NASAFYTOL® supplementation in adults hospitalized with COVID-19 infection: results from an exploratory open-label randomized controlled trial.

Objectives: The effect and safety of Nasafytol®, a food supplement combining curcumin, quercetin, and Vitamin D, on hospitalized COVID-19-positive patients as support to standard of care were to be assessed. Methods: This exploratory, open-label, randomized, controlled trial was carried out among hospitalized adults with COVID-19 infection. Participants were randomly assigned to receive Nasafytol® or Fultium® control. The improvement of the clinical condition and occurrence of (serious) adverse events were evaluated. The study was registered on clincaltrials.gov with the identifier NCT04844658. Results: Twenty-five patients received Nasafytol®, and 24 received Fultium®. Demographic characteristics were well balanced between the groups. On day 14 (or at hospital leave if < 14 days), no difference was observed between groups regarding their clinical condition, fever, or the need of oxygen therapy. At day 7, however, 19 participants had been discharged from the hospital in the Nasafytol® arm compared to 10 participants in the Fultium® arm. No participants were transferred to the ICU or died in the Nasafytol® arm, vs. 4 transfers and 1 death in the Fultium® arm. The clinical condition of participants in the Nasafytol® arm had improved, as evidenced by a decrease in the COVID-19 WHO score. Interestingly, five SAEs occurred with Fultium®, while no SAE was observed with Nasafytol®. Conclusion: Supplementation with Nasafytol®, in addition to standard-of-care treatment, led to a faster discharge from the hospital, improved clinical conditions of participants, and a reduced risk of serious outcomes, including transfer to the intensive care unit or death, in patients hospitalized with COVID-19.

A review on plant-based remedies for the treatment of multiple sclerosis.

Multiple sclerosis (MS) is a complex autoimmune disease of central nervous system, which is degenerative in nature usually appears between 20-40years of age. The exact cause of MS is still not clearly known. Loss of myelin sheath and axonal damage are the main features of MS that causes induction of inflammatory process and blocks free conduction of impulses. Till date FDA has approved 18 drugs to treat or modify MS symptoms. These medicines are disease-modifying in nature directed to prevent relapses or slow down the progression of disease. The use of the synthetic drug over an extended period causes undesirable effects that prompt us to look at Mother Nature. Complementary and alternative medicine involves the use of medicinal plants as an alternative to the existing modern medical treatment. However, modern drugs cannot be replaced completely with medicinal plants, but the two types of drugs can be used harmoniously with later one can be added as an adjuvant to the existing treatment. These medicinal plants have the potential to prevent progression and improve the symptoms of MS. Various plants such like Nigella sativa, ginger, saffron, pomegranate, curcumin, resveratrol, ginsenoside have been tested as therapeutics for many neurodegenerative diseases. The purpose of this write-up is to make information available about medicinal plants in their potential to treat or modify the symptoms of MS. Chronically ill patients tend to seek medicinal plants as they are easily available and there is a general perception about these medicines of having fewer undesirable effects.

Is Curcumine Useful in the Treatment and Prevention of the Tendinopathy and Myotendinous Junction Injury? A Scoping Review.

Physical activity in general and sports in particular, is a mechanism that produces stress and generates great force in the tendon and in the muscle-tendon unit, which increases the risk of injury (tendinopathies). Eccentric and repetitive contraction of the muscle precipitates persistent microtraumatism in the tendon unit. In the development of tendinopathies, the cellular process includes inflammation, apoptosis, vascular, and neuronal changes. Currently, treatments with oral supplements are frequently used. Curcumin seems to preserve, and even repair, damaged tendons. In this systematic review, we focus more especially on the benefits of curcumin. The biological actions of curcumin are diverse, but act around three systems: (a) inflammatory, (b) nuclear factor B (NF-κB) related apoptosis pathways, and (c) oxidative stress systems. A bibliographic search is conducted under the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) as a basis for reporting reliable systematic reviews to perform a Scoping review. After analysing the manuscripts, we can conclude that curcumin is a product that demonstrates a significant biological antialgic, anti-inflammatory, and antioxidant power. Therefore, supplementation has a positive effect on the inflammatory and regenerative response in tendinopathies. In addition, curcumin decreases and modulates the cell infiltration, activation, and maturation of leukocytes, as well as the production of pro-inflammatory mediators at the site of inflammation.

