Efficacy and safety of curcumin therapy for knee osteoarthritis: A Bayesian network meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumin, a polyphenolic compound extracted from turmeric (Curcuma longa L.), is widely used in traditional Chinese medicine to treat osteoarthritis and rheumatoid arthritis. Clinical and experimental studies show that curcuminoid formulations have considerable clinical application value in the treatment of knee osteoarthritis (KOA). AIM OF THE STUDY: To evaluate the efficacy and safety of curcumin, both alone and in combination with other drugs, in KOA treatment through a Bayesian network meta-analysis (NMA). METHODS: We searched PubMed, Embase and Cochrane Library for randomized controlled trials of curcumin for KOA treatment. The time range of the search was from the establishment of each database to April 26, 2023. The NMAs of outcome indicators were all performed using a random-effects model. NMAs were calculated and graphed in R using MetaInsight and Stata 140 software. Measurement data were represented by the mean difference (MD), while count data were represented by the odds ratio (OR); the 95% confidence interval (CI) of each effect size was also calculated. RESULTS: This study included 23 studies from 7 countries, including 2175 KOA patients and 6 interventions. The NMA results showed that compared with placebo, curcumin significantly reduced the visual analogue scale pain score (MD = -1.63, 95% CI: -2.91 to -0.45) and total WOMAC score (MD = -18.85, 95% CI: -29.53 to -8.76). Compared with placebo, curcumin (OR = 0.17, 95% CI: 0.08 to 0.36), curcumin + NSAIDs (OR = 0.01, 95% CI: 0.00 to 0.13) and NSAIDs (OR = 0.11, 95% CI: 0.02 to 0.47) reduced the use of rescue medication. Compared with NSAIDs, curcumin (OR = 0.51, 95% CI: 0.25 to 0.94) and curcumin + NSAIDs (OR = 0.23, 95% CI: 0.06 to 0.9) had a reduced incidence of adverse reactions. The surface under the cumulative ranking curve results indicated that curcumin monotherapy, curcumin + chondroprotective agents, and curcumin + NSAIDs have good clinical value in KOA treatment. CONCLUSIONS: Curcumin, either alone or in combination with other treatments, is considered to have good clinical efficacy and safety in KOA treatment. Drug combinations containing curcumin may have the dual effect of enhancing efficacy and reducing adverse reactions, but this possibility still needs to be confirmed by further clinical and basic research.

Estudo da encapsulação de fármacos antineoplásicos em sistemas nanoestruturados: Caracterização estrutural e efeito sinérgico de fármacos / Study of the encapsulation of antineoplastic drugs in nanostructured systems: Structured characterization and synergistic effect of drugs

