Novel coronaviruses (CoV) have emerged periodically around the world in recent years. The recurrent spreading of CoVs imposes an ongoing threat to global health and the economy. Since no specific therapy for these CoVs is available, any beneficial approach (including nutritional and dietary approach) is worth investigation. Based on recent advances in nutrients and phytonutrients research, a novel combination of vitamin C, curcumin and glycyrrhizic acid (VCG Plus) was developed that has potential against CoV infection. System biology tools were applied to explore the potential of VCG Plus in modulating targets and pathways relevant to immune and inflammation responses. Gene target acquisition, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment were conducted consecutively along with network analysis. The results show that VCG Plus can act on 88 hub targets which are closely connected and associated with immune and inflammatory responses. Specifically, VCG Plus has the potential to regulate innate immune response by acting on NOD-like and Toll-like signaling pathways to promote interferons production, activate and balance T-cells, and regulate the inflammatory response by inhibiting PI3K/AKT, NF-κB and MAPK signaling pathways. All these biological processes and pathways have been well documented in CoV infections studies. Therefore, our findings suggest that VCG Plus may be helpful in regulating immune response to combat CoV infections and inhibit excessive inflammatory responses to prevent the onset of cytokine storm. However, further in vitro and in vivo experiments are warranted to validate the current findings with system biology tools. Our current approach provides a new strategy in predicting formulation rationale when developing new dietary supplements.

Ultrasound and microbubbles-mediated drug delivery has become a promising strategy to promote drug delivery and its therapeutic efficacy. The aim of this research was to assess the effects of microbubbles (MBs)-combined low-intensity pulsed ultrasound (LPUS) on the delivery and cytotoxicity of curcumin (Cur) to human breast cancer MDA-MB-231 cells. Under the experimental condition, MBs raised the level of acoustic cavitation and enhanced plasma membrane permeability; and cellular uptake of Cur was notably improved by LPUS-MBs treatment, aggravating Cur-induced MDA-MB-231 cells death. The combined treatment markedly caused more obvious changes of cell morphology, F-actin cytoskeleton damage and cell migration inhibition. Our results demonstrated that combination of MBs and LPUS may be an efficient strategy for improving anti-tumor effect of Cur, suggesting a potential effective method for antineoplastic therapy.

The antigenotoxic effect of some phytoproducts like carotenoid (beta-carotene), curcumin, ascorbic acid and flavonoid (genistein)was demonstrated on the genotoxicity induced by hydrocortisone. Human lymphocyte cultures were studied for the induction of chromosomal aberrations, sister chromatid exchanges and effect on cell cycle kinetics with or without the presence of metabolic activation (S9 mix). The phytoproducts were studied in two most effective doses viz. carotenoid (0.5 and 0.7 microM), curcumin (15 and 25 microM), ascorbic acid (60 and 80 microM) and flavonoid (25 and 40 microM) in 24, 48 and 72 h cultures, and they were found to reduce chromosomal aberrations, sister chromatid exchange and increase replication index. The present study showed that the ascorbic acid and curcumin were more effective than carotenoid and flavonoid, though all provide protection against the genotoxicity of hydrocortisone.

INTRODUCTION:Considering the importance of prevention in periodontal diseases and the important role of Aggregatibacter actinomycetemcomitans in induction and progression of these diseases, the aim of the present in vitro study was to compare the antimicrobial effects of chlorhexidine digluconate (CHX), curcumin and light-emitting diode (LED) laser, on this bacterium.

METHODS:Antimicrobial activity of curcumin (5 mg/ml), CHX (2%), LED (120 J/cm(2)) and LED + curcumin (120 J/cm(2) + 2.5 mg/ml) against A. actinomycetemcomitans were tested in vitro, using micro-broth dilution test. One-way analysis of variance (ANOVA) and Tukey's HSD tests served for statistical analysis.

RESULTS:Regarding the minimum inhibitory concentration (MIC), CHX had a significantly lower MIC than curcumin (P<0.05). Sorted out by bacterial growth from lowest to highest, were CHX, LED + curcumin, curcumin, and LED groups. All the differences were found to be statistically significant (P<0.05) except for the LED group.

CONCLUSION:We conclude that curcumin is an effective substance in preventing the growth of A. actinomycetemcomitans, whose impact is reinforced when used simultaneously with photodynamic therapy (PDT).

INTRODUCTION:Considering the importance of prevention in periodontal diseases and the important role of Aggregatibacter actinomycetemcomitans in induction and progression of these diseases, the aim of the present in vitro study was to compare the antimicrobial effects of chlorhexidine digluconate (CHX), curcumin and light-emitting diode (LED) laser, on this bacterium.

