central nervous system (CNS). Resting microglia regulate the homeostasis of the CNS via phagocytic activity to clear pathogens and cell debris. Sometimes, however, to protect neurons and fight invading pathogens, resting microglia transform to an activated-form, producing inflammatory mediators, such as cytokines, chemokines, iNOS/NO and cyclooxygenase-2 (COX-2). Excessive inflammation, however, leads to damaged neurons and neurodegenerative diseases (NDs), such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Curcumin is a phytochemical isolated from Curcuma longa. It is widely used in Asia and has many therapeutic properties, including antioxidant, anti-viral, anti-bacterial, anti-mutagenic, anti-amyloidogenic and anti-inflammatory, especially with respect to neuroinflammation and neurological disorders (NDs). Curcumin is a pleiotropic molecule that inhibits microglia transformation, inflammatory mediators and subsequent NDs. In this mini-review, we discuss the effects of curcumin on microglia and explore the underlying mechanisms.

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PMID: 

PLoS One. 2019 ;14(5):e0216711. Epub 2019 May 21. PMID: 31112588

Abstract Title: 

Curcumin attenuates oxidative stress in RAW264.7 cells by increasing the activity of antioxidant enzymes and activating the Nrf2-Keap1 pathway.

Abstract: 

Large-scale breeding environments often lead to oxidative stress. Macrophages play an important role in the immune system and are vulnerable to reactive oxygen species (ROS), which result in macrophage death. Curcumin is the main active component of turmeric and exerts antioxidant effects. Here, we measured the activity of some antioxidant enzymes and chose the Nrf2-Keap1 signaling pathway to study the protective effects of curcumin on macrophages under oxidative stress in vitro. We used RAW264.7 cells as a research model, and oxidative damage was induced by hydrogen peroxide (H2O2). Cell viability was measured by an MTT assay. Flow cytometry was used to measure cellular ROS and apoptosis. The effect of curcumin on Nrf2-Keap1 signaling pathway-related genes was analyzed by qRT-PCR. Furthermore, the translocation of Nrf2 protein was also investigated by Western blot analysis of total and nuclear proteins. All curcumin-treated groups exhibited increased activity of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). Low- and middle-dose curcumin decreased malondialdehyde (MDA) and ROS levels, but high-dose curcumin increased MDA and ROS production. We found that low-dose curcumin protected cells from apoptosis, while apoptosis in the middle- and high-dose curcumin-treated groups were stagnant in the early stage. Furthermore, middle-dose curcumin upregulated Nrf2 expression after H2O2 treatment for 4 h. Low- and middle-dose curcumin could activate Nrf2 and promote it to migrate into nuclei. The translocation of Nrf2 to the nucleus to upregulate the expression of haemoxygenase-1 (HO-1) was promoted in the low- and middle-dose curcumin-treated groups. The middle-dose curcumin-treated group also exhibited enhanced expression of glutamate-cysteine ligase, a modifier subunit (GLCM), but inhibited transcription of glutamate-cysteine ligase, a catalytic subunit (GCLC). Curcumin resisted oxidants by increasing the activity of antioxidant enzymes and activating the Nrf2-Keap1 pathway, which could potentially promote cell survival.

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PMID: 

Pharmacol Res. 2019 09 ;147:104353. Epub 2019 Jul 12. PMID: 31306775

Abstract Title: 

Targeting regulatory T cells by curcumin: A potential for cancer immunotherapy.

Abstract: 

Immune system has critical roles in fighting against several diseases like cancer. Cancer cells evolve several ways to escape from the immune system to remain alive and trigger new phases of cancer progression. Regulatory T cells are one of the key components in tumor immune tolerance and contribute to the evasion of cancer cells from the immune system. Targeting regulatory T cells could provide new horizons in designing and development of effective therapeutic platforms for the treatment of various malignancies. Curcumin is the bioactive pigment of turmeric and a well-known phytochemical with a wide range of pharmacological activities. A growing body of evidence has demonstrated that curcumin affects manifold molecular pathways that are implicated in tumorigenesis and cancer metastasis. In this regard, some studies have indicated that this phytochemical could target regulatory T cells and convert them into T helper 1 cells, which possess anti-tumor effects. On the contrary, curcumin is able to increase the number of regulatory T cells in other conditions such as inflammatory bowel disease. Herein, we describe the anti-cancer roles of curcumin via targeting regulatory T cells. Moreover, we summarize the effects of curcumin on regulatory T cell population in other diseases.

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PMID: 

Wound Manag Prev. 2020 04 ;66(4):38-46. PMID: 32294058

Abstract Title: 

The Effect of Oral Consumption of Propolis Alone and in Combination With Silver Nanoparticles on Wound Healing in Male Wistar Rats.

