Activity Of Curcumin Research Articles

Alginate hydrogel with enhanced curcumin release through HPβCD assisted host-guest interaction

The underprivileged pharmacodynamic action of curcumin, which arose from its low water solubility and rapid metabolism, restricts its therapeutic performance. In this study, (2-Hydroxy isopropyl)-β-cyclodextrin (HPβCD) as a macrocycle host molecule was employed to enhance the availability and control release of curcumin by forming a host-guest inclusion complex within an in-situ forming alginate hydrogel. The formation of the inclusion complexes of curcumin with a single host molecule was characterized by FTIR, XRD, TGA, SEM, and DLS analyses. The inclusion complex of curcumin and HPβCD (HPβCD-Cur) showed a high encapsulation efficiency of 88.2 %. According to DLS results, aqueous dispersion of HPβCD-Cur exhibited a unimodal histogram after 2 and 7 days with average particles size of 207.5 and 230.6 nm, respectively. This observation could be because of the formation of an inclusion complex that effectively distributed in solution and prevented curcumin agglomeration. The prepared alginate hydrogel containing HPβCD-Cur demonstrated >87 % reduction in colonies of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, which significantly is higher than that for Alg/Cur (<69 %). The Alg/HPβCD-Cur hydrogel exhibited a high water uptake of 470 % after 2 h, and a curcumin cumulative release of 80 % over 72 h, with proper cytocompatibility. Consequently, it was shown that the HPβCD carrier could act as an apt host molecule that can properly encapsulate curcumin and enhance its release from the Alg/HPβCD-Cur hydrogel.

Curcumin: A Review of its’ Efficacy in the Management of Psoriasis

Background:Psoriasis is a long-term chronic inflammatory, autoimmune and reoccur-ring skin condition. About 2% to 5% of the world's population is impacted by psoriasis. People af-fected by psoriasis are more prone to develop other health conditions including psoriatic arthritis, anxiety, depression and cardiovascular disorders. Long-term use of several synthetic medications used for their management has been showing typical severe side effects. Curcumin, a natural com-pound generated from the golden spice (Curcuma longa), has been recommended as a potential al-ternative for the management of psoriasis. Curcumin works at molecular level by binding with the various inflammatory receptors that play a key role in the initiation of psoriasis.Objective:The aim of this review is to report the use and discuss the mechanism of action of cur-cumin in the management of psoriasis and mutually overcome the side effects shown by the synthet-ic medications.Methods:For qualitative literature review PubMed, Scopus, Web of Science, Google Scholar, Google Books, and Science Direct meet the inclusion criteria.Results:Through ample literature surveys, curcumin has been proposed as a safe and therapeutic option for psoriasis as compared to synthetic medications.Conclusion:As traditional herb curcumin appears as a beneficiary medicament because of its anti-oxidant, anti-inflammatory and immune-modulating activities proposing minimal side effects. Thereby ensuring its defensive mechanism against psoriasis.

Protective effect of the curcumin-baicalein combination against macrovascular changes in diabetic angiopathy.

Endothelial dysfunction is an early pathological event in diabetic angiopathy which is the most common complication of diabetes. This study aims to investigate individual and combined actions of Curcumin (Cur) and Baicalein (Bai) in protecting vascular function. The cellular protective effects of Cur, Bai and Cur+Bai (1:1, w/w) were tested in H2O2 (2.5 mM) impaired EA. hy926 cells. Wistar rats were treated with vehicle control as the control group, Goto-Kakizaki rats (n=5 each group) were treated with vehicle control (model group), Cur (150 mg/kg), Bai (150 mg/kg), or Cur+Bai (75 mg/kg Cur + 75 mg/kg Bai, OG) for 4 weeks after a four-week high-fat diet to investigate the changes on blood vessel against diabetic angiopathy. Our results showed that Cur+Bai synergistically restored the endothelial cell survival and exhibited greater effects on lowering the fasting blood glucose and blood lipids in rats comparing to individual compounds. Cur+Bai repaired the blood vessel structure in the aortic arch and mid thoracic aorta. The network pharmacology analysis showed that Nrf2 and MAPK/JNK kinase were highly relevant to the multi-targeted action of Cur+Bai which has been confirmed in the in vitro and in vivo studies. In conclusion, Cur+Bai demonstrated an enhanced activity in attenuating endothelial dysfunction against oxidative damage and effectively protected vascular function in diabetic angiopathy rats.

