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Chinese Journal of Biotechnology ; (12): 2077-2084, 2021.
Article in Chinese | WPRIM | ID: wpr-887782


Curcumin is exclusively isolated from Zingiberaceae plants with a broad spectrum of bioactivities. In the present study, we used the diketide-CoA synthase (DCS) and curcumin synthase (CURS) genes to construct a non-natural fusion gene encoding diketide-CoA synthase::curcumin synthase (DCS::CURS). This fusion protein, together with the acetyl coenzyme A carboxylase (ACC) and the 4-coumarate coenzyme A ligase (4CL), were introduced into Escherichia coli for the production of curcumin from ferulic acid. The process is divided into two stages, the growth stage using LB medium and the fermentation stage using the modified M9 medium. The yield of curcumin reached 386.8 mg/L by optimizing the induction of protein expression in the growth stage, and optimizing the inoculum volume, medium composition and fermentation time in the fermentation stage, as well as the addition of macroporous resin AB-8 into the second medium to attenuate the toxicity of the end product. The exploitation of the non-natural fusion protein DCS::CURS for the production of curcumin provides a new alternative to further promoting the production of curcumin and the related analogues.

Curcumin/pharmacology , Escherichia coli/genetics , Fermentation
Braz. arch. biol. technol ; 64: e21200093, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153294


HIGHLIGHTS Sodium arsenite can cause neoplastic transformation in cells. Curcumin reduced cell viability and increased LDH activity in transformed Balb/c 3T3 cells. Curcumin caused DNA damage in transformed Balb/c 3T3 cells. Curcumin may play a protective role in sodium arsenite-induced toxicity.

Abstract Arsenic is a toxic substance that spreads widely around the environment and accumulates as metalloid in the earth's crust. Arsenic and its derivatives are found in drinking water, nutrients, soil, and air. Exposure to arsenic is associated with lung, blood, skin cancer and various lesions. Curcumin is a polyphenolic compound derived from Curcuma longa (turmeric) rhizome and is one of the main curcuminoids. Curcumin is known to be antioxidant, antibacterial, anti-inflammatory, analgesic effects. This study aimed to investigate the potential of sodium arsenite to transform embryonic fibroblast cells and to evaluate the cytotoxic and genotoxic effects of curcumin in neoplastic transformed cells. Neoplastic cells transformation was induced by sodium arsenite in Balb/c 3T3 cells at the end of 32 days. After transformation assay, the transformed cells were treated with various concentration of curcumin to evaluate cell viability, lactate dehydrogenase activity and DNA damage for 24h. The results revealed that curcumin decreased cell viability and increased the activity of lactate dehydrogenase enzyme in neoplastic transformed Balb/c 3T3 cells. In conclusion, the results demonstrated that curcumin has an anticancer effect on neoplastic transformed Balb/c 3T3 cells by causing DNA damage.

Animals , Mice , Arsenic/toxicity , DNA Damage , Cell Transformation, Neoplastic , Curcumin/pharmacology , Fibroblasts/drug effects , BALB 3T3 Cells , Fibroblasts/pathology
Article in Chinese | WPRIM | ID: wpr-878786


Orthogonal experiments were used to optimize the process parameters of curcumin TPP-PEG-PCL nanomicelles; the particle size, electric potential and morphology under the electron microscope were systematically detected for the curcumin TPP-PEG-PCL nanomicelles; and the stability and in vitro release of the curcumin TPP-PEG-PCL nanomicelles were investigated. With DID fluorescent dye as the fluorescent probe, flow cytometry was used to study the uptake of nanomicelles by breast cancer cells, and laser confocal microscopy was used to study the mitochondrial targeting and lysosomal escape functions of nanomicelles. Under the same dosage conditions, the effect of curcumin TPP-PEG-PCL nanomicelles on promoting the apoptosis of breast cancer cells was evaluated. The optimal particle size of curcumin TPP-PEG-PCL nanomicelle was(17.3±0.3) nm, and the Zeta potential was(14.6±2.6) mV in orthogonal test. Under such conditions, the micelle appeared as regular spheres under the transmission electron microscope. Fluorescence test results showed that TPP-PEG-PCL nanomicelles can promote drug uptake by tumor cells, escape from lysosomal phagocytosis, and target the mitochondria. The cell survival rate and Hoechst staining positive test results showed that curcumin TPP-PEG-PCL nanomicelles had a good effect on promoting apoptosis of breast cancer cells. The curcumin TPP-PEG-PCL micelles can significantly reduce the mitochondrial membrane potential of breast cancer cells, increase the release of cytochrome C, significantly increase the expression of pro-apoptotic protein Bcl-2 and reduce the expression of anti-apoptotic Bax protein. These test results were significantly better than those of curcumin PEG-PCL nanomicelles and curcumin, with statistically significant differences. The results revealed that curcumin TPP-PEG-PCL nanomicelles can well target breast cancer cell mitochondria and escape from the lysosomal capture, thereby enhancing the drug's role in promoting tumor cell apoptosis.

