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Over the past five decades, Curcumin (Cur), derived from turmeric (Curcuma longa), has gained considerable attention for its potential therapeutic applications. Synthesizing insights from clinical trials conducted over the last 25 years, this review delves into diseases where Cur has demonstrated promise, offering a nuanced understanding of its pharmacokinetics, safety, and effectiveness. Focusing on specific examples, the impact of Cur on various human diseases is explored. Endocrine glands and associated signaling pathways are highlighted, elucidating how Cur influences cellular signaling. The article underscores molecular mechanisms such as hormone level alteration, receptor interaction, cytokine and adipokine expression inhibition, antioxidant enzyme activity, and modulation of transcription factors. Cur showcases diverse protective mechanisms against inflammation and oxidative damage by suppressing antiapoptotic genes and impeding tumor promotion. This comprehensive overview emphasizes the potential of Cur as a natural agent for countering aging and degenerative diseases, calling for further dedicated research in this realm.
Assuntos
Curcuma , Curcumina , Doenças do Sistema Endócrino , Curcumina/farmacologia , Curcumina/uso terapêutico , Humanos , Curcuma/química , Doenças do Sistema Endócrino/tratamento farmacológico , Animais , Transdução de Sinais/efeitos dos fármacos , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacosRESUMO
Zoonotic diseases are major public health concerns and undeniable threats to human health. Among Zoonotic diseases, zoonotic viruses and prions are much more difficult to eradicate, as they result in higher infections and mortality rates. Several investigations have shown curcumin, the active ingredient of turmeric, to have wide spectrum properties such as anti-microbial, anti-vascular, anti-inflammatory, anti-tumor, anti-neoplastic, anti-oxidant, and immune system modulator properties. In the present study, we performed a comprehensive review of existing in silico, in vitro, and in vivo evidence on the antiviral (54 important zoonotic viruses) and anti-prion properties of curcumin and curcuminoids in PubMed, Google Scholar, Science Direct, Scopus, and Web of Science databases. Database searches yielded 13,380 results, out of which 216 studies were eligible according to inclusion criteria. Of 216 studies, 135 (62.5%), 24 (11.1%), and 19 (8.8%) were conducted on the effect of curcumin and curcuminoids against SARS-CoV-2, Influenza A virus, and dengue virus, respectively. This review suggests curcumin and curcuminoids as promising therapeutic agents against a wide range of viral zoonoses by targeting different proteins and signaling pathways.
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Antivirais , Curcumina , Curcumina/farmacologia , Animais , Humanos , Antivirais/farmacologia , Zoonoses/tratamento farmacológico , Zoonoses/virologia , SARS-CoV-2/efeitos dos fármacos , Príons/efeitos dos fármacos , Vírus da Influenza A/efeitos dos fármacos , Vírus da Dengue/efeitos dos fármacos , Tratamento Farmacológico da COVID-19 , COVID-19/virologiaRESUMO
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-beta plaques and neurofibrillary tangles, leading to neuronal loss. Curcumin, a polyphenolic compound derived from Curcuma longa, has shown potential neuroprotective effects due to its anti-inflammatory and antioxidant properties. This review aims to synthesize current preclinical data on the anti-neuroinflammatory mechanisms of curcumin in the context of AD, addressing its pharmacokinetics, bioavailability, and potential as a therapeutic adjunct. An exhaustive literature search was conducted, focusing on recent studies within the last 10 years related to curcumin's impact on neuroinflammation and its neuroprotective role in AD. The review methodology included sourcing articles from specialized databases using specific medical subject headings terms to ensure precision and relevance. Curcumin demonstrates significant neuroprotective properties by modulating neuroinflammatory pathways, scavenging reactive oxygen species, and inhibiting the production of pro-inflammatory cytokines. Despite its potential, challenges remain regarding its limited bioavailability and the scarcity of comprehensive human clinical trials. Curcumin emerges as a promising therapeutic adjunct in AD due to its multimodal neuroprotective benefits. However, further research is required to overcome challenges related to bioavailability and to establish effective dosing regimens in human subjects. Developing novel delivery systems and formulations may enhance curcumin's therapeutic potential in AD treatment.