Dual Mechanism of Action of Curcumin in Experimental Models of Multiple Sclerosis.

Background: Multiple sclerosis (MS) is characterized by a combination of inflammatory and demyelination processes in the spinal cord and brain. Conventional drugs generally target the autoimmune response, without any curative effect. For that reason, there is a great interest in identifying novel agents with anti-inflammatory and myelinating effects, to counter the inflammation and cell death distinctive of the disease. Methods and results: An in vitro assay showed that curcumin (Cur) at 10 µM enhanced the proliferation of C8-D1A cells and modulated the production of Th1/Th2/Th17 cytokines in the cells stimulated by LPS. Furthermore, two in vivo pathophysiological experimental models were used to assess the effect of curcumin (100 mg/kg). The cuprizone model mimics the de/re-myelination aspect in MS, and the experimental autoimmune encephalomyelitis model (EAE) reflects immune-mediated events. We found that Cur alleviated the neurological symptomatology in EAE and modulated the expression of lymphocytes CD3 and CD4 in the spinal cord. Interestingly, Cur restored motor and behavioral deficiencies, as well as myelination, in demyelinated mice, as indicated by the higher index of luxol fast blue (LFB) and the myelin basic protein (MBP) intensity in the corpus callosum. Conclusions: Curcumin is a potential therapeutic agent that can diminish the MS neuroimmune imbalance and demyelination through its anti-inflammatory and antioxidant effects.

Promiscuous or Dirty drug with Multifunctional Druggability nature of Curcumin (Curcuma longa Linn.); Repurposing in propranolol withdrawal-induced OCD related Anxiety: A promising drug discovery besides One-Drug-One-Receptor approach via in silico in vivo studies

Background: Curcumin (Curcuma longa) and propranolol display a plethora of pharmacological activity linked with multifunctional druggable nature designated as a promiscuous or dirty drug (magic shotguns) that hit 'on-target as well as 'off-target' (anti-target). Multifactorial origins, with complex neuronal networks and broad-spectrum symptomatology, operates most CNS disorders. Anxiety is one of the comorbidities in the psychogenic spectrum of obsessive-compulsive disorder (OCD). The present study of OCD has been based on its multifunctionality and diverse drug potential, tailoring together the morbidity and comorbidity patterns of OCD. Very few multimodal drugs did trial in this regard, which has multifunctional druggability, except selective serotonin reuptake inhibitors (SSRIs) that work via the one-drug-one-receptor-one-disease approach; however, with inter-individual variability, unwanted side effects and limited multifunctionality with the druggable targets. SSRI success rates in OCD and its related disorder are minimal, especially in the adversity of comorbidity pattern. Objective: The principal objective of the current research was to testify the multifunctional druggable plethora of curcumin via repurposing of its dirty drug nature to reverse the obsessed anxiety of propranolol withdrawal-induce mice, besides the "one drug one receptor" approach or magic bullet. Methods: The present study evaluated OCD related anxiety-like behavior after different periods of abstinence (24 h, 7 and 21 days) from repeated propranolol (10 mg/kg) administration in mice. In addition, we also examined the action of curcumin (EERCL-50 mg/kg) and fluoxetine (20 mg/kg) for the attenuation or reversal of OCD related anxiety-like behavior after seven days to 24 hours propranolol withdrawal. The initial stage of the hypothesis toward the target of curcumin was identified via in-silico using SwissADME drug-likeness study, followed by in-vivo studies using Swiss albino mice. Evaluation for the same did use elevated plus maze (EPM), marble-burying behaviour (MBB) and motor activity (MA) test as a model. Further, did also investigate the antioxidant activity. Result: The result revealed a decrease in all parameters 24 hours and 14 days after exposure to propranolol, indicating anxious behaviour. The administration of curcumin and fluoxetine after 24 hrs of abstinence reduced animal anxiety in EPM; after the abstinence periods, the drug reduced the MA in the MBB. Curcumin reversed the anxiogenic effect induced by propranolol in EPM. The value of p&lt;0.05 was considered statistically significant. Conclusion: Results revealed that propranolol might, to a large extent, impart to withdrawal-induced obsessed anxiety, and curcumin could effectively treat propranolol dependent obsessed mice. Further, curcumin anti-compulsive competency substantially showed promising success besides one drug-one receptor-one disease approach or magic bullet.