Apoptosis , Breast Neoplasms/drug therapy , Cell Line, Tumor , Curcumin/pharmacology , Humans , Lysosomes , Micelles , Mitochondria , Phosphatidylethanolamines , Polyethylene Glycols
Biol. Res ; 53: 31, 2020. graf
Article in English | LILACS | ID: biblio-1124214


BACKGROUND: In modern societies, sleep deprivation is a serious health problem. This problem could be induced by a variety of reasons, including lifestyle habits or neurological disorders. Chronic sleep deprivation (CSD) could have complex biological consequences, such as changes in neural autonomic control, increased oxidative stress, and inflammatory responses. The superior cervical ganglion (SCG) is an important sympathetic component of the autonomic nervous system. CSD can lead to a wide range of neurological consequences in SCG, which mainly supply innervations to circadian system and other structures. As the active component of Curcuma longa, curcumin possesses many therapeutic properties; including neuroprotective. This study aimed to evaluate the effect of CSD on the SCG histomorphometrical changes and the protective effect of curcumin in preventing these changes. METHODS: Thirty-six male rats were randomly assigned to the control, curcumin, CSD, CSD + curcumin, grid floor control, and grid floor + curcumin groups. The CSD was induced by a modified multiple platform apparatus for 21 days and animals were sacrificed at the end of CSD or treatment, and their SCGs removed for stereological and TUNEL evaluations and also spatial arrangement of neurons in this structure. RESULTS: Concerning stereological findings, CSD significantly reduced the volume of SCG and its total number of neurons and satellite glial cells in comparison with the control animals ( P < 0.05). Treatment of CSD with curcumin prevented these decreases. Furthermore, TUNEL evaluation showed significant apoptosis in the SCG cells in the CSD group, and treatment with curcumin significantly decreased this apoptosis ( P < 0.01). This decrease in apoptosis was observed in all control groups that received curcumin. CSD also changed the spatial arrangement of ganglionic neurons into a random pattern, whereas treatment with curcumin preserved its regular pattern. CONCLUSIONS: CSD could potentially induce neuronal loss and structural changes including random spatial distribution in the SCG neurons. Deleterious effects of sleep deprivation could be prevented by the oral administration of curcumin. Furthermore, the consumption of curcumin in a healthy person might lead to a reduction of cell death.

Animals , Male , Rats , Sleep Deprivation/pathology , Sleep Deprivation/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Superior Cervical Ganglion/drug effects , Curcumin/pharmacology , Rats, Sprague-Dawley
Braz. arch. biol. technol ; 63: e20200234, 2020. tab, graf
Article in English | LILACS | ID: biblio-1132219


Abstract Curcumin (CUR) shows potential use for treating cancer. However, CUR has low solubility and reduced bioavailability, which limit its clinical effect. Therefore, the development of nanocarriers can overcome these problems and can ensure the desired pharmacological effect. In addition, it is mandatory to prove the quality, the efficacy, and the safety for a novel nanomedicine to be approved. In that sense, this paper aimed (a) to prepare CUR-loaded polyethylene glycol-poly(ε-caprolactone) nanocapsules; (b) to validate an analytical method by high performance liquid chromatography (HPLC) for quantifying CUR in these nanoformulations; (c) to evaluate the physicochemical stability of these formulations; and to investigate their cytotoxicity on NIH-3T3 mouse fibroblast cells. The HPLC method was specific to CUR in the loaded nanocapsules, linear (r = 0.9994) in a range of 10.0 to 90.0 µg.mL-1 with limits of detection and quantification of 0.160 and 0.480 µg.mL-1, respectively. Precision was demonstrated by a relative standard deviation lower than 5%. Suitable accuracy (102.37 ± 0.92%) was obtained. Values of pH, particle size, polydispersity index, and zeta potential presented no statistical difference (p > 0.05) for CUR-loaded nanoparticles. No cytotoxicity was observed against NIH-3T3 mouse embryo fibroblast cell line using both the tetrazolium salt and sulforhodamine B assays. In conclusion, a simple and inexpensive HPLC method was validated for the CUR quantification in the suspensions of nanocapsules. The obtained polymeric nanocapsules containing CUR showed suitable results for all the performed assays and can be further investigated as a feasible novel approach for cancer treatment.

Animals , Mice , Curcumin/pharmacology , Embryonic Stem Cells/drug effects , Fibroblasts/drug effects , Chromatography, High Pressure Liquid , Toxicity Tests , Nanotechnology , NIH 3T3 Cells , Embryo, Mammalian/cytology , Nanocapsules
Int. j. morphol ; 37(2): 584-591, June 2019. tab, graf
Article in English | LILACS | ID: biblio-1002262


Following the success of the highly active antiretroviral therapy, the potential of multidrug combination regimen for the management of cancer is intensely researched. The anticancer effects of curcumin on some human cell lines have been documented. Lopinavir is a FDA approved protease inhibitor with known apoptotic activities. Dysregulated apoptosis is important for the initiation of cancer while angiogenesis is required for cancer growth and development, this study therefore investigated the effects of the combination of lopinavir and curcumin on cell viability, apoptosis and the mRNA expression levels of key apoptotic and angiogenic genes; BAX, BCL2 and VEGF165b in two human cervical cell lines; human squamous cell carcinoma cells - uterine cervix (HCS-2) and transformed normal human cervical cells (NCE16IIA). The two human cervical cell lines were treated with physiologically relevant concentrations of the agents for 120 h following which BAX, BCL2 and VEGF165b mRNA expression were determined by Real Time qPCR. The Acridine Orange staining for the morphological evaluation of apoptotic cells was also performed. The combination of lopinavir and curcumin up-regulated pro-apoptotic BAX and antiangiogenic VEGF165b but down-regulated the mRNA levels of anti-apoptotic BCL2 mRNA in the human squamous cell carcinoma (HCS-2) cells only. The fold changes were statistically significant. Micrographs from Acridine Orange staining showed characteristic evidence of apoptosis in the human squamous cell carcinoma (HCS-2) cells only. The findings reported here suggest that the combination of curcumin and the FDA approved drug-lopinavir modulate the apoptotic and angiogenic pathway towards the inhibition of cervical cancer.