Assuntos
Doença de Alzheimer , Anti-Inflamatórios , Curcumina , Fármacos Neuroprotetores , Curcumina/farmacologia , Curcumina/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Humanos , Fármacos Neuroprotetores/farmacologia , Anti-Inflamatórios/farmacologia , Animais , Doenças Neuroinflamatórias/tratamento farmacológico , Antioxidantes/farmacologia , Curcuma/química , Disponibilidade BiológicaRESUMO
BACKGROUND: Photodynamic therapy can be used to treat a variety of lesions noninvasively, including oral cancer. High-power laser therapy has also been used to treat oral squamous cell carcinomas. The two main components of photodynamic treatment are the photosensitizer and the light source. Herbal formulations of photosensitizers are used to mask the disadvantages of other photosensitizers. METHODOLOGY: A methanol-diluted 25 grams of Punica granatum was used to create an anthocyanin extract using the flash evaporation method. Dimethyl sulfoxide (DMSO) was used as the first dilution agent for curcumin; later further dilution was done with distilled water. Following that, MCF-7 cells (a cancer cell line) were cultured with the produced samples, and the mono-tetrazolium salt (MTT) assay was used to determine the vitality of the cells. RESULTS: Cell reduction was significantly evident in all three groups, but the most significant cell death was found in the anthocyanin-curcumin group, at 29%. CONCLUSION: The combination of anthocyanin-curcumin has one of the photophysical properties (dark cytotoxicity) and hence can aid as a photosensitizer.
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Incorporating Curcumin into animal diets holds significant promise for enhancing both animal health and productivity, with demonstrated positive impacts on antioxidant activity, anti-microbial responses. Therefore, this study aimed to determine whether adding Curcumin to the diet of dairy calves would influence ruminal fermentation, hematologic, immunological, oxidative, and metabolism variables. Fourteen Jersey calves were divided into a control group (GCON) and a treatment group (GTRA). The animals in the GTRA received a diet containing 65.1 mg/kg of dry matter (DM) Curcumin (74% purity) for an experimental period of 90 days. Blood samples were collected on days 0, 15, 45, and 90. Serum levels of total protein and globulins were higher in the GTRA group (P < 0.05) than the GCON group. In the GTRA group, there was a reduction in pro-inflammatory cytokines (IL-1ß and IL-6) (P < 0.05) and an increase in IL-10 (which acts on anti-inflammatory responses) (P < 0.05) when compared to the GCON. There was a significantly higher (P < 0.05) concentration of immunoglobulin A (IgA) in the serum of the GTRA than the GCON. A Treatment × Day interaction was observed for haptoglobin levels, which were higher on day 90 in animals that consumed Curcumin than the GCON (P < 0.05). The catalase and superoxide dismutase activities were significantly higher (P < 0.05) in GTRA, reducing lipid peroxidation when compared to the GCONT. Hematologic variables did not differ significantly between groups. Among the metabolic variables, only urea was higher in the GTRA group when compared to the GCON. Body weight and feed efficiency did not differ between groups (meaning the percentage of apparent digestibility of dry matter, crude protein, and acid detergent fiber (ADF) and neutral detergent fiber (NDF). There was a tendency (P = 0.09) for treatment effect and a treatment x day interaction (P = 0.05) for levels of short-chain fatty acids in rumen fluid, being lower in animals that consumed curcumin. There was a treatment vs. day interaction (P < 0.05) for the concentration of acetate in the rumen fluid (i.e., on day 45, had a reduction in acetate; on day 90, values were higher in the GTRA group when compared to the GCON). We conclude that there was no evidence in the results from this preliminary trial that Curcumin in the diet of dairy calves interfered with feed digestibility. Curcumin may have potential antioxidant, anti-inflammatory, and immune effects that may be desirable for the production system of dairy calves.