Effects and Mechanisms of Curcumin for the Prevention and Management of Cancers: An Updated Review.

Cancer is the leading cause of death in the world. Curcumin is the main ingredient in turmeric (Curcuma longa L.), and is widely used in the food industry. It shows anticancer properties on different types of cancers, and the underlying mechanisms of action include inhibiting cell proliferation, suppressing invasion and migration, promoting cell apoptosis, inducing autophagy, decreasing cancer stemness, increasing reactive oxygen species production, reducing inflammation, triggering ferroptosis, regulating gut microbiota, and adjuvant therapy. In addition, the anticancer action of curcumin is demonstrated in clinical trials. Moreover, the poor water solubility and low bioavailability of curcumin can be improved by a variety of nanotechnologies, which will promote its clinical effects. Furthermore, although curcumin shows some adverse effects, such as diarrhea and nausea, it is generally safe and tolerable. This paper is an updated review of the prevention and management of cancers by curcumin with a special attention to its mechanisms of action.

Proteomic alterations in Paracoccidioides brasiliensis caused by exposure to curcumin

Paracoccidioides spp. are the etiological agent of paracoccidioidomycosis, a disease that causes skin lesions and affect the lungs and other organs. The current management of the disease is long and has several side effects that often lead the patient to give up the treatment, sequelae and even death. The search for new forms of treatment that minimize these drawbacks is very important. Thus, natural compounds are targets of great interest. Curcumin is one of the main components of the tubers of Curcuma longa, presenting medicinal effects well described in the literature, including the antifungal effect on Paracocidioides brasiliensis. Nevertheless, the mechanisms related to the antifungal effect of such compound are still unknown, so the objective of the present research is to understand what changes occur in the metabolism of P. brasiliensis after exposure to curcumin and to identify the main targets of the compound. Proteomic analysis as based on nanoUPLC-MS analysis and the functional classification of the identified proteins. The main metabolic processes that were being regulated were biologically validated through assays such as fluorescence microscopy, EPR and phagocytosis. Proteomic analysis revealed that curcumin regulates several metabolic processes of the fungus, including important pathways for energy production, such as the glycolytic pathway, beta oxidation and the glyoxylate cycle. Protein synthesis was down-regulated in fungi exposed to curcumin. The electron transport chain and the tricarboxylic acid cycle were also down-regulated, indicating that both the mitochondrial membrane and the mitochondrial activity were compromised. Plasma membrane and cell wall structure were altered following exposure to the compound. The fungus' ability to survive the phagocytosis process by alveolar macrophages was reduced. Thus, curcumin interferes with several metabolic pathways in the fungus that causes paracoccidioidomycosis. Biological significanceThe challenges presented by the current treatment of paracoccidioidomycosis often contributing to patients' withdrawal from treatment, leading to sequelae or even death. Thus, the search for new treatment options against this disease is growing. The discovery that curcumin is active against Paracoccidioides was previously reported by our study group. Here, we clarify how the compound acts on the fungus causing its growth inhibition and decreased viability. Understanding the mechanisms of action of curcumin on P. brasiliensis elucidates how we can seek new alternatives and which metabolic pathways and molecular targets we should focus on in this incessant search to bring the patient a treatment with fewer adverse effects.