METHODS:Antimicrobial activity of curcumin (5 mg/ml), CHX (2%), LED (120 J/cm(2)) and LED + curcumin (120 J/cm(2) + 2.5 mg/ml) against A. actinomycetemcomitans were tested in vitro, using micro-broth dilution test. One-way analysis of variance (ANOVA) and Tukey's HSD tests served for statistical analysis.

RESULTS:Regarding the minimum inhibitory concentration (MIC), CHX had a significantly lower MIC than curcumin (P<0.05). Sorted out by bacterial growth from lowest to highest, were CHX, LED + curcumin, curcumin, and LED groups. All the differences were found to be statistically significant (P<0.05) except for the LED group.

CONCLUSION:We conclude that curcumin is an effective substance in preventing the growth of A. actinomycetemcomitans, whose impact is reinforced when used simultaneously with photodynamic therapy (PDT).

Curcumin, a yellow pigment extracted from rhizomes of the plant Curcuma longa (turmeric), has been widely used as food additive and also as a herbal medicine throughout Asia. The present study was designed to study the pharmacological, biochemical and neurochemical effects of daily administration of curcumin to rats subjected to chronic unpredictable stress. Curcumin treatment (20 and 40 mg/kg, i.p., 21 days) significantly reversed the chronic unpredictable stress-induced behavioral (increase immobility period), biochemical (increase monoamine oxidase activity) and neurochemical (depletion of brain monoamine levels) alterations. The combination of piperine (2.5 mg/kg, i.p., 21 days), a bioavailability enhancer, with curcumin (20 and 40 mg/kg, i.p., 21 days) showed significant potentiation of its anti-immobility, neurotransmitter enhancing (serotonin and dopamine) and monoamine oxidase inhibitory (MAO-A) effects as compared to curcumin effect per se. This study provided a scientific rationale for the use of curcumin and its co-administration with piperine in the treatment of depressive disorders.

Turmeric has been in use since ancient times as a condiment and due to its medicinal properties. Curcumin, the yellow colouring principle in turmeric, is polyphenolic and major active constituent. Besides anti-inflammatory, thrombolytic and anticarcinogenic activities, curcumin also possesses strong antioxidant property. In view of the novel combination of properties, neuroprotective efficacy of curcumin was studied in rat middle cerebral artery occlusion (MCAO) model. Rats were subjected to 2 h of focal ischemia followed by 72 h of reperfusion. They were pre-treated with curcumin (100 mg/kg, po) for 5 days prior to MCAO and for another 3 days after MCAO. The parameters studied were behavioural, biochemical and histological. Treatment with curcumin could significantly improve neurobehavioral performance compared to untreated ischemic rats as judged by its effect on rota-rod performance and grid walking. A significant inhibition in lipid peroxidation and an increase in superoxide dismutase (SOD) activity in corpus striatum and cerebral cortex was observed following treatment with curcumin in MCAO rats as compared to MCAO group. Intracellular calcium levels were decreased following treatment with curcumin in MCAO rats. Histologically, a reduction in the infarct area from 33% to 24% was observed in MCAO rats treated with curcumin. The study demonstrates the protective efficacy of curcumin in rat MCAO model.

In recent years, considerable interest has been focused on curcumin a compound, isolated from turmeric. Curcumin is used as a coloring, flavoring agent and has been traditionally used in medicine and cuisine in India. The varied biological properties of curcumin and lack of toxicity even when administered at higher doses makes it attractive to explore its use in various disorders like tumors of skin, colon, duodenum, pancreas, breast and other skin diseases. This chapter reviews the data on the use of curcumin for the chemoprevention and treatment of various skin diseases like scleroderma, psoriasis and skin cancer. Curcumin protects skin by quenching free radicals and reducing inflammation through nuclear factor-KB inhibition. Curcumin treatment also reduced wound-healing time, improved collagen deposition and increased fibroblast and vascular density in wounds thereby enhancing both normal and impaired wound-healing. Curcumin has also been shown to have beneficial effect as a proangiogenic agent in wound-healing by inducing transforming growth factor-beta, which induces both angiogenesis and accumulation of extracellular matrix, which continues through the remodeling phase of wound repair. These studies suggest the beneficial effects of curcumin and the potential of this compound to be developed as a potent nontoxic agent for treating skin diseases.