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Ração Animal , Curcumina , Dieta , Suplementos Nutricionais , Fermentação , Rúmen , Animais , Curcumina/administração & dosagem , Curcumina/farmacologia , Rúmen/metabolismo , Rúmen/efeitos dos fármacos , Bovinos , Ração Animal/análise , Dieta/veterinária , Suplementos Nutricionais/análise , Estresse Oxidativo/efeitos dos fármacos , Masculino , Citocinas/metabolismo , Desmame , Antioxidantes/metabolismo , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , FemininoRESUMO
Osteoarthritis (OA) is one of the most prevalent degenerative joint diseases. Several meta-analyses have shown that curcumin could improve the function of the knee and alleviate pain in OA, while some meta-analyses demonstrate controversial results. Hence, we assessed curcumin's effects on knee OA in an umbrella meta-analysis. PubMed, Scopus, Embase, and Web of Science databases were employed to find English-language meta-analyses of randomized controlled trials investigating the effect of curcumin supplementation on OA outcomes up to September 2023. The visual analog scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain, function, and stiffness scales were analyzed. Effect sizes and 95% confidence intervals were utilized to obtain the overall effect size. A random-effects model was applied to perform the meta-analysis. Heterogeneity was determined by I2 statistics and the Cochrane Q-test. The pooled effect of the 11 included meta-analyses showed that curcumin could significantly decrease the VAS score (weighted mean difference [WMD] and standardized mean difference [SMD]), WOMAC-total (SMD and WMD), WOMAC-Function (SMD and WMD), WOMAC-Pain (SMD), and WOMAC-Stiffness scores (SMD) (p ≤ 0.001, ≤0.001, ≤0.001, 0.007, ≤0.001, 0.002, ≤0.001, ≤0.001, respectively). The results strongly support curcuminoid supplementation in relieving pain, improving joint mobility and stiffness, and shortening medication usage of OA patients.
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Curcumina , Osteoartrite do Joelho , Curcumina/uso terapêutico , Humanos , Osteoartrite do Joelho/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição da Dor , Osteoartrite/tratamento farmacológicoRESUMO
The aim of this in vivo study was to investigate the effects of a novel mycotoxin detoxifier whose formulation includes clay (bentonite and sepiolite), phytogenic feed additives (curcumin and silymarin) and postbiotics (yeast products) on the health, performance and redox status of weaned piglets under the dietary challenge of fumonisins (FUMs). The study was conducted in duplicate in the course of two independent trials on two different farms. One hundred and fifty (150) weaned piglets per trial farm were allocated into two separate groups: (a) T1 (control group): 75 weaned piglets received FUM-contaminated feed and (b) T2 (experimental group): 75 weaned piglets received FUM-contaminated feed with the mycotoxin-detoxifying agent from the day of weaning (28 days) until 70 days of age. Thiobarbituric acid reactive substances (TBARSs), protein carbonyls (CARBs) and the overall antioxidant capacity (TAC) were assessed in plasma as indicators of redox status at 45 and 70 days of age. Furthermore, mortality and performance parameters were recorded at 28, 45 and 70 days of age, while histopathological examination was performed at the end of the trial period (day 70). The results of the present study reveal the beneficial effects of supplementing a novel mycotoxin detoxifier in the diets of weaners, including improved redox status, potential hepatoprotective properties and enhanced growth performance.
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Ração Animal , Curcumina , Oxirredução , Desmame , Animais , Curcumina/farmacologia , Ração Animal/análise , Suínos , Fumonisinas/toxicidade , Antioxidantes/farmacologia , Bentonita/farmacologia , Bentonita/química , Silicatos de Alumínio/química , Silicatos de Alumínio/farmacologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Contaminação de Alimentos/prevenção & controle , Carbonilação Proteica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Micotoxinas/toxicidadeRESUMO
Curcumin and exercise have been reported to show good anti-tumour effects. However, relevant research on the combined effects of physical exercise and curcumin supplementation on cancer and the underlying mechanisms is still lacking. The current study aimed to construct an anti-breast tumour mouse model using the combined effects of curcumin treatment and swimming exercise. Transcriptomic and metabolomic techniques were used to screen for differentially expressed genes and metabolites, evaluate the anticancer effects, and analyse the molecular regulatory mechanisms related to metabolism. Observation of the mouse phenotypes, including tumour appearance, in-vivo tumour imaging, and HE staining results of pathological sections, suggested a more obvious inhibitory effect of the combination of curcumin administration and exercise intervention on breast cancer than that of a single treatment. The combination treatment group had a total of 445 differentially expressed (154 upregulated and 291 downregulated) genes. Functional enrichment analysis showed the calcium signalling pathway, Wnt signalling pathway, PI3K Akt signalling pathway, and IL-17 signalling pathway to significantly participate in the anti-breast cancer process of curcumin-exercise combination treatment. Results of the intergroup differential metabolite analysis showed that the combined effect of curcumin and exercise involves two unique pathways, namely the amino sugar and nucleotide sugar metabolism, which includes chitosan, d-glucosamine 6-phosphate, l-fucose, and N-acetyl beta-mannosamine, and the amino acid biosynthesis, which includes dl-isoleucine, dl-tyrosine, and homocysteine. Collectively, the top-ranked genes and metabolites with the highest degree of associations were further revealed by O2PLS analysis. Overall, the study helped reveal the mechanism of action of curcumin-exercise combination treatment on breast cancer at multi-omics level.