Formulated Curcumin Prevents Paclitaxel-Induced Peripheral Neuropathy through Reduction in Neuroinflammation by Modulation of α7 Nicotinic Acetylcholine Receptors

Paclitaxel is widely used in the treatment of various types of solid malignancies. Paclitaxel-induced peripheral neuropathy (PIPN) is often characterized by burning pain, cold, and mechanical allodynia in patients. Currently, specific pharmacological treatments against PIPN are lacking. Curcumin, a polyphenol of Curcuma longa, shows antioxidant, anti-inflammatory, and neuroprotective effects and has recently shown efficacy in the mitigation of various peripheral neuropathies. Here, we tested, for the first time, the therapeutic effect of 1.5% dietary curcumin and Meriva (a lecithin formulation of curcumin) in preventing the development of PIPN in C57BL/6J mice. Curcumin or Meriva treatment was initiated one week before injection of paclitaxel and continued throughout the study (21 days). Mechanical and cold sensitivity as well as locomotion/motivation were tested by the von Frey, acetone, and wheel-running tests, respectively. Additionally, sensory-nerve-action-potential (SNAP) amplitude by caudal-nerve electrical stimulation, electronic microscopy of the sciatic nerve, and inflammatory-protein quantification in DRG and the spinal cord were measured. Interestingly, a higher concentration of curcumin was observed in the spinal cord with the Meriva diet than the curcumin diet. Our results showed that paclitaxel-induced mechanical hypersensitivity was partially prevented by the curcumin diet but completely prevented by Meriva. Both the urcumin diet and the Meriva diet completely prevented cold hypersensitivity, the reduction in SNAP amplitude and reduced mitochondrial pathology in sciatic nerves observed in paclitaxel-treated mice. Paclitaxel-induced inflammation in the spinal cord was also prevented by the Meriva diet. In addition, an increase in α7 nAChRs mRNA, known for its anti-inflammatory effects, was also observed in the spinal cord with the Meriva diet in paclitaxel-treated mice. The use of the α7 nAChR antagonist and α7 nAChR KO mice showed, for the first time in vivo, that the anti-inflammatory effects of curcumin in peripheral neuropathy were mediated by these receptors. The results presented in this study represent an important advance in the understanding of the mechanism of action of curcumin in vivo. Taken together, our results show the therapeutic potential of curcumin in preventing the development of PIPN and further confirms the role of α7 nAChRs in the anti-inflammatory effects of curcumin.

Curcumin alleviated lipopolysaccharide-induced lung injury via regulating the Nrf2-ARE and NF-κB signaling pathways in ducks.

Under the intensive modern poultry farming system, the lung of duck is one of the main target organs for various bacterial and viral infections. Curcumin is a kind of natural polyphenol compound for which various beneficial biological functions exist, including being an anti-inflammatory, antioxidant, and antiviral. The aim of this work was to investigate the mechanism of curcumin-alleviated lipopolysaccharide (LPS)-induced lung damage by the nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant reaction element (ARE) and nuclear factor kappa B (NF-κB) signaling pathway in ducks. In total, 450 one-day-old male specific pathogen-free ducks were randomly assigned into three dietary treatments: CON, basal diet; LPS, basal diet + LPS treatment; LPS + CUR, basal diet + LPS + 500 mg kg-1 of curcumin. At the end of the experiment (21 days), ducks in LPS treatment were challenged with 5mg LPS per kilogram of body weight and the other two treatments were injected with the same dose of phosphate-buffered saline solution. The results showed that LPS caused acute inflammation, oxidation stress, and lung injury. Dietary addition of curcumin significantly relieved the oxidation stress and inflammation parameters. Moreover, the results showed that remission may be through the signaling pathways of both Nrf2-ARE and NF-κB. In conclusion, dietary supplementation of 500 mg kg-1 of curcumin exhibited a lung-protective effect in ducks. This experiment broadens the mode of metabolism actions of curcumin in the target organs and provides an insight for the application of curcumin in waterfowl feed. © 2022 Society of Chemical Industry.