Curcumin attenuates intracerebral hemorrhage-induced neuronal apoptosis and neuroinflammation by suppressing JAK1/STAT1 pathway.

Intracerebral hemorrhage (ICH) is a kind of fatal stroke with the highest mortality and morbidity in the world. To date, there is no effective treatment strategy for ICH. Curcumin, a major active ingredient of Curcuma longa L., possesses a potential anti-inflammatory activity in many types of disease. In the current study, the mechanism underlying curcumin attenuated ICH-induced neuronal apoptosis and neuroinflammation was explored. Herein, we studied that curcumin decreased brain edema and improved neurological function by using brain edema measurement, assessment of neurological-deficient score, immunofluorescence, and Western blotting analyses after ICH. The results showed that curcumin improved ICH-induced neuronal apoptosis and neuroinflammation. Functionally, the polarization of microglia was assessed by immunofluorescence and Western blotting analyses after ICH in the absence or presence of curcumin. The results suggested that the M1-type microglia were activated after ICH, while the effect was blocked by curcumin treatment, suggesting that curcumin alleviates the neuroinflammation and apoptosis of neurons by suppressing the M1-type polarization of microglia. Mechanically, M1 polarization of microglia was regulated by JAK1/STAT1, and the activation of JAK1/STAT1 was blocked by curcumin. Meanwhile, the protective function of curcumin can be blocked by RO8191, an activator of JAK1. Taken together, our study suggested that curcumin improved the ICH-induced brain injury through alleviating M1 polarization of microglia/macrophage and neuroinflammation via suppressing the JAK1/STAT1 pathway.

Efecto citotóxico y genotóxico in vitro del extracto crudo y etanólico del rizoma de Curcuma longa L / In vitro cytotoxic and genotoxic effect of the crude and ethanolic extract from the rhizome of Curcuma longa L

RESUMEN Objetivos: Determinar el efecto citotóxico y genotóxico in vitro del extracto crudo y etanólico del rizoma de Curcuma longa L. Materiales y métodos: El efecto citotóxico fue evaluado utilizando líneas celulares DU-145, HT-29, 3T3 BALB/c. Se hallaron los porcentajes de crecimiento en 48 horas y se determinó la concentración inhibitoria 50 (CI50). El efecto genotóxico en el ADN genómico humano se determinó mediante el método Tomasevich. Resultados: El extracto crudo produjo una CI50 de 12,98 ± 0,21 μg/mL para la línea celular tumoral HT-29, que es inferior a DU-145 con una CI50 de 36,77 ± 9,12 μg/mL; el extracto etanólico presentó una CI50 de 13,24 ± 0,77 y 20,54 ± 2,58 µg/mL para ambas líneas celulares, respectivamente; el compuesto estándar curcumina presentó una CI50 de 3,96 ± 0,60 y 13,94 ± 2,79 μg/mL, respectivamente. El extracto crudo a concentraciones de 50 y 100 mg/mL fragmentó entre el 40% a 95% de ADN genómico humano; mientras que, a 200 mg/mL, la fragmentación fue mayor al 95%. El extracto etanólico a todas las concentraciones no fragmentó el ADN. La curcumina a 200 mg/mL fragmentó menos del 5% de ADN genómico humano. Conclusiones: Los extractos crudo y etanólico de Curcuma longa L. demuestran efecto citotóxico in vitro diferencial para la línea celular tumoral humana DU-145 y HT29 semejante al compuesto estándar curcumina. El extracto crudo de Curcuma longa L. presenta una potente actividad genotóxica in vitro frente al ADN genómico humano, esta actividad está ausente en el extracto etanólico.