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Curcumin and omega-3 polyunsaturated fatty acids (ω-3 PUFA) are multifunctional compounds which play an important role in Alzheimer's disease (AD) and little has been addressed about the role of these two compounds together in the progression of the disease. There is evidence of the beneficial effect of combined administration of ω-3 PUFA and other dietary supplements such as vitamins and polyphenols in the prevention of AD, although much remains to be understood about their possible complementary or synergistic activity. Therefore, the objective of this work is to review the research focused on studying the effect and mechanisms of action of curcumin, ω-3 PUFA, and the combination of these nutraceutical compounds, particularly on AD, and to integrate the possible ways in which these compounds can potentiate their effect. The most important pathophysiologies that manifest in AD will be addressed, in order to have a better understanding of the mechanisms of action through which these bioactive compounds exert a neuroprotective effect.
Assuntos
Doença de Alzheimer , Curcumina , Suplementos Nutricionais , Ácidos Graxos Ômega-3 , Fármacos Neuroprotetores , Curcumina/uso terapêutico , Curcumina/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/prevenção & controle , Humanos , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Sinergismo FarmacológicoRESUMO
Curcumin, a natural bioactive polyphenol with diverse molecular targets, is well known for its anti-oxidation and anti-inflammatory potential. However, curcumin exhibits low solubility (<1 µg mL-1), poor tissue-targeting ability, and rapid oxidative degradation, resulting in poor bioavailability and stability for inflammatory therapy. Here, poly(diselenide-oxalate-curcumin) nanoparticle (SeOC-NP) with dual-reactive oxygen species (ROS) sensitive chemical moieties (diselenide and peroxalate ester bonds) is fabricated by a one-step synthetic strategy. The results confirmed that dual-ROS sensitive chemical moieties endowed SeOC-NP with the ability of targeted delivery of curcumin and significantly suppress oxidative degradation of curcumin for high-efficiency inflammatory therapy. In detail, the degradation amount of curcumin for SeOC is about 4-fold lower than that of free curcumin in an oxidative microenvironment. As a result, SeOC-NP significantly enhanced the antioxidant activity and anti-inflammatory efficacy of curcumin in vitro analysis by scavenging intracellular ROS and suppressing the secretion of nitric oxide and pro-inflammatory cytokines. In mouse colitis models, orally administered SeOC-NP can remarkably alleviate the symptoms of IBD and maintain the homeostasis of gut microbiota. This work provided a simple and effective strategy to fabricate ROS-responsive micellar and enhance the oxidation stability of medicine for precise therapeutic inflammation.
Assuntos
Colite , Curcumina , Nanopartículas , Espécies Reativas de Oxigênio , Curcumina/química , Curcumina/farmacologia , Animais , Colite/tratamento farmacológico , Colite/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas/química , Células RAW 264.7 , Oxirredução , Antioxidantes/química , Antioxidantes/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Camundongos Endogâmicos C57BL , MasculinoRESUMO
Cancer, namely breast and prostate cancers, is the leading cause of death in many developed countries. Controlled drug delivery systems are key for the development of new cancer treatment strategies, to improve the effectiveness of chemotherapy and tackle off-target effects. In here, we developed a biomaterials-based wireless electrostimulation system with the potential for controlled and on-demand release of anti-cancer drugs. The system is composed of curcumin-loaded poly(3,4-ethylenedioxythiophene) nanoparticles (CUR/PEDOT NPs), encapsulated inside coaxial poly(glycerol sebacate)/poly(caprolactone) (PGS/PCL) electrospun fibers. First, we show that the PGS/PCL nanofibers are biodegradable, which allows the delivery of NPs closer to the tumoral region, and have good mechanical properties, allowing the prolonged storage of the PEDOT NPs before their gradual release. Next, we demonstrate PEDOT/CUR nanoparticles can release CUR on-demand (65 % of release after applying a potential of -1.5 V for 180 s). Finally, a wireless electrostimulation platform using this NP/fiber system was set up to promote in vitro human prostate cancer cell death. We found a decrease of 67 % decrease in cancer cell viability. Overall, our results show the developed NP/fiber system has the potential to effectively deliver CUR in a highly controlled way to breast and prostate cancer in vitro models. We also show the potential of using wireless electrostimulation of drug-loaded NPs for cancer treatment, while using safe voltages for the human body. We believe our work is a stepping stone for the design and development of biomaterial-based future smarter and more effective delivery systems for anti-cancer therapy.