Dentro da área da nanotecnologia, o sistema drug delivery vem sendo amplamente utilizado, cujo objetivo é proporcionar uma maior eficácia dos ativos farmacêuticos, podendo envolver desde uma distribuição mais seletiva dentro do organismo até a taxa que as moléculas serão liberadas e/ou a atenuação dos efeitos adversos provocados. Para isso, os ativos são encapsulados em nanoestruturas, podendo estas serem de natureza sintética ou natural. Dentre os nanocarreadores promissores encontram-se os cubossomos, que são nanoestruturas complexas capazes de encapsular ativos tanto hidrofílicos quanto hidrofóbicos. O objetivo deste projeto foi estudar a encapsulação de fármacos antineoplásicos em sistemas drug delivery contra linhagens celulares, investigando também as alterações estruturais sofridas pelos cubossomos e os efeitos sinérgicos dos fármacos, sendo eles: a doxorrubicina, a cisplatina, a vemurafenibe e a curcumina. As metodologias empregadas para elucidar o efeito das combinações dos fármacos, a estruturação da nanopartícula e sua citotoxicidade foram: os estudos de viabilidade celular pós-exposição, espalhamento dinâmico de luz, potencial zeta, análise de rastreamento de nanopartículas, espalhamento de raios-x a baixos ângulos, criomicroscopia eletrônica de transmissão, eficiência de encapsulação e ensaio de liberação. Inicialmente os fármacos foram testados isoladamente e em duplas, sendo utilizadas cinco linhagens celulares, afim de se promover um delineamento aos ensaios futuros. A partir destes resultados, foi-se optado por manter duas linhagens celulares, a HeLa, como representante de tecidos tumorais, e a HaCat, modelo de tecido saudável, devido a menor resistência apresentada por elas. Em relação as combinações entre as drogas, pode-se observar que todas as duplas formadas apresentaram resultados sinérgicos na linhagem tumoral, sendo mantida para os testes seguintes a combinação curcumina e vemurafenibe. Os cubossomos foram sintetizados eficientemente, sendo produzidos na ausência de fármacos bem como contendo curcumina e vemurafenibe. As nanopartículas apresentaram uma variação de diâmetro entre 189 ± 3 nm e 224 ± 2 nm, sendo o PDI entre 0,08 e 0,25. A conformação do cubossomo foi confirmada através da criomicroscopia eletrônica de transmissão e pelo espalhamento de raios-x a baixos ângulos, onde foi determinada uma estruturação característica de Pn3m. Para a eficiência de encapsulação os valores variaram entre 79% de encapsulação para a curcumina e 72% para a vemurafenibe, quando utilizadas isoladamente. No caso da encapsulação em dupla, os valores se converteram para 63% e 53% para a curcumina e vemurafenibe, respectivamente. A liberação das drogas do interior da nanopartícula oscilou entre 1500, 480 e 420 minutos para os cubossomos de curcumina, vemurafenibe e curcumina + vemunafenibe, respectivamente. Os testes de citotoxicidade demonstraram que as concentrações de 0,01 e 0,03 mg/mL foram capazes de promover uma viabilidade acima de 70%, porém, utilizando estas proporções não foi possível observar resultados significativos. Por fim, o sistema se mostrou estável e homogêneo, sendo capaz de promover a encapsulação dos fármacos tanto singularmente quanto em dupla e, apesar da quantidade de fármacos não ter sido suficiente para ocasionar alterações ao sistema celular, a execução deste trabalho abre portas para que novos estudos sejam realizados, podendo-se testar diferentes ativos bem como alterando a composição da nanopartícula afim de se reduzir a citotoxicidade

Within the area of nanotechnology, the drug delivery system has been widely used, whose objective is to provide greater effectiveness of pharmaceutical active ingredients, which may range from a more selective distribution within the organism to the rate at which the molecules will be released and/or the attenuation of adverse effects caused. To achieve this, the active ingredients are encapsulated in nanostructures, which may be synthetic or natural in nature. Among the promising nanocarriers are cubosomes, which are complex nanostructures capable of encapsulating both hydrophilic and hydrophobic active ingredients. The objective of this project was to study the encapsulation of antineoplastic drugs in drug delivery systems against cell lines, also investigating the structural changes undergone by the cubosomes and the synergistic effects ofthe drugs, namely: doxorubicin, cisplatin, vemurafenib and curcumin. The methodologies used to elucidate the effect of drug combinations, the structuring of the nanoparticle and its cytotoxicity were: post-exposure cell viability studies, dynamic light scattering, zeta potential, nanoparticle tracking analysis, small angle x-rays scattering, transmission electron cryomicroscopy, encapsulation efficiency and release assay. Initially, the drugs were tested alone and in pairs, using five cell lines, in order to promote a design for future trials. Based on these results, it was decided to maintain two cell lines, HeLa, as a representative oftumor tissues, and HaCat, a model ofhealthy tissue, due to their lower resistance. Regarding the combinations between the drugs, it can be observed that all the pairs formed presented synergistic results in the tumor lineage, with the combination of curcumin and vemurafenib being maintained for the following tests. Cubosomes were efficiently synthesized, being produced in the absence of drugs as well as containing curcumin and vemurafenib. The nanoparticles varied in diameter between 189 ± 3 nm and 224 ± 2 nm, with the PDI being between 0.08 and 0.25. The conformation ofthe cubosome was confirmed through transmission electron cryomicroscopy and small angle x-rays scattering, where a characteristic structure of Pn3m was determined. For encapsulation efficiency, values varied between 79% encapsulation for curcumin and 72% for vemurafenib, when used alone. ln the case of double encapsulation, the values converted to 63% and 53% for curcumin and vemurafenib, respectively. The release of drugs from the interior of the nanoparticle ranged between 1500, 480 and 420 minutes for the curcumin, vemurafenib and cubosomes with curcumin + vemunafenib, respectively. Cytotoxicity tests demonstrated that concentrations of 0.01 and 0.03 mg/mL were capable of promoting viability above 70%, however, using these proportions it was not possible to observe significant results. Finally, the system proved to be stable and homogeneous, being able to promote the encapsulation of drugs both singly and in pairs and, although the quantity of drugs was not enough to cause changes to the cellular system, the execution of this work opens doors for new studies are carried out, with the possibility oftesting different active ingredients as well as changing the composition of the nanoparticle in order to reduce cytotoxicity