Tras el éxito de la terapia antirretroviral altamente activa, se investiga intensamente el potencial del régimen de combinación de múltiples fármacos para el tratamiento del cáncer. Se han documentado los efectos anticancerígenos de la curcumina en algunas líneas celulares humanas. Lopinavir es un inhibidor de proteasa aprobado por la FDA con actividades apoptóticas conocidas. La apoptosis disrregulada es importante para el inicio del cáncer, mientras que la angiogénesis es necesaria para el crecimiento y desarrollo del cáncer. Por lo tanto, este estudio investigó los efectos de la combinación de lopinavir y curcumina sobre la viabilidad celular, la apoptosis y los niveles de expresión del ARNm de genes apoptóticos y angiogénicos clave: BAX, BCL2 y VEGF165b en dos líneas celulares cervicales humanas; células de carcinoma de células escamosas humanas: cérvix uterino (HCS-2) y células cervicales humanas transformadas (NCE16IIA). Las dos líneas celulares cervicales humanas se trataron con concentraciones fisiológicamente relevantes de los agentes durante 120 horas, después de lo cual la expresión de ARNm de BAX, BCL2 y VEGF165b se determinó mediante qPCR en tiempo real. También se realizó la tinción con naranja de acridina para la evaluación morfológica de células apoptóticas. La combinación de lopinavir y curcumina reguló incrementando BAX proapoptósicos y VEGF165b antiangiogénicos, pero reguló a la baja los niveles de ARNm del BCL2 antiapoptótico en células de carcinoma de células escamosas humanas (HCS-2) únicamente. Los cambios en el pliegue fueron estadísticamente significativos. Las micrografías de la tinción con naranja de acridina mostraron evidencia característica de apoptosis solo en las células del carcinoma de células escamosas humanas (HCS-2). Los hallazgos reportados aquí sugieren que la combinación de curcumina y el fármaco aprobado por la FDA lopinavir modulan la vía apoptótica y angiogénica hacia la inhibición del cáncer cervical.

Humans , Female , Carcinoma, Squamous Cell/drug therapy , Uterine Cervical Neoplasms/drug therapy , Curcumin/pharmacology , Lopinavir/pharmacology , Antineoplastic Agents/pharmacology , Cell Survival/drug effects , Apoptosis/drug effects , Cell Line, Tumor/drug effects , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/genetics , bcl-2-Associated X Protein/drug effects , bcl-2-Associated X Protein/genetics , Real-Time Polymerase Chain Reaction
Braz. J. Pharm. Sci. (Online) ; 55: e18276, 2019. graf
Article in English | LILACS | ID: biblio-1011640


To study the effect of small interfering RNA targeting metastasis-associated lung adenocarcinoma transcript1 (si-MALAT1) combining with curcumin on the invasion and migration abilities of human colon cancer SW480 cells, and to explore the involved molecular mechanism. The recombinant lentiviral vector expressing si-MALAT1 was constructed, and its titer was determined by gradient dilution method. The colon cancer SW480 cells with stable expression of si-MALAT1 was established, followed by treatment with curcumin at different concentrations. The effect of curcumin or si-MALAT1 alone and the combination of the two on the cell activity was detected by MTT assay. The cell invasion and migration abilities were detected by transwell and scratch-wound assay. The relative expression level of MALAT1 was detected by RT-qPCR. The protein expression was determined by Western blot analysis. The IC50 of curcumin alone was 77.69 mmol/L, which was 51.17 mol/L when combined with curcumin and random sequence. The IC50 of curcumin was 30.02 mmol/L when combined with si-MALAT1. The increased susceptibility multiples was 2.58. The wound healing rates were 30.9% and 67.5% after treatment with si-MALAT1 combined with curcumin for 24 hrs and 48 hrs, respectively. The numbers of invasion cells were 200±12, 162±13, 66±8, 53±4 and 16±3 after treatment with si-MALAT1 combined with curcumin for 48 hrs. The relative expression level of lncRNA-MALAT1 in the curcumin group was 68%, and the relative expression level of lncRNA-MALAT1 in si-MALAT1group was 56%, and that for the combination treatment group was about 21%. The protein expression levels of β- catenin, c-myc and cyclinD1 were significantly down-regulated upon treatment with certain concentration of si-MALAT1 alone or combined with could significantly inhibit the invasion and migration of SW480 cells by enhancing the sensitivity of SW480 cells to curcumin. The mechanism involved mignt be related to the down-regulation of β-catenin, c-myc and cyclinD1 proteins.