Ivermectin and curcumin cause plasma membrane rigidity in Leishmania amazonensis due to oxidative stress

Spin label electron paramagnetic resonance (EPR) spectroscopy was used to study the mechanisms of action of ivermectin and curcumin against Leishmania (L.) amazonensis promastigotes. EPR spectra showed that treatment of the parasites with both compounds results in plasma membrane rigidity due to oxidative processes. With the IC50 and EPR measurements for assays using different parasite concentrations, estimations could be made for the membrane-water partition coefficient (KM/W), and the concentration of the compound in the membrane (cm50) and in the aqueous phase (cw50), which inhibits cell growth by 50%. The KM/W values indicated that ivermectin has a greater affinity than curcumin for the parasite membrane. Therefore, the activity of ivermectin was higher for experiments with low cell concentrations, but for concentrations greater than 1.5 × 108 parasites/mL the compounds did not show significantly different results. The cm50 values indicated that the concentration of compound in the membrane leading to growth inhibition or membrane alteration is approximately 1 M for both ivermectin and curcumin. This high membrane concentration suggests that many ivermectin molecules per chlorine channel are needed to cause an increase in chlorine ion influx.

Extending the lore of curcumin as dipteran Butyrylcholine esterase (BChE) inhibitor: A holistic molecular interplay assessment.

Since its origin, the emergence of vector-borne infections has taken a toll on incalculable human lives. The use of chemical insecticides is one of the early known methods of vector control and although their use is still a prevalent way to combat insect population sadly the perils of insects related transmission still persists. Most commonly, the existing insecticides face the wrath of getting resisted repeatedly, paying way to develop resilient, efficient, and cost-effective natural insecticides. In this study, computational screening was performed using homology modelling, E-pharmacophore feature mapping, molecular docking, Density Function Theory (DFT) assessment, Molecular mechanics generalized Born surface area (MM-GBSA) based binding free energy calculations and Molecular Dynamics (MD) simulation to identify a potential lead phytochemical out of a manually curated library from published literature. The protein target used under this study is insect Butyrylcholine esterase (BChE). Additionally, in vitro insect (Aedes aegypti) BChE inhibition assay was also performed with the top phytochemical identified from in silico assessments. Our research highlights that curcumin leads to inhibition of enzyme BChE of Ae. aegypti. The identified mode of action of curcumin as an insect BChE inhibitor indicates the possibility of its use as an environment friendly and natural futuristic insecticide.

Curcumin: Useful add-on for Rheumatic Diseases?

Plant-derived nutraceuticals are proposed as new key instruments to represent a profound “back to basics” shift in medical treatment. Data accumulated over the past ten years suggest that curcumin, the major active compound of the turmeric plant, has anti-inflammatory properties. It has yet to be determined whether the anti-inflammatory profile of curcumin is potent enough to justify the application of this substance as a nutritional supplement for patients with rheumatic diseases. To address this question, the most relevant in vitro studies that investigate the mechanism of action of curcumin were reviewed in this article. In addition, a total of 18 animal and human trials were evaluated. The pleiotropic, anti-inflammatory and immunomodulatory effects of curcumin were observed in animal studies. In addition, human trials demonstrated promising findings. In these studies, curcumin was able to reduce the expression of proinflammatory cytokines, lower the level of the C-reactive protein and improve clinical parameters. A limiting factor of the application of curcumin is the inconsistent bioavailability of the substance. Therefore, new formulations have been developed to improve the pharmacodynamic profile of curcumin. The future acceptance of the substance is dependent on new controlled clinical trials with a standardised formulation of curcumin administered as well as standard of care.

Impact of curcumin, quercetin, or resveratrol on the pathophysiology of endometriosis: A systematic review.