Caracterização de cubossomos não-iônicos em presença de proteínas modelo: uma abordagem estrutural e funcional / Characterization of non-ionic cubosomes in the presence of model pro­teins: a structural and functional approach

Uma área de pesquisa que vem ganhando muita atenção nos últimos anos é a nanome­dicina, com especial atenção para os sistemas com entrega controlada de fármacos, ou drug delivery. Dentre as diversas nanopartículas utilizadas para este fim, destacam-se os sistemas formados por lipídeos e polímeros, como por exemplo os lipossomos e os cubossomos. Neste trabalho, é estudada a influência estrutural da lisozima e da curcumina, proteínas modelo. A lisozima é uma enzima antimicrobiana produzida por animais e que faz parte do sistema imunológico. Ela é uma hidrolase glicosídica que catalisa a hidrólise dos componentes da parede celular de bactérias gram-positivas. Esta hidrólise, por sua vez, compromete a integridade das paredes celulares, causando a lise (e como consequência a morte) das bactérias. Curcumina é um composto cristalino de cor amarelada brilhante, encontrada no caule da Curcuma longa (ou açafrão), que tem sido utilizada como corante ou até mesmo como aditivo alimentar. Este composto tem sido uma grande aposta no tratamento de doenças crônicas como inflamação, artrite, síndrome metabólica, doença hepática, obesidade, doenças neurodegenerativas e principalmente canceres, sendo também utilizada em estudos como potencial agente antibacteriano. O principal objetivo deste trabalho é construir sistemas nanoestruturados com potencial de atuarem como sistemas antimicrobianos, com a liberação controlada de ambos dos fármacos. Estes sistemas são compostos por cubossomos de fitantriol (PHY) em ausência e presença da lisozima, da curcumina e de suas combinações, a fim de analisar ação antimicrobiana conjunta da lisozima e da curcumina. As técnicas biofísicas utilizadas para caracterizar essas partículas são SAXS (espalhamento de raios-X em baixos ângulos), DLS (espalhamento dinâmico de luz), Cryo-TEM (criomicroscopia eletrônica de transmissão) e NTA (análise de rastreamento de nanopartículas). Foi possível verificar que as formulações lipídicas são eficazes na formação de estruturas cúbicas com estabilidade desejável. As nanopartículas cúbicas demonstraram alta capacidade de encapsulação da lisozima e da curcumina. A cinética de liberação desses medicamentos mostrou-se promissora, sugerindo que a encapsulação dos fármacos é eficaz, bem como a liberação controlada e direcionada. Duas linhagens de bactérias foram estudadas, sendo que a E. coli, não sofreu nenhum dano citotóxico, enquanto a Bacillus subtilis sim. Tal resultado indica o potencial antimicrobiano do sistema para alguns tipos de bactérias