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Compostos Bicíclicos Heterocíclicos com Pontes , Glicerol/análogos & derivados , Nanopartículas , Poliésteres , Polímeros , Tecnologia sem Fio , Humanos , Compostos Bicíclicos Heterocíclicos com Pontes/química , Nanopartículas/química , Polímeros/química , Poliésteres/química , Curcumina/administração & dosagem , Curcumina/química , Glicerol/química , Masculino , Neoplasias da Próstata/terapia , Antineoplásicos/administração & dosagem , Decanoatos/química , Nanofibras/química , Sistemas de Liberação de Medicamentos/instrumentação , Sistemas de Liberação de Medicamentos/métodos , Linhagem Celular Tumoral , Estimulação Elétrica/instrumentação , Estimulação Elétrica/métodosRESUMO
Turmeric has been gaining popularity as a treatment option for digestive disorders, although a rigorous synthesis of efficacy has not been conducted. This study aimed to summarize the evidence for the efficacy and safety of turmeric in the treatment of digestive disorders, including inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), dyspepsia, gastroesophageal reflux disease, and peptic ulcers. Literature searches were conducted in Medline, EMBASE, AMED, the Cochrane Central Register of Control Trials, and Dissertation Abstracts from inception to November 15, 2021. Dual independent screening of citations and full texts was conducted and studies meeting inclusion criteria were retained: randomized controlled trials (RCT) and comparative observational studies evaluating turmeric use in people of any age with one of the digestive disorders of interest. Extraction of relevant data and risk of bias assessments were performed by two reviewers independently. Meta-analysis was not conducted due to high heterogeneity. From 1136 citations screened, 26 eligible studies were retained. Most studies were assessed to have a high risk of bias, and many had methodological limitations. Descriptive summaries suggest that turmeric is safe, with possible efficacy in patients with IBD or IBS, but its effects were inconsistent for other conditions. The efficacy of turmeric in digestive disorders remains unclear due to the high risk of bias and methodological limitations of the included studies. Future studies should be designed to include larger sample sizes, use rigorous statistical methods, employ core outcome sets, and adhere to reporting guidance for RCTs of herbal interventions to facilitate more meaningful comparisons and robust conclusions.
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Curcuma , Humanos , Curcuma/química , Ensaios Clínicos Controlados Aleatórios como Assunto , Extratos Vegetais/uso terapêutico , Extratos Vegetais/efeitos adversos , Síndrome do Intestino Irritável/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças do Sistema Digestório/tratamento farmacológicoRESUMO
In this study, a novel selenium@zeolitic imidazolate framework core/shell nanocomposite stabilised with alginate was used to improve the anti-tumour activity of curcumin. The developed alginate-stabilised curcumin-loaded selenium@zeolitic imidazolate framework (Alg@Cur@Se@ZIF-8) had a mean diameter of 159.6 nm and polydispersity index < 0.25. The release of curcumin from the nanocarrier at pH 5.4 was 2.69 folds as high as at pH 7.4. The bare nanoparticles showed haemolytic activity of about 12.16% at a concentration of 500 µg/mL while covering their surface with alginate reduced this value to 5.2%. By investigating cell viability, it was found that Alg@Cur@Se@ZIF-8 caused more cell death than pure curcumin. Additionally, in vivo studies showed that Alg@Cur@Se@ZIF-8 dramatically reduced tumour growth compared to free curcumin in 4T1 tumour-bearing mice. More importantly, the histological study confirmed that the developed drug delivery system successfully inhibited lung and liver metastasis while causing negligible toxicity in vital organs. Overall, due to the excellent inhibitory activity on cancerous cell lines and tumour-bearing animals, Alg@Cur@Se@ZIF-8 can be considered promising for breast cancer therapy.