Cell Migration Inhibition/drug effects , Colonic Neoplasms , Curcumin/pharmacology , Neoplasms/prevention & control , RNA , RNA, Small Interfering/drug effects
Acta cir. bras ; 34(6): e201900604, 2019. graf
Article in English | LILACS | ID: biblio-1019261


Abstract Purpose In view of the principal role of Toll-like receptor 4 (TLR4) in mediating sterile inflammatory response contributing to osteoarthritis (OA) pathogenesis, we used lipopolysaccharide (LPS), a known TLR4 activator, to clarify whether modulation of TLR4 contributed to the protective actions of intra-articular administration of curcumin in a classical rat OA model surgically induced by anterior cruciate ligament transection (ACLT). Methods The rats underwent ACLT and received 50μl of curcumin at the concentration of 1 mg mL-1 and 10 μg LPS by intra-articular injection once a week for 8 weeks. Morphological changes of the cartilage and synovial tissues were observed. Apoptotic chondrocytes were detected using TUNEL assay. The concentrations of IL-1β and TNF-ɑ in synovial fluid were determined using ELISA kits. The mRNA and protein expression levels of TLR4 and NF-κB p65 were detected by real-time PCR and Western blotting, respectively. Results Intra-articular administration of curcumin significantly improved articular cartilage injury, suppressed synovial inflammation and down-regulated the overexpression of TLR4 and its downstream NF-κB caused by LPS-induced TLR4 activation in rat osteoarthritic knees. Conclusion The data suggested that the inhibition of TLR4 signal might be an important mechanism underlying a protective effect of local curcumin administration on OA.

Animals , Male , Rats , Osteoarthritis/prevention & control , Anterior Cruciate Ligament/surgery , Curcumin/pharmacology , Osteoarthritis/chemically induced , Osteoarthritis/metabolism , Enzyme-Linked Immunosorbent Assay , Lipopolysaccharides , Blotting, Western , Polymerase Chain Reaction , Anterior Cruciate Ligament/pathology , NF-kappa B/metabolism , Lymphotoxin-alpha/metabolism , Disease Models, Animal , Toll-Like Receptor 4/drug effects , Toll-Like Receptor 4/metabolism , Interleukin-1beta/metabolism , Injections, Intra-Arterial
Arch. endocrinol. metab. (Online) ; 62(4): 438-445, July-Aug. 2018. tab, graf
Article in English | LILACS | ID: biblio-950087


ABSTRACT Objective: This study evaluated the effects of combination therapy of curcumin and alendronate on BMD and bone turnover markers in postmenopausal women with osteoporosis. Subjects and methods: In a randomized, double-blind trial study, 60 postmenopausal women were divided into three groups: control, alendronate, and alendronate + curcumin. Each group included 20 patients. Total body, total hip, lumbar spine and femoral neck BMDs were measured by dual-energy X-ray absorptiometry (DXA) at baseline and after 12 months of therapy. Bone turnover markers such as bone-specific alkaline phosphatase (BALP), osteocalcin and C-terminal cross-linking telopeptide of type I collagen (CTx) were measured at the outset and 6 months later. Results: Patients in the control group suffered a significant decrease in BMD and increased bone turnover markers at the end of study. The group treated with only alendronate showed significantly decreased levels of BALP and CTx and increased levels of osteocalcin compared to the control group. The alendronate group also showed significant increases in the total body, total hip, lumbar spine and femoral neck BMDs at the end of study compared to the control group. In the curcumin + alendronate group, BALP and CTx levels decreased and osteocalcin levels increased significantly at the end of study compared to the control and alendronate groups. BMD indexes also increased in four areas significantly at the end of study compared to the control and alendronate groups. Conclusion: The combination of curcumin and alendronate has beneficial effects on BMD and bone turnover markers among postmenopausal women with osteoporosis. Arch Endocrinol Metab. 2018;62(4):438-45

Humans , Female , Middle Aged , Aged , Bone Density/drug effects , Osteoporosis, Postmenopausal/metabolism , Alendronate/pharmacology , Curcumin/pharmacology , Bone Density Conservation Agents/pharmacology , Peptide Fragments/drug effects , Peptide Fragments/urine , Osteocalcin/analysis , Osteocalcin/drug effects , Double-Blind Method , Bone Remodeling/drug effects , Collagen Type II/drug effects , Collagen Type II/urine , Drug Therapy, Combination/methods , Alkaline Phosphatase/analysis , Alkaline Phosphatase/drug effects
Acta cir. bras ; 33(6): 533-541, June 2018. graf
Article in English | LILACS | ID: biblio-949351


Abstract Purpose: To investigate the specific molecular mechanisms and effects of curcumin derivative J147 on diabetic peripheral neuropathy (DPN). Methods: We constructed streptozotocin (STZ)-induced DPN rat models to detected mechanical withdrawal threshold (MWT) in vivo using Von Frey filaments. In vitro, we measured cell viability and apoptosis, adenosine 5'-monophosphate-activated protein kinase (AMPK) and transient receptor potential A1 (TRPA1) expression using MTT, flow cytometry, qRT-PCR and western blot. Then, TRPA1 expression level and calcium reaction level were assessed in agonist AICAR treated RSC96cells. Results: The results showed that J147reduced MWT in vivo, increased the mRNA and protein level of AMPK, reduced TRPA1 expression and calcium reaction level in AITCR treated RSC96 cells, and had no obvious effect on cell viability and apoptosis. Besides, AMPK negative regulated TRPA1 expression in RSC96 cells. Conclusions: J147 could ameliorate DPN via negative regulation AMPK on TRPA1 in vivo and in vitro. A curcumin derivative J147might be a new therapeutic potential for the treatment of DPN.