Endometriosis, a gynecological disease that affects reproductive age women is difficultly controlled in the long term by currently available treatments, prompting patients to adopt self-controlled interventions including dietary changes. The aim of this review is to provide evidence of how curcumin, quercetin, and resveratrol can act as natural interventions to control endometriosis. The review followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search was carried out in PubMed, Scopus, and Web of Science to gather together all the articles that study the specific actions of curcumin, resveratrol, or quercetin in endometriosis pathophysiology. All types of study designs including experimental data were considered. Thirty articles, including a clinical trial, were included. For the assessment of the quality of the selected studies that globally have "good quality", the GRADE (Grading of Recommendations Assessment, Development and Evaluation) and the SYRCLE ROB tool criteria were used. By acting on mechanisms of inflammation, oxidative stress, cell proliferation, invasion and adhesion, apoptosis, angiogenesis and glucose and lipid metabolism, curcumin, quercetin, and resveratrol showed to have beneficial effects, evidencing their potential application in the endometriosis treatment. However, future clinical studies are necessary to determine the real efficacy of these compounds in human endometriosis.

Mechanisms Underlying Curcumin-Induced Neuroprotection in Cerebral Ischemia.

Ischemic stroke is the leading cause of death and disability worldwide, and restoring the blood flow to ischemic brain tissues is currently the main therapeutic strategy. However, reperfusion after brain ischemia leads to excessive reactive oxygen species production, inflammatory cell recruitment, the release of inflammatory mediators, cell death, mitochondrial dysfunction, endoplasmic reticulum stress, and blood–brain barrier damage; these pathological mechanisms will further aggravate brain tissue injury, ultimately affecting the recovery of neurological functions. It has attracted the attention of researchers to develop drugs with multitarget intervention effects for individuals with cerebral ischemia. A large number of studies have established that curcumin plays a significant neuroprotective role in cerebral ischemia via various mechanisms, including antioxidation, anti-inflammation, anti-apoptosis, protection of the blood–brain barrier, and restoration of mitochondrial function and structure, restoring cerebral circulation, reducing infarct volume, improving brain edema, promoting blood–brain barrier repair, and improving the neurological functions. Therefore, summarizing the results from the latest literature and identifying the potential mechanisms of action of curcumin in cerebral ischemia will serve as a basis and guidance for the clinical applications of curcumin in the future.

Curcumin Protects Diabetic Mice against Isoproterenol-Induced Myocardial Infarction by Modulating CB2 Cannabinoid Receptors.

Molecular docking revealed curcumin as a potent CB2 cannabinoid receptor (CB2R) agonist. Since CB2R is involved in cardioprotective functions, we explored its role in ameliorative actions of curcumin against myocardial damage triggered by isoproterenol in diabetic animals. Mice were kept on a high-fat diet (HFD) throughout the experiment (30 days). Following 7 days of HFD feeding, streptozotocin was administered (150 mg/kg, intraperitoneal) to induce diabetes. From day 11 to 30, diabetic mice received either curcumin (100 or 200 mg/kg/day, oral), CB2R antagonist AM630 (1 mg/kg/day, intraperitoneal) or both, with concurrent isoproterenol (150 mg/kg, subcutaneous) administration on day 28 and 29. Diabetic mice with myocardial infarction showed an altered hemodynamic pattern and lipid profile, reduced injury markers, antioxidants with increased lipid peroxidation in the myocardium, and elevated glucose and liver enzymes in the blood. Moreover, an increased pro-inflammatory markers, histological severity, myonecrosis, and edema were observed. Curcumin compensated for hemodynamic fluctuations, restored biochemical markers, preserved antioxidant capacity, decreased cytokines levels, and restored cardiac functionality. However, the AM630 pre-treatment attenuated the effects of curcumin. The data suggest the involvement of CB2R in the actions of curcumin such as in the prevention of myocardial stress and in the improvement of the normal status of the myocardial membrane associated with diabetes.

Anticancer Properties of Curcumin Against Colorectal Cancer: A Review.