ABSTRACT Objectives: To determine the in vitro cytotoxic and genotoxic effect of the crude and ethanolic extract from the Curcuma longa L. rhizome. Materials and methods: The cytotoxic effect was evaluated using DU-145, HT-29, 3T3 BALB/c cell lines. The growth percentages in 48 hours; and the half maximal inhibitory concentration (IC50) were determined. The genotoxic effect on human genomic DNA was determined using the Tomasevich method. Results: Crude extract produced an IC50 of 12.98 ± 0.21 μg/mL for the HT-29 tumor cell line, which is lower than the value obtained for DU-145, with an IC50 of 36.77 ± 9.12 μg/mL. The ethanolic extract presented an IC50 of 13.24 ± 0.77 and 20.54 ± 2.58 μg/mL for both cell lines, respectively; the curcumin standard compound presented an IC50 of 3.96 ± 0.60 and 13.94 ± 2.79 μg/mL, respectively. Crude extract concentrations of 50 and 100 mg/mL fragmented between 40% to 95% of human genomic DNA; while at 200 mg/mL, fragmentation was greater than 95%. The ethanolic extract at all concentrations did not fragment the DNA. Curcumin at 200 mg/mL fragmented less than 5% of human genomic DNA. Conclusions: The crude and ethanolic extracts of Curcuma longa L. demonstrate different in vitro cytotoxic effects for the human tumor cell lines DU-145 and HT-29; similar to the standard curcumin compound. The crude extract of Curcuma longa L. shows a potent genotoxic in vitro activity against human genomic DNA; this type of effect is not produced by the ethanolic extract.

Reversal of P-glycoprotein-mediated multidrug resistance by novel curcumin analogues in paclitaxel-resistant human breast cancer cells.

Multidrug resistance (MDR) is a major obstacle for successful cancer chemotherapy, and the main cause of MDR has been attributed to overexpression of P-glycoprotein (P-gp). In this present study, four P-gp modulators (E,E)-4,6-bis(styryl)-2-(substituted amino)-pyrimidines were evaluated for their activity in a breast cancer cell line overexpressing P-gp (LCC6MDR). The four modulators displayed significantly better P-gp modulating activity compared with the positive control verapamil (RF = 5.4), with a relative fold (RF) increase in activity ranging from 33.3 to 86.0. In contrast to compounds a and c that exhibited lower cytotoxicity, compounds b and d were nontoxic towards both cancer cells and normal cells, with IC50 values greater than 100 µmol/L. The qRT-PCR results demonstrated that after exposure to 2 µmol/L of compounds a, b, c, and d, the mRNA expression level of MDR1 in LCC6MDR cells decreased to 45%, 50%, 38%, and 51%, respectively. However, the Western-blot results indicated that compound c could reverse P-gp mediated MDR, but not via decreases in protein expression. DOX and Rh123 accumulation and efflux results further confirmed that the reversal of MDR activity happens via inhibition of P-gp efflux and increases in intracellular drug accumulation. These results demonstrated that compound c has low toxicity and is an efficient P-gp modulator, highlighting its potential as a promising candidate for P-gp-mediated reversal of MDR.

Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes.

Breast cancer is a worldwide commonly found malignancy in women and effective treatment is regarded as a huge clinical challenge even in the presence of several treatment options. Extensive literature is available demonstrating polyphenols as phytopharmaceutical anticancer agents. Among the polyphenols, quercetin and curcumin have been reported to have a strong potential against breast cancer. However, so far, no comprehensive study has been performed to demonstrate the anticarcinogenic effects of curcumin, quercetin, and their combinations with somatostatin on the fatty acid profile of breast cancer cell membranes. We used MCF-7 and MDA-MB231 breast cancer cells incubated with curcumin and quercetin for 24 h, in the absence and presence of somatostatin, at their EC50 concentrations to evaluate membrane fatty acid based functional lipidomics together with the followup of EGFR and MAPK signaling pathways. The two cell lines gave different membrane free fatty acid reorganization. In MCF-7 cells, the following changes were observed: an increase of ω6 linoleic acid in the cells incubated with somatostatin + quercetin and quercetin and a decrease of ω3 acids in the cells incubated with somatostatin + curcumin compared to somatostatin and significant increases of monounsaturated fatty acid (MUFA), mono-trans arachidonic acid levels and docosapentaenoic acid for the cells incubated with somatostatin + quercetin compared to the control cells. In MDA-MB231 cells, incubations with curcumin, quercetin, and somatostatin + quercetin induced the most significant membrane remodeling with the increase of stearic acid, diminution of ω6 linoleic, arachidonic acids, and ω3 (docosapentaenoic and docosahexaenoic acids). Distinct signaling pathway changes were found for these cell lines. In MCF-7 cells, separate or combined incubations with somatostatin and quercetin, significantly decreased EGFR and incubation with curcumin decreased MAPK signaling. In MDA-MB231 cells, incubation with curcumin decreased AKT1 and p-AKT1 (Thr308) levels. Incubation with curcumin and quercetin decreased the EGFR levels. Our results showed that cytostatic and antioxidant treatments can be combined to induce membrane fatty acid changes, including lipid isomerization as specific free radical driven process, and to influence signaling pathways. This study aimed to contribute to the literature on these antioxidants in the treatment of breast cancer to clarify the effects and mechanisms in combination with somatostatin.