Animals , Male , Curcumin/analogs & derivatives , Curcumin/pharmacology , Diabetic Neuropathies/drug therapy , AMP-Activated Protein Kinases/drug effects , TRPA1 Cation Channel/drug effects , Time Factors , Cell Survival/drug effects , Cells, Cultured , Blotting, Western , Calcium/analysis , Reproducibility of Results , Apoptosis/drug effects , Streptozocin , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/metabolism , Diabetic Neuropathies/metabolism , AMP-Activated Protein Kinases/analysis , Real-Time Polymerase Chain Reaction , TRPA1 Cation Channel/analysis , Microscopy, Fluorescence
Acta cir. bras ; 33(6): 499-507, June 2018. tab, graf
Article in English | LILACS | ID: biblio-949358


Abstract Purpose: To evaluate the impact of systemic cyclophosphamide treatment on the rat uterus and investigate the potential therapeutic effects of natural antioxidant preparations curcumin and capsaicin against cyclophosphamide side effects. Methods: A 40 healthy adult female Wistar albino rats were used in this study. Rats were randomly divided into four groups to determine the effects of curcumin and capsaicin against Cyclophosphamide side effects on the uterus (n=10 in each group); Group 1 was the control group (sham-operated), Group 2 was the cyclophosphamide group, Group 3 was the cyclophosphamide + curcumin (100mg/kg) group, and Group 4 was the cyclophosphamide + capsaicin (0.5 mg/kg) group. Results: Increased tissue oxidative stress and histological damage in the rat uterus were demonstrated due to the treatment of systemic cyclophosphamide chemotherapy alone. The level of tissue oxidant and antioxidant markers and histopathological changes were improved by the treatment of curcumin and capsaicin. Conclusion: Cytotoxic effects of natural alkylating chemotherapeutic agents like cyclophosphamide on the uterus can be prevented by curcumin and capsaicin.

Animals , Female , Uterus/drug effects , Capsaicin/pharmacology , Antineoplastic Agents, Alkylating/adverse effects , Curcumin/pharmacology , Cyclophosphamide/adverse effects , Antioxidants/pharmacology , Superoxide Dismutase/analysis , Uterine Diseases/chemically induced , Uterine Diseases/prevention & control , Uterus/pathology , Catalase/analysis , Random Allocation , Reproducibility of Results , Rats, Wistar , Oxidative Stress/drug effects , Glutathione/analysis , Glutathione Peroxidase/analysis , Malondialdehyde/analysis
Acta cir. bras ; 33(2): 110-116, Feb. 2018. tab, graf
Article in English | LILACS | ID: biblio-886264


Abstract Purpose: To investigate thymoquinone, curcumin and a combination of these two drugs were effective or not at the growth of liver. Methods: Forty female Wistar-Albino rats distributed into five groups of eight rats each, control, thymoquinone, curcumin, and thymoquinone/curcumin groups. Pathological specimens were studied using the Ki-67 Proliferation Index(PI); and arginase(Arg), tissue plasminogen activator(tPA), ceruloplasmin(Cer) and nitric oxide(NO) were studied in biochemical analysis. Results: Our results showed that Ki-67 proliferation index was low in Groups 1. The proliferation coefficient was significantly higher in the Group 2 and Group 4 than in the Group 1 and Group 3.(P < 0.001 between Groups 1 and 2, 1 and 4, and 3 and 4). There was no difference between Groups 2 and 4 (P = 1). The results of the biochemical Arg, tPA and Cer test showed statistically between the Group 1 and Group 2. NO showed significant differences Group 1 and 3. Conclusions: Thymoquinone and curcumin both have known positive effects on the organism. Histological and biochemical tests showed that thymoquinone is more effective than curcumin.

Animals , Female , Rats , Liver Regeneration/drug effects , Antioxidants/pharmacology , Arginase/blood , Ceruloplasmin/analysis , Biomarkers/blood , Benzoquinones/pharmacology , Liver Transplantation , Tissue Plasminogen Activator/blood , Rats, Wistar , Ki-67 Antigen/analysis , Curcumin/pharmacology , Cell Proliferation , Hepatectomy/methods , Liver/pathology , Liver Neoplasms/surgery , Antineoplastic Agents/pharmacology , Nitric Oxide/blood
J. coloproctol. (Rio J., Impr.) ; 37(4): 312-319, Oct.-Dec. 2017. tab, graf
Article in English | LILACS | ID: biblio-894005


ABSTRACT Purpose: To verify if the application of enemas containing oily extracts of curcumin preserves the tissue content of mucins in the glands of the colonic mucosa without fecal stream. Method: Thirty-six Wistar rats were submitted to diversion of the fecal stream by proximal colostomy and distal mucous fistula. The animals were subdivided into three groups, and accordingly received enemas with saline and oily extract of curcumin at concentrations of 50 mg/kg/day or 200 mg/kg/day. After two or four weeks of intervention, the irrigated colic segments were removed. Neutral and acidic mucins were identified by Periodic-acid Schiff and Alcian-Blue techniques, respectively. The content of both mucin subtypes was measured by computerized morphometry. Mann-Whitney test was used to analyze the results, adopting a significance level of 5% (p ≤ 0.05). Results: There was an increase in the tissue content of neutral mucins in animals treated with curcumin at a concentration of 50 mg/kg/day for four weeks, whereas in the group treated with 200 mg/kg/day there was an increase independent of the time of intervention. The content of acidic mucins increased in animals treated with 200 mg/kg/day regardless of the intervention time, whereas in those treated with 50 mg/kg/day an increase was observed only after four weeks. Conclusion: Enemas with curcumin preserve the content of neutral and acidic mucins in the colonic epithelium without fecal stream.