Colorectal cancer (CRC) is one of the most common and reoccurring diseases, as well as the world’s second largest cause of mortality. Despite existing preventative, diagnostic, and treatment methods, such as chemotherapy, the number of instances rises year after year. As a result, new effective medications targeting specific checkpoints should be developed to combat CRC. Natural compounds, such as curcumin, have shown significant anti-colorectal cancer characteristics among medications that can be used to treat CRC. These chemicals are phenolic compounds that belong to the curcuminoids category. Curcumin exerts its anti-proliferative properties against CRC cell lines in vitro and in vivo via a variety of mechanisms, including the suppression of intrinsic and extrinsic apoptotic signaling pathways, the stoppage of the cell cycle, and the activation of autophagy. Curcumin also has anti-angiogenesis properties. Thus, this review is aimed at emphasizing the biological effect and mode of action of curcumin on CRC. Furthermore, the critical role of these substances in CRC chemoprevention was emphasized.

Curcumin and Ethanol Effects in Trembler-J Schwann Cell Culture.

Charcot-Marie-Tooth (CMT) syndrome is the most common progressive human motor and sensory peripheral neuropathy. CMT type 1E is a demyelinating neuropathy affecting Schwann cells due to peripheral-myelin-protein-22 (PMP22) mutations, modelized by Trembler-J mice. Curcumin, a natural polyphenol compound obtained from turmeric (Curcuma longa), exhibits dose- and time-varying antitumor, antioxidant and neuroprotective properties, however, the neurotherapeutic actions of curcumin remain elusive. Here, we propose curcumin as a possible natural treatment capable of enhancing cellular detoxification mechanisms, resulting in an improvement of the neurodegenerative Trembler-J phenotype. Using a refined method for obtaining enriched Schwann cell cultures, we evaluated the neurotherapeutic action of low dose curcumin treatment on the PMP22 expression, and on the chaperones and autophagy/mammalian target of rapamycin (mTOR) pathways in Trembler-J and wild-type genotypes. In wild-type Schwann cells, the action of curcumin resulted in strong stimulation of the chaperone and macroautophagy pathway, whereas the modulation of ribophagy showed a mild effect. However, despite the promising neuroprotective effects for the treatment of neurological diseases, we demonstrate that the action of curcumin in Trembler-J Schwann cells could be impaired due to the irreversible impact of ethanol used as a common curcumin vehicle necessary for administration. These results contribute to expanding our still limited understanding of PMP22 biology in neurobiology and expose the intrinsic lability of the neurodegenerative Trembler-J genotype. Furthermore, they unravel interesting physiological mechanisms of cellular resilience relevant to the pharmacological treatment of the neurodegenerative Tremble J phenotype with curcumin and ethanol. We conclude that the analysis of the effects of the vehicle itself is an essential and inescapable step to comprehensibly assess the effects and full potential of curcumin treatment for therapeutic purposes.

Curcumin Mitigates TNFα-Induced Caco-2 Cell Monolayer Permeabilization Through Modulation of NF-κB, ERK1/2, and JNK Pathways.

This work studies the capacity of curcumin to inhibit tumor necrosis alpha (TNFα)-induced inflammation, oxidative stress, and loss of intestinal barrier integrity, characterizing the underlying mechanisms. Caco-2 cell monolayers are incubated with TNFα (10ng mL-1 ), in the absence or presence of curcumin. TNFα causes an increase in interleukin (IL)-6 and IL-8 release, which is inhibited by curcumin in a dose-dependent manner (half-maximal inhibitory concentration (IC50 ) = 3.4 µM for IL-6). Moreover, TNFα leads to: i) increased intercellular adhesion molecule 1 (ICAM-1) and NLRP3 inflammasome expression; ii) increased cell monolayer permeability and decreased levels of tight junction proteins; iii) increased cellular and mitochondrial oxidant production; iv) decreased mitochondrial membrane potential and complex I-III activity; v) activation of redox-sensitive pathways, i.e., nuclear factor-kappa B (NF-κB), extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinases (JNK); and vi) increased myosin light-chain kinase (MLCK) expression and phosphorylation levels of myosin light-chain protein MLC. Curcumin (2-8 µM) inhibits all these TNFα-triggered undesirable outcomes, mostly showing dose-dependent effects. The inhibition of NF-κB, ERK1/2, and JNK activation could be in part involved in the capacity of curcumin to mitigate intestinal inflammation, oxidant production, activation of redox-sensitive pathways, and prevention of monolayer permeabilization. These results support an action of dietary curcumin in sustaining gastrointestinal tract physiology.