Effect of dietary curcumin and capsaicin on testicular and hepatic oxidant-antioxidant status in rats fed a high-fat diet.

This study investigated the effects of curcumin and capsaicin on testicular and hepatic oxidant-antioxidant status in rats fed a high-fat diet (HFD). Male Sprague-Dawley rats were divided into 5 groups (8 rats per group). The control group was fed a normal control diet (standard laboratory chow), the HFD group was fed HFD (60% of total calories from fat), the HFD+CUR group received HFD supplemented with curcumin (1.5 g curcumin/kg HFD), the HFD+CAP group was given HFD supplemented with capsaicin (0.15 g capsaicin/kg HFD), and the HFD+CUR+CAP group received HFD supplemented with curcumin and capsaicin for 16 weeks. Hepatic and testicular thiobarbituric acid reactive substances (TBARS), reactive oxygen species (ROS), glutathione (GSH) levels, glutathione transferase activity, and Cu-Zn superoxide dismutase, glutathione peroxidase, and catalase protein expression and enzyme activities were measured. Protein expression was determined by Western blotting. GSH levels and antioxidant enzyme activities were measured with colorimetric methods. HFD slightly increased hepatic and testicular oxidative stress parameters. GSH levels did not change between groups. TBARS and ROS levels were significantly reduced in the HFD+CUR+CAP group compared with the HFD group. Liver and testis antioxidant enzyme activities and expression increased significantly with combined capsaicin and curcumin treatment. Curcumin and capsaicin treatment attenuated testicular and hepatic oxidative stress and enhanced the antioxidant defense system. The combination of capsaicin and curcumin with HFD seems to have some remarkable and beneficial effects on testicular oxidative damage in the fatty liver rat model.

Innovative material containing the natural product curcumin, with enhanced antimicrobial properties for active packaging.

Curcumin (Curc) reacts with zinc di­iodine (ZnI2) in 2:1molar ratio in the presence of an excess of a base triethylamine ((CH3CH2)3N) in methanol (CH3OH) solution towards the amorphous solid material of formula [ZnI2(Curc)2] (1). The complex was characterized by melting point (m.p.), Fourier Transform-Infra Red (FT-IR) and Nuclear Magnetic Resonance of hydrogen nucleus (1H NMR) spectroscopy. The formula of 1 was determined by X-ray fluorescence (XRF) analysis. The retention of the structure in solution was confirmed by 1H NMR spectroscopy. The antimicrobial activity of the complex has been studied against the bacteria Pseudomonas aeruginosa (PAO1). The Minimum Inhibitory Concentrations (MIC) of the compounds 1 and Curc against P. aeruginosa (PAO1) are: 71.3µΜ (75.3µg/mL) for [ZnI2(Curc)2] and 339µM (125µg/mL) for Curc, respectively. Moreover, the antimicrobial activity of the new material which was diffused in polystyrene against biofilm formed by PAO1 was also calculated.

Curcumin supplementation ameliorated vascular dysfunction and improved antioxidant status in rats fed a high-sucrose, high-fat diet.