Curcumin is widely consumed in Asia either as turmeric directly or as one of the culinary ingredients in food recipes. The benefits of curcumin in different organ systems have been reported extensively in several neurological diseases and cancer. Curcumin has got its global recognition because of its strong antioxidant, anti-inflammatory, anti-cancer, and antimicrobial activities. Additionally, it is used in diabetes and arthritis as well as in hepatic, renal, and cardiovascular diseases. Recently, there is growing attention on usage of curcumin to prevent or delay the onset of neurodegenerative diseases. This review summarizes available data from several recent studies on curcumin in various neurological diseases such as Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Huntington's disease, Prions disease, stroke, Down's syndrome, autism, Amyotrophic lateral sclerosis, anxiety, depression, and aging. Recent advancements toward increasing the therapeutic efficacy of curcuma/curcumin formulation and the novel delivery strategies employed to overcome its minimal bioavailability and toxicity studies have also been discussed. This review also summarizes the ongoing clinical trials on curcumin for different neurodegenerative diseases and patent details of curcuma/curcumin in India.

This study was aimed to evaluate the combined effect of curcumin with vitamin C supplementation on hyperglycemic and dyslipidemia conditions and endothelial cell dysfunction induced in diabetic rats. Wistar Furth rats were used and divided into four groups: control (single injection of 0.9% sterile saline), STZ (streptozotocin, Sigma, 55 mg/kg.BW, i.v.), STZ-vitC (1 g/l ascorbic acid mixed in drinking water), STZ-cur (daily oral treatment of 300 mg/kg.BW curcumin; Cayman Chemical Co., USA), and STZ-cur+vitC (1 g/l ascorbic acid mixed in drinking water and oral treatment of 300 mg/kg.BW curcumin). On 8th week after STZ-injection, the microcirculation in the iris tissue was observed using intravital fluorescence videomicroscopy, and also leukocyte adhesion in the venule was examined for each group. Blood glucose (BG), lipid profiles, glycosylated hemoglobin (HbA1c) were measured in blood samples collected at the end of each experiment. The contents of liver malondialdehyde (MDA) were also quantified for each group. Feeding curcumin (STZ-cur) could decrease BG, HbA1c, dyslipidemia, and MDA significantly, compared to STZ. In cases of feedings curcumin with vitamin C, these results were more effective in all aspects, including leukocyte adhesion. In conclusion, curcumin might increase the effect of vitamin C in protecting the function of endothelial cells through its anti-oxidant with hypoglycemic and hypolipidemic actions.

AIM:The aim of this study was investigate the effect of photodynamic therapy (PDT) using curcumin (C) as a photosensitizing agent irradiated with an LED (L) in the blue wavelength as a light source on a standard and clinical isolate of Streptococcus mutans (S. mutans) in a planktonic suspension model.

MATERIALS AND METHODS:Suspensions of both strains were divided into 4 groups as follows: absence of C and L (control group: C-L-), with C and without L (C group: C+L-), absence of C with L (L group: C-L+) and presence of C and L (PDT group: C+L+). Three different concentrations of curcumin (0.75 mg/ml, 1.5 mg/ml and 3 mg/ml) and three light fluences of studied light source (24, 48 and 72 J cm(-2)) were tested. Aliquots of each studied group was plated in BHI agar and submitted to colony forming units counting (CFU/ml) and the data transformed into logarithmical scale.

RESULTS:A high photoinactivation rate of more than 70% was verified to standard S. mutans strain submitted to PDT whereas the clinical isolate showed a lower sensitivity to all the associations of curcumin and LED. A slight bacterial reduction was verified to C+L- and C-L+, demonstrating no toxic effects to the isolated application of light and photosensitizer to both S. mutans strains tested.

CONCLUSION:Photodynamic therapy using a combination of curcumin and blue LED presented a substantial antimicrobial effect on S. mutans standard strain in a planktonic suspension model with a less pronounced effect on its clinical isolate counterparts due to resistance to this alternative approach.

CLINICAL SIGNIFICANCE:Alternative antimicrobial approaches, as photodynamic therapy, should be encouraged due to optimal results against cariogenic bacteria aiming to prevent or treat dental caries.

AIM:The aim of this study was investigate the effect of photodynamic therapy (PDT) using curcumin (C) as a photosensitizing agent irradiated with an LED (L) in the blue wavelength as a light source on a standard and clinical isolate of Streptococcus mutans (S. mutans) in a planktonic suspension model.

MATERIALS AND METHODS:Suspensions of both strains were divided into 4 groups as follows: absence of C and L (control group: C-L-), with C and without L (C group: C+L-), absence of C with L (L group: C-L+) and presence of C and L (PDT group: C+L+). Three different concentrations of curcumin (0.75 mg/ml, 1.5 mg/ml and 3 mg/ml) and three light fluences of studied light source (24, 48 and 72 J cm(-2)) were tested. Aliquots of each studied group was plated in BHI agar and submitted to colony forming units counting (CFU/ml) and the data transformed into logarithmical scale.