The Natural Product Curcumin as an Antibacterial Agent: Current Achievements and Problems.

The rapid spread of antibiotic resistance and lack of effective drugs for treating infections caused by multi-drug resistant bacteria in animal and human medicine have forced us to find new antibacterial strategies. Natural products have served as powerful therapeutics against bacterial infection and are still an important source for the discovery of novel antibacterial drugs. Curcumin, an important constituent of turmeric, is considered safe for oral consumption to treat bacterial infections. Many studies showed that curcumin exhibited antibacterial activities against Gram-negative and Gram-positive bacteria. The antibacterial action of curcumin involves the disruption of the bacterial membrane, inhibition of the production of bacterial virulence factors and biofilm formation, and the induction of oxidative stress. These characteristics also contribute to explain how curcumin acts a broad-spectrum antibacterial adjuvant, which was evidenced by the markedly additive or synergistical effects with various types of conventional antibiotics or non-antibiotic compounds. In this review, we summarize the antibacterial properties, underlying molecular mechanism of curcumin, and discuss its combination use, nano-formulations, safety, and current challenges towards development as an antibacterial agent. We hope that this review provides valuable insight, stimulates broader discussions, and spurs further developments around this promising natural product.

Natural Plant Compounds: Does Caffeine, Dipotassium Glycyrrhizinate, Curcumin, and Euphol Play Roles as Antitumoral Compounds in Glioblastoma Cell Lines?

Many plant-derived compounds are shown to be promising antitumor therapeutic agents by enhancing apoptosis-related pathways and cell cycle impairment in tumor cells, including glioblastoma (GBM) cell lines. We aimed to review four natural plant compounds effective in GBM cell lines as caffeine, dipotassium glycyrrhizinate (DPG), curcumin, and euphol. Furthermore, antitumoral effect of these plant compounds on GBM cell lines through microRNAs (miRs) modulation was investigated. However, only DPG and curcumin were found as effective on miR modulation. Caffeine arrests GBM cell cycle in G0/G1 phase by cyclin-dependent kinases (CDK) complex inhibition and by decreasing BCL-2 and increasing FOXO1 expression levels causing greater apoptotic activity. Caffeine can also directly inhibit IP3R3, p38 phosphorylation, and rho-associated protein kinase (ROCK), decreasing cell invasion and migration capacity or indirectly by inhibiting the tissue inhibitor metalloproteinase-1 (TIMP-1) and integrins β1 and β3, leading to lower matrix metalloproteinases, MMP-2 and MMP-9. DPG presents antitumoral effect in GBM cells related to nuclear factor kappa B (NF-κB) pathway suppression by IRAK2 and TRAF6-mediating miR-16 and miR-146a, respectively. More recently, it was observed that DPG upregulated miR-4443 and miR-3620, responsible for post-transcriptional inhibition of the NF-κB pathway by CD209 and TNC modulation, respectively leading to lower MMP-9 and migration capacity. Curcumin is able to increase miR-223-3p, miR-133a-3p, miR-181a-5p, miR-34a-5p, miR-30c-5p, and miR-1290 expression leading to serine or threonine kinase (AKT) pathway impairment and also it decreases miR-27a-5p, miR-221-3p, miR-21-5p, miR-125b-5p, and miR-151-3p expression causing p53-BCL2 pathway inhibition and consequently, cellular apoptosis. Interestingly, lower expression of miR-27a by curcumin action enhanced the C/EBP homologous protein(CHOP) expression, leading to paraptosis. Curcumin can inhibit miR-21 expression and consequently activate apoptosis through caspase 3 and death receptor (DR) 4 and 5 activation. Autophagy is controlled by the LC-3 protein that interacts with Atg family for the LC3-II formation and autophagy activation. Euphol can enhance LC3-II levels directly in GBM cells or inhibits tumor invasion and migration through PDK1 modulation.