Vascular endothelial dysfunction is a potential risk factor for cardiovascular disease. This study evaluated the effect of curcumin on factors associated with vascular dysfunction using rats fed a high-sucrose, high-fat (HSF) diet. The experiment included 2 animal feeding phases. In the first feeding phase, male Sprague-Dawley rats were randomly divided into 2 groups: the control group (n = 8) was fed a standard diet (AIN-93G) and the HSF group (n = 24) was fed an HSF diet for 8 weeks to induce obesity. In the second feeding phase, lasting 4 weeks, the HSF group was randomly divided into 3 subgroups: the O group (n = 8) continued feeding on the HSF diet, the OA group (n = 8) had the HSF diet replaced with AIN-93G, and the OC group (n = 8) was fed the HSF diet supplemented with curcumin (300 mg/kg body weight daily). After 8 weeks, the HSF diet significantly elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), insulin, homeostatic model assessment insulin resistance (HOMA-IR), low-density lipoprotein cholesterol (LDL-C), homocysteine (Hcy), C-reactive protein (CRP), vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) but significantly reduced levels of nitric oxide (NO) and high-density lipoprotein cholesterol (HDL-C). After dietary intervention, the OA and OC groups exhibited significantly lower levels of AST, ALT, HOMA-IR, cholesterol, LDL-C, Hcy, CRP, VCAM-1, and ICAM-1 and higher levels of NO and catalase (CAT) activity compared with the O group. Superoxide dismutase, CAT, and glutathione peroxidase activities were increased in the OA group, while CAT levels were enhanced in the OC group. In conclusion, this study showed that curcumin supplementation and diet modification can inhibit HSF diet-induced vascular dysfunction potentially by enhancing NO production and antioxidant enzyme activities, thereby suppressing inflammation and oxidative damage in the vascular endothelium.

Electrostimulated Release of Neutral Drugs from Polythiophene Nanoparticles: Smart Regulation of Drug-Polymer Interactions.

Poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles are loaded with curcumin and piperine by in situ emulsion polymerization using dodecyl benzene sulfonic acid both as a stabilizer and a doping agent. The loaded drugs affect the morphology, size, and colloidal stability of the nanoparticles. Furthermore, kinetics studies of nonstimulated drug release have evidenced that polymer···drug interactions are stronger for curcumin than for piperine. This observation suggests that drug delivery systems based on combination of the former drug with PEDOT are much appropriated to show an externally tailored release profile. This is demonstrated by comparing the release profiles obtained in presence and absence of electrical stimulus. Results indicate that controlled and time-programmed release of curcumin is achieved in a physiological medium by applying a negative voltage of -1.25 V to loaded PEDOT nanoparticles.

Curcumin protects neuronal cells against status-epilepticus-induced hippocampal damage through induction of autophagy and inhibition of necroptosis.

Status epilepticus, the most severe form of epilepsy, is characterized by progressive functional and structural damage in the hippocampus, ultimately leading to the development and clinical appearance of spontaneous, recurrent seizures. Although the pathogenesis underlying epileptogenesis processes remains unclear, a substantial body of evidence has shown that status epilepticus acts as an important initial factor in triggering epileptogenesis. Notably, besides classical cell death mechanisms such as apoptosis and necrosis, 2 novel regulators of cell fate known as necroptosis and autophagy, are demonstrated to be involved in neuronal damage in various neurodegenerative and neuropsychiatric disorders. However, whether necroptosis and autophagy play a role in post-status-epilepticus rat hippocampus and other epilepsy mechanisms deserves further research effort. In addition, research is needed to determine whether compounds from traditional Chinese herbs possess antiepileptic effects through the modulation of necroptosis and autophagy. In this study, we found that curcumin, a polyphenolic phytochemical extracted from the Curcuma longa plant, protects neuronal cells against status-epilepticus-induced hippocampal neuronal damage in the lithium-pilocarpine-induced status epilepticus rat model through induction of autophagy and inhibition of necroptosis.

Curcumin improves the metabolic syndrome in high-fructose-diet-fed rats: role of TNF-α, NF-κB, and oxidative stress.