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Curcumina , Nanocompostos , Nanopartículas , Neoplasias , Selênio , Camundongos , Animais , Portadores de Fármacos , Alginatos , Neoplasias/tratamento farmacológico , Concentração de Íons de HidrogênioRESUMO
In the context of treating spinal cord injury (SCI), the modulation of inflammatory responses, and the creation of a suitable region for tissue regeneration may present a promising approach. This study aimed to evaluate the effects of curcumin (Cur)-loaded bovine serum albumin nanoparticles (Cur-BSA NPs) cross-linked with an acellular spinal cord scaffold (ASCS) on the functional recovery in a rat model of SCI. We developed an ASCS using chemical and physical methods. Cur-BSA, and blank (B-BSA) NPs were fabricated and cross-linked with ASCS via EDC-NHS, resulting in the production of Cur-ASCS and B-ASCS. We assessed the properties of scaffolds and NPs as well as their cross-links. Finally, using a male rat hemisection model of SCI, we investigated the consequences of the resulting scaffolds. The inflammatory markers, neuroregeneration, and functional recovery were evaluated. Our results showed that Cur was efficiently entrapped at the rate of 42% ± 1.3 in the NPs. Compared to B-ASCS, Cur-ASCS showed greater effectiveness in the promotion of motor recovery. The implantation of both scaffolds could increase the migration of neural stem cells (Nestin- and GFAP-positive cells) following SCI with the superiority of Cur-ASCS. Cur-ASCS was successful to regulate the gene expression and protein levels of NLRP3, ASC, and Casp1in the spinal cord lesion. Our results indicate that using ASCS can lead to the entrance of cells into the scaffold and promote neurogenesis. However, Cur-ASCS had greater effects in terms of inflammation relief and enhanced neurogenesis.
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Curcumina , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Neurogênese , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Medula Espinal , Alicerces Teciduais , Animais , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/terapia , Curcumina/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Neurogênese/efeitos dos fármacos , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Masculino , Recuperação de Função Fisiológica/efeitos dos fármacos , Alicerces Teciduais/química , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Nanopartículas/química , Preparações de Ação Retardada/farmacologia , Modelos Animais de Doenças , Soroalbumina Bovina/químicaRESUMO
This study evaluated the alleviative effect of curcumin (CUR) on the diquat (DQ)-induced cecal injury in broilers. A total of 320 one-day-old Cobb broilers were selected and randomly divided into 4 treatments, namely control, DQ, CUR 100, and CUR150 groups. The control and DQ groups were fed a basal diet, while the CUR 100 and CUR150 groups were fed the basal diet supplemented with 100 and 150 mg/kg CUR, respectively. Each group had 8 replicates, with 10 broilers per replicate. On day 21 of the experiment, 1 broiler was selected from each replicate and intraperitoneally injected 20 mg/kg body weight of DQ for DQ, CUR 100, and CUR 150 groups. Broilers in control group received equivalent volume of saline. Broilers were euthanized 48h postinjection for tissue sampling. The results showed that DQ injection could cause oxidative stress and inflammatory reactions in the cecum, affecting the fatty acid production and flora structure, thus leading to cecum damage. Compared with the DQ group, the activity of superoxide dismutase, the level of interleukin 10, acetic acid, and total volatile fatty, and the abundance of nuclear factor E2-related factor 2, copper and zinc superoxide dismutase and catalase mRNA in the cecal mucosa of broilers in the CUR group increased significantly (P < 0.05). However, the levels of malondialdehyd, reactive oxygen species, tumor necrosis factor-alpha, and the expression of cysteine-aspartic acid protease-3 and tumor necrosis factor-alpha decreased significantly (P < 0.05) in the CUR group. In addition, CUR treatment alleviated the damage to the cecum and restored the flora structure, and Lactobacillus and Lactobacillaceae promoted the alleviative effect of CUR on DQ. In summary, CUR could alleviate the cecal injury caused by DQ-induced oxidative damage and inflammatory reactions by regulating the Nrf2-ARE signaling pathway and intestinal flora, thus protecting the cecum.