RESULTS:A high photoinactivation rate of more than 70% was verified to standard S. mutans strain submitted to PDT whereas the clinical isolate showed a lower sensitivity to all the associations of curcumin and LED. A slight bacterial reduction was verified to C+L- and C-L+, demonstrating no toxic effects to the isolated application of light and photosensitizer to both S. mutans strains tested.

CONCLUSION:Photodynamic therapy using a combination of curcumin and blue LED presented a substantial antimicrobial effect on S. mutans standard strain in a planktonic suspension model with a less pronounced effect on its clinical isolate counterparts due to resistance to this alternative approach.

CLINICAL SIGNIFICANCE:Alternative antimicrobial approaches, as photodynamic therapy, should be encouraged due to optimal results against cariogenic bacteria aiming to prevent or treat dental caries.

Cadmium (Cd), a well known environmental carcinogen, is a potent immunotoxicant. In rodents, it is primarily characterized by marked thymic atrophy and splenomegaly. Cadmium induces apoptosis in murine lymphocytes and alters the immune functions. Thus, for the amelioration of its effect, three structurally different bioactive herbal extracts such as piperine-alkaloid, picroliv-glycosides and curcumin-polyphenols were evaluated and their efficacy compared. For ascertaining their immunomodulatory role, various biochemical indices of cell damage such as cytotoxicity, oxidative stress (ROS, GSH), apoptosis (mitochondrial membrane potential, caspase-3 activity, phosphatidylserine externalization, apoptotic DNA) along with lymphocyte phenotyping, blastogenesis and cytokine secretion were assessed in thymic and splenic cell suspensions. Of the three herbals examined, piperine displayed maximum efficacy. All the three doses of piperine (1, 10 and 50 microg/ml) increased cell viability in a dose dependent manner, whereas curcumin and picroliv were also effective, but to a lesser degree. Only the two higher doses exhibited cell viability efficacy. The median doses ie 10 microg/ml, were therefore selected, for comparison of their antioxidant, anti-apoptotic and immune function modulation. Restoration of ROS and GSH was most prominent with piperine. The anti-apoptotic potential was directly proportional to their antioxidant nature. In addition, Cd altered blastogenesis, T and B cell phenotypes and cytokine release were also mitigated best with piperine. The ameliorative potential was in order of piperine > curcumin > picroliv and former could be considered the drug of choice under immunocompromised conditions.

Curcuma longa, a perennial herb, is a member of the Zingiberaceae (ginger) family. The plant grows to a height of three to five feet, and is cultivated extensively in Asia, India, China, and other countries with a tropical climate. It has oblong, pointed leaves and bears funnel-shaped yellow flowers. The rhizome is the portion of the plant used medicinally; it is usually boiled, cleaned, and dried, yielding a yellow powder. Dried Curcuma longa is the source of the spice turmeric, the ingredient that gives curry powder its characteristic yellow color. Turmeric is used extensively in foods for both its flavor and color. Turmeric has a long tradition of use in the Chinese and Ayurvedic systems of medicine, particularly as an anti-inflammatory agent, and for the treatment of flatulence, jaundice, menstrual difficulties, hematuria, hemorrhage, and colic. Turmeric can also be applied topically in poultices to relieve pain and inflammation. Current research has focused on turmeric's antioxidant, hepatoprotective, anti-inflammatory, anticarcinogenic, and antimicrobial properties, in addition to its use in cardiovascular disease and gastrointestinal disorders.

The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.