This study aimed to investigate effects of curcumin on high fructose diet (HFD)-induced metabolic syndrome (MetS) in rats and the possible mechanisms involved. MetS was induced in male albino rats (n = 20), over 8 weeks, by 65% HFD. For 8-week experiment period, rats were assigned to 2 equal groups: curcumin-treated rats received curcumin (200 mg/kg, p.o, once daily) along with HFD, and untreated rats were fed with HFD only. We evaluated body mass (BM), systolic blood pressure (SBP), homeostasis model assessment of insulin resistance (HOMA-IR), and serum levels of glucose, insulin, leptin, total cholesterol (TC), triglycerides (TGs), uric acid, malondialdehyde (MDA; lipid peroxidation product), and tumor necrosis factor-α (TNF-α; inflammatory cytokine), and serum catalase (endogenous antioxidant) activity and immunohistochemical expression of nuclear factor κB (NF-κB; inflammation-related transcription factor) in hepatocytes. HFD produced increases in BM, SBP, HOMA-IR, and serum levels of glucose, insulin, leptin, TC, TGs, uric acid, MDA, and TNF-α, a decrease in catalase activity, and strong positive expression of NF-κB in hepatocytes. Curcumin, in presence of HFD, produced significant improvements in all glucose and fat metabolism parameters, and in oxidative stress and inflammation biomarkers. Curcumin may potentially be useful in the treatment of MetS through its ability to modulate oxidation stress status and inflammation cascades.

Effect of curcumine in regulating the balance between regulatory T cells/helper T lymphocyte 17 via SOCS3 in inflammatory bowel disease in immature rat / 中华实用儿科临床杂志

Objective To determine the therapeutic efficacy of curcumine on inflammatory bowel disease(IBD)and its underlying mechanisms.Methods The rat ulcerative colitis model was developed by using 30 g/L dextran sulfate sodium.Twenty-four young rats were divided into 4 groups:normal group,model group,curcumin 100 mg/kg group(curcumin 100 group),and curcumin 300 mg/kg group(curcumin 300 group).Curcumin was given through gastric gavage once a day for 7 days.General condition,disease activity index(DAI)and histopathological score(HPS)were evaluated.The proportions of CD4+ CD25+ Foxp3+ regulatory T cells(Treg)and CD4+ IL-17+ helper T lymphocyte 17(Th17)in CD4+ T cells in rats,and spleen cells were calculated by using flow cytometry.Immunohistochemical method was performed to determine the level of SOCS3 in colon tissues.Results After curcumin administered through gastric gavage for 5 days,compared with the DAI in the model group[(7.50±0.32)scores],HPS in the curcumin 100 group[(4.00±1.10)scores] and the curcumin 300 group [(5.00±0.89)scores] significantly reduced,and the difference was significant(F=12.469,P0.05).Compared with the model group[(6.5±1.5)％],the propotion of CD4+ CD25+ Foxp3+ Treg cells in CD4+ T cells in the curcumin 100 group[(9.9±1.0)％],the curcumin 300 group [(9.3±0.7)％] and the normal group[(9.6±1.1)％]was obviously upregulated(F=16.635,P0.05).Compared with the model group[(3.5±1.4)％],the propotion of CD4+ IL-17+ Th17 cells in CD4+ T cells in the curcumin 100 group[(2.0±0.9)％],the curcumin 300 group [(1.2±0.6)％] and the normal group[(2.0±0.9)％] was downregulated(F=5.155,P0.05).There was no obvious difference between the curcumin 100 group and the curcumin 300 group in these indicators respectively(all P>0.05).Conclusions Curcumin probably attenuates IBD severity,reduces inflammation and regulates the balance of Treg/Th17 through the inhibition of SOCS3 expression.

Resveratrol and curcumin as protective agents in an experimental rat model of intestinal ischemia and reperfusion.

The aim of this study was to evaluate the protective effects of resveratrol and curcumin in an experimental rat model of intestinal ischemia-reperfusion (I/R). Forty-eight adult Wistar rats were used: 12 animals undergoing the sham surgery and 36 animals undergoing laparotomy, with 15 min of mesentric artery clamping. The animals from the latter group (n = 12) were pretreated, for 1 week, with vehicle (CTR), resveratrol (RES), and curcumin (CUR). After 1 h and 6 h of reperfusion, respectively, cyclooxigenase (COX)-2, mucin-1, E-cadherin, nuclear factor (NK)-κB expressions, and tumor necrosis factor related apoptosis-inducing ligand (TRAIL) were assessed in the small intestine. Oxidative stress markers were determined in tissue homogenate and serum, and histopathological analysis was performed. Pretreatment with RES decreased the expression of COX-2 and NF-κB at both intervals and increased E-cadherin (p < 0.05) and mucin-1 production after 1 h. CUR had a beneficial effect on COX-2, NF-κB, and E-cadherin expressions, both after 1 h and after 6 h (p < 0.0001). The two compounds increased TRAIL levels and had a protective effect on oxidative stress and histopathological lesions, both after 1 h and after 6 h. Our results suggested that RES and CUR had beneficial effects in intestinal I/R and may represent a promising option for complementary treatment of this pathological condition.

Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 µg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels.

Determination of Berberine Hydrochloride and Curcumine in Shangke Dieda Paste by HPLC / 中国药师

Objective: To establish a method for the determination of curcumine and berberine hydrochloride in Shangke Dieda paste. Methods:An HPLC method was adopted to determine the content of curcumine and berberine hydrochloride in Shangke Dieda paste. For curcumine, the column was InertSutain C18 (250 mm × 4. 6 mm,5 μm); the mobile phase was acetonitrile and 4% acetic acid solution (44 ∶56);the flow rate was 1. 0 ml·min-1;the column temperature was 25℃;the detection wavelength was 430 nm;the sample size was 10μl. For berberine hydrochloride, the column was InertSutain C18 (250 mm × 4. 6 mm,5μm);the mobile phase consisted of acetonitrile-0. 1% phosphoric acid (44 ∶56, 0. 2 g dodecyl sodium sulfate was added to 100 ml solution); the flow rate was 1. 0 ml·min-1;the column temperature was 25℃ ;the detection wavelength was 345 nm;the sample size was 10 μl. Results:A good linear correlation was obtained within the range of 0.01-0.50 μg (r =0.999 3) for curcumin and 0.02-0.16 μg(r =0. 999 9) for berberine hydrochloride. The average recovery was 101. 03% with RSD of 1. 75% for curcumin and 99. 20% with RSD of 0. 64% for berberine hydrochloride (n=9). Conclusion:The established method is simple, accurate, sensitive and specific, which can be used for the quality control of Shangke Dieda paste.

Inhibitory effect of curcumin, salvia miltiorrhiza and matrine on IL-1β-induced proliferation of rabbit RPE cells in vitro / 中华实验眼科杂志

Background Proliferative vitreoretinopathy (PVR) is a common cause of vision loss clinically,and retinal pigment epithelium (RPE) cells play a major part in this disease.Studying the effect of traditional Chinese medicine on RPE cells are of great importance to reveal the pathogenesis and prevention of PVR,which were rarely reported.Objective This study was to study and compare the inhibition effect among curcumin,salvia miltiorrhiza and matrine on IL-1β-induced proliferation of rabbit RPE cells.Methods RPE cells at passages 3-4 were enrolled for the research and identified by transmission electron microscope.The proliferation effect of IL-1 β (2.5,5.0,10.0,20.0 μg/L) and inhibitory effect of curcumin (5,10,20 μg/ml),salvia miltiorrhiza (5,10,20 μg/ml)or matrine (100,200,400 μg/ml) on RPE cells 24,48 and 72 hours after cultivation were studied by MTT assay.The 50％ inhibitory dose (IC50) of the three medicines were analyzed by regression analysis.The use and feeding of the experimental animals were followed by the ARVO Statement.Results RPE cells isolated from the rabbit eye were in round shape and abundant in melanin;The melanin significantly decreased in the fourth generations of RPE cells.Immunohistochemistry showed that the RPE cells was positive for keratin (AE1/AE3).The proliferation rates of RPE cells were statistically different among different concentrations of IL-1β 24,48 and 72 hours after cultivation (Ftime =30.33,P =0.00;Fconcentration =9.37,P =0.00);The proliferation rates of RPE were significantly different among different time points or different concentrations of IL-1β (all at P ＜ 0.05).And the proliferation rate run up to maximum at 10 μg/L after 72 hours of cultivation.The inhibitory rates of the three medicines were statistically different among different time points or different concentrations (curcumin:Ftime =128.75,P =0.00;Fconcentration =334.05,P=0.00.salvia miltiorrhiza:Ftime =39.32,P=0.00;Fconcentration =165.57,P=0.00.matrine:Ftime =267.76,P =0.00;Fconcentration =912.34,P =0.00).The three medicines dose-dependently and time-dependently inhibit IL-1β-induced proliferation of RPE cells,with significant differences between the adjacent time points and concentrations (all at P＜0.05).The IC50 were 26.77,19.01 and 9.45 μg/ml for curcumin;33.72,23.47 and 12.56 μg/ml for salvia miltiorrhiza,570.96,352.25 and 97.50μg/ml for matrine 24,48 and 72 hours after cultivation.Conclusions The proliferation of RPE cells can be stimulated by IL-1β,and the maximal proliferation occurred with a concentration of 10.0 μg/L IL-1β.Curcumin,salvia miltiorrhiza and matrine dose-dependently and time-dependently inhibit proliferation of RPE cells induced by IL-1β.Curcumin is the best medicine to inhibit the proliferation of RPE cells.