RESUMO Objetivo: Verificar se a aplicação de clisteres com extrato oleoso de curcumina preserva o conteúdo de mucinas nas glândulas da mucosa cólica sem trânsito intestinal. Método: Trinta e seis ratos Wistar foram submetidos à derivação intestinal por colostomia proximal e fístula mucosa distal. Os animais foram subdivididos em três grupos, segundo receberem clisteres com soro fisiológico 0,9%, extrato oleoso de curcumina nas concentrações de 50 mg/kg/dia ou 200 mg/kg/dia. Após duas ou quatro semanas de intervenção foram removidos os segmentos cólicos irrigados. As mucinas neutras e ácidas foram identificadas pelas técnicas do PAS e Alcian-Blue, respectivamente. O conteúdo tecidual de ambos os subtipos de mucinas foi mensurado por morfometria computadorizada. Utilizou-se teste de Mann-Whitney para análise dos resultados adotando-se nível de significância de 5% (p ≤ 0,05). Resultados: Houve aumento no conteúdo de mucinas neutras nos animais tratados com curcumina na concentração de 50 mg/kg/dia por quatro semanas, enquanto nos tratados com 200 mg/kg/dia houve aumento independente do tempo de intervenção. O conteúdo de mucinas ácidas aumentou nos animais tratados com 200 mg/kg/dia independente do tempo de intervenção, enquanto nos tratados com 50 mg/kg/dia encontrou-se aumento apenas após quatro semanas. Conclusão: Clisteres com curcumina preservam o conteúdo de mucinas neutras e ácidas no epitélio cólico sem trânsito intestinal.

Animals , Rats , Curcumin/pharmacology , Mucins/drug effects , Rats, Wistar , Colitis/drug therapy
Arq. neuropsiquiatr ; 75(8): 546-552, Aug. 2017. tab, graf
Article in English | LILACS | ID: biblio-888308


ABSTRACT Recent studies have demonstrated that curcumin (Cur) has antioxidant, anti-inflammatory and anti-fibrotic effects. Ethidium bromide (EB) injections into the central nervous system (CNS) are known to induce local oligodendroglial and astrocytic loss, resulting in primary demyelination and neuroinflammation. Peripheral astrogliosis is seen around the injury site with increased immunoreactivity to glial fibrillary acidic protein (GFAP). This investigation aimed to evaluate the effect of Cur administration on astrocytic response following gliotoxic injury. Wistar rats were injected with EB into the cisterna pontis and treated, or not, with Cur (100 mg/kg/day, intraperitoneal route) during the experimental period. Brainstem sections were collected at 15, 21 and 31 days after EB injection and processed for GFAP immunohistochemical staining. Astrocytic reactivity was measured in a computerized system for image analysis. In Cur-treated rats, the GFAP-stained area around the lesion was significantly smaller in all periods after EB injection compared to untreated animals, showing that Cur reduces glial scar development following injury.

RESUMO Estudos recentes têm demonstrado que a curcumina (Cur) possui efeitos antioxidantes, anti-inflamatórios e antifibróticos. Sabe-se que a injeção de brometo de etídio (EB) no sistema nervoso central induz a perda oligodendroglial e astrocitária, resultando em desmielinização primária e neuroinflamação. Astrogliose periférica é observada ao redor da lesão com aumento da imunorreatividade à proteína glial fibrilar ácida (GFAP). A presente investigação objetivou avaliar o efeito da Cur sobre a resposta astrocitária após injúria gliotóxica. Ratos Wistar foram injetados com EB na cisterna basal e tratados ou não com Cur (100 mg/kg/dia, via intraperitoneal) durante o período experimental. Amostras do tronco encefálico foram coletadas aos 15, 21 e 31 dias pós-injeção de EB e processadas para estudo imuno-histoquímico para a GFAP. A reatividade astrocitária foi medida em um sistema computadorizado para análise de imagem. Nos ratos tratados com Cur, a área marcada para GFAP foi significantemente menor em todos os períodos pós-injeção de EB, indicando que a Cur reduz o desenvolvimento da cicatriz glial após injúria.

Animals , Male , Rats , Brain Stem/pathology , Astrocytes/drug effects , Demyelinating Diseases/pathology , Curcumin/therapeutic use , Staining and Labeling , Brain Stem/drug effects , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Astrocytes/pathology , Demyelinating Diseases/chemically induced , Rats, Wistar , Curcumin/pharmacology , Disease Models, Animal , Ethidium , Glial Fibrillary Acidic Protein/metabolism
Braz. J. Pharm. Sci. (Online) ; 53(1): e16136, 2017. tab, graf
Article in English | LILACS | ID: biblio-839443


Abstract Curcuma longa, which contains curcumin as a major constituent, has been shown many pharmacological effects, but it is limited using in clinical due to low bioavailability. In this study, we developed a phytosome curcumin formulation and evaluated the hepatoprotective effect of phytosome curcumin on paracetamol induced liver damage in mice. Phytosome curcumin (equivalent to curcumin 100 and 200 mg/kg body weight) and curcumin (200 mg/kg body weight) were given by gastrically and toxicity was induced by paracetamol (500 mg/kg) during 7 days. On the final day animals were sacrificed and liver function markers (ALT, AST), hepatic antioxidants (SOD, CAT and GPx) and lipid peroxidation in liver homogenate were estimated. Our data showed that phytosome has stronger hepatoprotective effect compared to curcumin-free. Administration of phytosome curcumin effectively suppressed paracetamol-induced liver injury evidenced by a reduction of lipid peroxidation level, and elevated enzymatic antioxidant activities of superoxide dismutase, catalase, glutathione peroxidase in mice liver tissue. Our study suggests that phytosome curcumin has strong antioxidant activity and potential hepatoprotective effects.