An area of research that has gained significant attention in recent years is nanomedicine, with a particular focus on drug delivery systems. Among the various nanoparticles used for this purpose, lipid and polymer-based systems, such as liposomes and cubosomes stand out. This study investigate the structural influence of encapsulating lysozyme and curcumin, model compounds. Lysozyme is an antimicrobial enzyme produced by animals and is part of the immune system. It is a glycosidic hydrolase that catalyzes the hydrolysis of components in the cell walls of gram-positive bacteria. This hydrolysis compromises the integrity of cell walls, leading to the lysis (and consequently the death) of bacteria. Curcumin is a bright yellow crystalline compound found in the stem of Curcuma longa (or turmeric), commonly used as a dye or even as a food additive. It has been a significant focus in the treatment of chronic diseases such as inflammation, arthritis, metabolic syndrome, liver disease, obesity, neurodegenerative diseases, and especially cancers. It is also studied as a potential antibacterial agent. The main objective of this study is to construct nanostructured systems with the potential to act as antimicrobial agents, with controlled release of both drugs. These systems consist of phytantriol (PHY) cubosomes in the absence and presence of lysozyme, curcumin, and their combinations to analyze the joint antimicrobial action of lysozyme and curcumin. Biophysical techniques used for characterization include Small-Angle X-ray Scattering (SAXS), Dynamic Light Scattering (DLS), Cryo-Transmission Electron Microscopy (Cryo-TEM), and Nanoparticle Tracking Analysis (NTA). It was observed that lipid formulations are effective in forming cubic structures with desirable stability. Cubic nanoparticles have demonstrated a high encapsulation capacity for lysozyme and curcumin. The release kinetics of these drugs have shown promise, suggesting that drug encapsulation is effective, as well as their controlled and targeted release. Two bacterial strains were studied, with E. coli showing no cytotoxic damage, while Bacillus subtilis did. This result indicates the antimicrobial potential of the system against types of bacteria

Curcumin interrupts leptin-regulated microRNA-122 in hepatic stellate cells in vitro and in vivo.

The purpose of this study was to evaluate the effect of curcumin, an active polyphenol, on the leptin induced lowering of miR-122 in Hepatic stellate cells (HSCs) in vivo and an animal model. Gene expression was evaluated by transfection assay, real-time PCR, or Western blot analysis. The liver fibrosis model of leptin deficient mouse was used for in vivo experiment. As a result, curcumin showed inhibitory effect on leptin induced lowering of the miR-122 in HSCs. Curcumin suppressed leptin induced sonic hedgehog (Shh) expression and blocked leptin induced Shh signaling pathway, which was essential for curcumin inhibition of the negative role of leptin in miR-122 expression in HSCs. The influence of curcumin on the negative effect of leptin on miR-122 level was followed by the attenuation of liver fibrosis caused by leptin in leptin-deficient mouse model. In conclusion, curcumin could reduce the decrease of miR-122 level in HSCs induced by leptin and inhibit liver fibrosis induced by leptin. These data may have potential implications to treat with liver fibrosis by elevating the expression of leptin in humans especially obese patients.

Sensitization of GSH synthesis by curcumin curtails acrolein-induced alveolar epithelial apoptosis via Keap1 cysteine conjugation: A randomized controlled trial and experimental animal model of pneumonitis.