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Ceco , Galinhas , Curcumina , Diquat , Microbioma Gastrointestinal , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Animais , Estresse Oxidativo/efeitos dos fármacos , Curcumina/farmacologia , Curcumina/administração & dosagem , Ceco/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Microbioma Gastrointestinal/efeitos dos fármacos , Doenças das Aves Domésticas/induzido quimicamente , Doenças das Aves Domésticas/tratamento farmacológico , Distribuição Aleatória , Masculino , Proteínas Aviárias/metabolismo , Proteínas Aviárias/genética , Dieta/veterinária , Suplementos Nutricionais/análiseRESUMO
Cancer, with its diversity, heterogeneity, and complexity, is a significant contributor to global morbidity, disability, and mortality, highlighting the necessity for transformative treatment approaches. Photodynamic therapy (PDT) has aroused continuous interest as a viable alternative to conventional cancer treatments that encounter drug resistance. Nanotechnology has brought new advances in medicine and has shown great potential in drug delivery and cancer treatment. For precise and efficient therapeutic utilization of such a tumor therapeutic approach with high spatiotemporal selectivity and minimal invasiveness, the carrier-free noncovalent nanoparticles (NPs) based on chemo-photodynamic combination therapy is essential. Utilizing natural products as the foundation for nanodrug development offers unparalleled advantages, including exceptional pharmacological activity, easy functionalization/modification, and well biocompatibility. The natural-product-based, carrier-free, noncovalent NPs revealed excellent synergistic anticancer activity in comparison with free photosensitizers and free bioactive natural products, representing an alternative and favorable combination therapeutic avenue to improve therapeutic efficacy. Herein, a comprehensive summary of current strategies and representative application examples of carrier-free noncovalent NPs in the past decade based on natural products (such as paclitaxel, 10-hydroxycamptothecin, doxorubicin, etoposide, combretastatin A4, epigallocatechin gallate, and curcumin) for tumor chemo-photodynamic combination therapy. We highlight the insightful design and synthesis of the smart carrier-free NPs that aim to enhance PDT efficacy. Meanwhile, we discuss the future challenges and potential opportunities associated with these NPs to provide new enlightenment, spur innovative ideas, and facilitate PDT-mediated clinical transformation.
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Produtos Biológicos , Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Animais , Neoplasias/tratamento farmacológico , Nanopartículas/química , Produtos Biológicos/química , Produtos Biológicos/uso terapêutico , Produtos Biológicos/farmacologia , Produtos Biológicos/administração & dosagem , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/administração & dosagemRESUMO
BACKGROUND: Oxidative stress is considered the main cause of granulosa cell apoptosis in ovarian disease. Curcumin has various biological roles, but its potential role in protecting granulosa cells from oxidative damage remains unidentified. PURPOSE: The study revealed the protective effect of curcumin on granulosa cell survival under oxidative stress, and explored its mode of action. STUDY DESIGN: The protective effect of curcumin on oxidative stress-induced ovarian cell apoptosis was evaluated in vivo and in vitro, and the role of autophagy and AMPK/mTOR signaling pathway in this process was also demonstrated. METHODS: First, mice were injected to 3-nitropropionic acid (3-NPA, 20 mg/kg/day) for 14 consecutive days to establish the ovarian oxidative stress model, at same time, curcumin (50, 100, 200 mg/kg/day) was given orally. Thereafter, functional changes, cell apoptosis, and autophagy in ovarian tissue were evaluated by hematoxylin-eosin staining, enzyme-linked immunosorbent assay, western blotting, TUNEL assays, and transmission electron microscopy. Finally, oxidative stress model of granulosa cells was established with H2O2in vitro and treated with curcumin. The underlying mechanisms of curcumin to protect the apoptosis under oxidative stress in vitro were determined using western blotting and TUNEL assays. RESULTS: In our study, after curcumin treatment, the mouse ovarian function disorder under 3-nitropropionic acid-induced oxidative stress recovered significantly, and ovarian cell apoptosis decreased. H2O2 induced granulosa cell apoptosis in vitro, and curcumin antagonized this process. Autophagy contributes to tissue and cell survival under stress. We therefore examined the role of autophagy in this process. According to the in vivo and in vitro results, curcumin restored autophagy under oxidative stress. The autophagy inhibitor (chloroquine) exhibited the same effect as curcumin, whereas the autophagy activator (rapamycin) antagonized the effect of curcumin. In addition, the study found that the AMPK/mTOR pathway plays a crucial role in curcumin- mediated autophagy to protect against oxidative stress-induced apoptosis. CONCLUSION: Our findings for the first time systematically revealed a new mechanism through which curcumin protects ovarian granulosa cells from oxidative stress-induced damage through AMPK/mTOR-mediated autophagy and suggested that it can be a new therapeutic direction for female ovarian diseases.