Animals , Male , Female , Rats , Rats/classification , Curcumin/pharmacology , Curcuma/adverse effects , Chemical and Drug Induced Liver Injury/prevention & control , Hepatoprotector Drugs , Acetaminophen/adverse effects
Rev. ADM ; 73(5): 245-249, sept.-oct. 2016.
Article in Spanish | LILACS | ID: biblio-835302


La curcumina es una sustancia derivada de una planta llamada Curcuma longa. A esta sustancia se le han atribuido diversos efectos terapéuticos. En relación con la clínica dental, se ha observado que, además de ayudaren el control del dolor, ha sido efectiva contra la periodontitis, estomatitis y mucositis pediátrica. El control del dolor e inflamación son aspectos muy importantes para la mayoría de los tratamientos en odontología; la búsqueda de nuevas alternativas analgésicas y antiinflamatorias que, en comparación con las actuales, sean más eficientes, efectivas y tengan menos efectos colaterales es uno de los grandes retos de las ciencias biomédicas. La presente revisión muestra algunas evidencias científicas de los efectos de la curcumina como un antiinflamatorio y analgésico, con el propósito de sentar las bases para futuros estudios clínicos y de ciencia básica que aporten un mayor entendimiento de los procesos celulares, bioquímicos, moleculares, fisiológicos y farmacológicos de la curcumina como una sustancia potencialmente útilen el consultorio dental.

Curcumin is a substance derived from the plant Curcuma longa andone that has been attributed a range of therapeutic eff ects. In dentalpractice, curcumin has not only been found to help with pain control, buthas also been eff ective against periodontitis, stomatitis, and pediatricmucositis. Controlling pain and infl ammation are both very importantaspects of most dental treatments. The search for more effi cient andeff ective analgesic and anti-infl ammatory alternatives with fewerside eff ects compared to those currently used is one of the greatestchallenges for biomedical science. This review presents some of thescientifi c evidence of the eff ects of curcumin, both as an analgesic andan anti-infl ammatory agent, in order to establish the foundations forfurther clinical and basic science studies that will provide a greaterunderstanding of the cellular, biochemical, molecular, physiological,and pharmacological processes of curcumin as a potentially usefulsubstance in dental practice.

Humans , Analgesics/classification , Anti-Inflammatory Agents, Non-Steroidal/classification , Curcumin/pharmacology , Curcumin/therapeutic use , Antineoplastic Agents/classification , Antineoplastic Agents/therapeutic use , Mouthwashes/classification , Mouthwashes/therapeutic use , Periodontal Diseases/drug therapy , Stomatitis/drug therapy
Yonsei Medical Journal ; : 664-673, 2016.
Article in English | WPRIM | ID: wpr-21847


PURPOSE: Diabetic nephropathy is a serious complication of type 2 diabetes mellitus, and delaying the development of diabetic nephropathy in patients with diabetes mellitus is very important. In this study, we investigated inflammation, oxidative stress, and lipid metabolism to assess whether curcumin ameliorates diabetic nephropathy. MATERIALS AND METHODS: Animals were divided into three groups: Long-Evans-Tokushima-Otsuka rats for normal controls, Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats for the diabetic group, and curcumin-treated (100 mg/kg/day) OLETF rats. We measured body and epididymal fat weights, and examined plasma glucose, adiponectin, and lipid profiles at 45 weeks. To confirm renal damage, we measured albumin-creatinine ratio, superoxide dismutase (SOD), and malondialdehyde (MDA) in urine samples. Glomerular basement membrane thickness and slit pore density were evaluated in the renal cortex tissue of rats. Furthermore, we conducted adenosine monophosphate-activated protein kinase (AMPK) signaling and oxidative stress-related nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling to investigate mechanisms of lipotoxicity in kidneys. RESULTS: Curcumin ameliorated albuminuria, pathophysiologic changes on the glomerulus, urinary MDA, and urinary SOD related with elevated Nrf2 signaling, as well as serum lipid-related index and ectopic lipid accumulation through activation of AMPK signaling. CONCLUSION: Collectively, these findings indicate that curcumin exerts renoprotective effects by inhibiting renal lipid accumulation and oxidative stress through AMPK and Nrf2 signaling pathway.

Albuminuria , Animals , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Curcumin/pharmacology , Diabetes Mellitus, Type 2/metabolism , Diabetic Nephropathies/complications , Gene Expression/drug effects , Inflammation , Kidney/drug effects , Kidney Glomerulus/metabolism , Lipid Metabolism/drug effects , Male , Malondialdehyde/metabolism , Oxidative Stress/drug effects , Rats , Rats, Inbred OLETF , Rats, Long-Evans , Superoxide Dismutase/metabolism
Hist. ciênc. saúde-Manguinhos ; 22(1): 179-200, Jan-Mar/2015.
Article in English | LILACS, BDS | ID: lil-741513


This article examines the politics of midwifery and the persecution of untitled female assistants in childbirth in early republican Peru. A close reading of late colonial publications and the works of Benita Paulina Cadeau Fessel, a French obstetriz director of a midwifery school in Lima, demonstrates both trans-Atlantic and local influences in the campaign against untitled midwives. Cadeau Fessel's efforts to promote midwifery built upon debates among writers in Peru's enlightened press, who vilified untrained midwives' and wet nurses' vernacular medical knowledge and associated them with Lima's underclass. One cannot understand the transfer of French knowledge about professional midwifery to Peru without reference to the social, political, and cultural context.