Effects of curcumin and captopril on the functions of kidney and nerve in streptozotocin-induced diabetic rats: role of angiotensin converting enzyme 1.

Oxidative stress and inflammation are involved in the development and progression of diabetes and its complications. The renin-angiotensin system also plays an important role in the pathogenesis of diabetes and its complications. We hypothesized that curcumin and captopril would restore the kidney and nerve functions of diabetic rats through their angiotensin converting enzyme 1 (ACE1) inhibiting activity as well as their antioxidant and anti-inflammatory effects. Diabetes was induced by a single intraperitoneal injection of streptozotocin (100 mg·kg(-1) body weight). One week after induction of diabetes, rats were treated with 100 mg·kg(-1)·day(-1) curcumin or 50 mg·kg(-1)·day(-1) captopril orally for 6 weeks. Compared with diabetic control rats, curcumin- or captopril-treated diabetic rats had significantly improved blood glucose, lipid profile, kidney/body weight ratio, serum creatinine, blood urea nitrogen (BUN), and pain thresholds assessed by Von Frey filaments, hot plate test, and tail-flick test. Diabetic control rats showed increased levels of total peroxide, renal and neural tumor necrosis factor-α and interleukin-10, and renal ACE1 compared with nondiabetic rats. Although treatment with either curcumin or captopril restored the altered variables, captopril was more effective in reducing these variables. ACE1 was positively correlated with BUN and creatinine and negatively correlated with paw withdrawal threshold, hot plate reaction time, and tail-flick latency, suggesting a possible causal relationship. We conclude that curcumin and captopril protect against diabetic nephropathy and neuropathy by inhibiting ACE1 as well as oxidation and inflammation. These findings suggest that curcumin and captopril may have a role in the treatment of diabetic nephropathy and neuropathy.

Anti-CD20 single chain variable antibody fragment-apolipoprotein A-I chimera containing nanodisks promote targeted bioactive agent delivery to CD20-positive lymphomas.

A fusion protein comprising an α-CD20 single chain variable fragment (scFv) antibody, a spacer peptide, and human apolipoprotein (apo) A-I was constructed and expressed in Escherichia coli. The lipid interaction properties intrinsic to apoA-I as well as the antigen recognition properties of the scFv were retained by the chimera. scFv•apoA-I was formulated into nanoscale reconstituted high-density lipoprotein particles (termed nanodisks; ND) and incubated with cultured cells. α-CD20 scFv•apoA-I ND bound to CD20-positive non-Hodgkins lymphoma (NHL) cells (Ramos and Granta) but not to CD20-negative T lymphocytes (i.e., Jurkat). Binding to NHL cells was partially inhibited by pre-incubation with rituximab, a monoclonal antibody directed against CD20. Confocal fluorescence microscopy analysis of Granta cells following incubation with α-CD20 scFv•apoA-I ND formulated with the intrinsically fluorescent hydrophobic polyphenol, curcumin, revealed α-CD20 scFv•apoA-I localizes to the cell surface, while curcumin off-loads and gains entry to the cell. Compared to control incubations, viability of cultured NHL cells was decreased upon incubation with α-CD20 scFv•apoA-I ND harboring curcumin. Thus, formulation of curcumin ND with α-CD20 scFv•apoA-I as the scaffold component confers cell targeting and enhanced bioactive agent delivery, providing a strategy to minimize toxicity associated with chemotherapeutic agents.