The aim of this study was to analyze the effects of oral consumption of curcumin and piperine in combination on the recovery kinetics after exercise-induced muscle damage. Forty-eight hours before and following exercise-induced muscle damage, ten elite rugby players consumed curcumin and piperine (experimental condition) or placebo. A randomized cross-over design was performed. Concentric and isometric peak torque for the knee extensors, one leg 6 seconds sprint performance on a non-motorized treadmill, counter movement jump performance, blood creatine kinase concentration and muscle soreness were assessed immediately after exercise, then at 24h, 48h and 72h post-exercise. There were moderate to large effects of the exercise on the concentric peak torque for the knee extensors (Effect size (ES) = -1.12; Confidence interval at 90% (CI90%): -2.17 to -0.06), the one leg 6 seconds sprint performance (ES=-1.65; CI90% = -2.51to -0.80) and the counter movement jump performance (ES = -0.56; CI90% = -0.81 to -0.32) in the 48h following the exercise. There was also a large effect of the exercise on the creatine kinase level 72h after the exercise in the control group (ES = 3.61; CI90%: 0.24 to 6.98). This decrease in muscle function and this elevation in creatine kinase indicate that the exercise implemented was efficient to induce muscle damage. Twenty four hours post-exercise, the reduction (from baseline) in sprint mean power output was moderately lower in the experimental condition (-1.77± 7.25%; 1277 ± 153W) in comparison with the placebo condition (-13.6 ± 13.0%; 1130 ± 241W) (Effect Size = -1.12; Confidence Interval 90%=-1.86 to -0.86). However, no other effect was found between the two conditions. Curcumin and piperine supplementation before and after exercise can attenuatesome, but not all, aspects of muscle damage.

It is known that curcumin, a dietary pigment from the plant Curcuma longa, inhibits cell proliferation and induces apoptosis in different cell lines; however, the therapeutic benefit is hampered by very low absorption after transdermal or oral application. Recent studies from our laboratory have demonstrated that curcumin at low concentrations (0.2-1 microg/ml) offered the described effects only when applied with UVA or visible light. Nevertheless, the in vivo efficacy of this combination is lacking. In the present study, we used a xenograft tumor model with human epithelial carcinoma A431 cells to test the effect of curcumin and visible light on tumor growth. It was found that tumor growth was significantly inhibited in mice that were i.p. injected with curcumin and consecutively irradiated with visible light. Furthermore, immunohistochemistry showed a reduction of Ki 67 expression, indicating a decrease of cycling cells and induction of apoptotic bodies. The effect on apoptosis was further confirmed by Western blot analysis showing enhanced activation of caspases-9. Vice versa inhibition of extracellular regulated kinases (ERK) 1/2 and epidermal growth factor receptor (EGF-R) was observed which may aid inhibition of proliferation and induction of apoptosis. In summary, the present findings suggest a combination of curcumin and light as a new therapeutic concept to increase the efficacy of curcumin in the treatment of cancer.

Vascular endothelial function is declines with aging and is associated with an increased risk of cardiovascular disease. Lifestyle modification, particularly aerobic exercise and dietary adjustment, has a favorable effect on vascular aging. Curcumin is a major component of turmeric with known anti-inflammatory and anti-oxidative effects. We investigated the effects of curcumin ingestion and aerobic exercise training on flow-mediated dilation as an indicator endothelial function in postmenopausal women. A total of 32 postmenopausal women were assigned to 3 groups: control, exercise, and curcumin groups. The curcumin group ingested curcumin orally for 8 weeks. The exercise group underwent moderate aerobic exercise training for 8 weeks. Before and after each intervention, flow-mediated dilation was measured. No difference in baseline flow-mediated dilation or other key dependent variables were detected among the groups. Flow-mediated dilation increased significantly and equally in the curcumin and exercise groups, whereas no changes were observed in the control group. Our results indicated that curcumin ingestion and aerobic exercise training can increase flow-mediated dilation in postmenopausal women, suggesting that both can potentially improve the age-related decline in endothelial function.

Ultraviolet B (UVB) irradiation of skin induces an acute inflammation. Cyclooxygenase-2 (COX-2) protein plays key roles in acute inflammation in UVB-irradiated keratinocyte cell line HaCaT. Recently, curcumin has been regarded as a promising anti-inflammatory agent due to its ability to inhibit COX-2 expression. However, it remains largely unknown whether curcumin inhibits the UVB-induced COX-2 expression in HaCaT cells. This study was undertaken to clarify the effect of curcumin on the expression of COX-2 in UVB- irradiated HaCaT cells and further determined the molecular mechanisms associated with this process. In this study, we have found that the expression of COX-2 mRNA and protein were up-regulated in UVB-irradiated HaCaT cells in a dose- and time-dependent manner. Interestingly, treatment with curcumin strongly inhibited COX-2 mRNA and protein expressions in UVB-irradiated HaCaT cells. Notably, there was effective inhibition by curcumin on UVB-induced activations of p38 MAPK and JNK in HaCaT cells. The DNA binding activity of AP-1 transcription factor was also markedly decreased with curcumin treatment in UVB-irradiated HaCaT cells. These results collectively suggest that curcumin may inhibit COX- 2 expression by suppressing p38 MAPK and JNK activities in UVB-irradiated HaCaT cells. We propose that curcumin may be applied as an effective and novel sunscreen drug for the protection of photoinflammation.