Este artigo analisa as políticas de práticas de parteiras profissionais e a condenação de parteiras leigas nos primórdios do Peru republicano. A leitura atenta de publicações de fins do período colonial e dos trabalhos de Benita Paulina Cadeau Fessel, obstetriz francesa diretora de uma escola de parteiras em Lima, revela influência tanto transatlântica como local na campanha contra as parteiras sem titulação. Cadeau Fessel promovia seu ofício com base em debates veiculados na imprensa peruana ilustrada, que aviltavam o conhecimento tradicional de amas de leite e parteiras leigas e as associavam às classes desfavorecidas. Só é possível compreender a transferência do conhecimento francês sobre trabalho de parteiras profissionais para o Peru relacionando-a ao contexto social, político e cultural.

Animals , Male , Antiparkinson Agents/pharmacology , Curcumin/pharmacology , Hippocampus/drug effects , Neuroprotective Agents/pharmacology , Oxidopamine , Parkinsonian Disorders/drug therapy , Behavior, Animal/drug effects , Brain-Derived Neurotrophic Factor/metabolism , Cytoprotection , Disease Models, Animal , Dose-Response Relationship, Drug , Dopamine/metabolism , Hippocampus/metabolism , Hippocampus/pathology , Nerve Regeneration/drug effects , Norepinephrine/metabolism , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/metabolism , Parkinsonian Disorders/pathology , Parkinsonian Disorders/psychology , /metabolism , Rats, Sprague-Dawley , Receptor, trkB/metabolism , Signal Transduction/drug effects
Alexandria Journal of Veterinary Science [AJVS]. 2015; 45 (April): 43-50
in English | IMEMR | ID: emr-175681


The objective of the present study was to elucidate whether serum ATX activity might be a target for regulation of liver fibrosis and to evaluate the hepatoprotective and antifibrotic effect of curcumin in TAA induced liver fibrosis in rats. Therefore 40 healthy adult albino rats, divided into 4 groups [10 rats in each]. Rats in the 2[nd] group received curcumin [500 mg/kg b. wt /orally every day], the 3[rd] group injected by thioacetamide [TAA] intraperioteneal [250 mg/kg b. wt] three times a week, the 4[th] group injected by TAA intraperioteneal [250 mg/kg b. wt] three times a weeks and received curcumin orally [500 mg/kg b. wt every day]. The changes in body weight index and histopathological examination. In addition, selected biochemical parameters were also determined. The present study revealed that, oral supplementation of curcumin causing increase of liver weight index, autotaxin [ATX], HDL-c level and decrease of total protein, urea, creatinine and ammonia, total cholesterol, LDL-c and triacylglycerols. Treatment with TAA induced increase in the liver weight index, ATX, ALT, triacylglycerols, ammonia levels and decrease in serum proteins, urea, total cholesterol, HDL-c and LDL-c levels. Histopathological examination revealed severs necrosis, inflammatory cellular infiltration and nodules in TAA group. While the supplementation of rats with TAA and curcumin orally together resulted in increase in liver weight index, ATX, ALT, triacylglycerols levels and decrease in serum total protein, urea, total cholesterol, HDL-c, LDL-c concentration moreover, revealed mild inflammation and necrosis by histopathological examination. Conclusively, the use of curcumin ameliorated the effect of TAA induced liver fibrosis but cannot reach the normal levels

Animals, Laboratory , Liver Cirrhosis , Fibrosis , Phosphoric Diester Hydrolases , Curcumin/pharmacology , Thioacetamide , Rats
Korean Journal of Urology ; : 656-665, 2015.
Article in English | WPRIM | ID: wpr-47846


PURPOSE: Curcumin is a nontoxic, chemopreventive agent possessing multifaceted functions. Our previous study showed that curcumin inhibits androgen receptor (AR) through modulation of Wnt/beta-catenin signaling in LNCaP cells. Therefore, we investigated the in vivo effects of curcumin by using LNCaP xenografts. MATERIALS AND METHODS: LNCaP cells were subcutaneously inoculated in Balb/c nude mice. When the tumor volume reached greater than 100 mm3, either curcumin (500 mg/kg body weight) or vehicle was administered through oral gavage three times weekly for 4 weeks. The expression of AR and intermediate products of Wnt/beta-catenin were assessed. RESULTS: Curcumin had an inhibitory effect on tumor growth during the early period, which was followed by a slow increase in growth over time. Tumor growth was delayed about 27% in the curcumin group. The mean prostate-specific antigen (PSA) doubling time in the curcumin group was approximately twice that in the untreated group. Curcumin significantly decreased AR expression at both the mRNA and protein level. The PSA levels tended to be reduced in the curcumin group. However, there were no significant changes in expression of Wnt/beta-catenin pathway intermediates. CONCLUSIONS: This study revealed that curcumin initially interferes with prostate cancer growth by inhibiting AR activity and possibly by reducing PSA expression. Further research is needed to investigate the plausible mechanism of the antiandrogenic action of curcumin.

Adenocarcinoma/drug therapy , Animals , Antineoplastic Agents/pharmacology , Curcumin/pharmacology , Cyclin D1/genetics , Heterografts , Humans , Male , Mice, Inbred BALB C , Prostate-Specific Antigen/blood , Prostatic Neoplasms/drug therapy , RNA, Messenger/metabolism , Receptors, Androgen/genetics , Wnt Signaling Pathway/drug effects , beta Catenin/genetics