Abstract: 

: Research to identify and develop compounds that facilitate wound healing is important, especially for hard-to-heal chronic wounds.PURPOSE: This study was conducted to investigate the effects of orally administered propolis (a resinous substance found in beehives), alone and in combination with silver nanoparticles (SNPs), on the wound healing process in male rats.METHODS: Forty (40) male Wistar rats were randomly divided into 4 groups of 10 each: 1 control group received no treatment, and 3 study groups received a daily dose of 1) propolis (100 mg/kg), 2) propolis + 30 ppm SNPs, or 3) propolis + 60 ppm SNPs. Healing rate was determined by wound surface area reduction on days 4, 6, 8, and 10 post-surgery. On day 12 after wound creation, histological changes of wound healing, including number of new vessels, inflammatory cells (neutrophils, eosinophils, and mast cells) and fibroblasts were counted based on morphology using a 400x objective lens, and collagen deposition density was determined using hematoxylin and eosin and trichrome staining, respectively. The histological scores were based on a 0 to 4 scale from lowest to highest amount of improving tissue status and were analyzed using one-way analysis of variance, Tukey test, Kruskal-Wallis test, t test, and Mann-Whitney U test to examine differences among the groups. Significance was set at P

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PMID: 

Eur J Pharm Biopharm. 2020 Apr 17. Epub 2020 Apr 17. PMID: 32311428

Abstract Title: 

Biogenic silver nanoparticles: in vitro and in vivo antitumor activity in bladder cancer.

Abstract: 

ladder cancer is the fifth most common disease in the United States, and the treatment and alternatives for patients have not changed in the last decades. Silver nanoparticles (AgNP) have been used in the treatment of various cancer, mainly because of the antineoplastic activity; however, their use and the molecular mechanisms towards bladder cancer still unexplored. Therefore, this work aims to evaluate in vitro and in vivo the antitumoral mechanisms of biogenic silver nanoparticles synthesized from Fusarium sp. First, AgNP showed cytotoxicity in a dose- and time-response relationship, and detailed analysis demonstrated the induction of cell death via apoptosis, also inhibiting cell migration and proliferation. Next, it was evaluated the antitumoral activity of AgNP against non-muscle invasive bladder cancer (NMIBC). Bladder cancer was chemically induced with N-methyl-N-nitrosourea (MNU) on C57BL/6Junib female mice and treated by intravesical route with AgNP concentrations of 0.5, 0.2, and 0.05 mg/mL. Finally, treatment with AgNP (0.05 mg/mL) led to 57.13% of tumor regression, with 14.28% of the animals showing normal urothelium and 42.85% showing flat hyperplasia, considered to be a benign lesion. Overall, these findings demonstrated that AgNP might be a cost-effective alternative and promising candidate for the treatment of bladder cancer.

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PMID: 

J Ethnopharmacol. 2020 Apr 16 ;257:112876. Epub 2020 Apr 16. PMID: 32305638

Abstract Title: 

Ashwagandha in brain disorders: A review of recent developments.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (Family: Solanaceae), commonly known as Ashwagandha or Indian ginseng is distributed widely in India, Nepal, China and Yemen. The roots of plant consist of active phytoconstituents mainly withanolides, alkaloids and sitoindosides and are conventionally used for the treatment of multiple brain disorders.AIM OF THE REVIEW: This review aims to critically assess and summarize the current state and implication of Ashwagandha in brain disorders. We have mainly focussed on the reported neuroactive phytoconstituents, available marketed products, pharmacological studies, mechanism of action and recent patents published related to neuroprotective effects of Ashwagandha in brain disorders.MATERIALS AND METHODS: All the information and data was collected on Ashwagandha using keywords"Ashwagandha"along with"Phytoconstituents","Ayurvedic, Unani and Homeopathy marketed formulation","Brain disorders","Mechanism"and"Patents". Following sources were searched for data collection: electronic scientific databases such as Science Direct, Google Scholar, Elsevier, PubMed, Wiley On-line Library, Taylor and Francis, Springer; books such as AYUSH Pharmacopoeia; authentic textbooks and formularies.RESULTS: Identified neuroprotective phytoconstituents of Ashwagandha are sitoindosides VII-X, withaferin A, withanosides IV, withanols, withanolide A, withanolide B, anaferine, beta-sitosterol, withanolide D with key pharmacological effects in brain disorders mainly anxiety, Alzheimer's, Parkinson's, Schizophrenia, Huntington's disease, dyslexia, depression, autism, addiction, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder and bipolar disorders. The literature survey does not highlight any toxic effects of Ashwagandha. Further, multiple available marketed products and patents recognized its beneficial role in various brain disorders; however, very few data is available on mechanistic pathway and clinical studies of Ashwagandha for various brain disorders is scarce and not promising.CONCLUSION: The review concludes the results of recent studies on Ashwagandha suggesting its extensive potential as neuroprotective in various brain disorders as supported by preclinical studies, clinical trials and published patents. However vague understanding of the mechanistic pathways involved in imparting the neuroprotective effect of Ashwagandha warrants further study to promote it as a promising drug candidate.

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