Assuntos
Autofagia , Curcumina , Ovário , Estresse Oxidativo , Serina-Treonina Quinases TOR , Animais , Feminino , Camundongos , Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Curcumina/farmacologia , Células da Granulosa/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Nitrocompostos , Ovário/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Propionatos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
Lung cancer and Mycobacterium avium complex infection are lung diseases associated with high incidence and mortality rates. Most conventional anticancer drugs and antibiotics have certain limitations, including high drug resistance rates and adverse effects. Herein, we aimed to synthesize mannose surface-modified solid lipid nanoparticles (SLNs) loaded with curcumin (Man-CUR SLN) for the effective treatment of lung disease. The synthesized Man-CUR SLNs were analyzed using various instrumental techniques for structural and physicochemical characterization. Loading curcumin into SLNs improved the encapsulation efficiency and drug release capacity, as demonstrated by high-performance liquid chromatography analysis. Furthermore, we characterized the anticancer effect of curcumin using the A549 lung cancer cell line. Cells treated with Man-CUR SLN exhibited an increased cellular uptake and cytotoxicity. Moreover, treatment with free CUR could more effectively reduce cancer migration than treatment with Man-CUR SLNs. Similarly, free curcumin elicited a stronger apoptosis-inducing effect than that of Man-CUR SLNs, as demonstrated by reverse transcription-quantitative PCR analysis. Finally, we examined the antibacterial effects of free curcumin and Man-CUR SLNs against Mycobacterium intracellulare (M.i.) and M.i.-infected macrophages, revealing that Man-CUR SLNs exerted the strongest antibacterial effect. Collectively, these findings indicate that mannose-receptor-targeted curcumin delivery using lipid nanoparticles could be effective in treating lung diseases. Accordingly, this drug delivery system can be used to target a variety of cancers and immune cells.
Assuntos
Curcumina , Lipossomos , Neoplasias Pulmonares , Nanopartículas , Humanos , Curcumina/farmacologia , Curcumina/química , Manose , Lipídeos , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
Patients with intermediate-high risk MGUS are not offered therapeutic options to date and standard of care remains observation with re-evaluations of the patient every 3 to 6 months. Given the persistent risk of progression as well as potential complications experienced by some, and anxiety experienced by most patients, early intervention with non-toxic curcumin, aimed at potentially slowing down or stopping disease progression might be therapeutic. We present here an intermediate-high risk MGUS patient who has been taking curcumin for 16 years and has shown a decrease in disease markers and an increase in uninvolved immunoglobulins, adding to the body of evidence of benefit of curcumin to MGUS patients.
Assuntos
Curcumina , Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Humanos , Gamopatia Monoclonal de Significância Indeterminada/tratamento farmacológico , Gamopatia Monoclonal de Significância Indeterminada/complicações , Curcumina/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Progressão da DoençaRESUMO
BACKGROUND: Oral health remains a significant global concern with the prevalence of oral pathogens and the increasing incidence of oral cancer posing formidable challenges. Additionally, the emergence of antibiotic-resistant strains has complicated treatment strategies, emphasizing the urgent need for alternative therapeutic approaches. Recent research has explored the application of plant compounds mediated with nanotechnology in oral health, focusing on the antimicrobial and anticancer properties. METHODS: In this study, curcumin (Cu)-mediated zinc oxide nanoparticles (ZnO NPs) were synthesized and characterized using SEM, EDAX, UV spectroscopy, FTIR, and XRD to validate their composition and structural features. The antioxidant and antimicrobial activity of ZnO-CU NPs was investigated through DPPH, ABTS, and zone of inhibition assays. Apoptotic assays and gene expression analysis were performed in KB oral squamous carcinoma cells to identify their anticancer activity. RESULTS: ZnO-CU NPs showcased formidable antioxidant prowess in both DPPH and ABTS assays, signifying their potential as robust scavengers of free radicals. The determined minimal inhibitory concentration of 40 µg/mL against dental pathogens underscored the compelling antimicrobial attributes of ZnO-CU NPs. Furthermore, the interaction analysis revealed the superior binding affinity and intricate amino acid interactions of ZnO-CU NPs with receptors on dental pathogens. Moreover, in the realm of anticancer activity, ZnO-CU NPs exhibited a dose-dependent response against Human Oral Epidermal Carcinoma KB cells at concentrations of 10 µg/mL, 20 µg/mL, 40 µg/mL, and 80 µg/mL. Unraveling the intricate mechanism of apoptotic activity, ZnO-CU NPs orchestrated the upregulation of pivotal genes, including BCL2, BAX, and P53, within the KB cells. CONCLUSIONS: This multifaceted approach, addressing both antimicrobial and anticancer activity, positions ZnO-CU NPs as a compelling avenue for advancing oral health, offering a comprehensive strategy for tackling both oral infections and cancer.