INTRODUCTION: Epidemiological studies have reported an association between exposures to ambient air pollution and respiratory diseases, including chronic obstructive pulmonary disease (COPD). Pneumonitis is a critical driving factor of COPD and exposure to air pollutants (e.g., acrolein) is associated with increased incidence of pneumonitis. OBJECTIVES: Currently available anti-inflammatory therapies provide little benefit against respiratory diseases. To this end, we investigated the preventive role of curcumin against air pollutant-associated pneumonitis and its underlying mechanism. METHODS: A total of 40 subjects was recruited from Chengdu, China which is among the top three cities in terms of respiratory mortality related to air pollution. The participants were randomly provided either placebo or curcumin supplements for 2 weeks and blood samples were collected at the baseline and at the end of the intervention to monitor systemic markers. In our follow up mechanistic study, C57BL/6 mice (n = 40) were randomly allocated into 4 groups: Control group (saline + no acrolein), Curcumin only group (curcumin + no acrolein), Acrolein only group (saline + acrolein), and Acrolein + Curcumin group (curcumin + acrolein). Curcumin was orally administered at 100 mg/kg body weight once a day for 10 days, and then the mice were subjected to nasal instillation of acrolein (5 mg/kg body weight). Twelve hours after single acrolein exposure, all mice were euthanized. RESULTS: Curcumin supplementation, with no noticeable adverse responses, reduced circulating pro-inflammatory cytokines in association with clinical pneumonitis as positive predictive while improving those of anti-inflammatory cytokines. In the pre-clinical study, curcumin reduced pneumonitis manifestations by suppression of intrinsic and extrinsic apoptotic signaling, which is attributed to enhanced redox sensing of Nrf2 and thus sensitized synthesis and restoration of GSH, at least in part, through curcumin-Keap1 conjugation. CONCLUSIONS: Our study collectively suggests that curcumin could provide an effective preventive measure against air pollutant-enhanced pneumonitis and thus COPD.

Curcumin Mediated Gold Nanoparticles and Analysis of its Antioxidant, Anti-inflammatory, Antimicrobial Activity Against Oral Pathogens

ABSTRACT Objective: To green synthesise gold nanoparticles using curcumin and to analyse its antioxidant, anti-inflammatory, and antimicrobial activity among oral pathogens. Material and Methods: Biosynthesised Curcumin Gold nanoparticles (CuAuNP) were evaluated by UV-visible spectrophotometer (UV-Vis), Transmission Electron Microscopy (TEM), and evaluation of antioxidant, anti-inflammatory and antibacterial activity against oral pathogens. Results: Synthesized CuAuNP were characterized using UV-visible spectrophotometry and showed peak absorption at 530nm. CuAuNp showed a 90.3% maximum scavenging ability of DPPH at a concentration of 50 μg/mL. CuAuNP exhibited 79.6 % of the highest anti-inflammatory activity at 50μg/mL than the standard drug diclofenac. TEM image clearly showed uniformly dispersed spherical-shaped gold nanoparticles with a size of about 20 nm. The biosynthesized nanoparticle was tested for its antimicrobial effect, and it showed a potent effect against S. aureus, E. faecalis, and C. albicans at 100µg/ mL. Enterococcus faecalis has a maximum zone of inhibition of 14 mm at 100µg/ mL of CuAuNp. Among gram-positive bacteria, a maximum zone of inhibition of 12 mm at 100µg/ mL was seen in S. aureus compared to S mutans. Candida albicans showed a maximum zone of inhibition of 18 mm at 25 μg/mL of CuAuNp. Conclusion: Curcumin-mediated gold nanoparticles with 20 nm size were effective and had strong antioxidant and anti-inflammatory activity at 50µg/ mL, antimicrobial action inhibiting microbes at 100µg/mL concentration that can be used in treating various Oral mucosal lesions.

Efficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background: Dietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its therapeutic effect, and some studies have inconsistent results. The effectiveness of dietary polyphenols in the treatment of NAFLD is still controversial. The aim of this study was to evaluate the therapeutic efficacy of oral dietary polyphenols in patients with NAFLD. Methods: The literature (both Chinese and English) published before 30 April 2022 in PubMed, Cochrane, Medline, CNKI, and other databases on the treatment of NAFLD with dietary polyphenols was searched. Manual screening, quality assessment, and data extraction of search results were conducted strictly according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the meta-analysis. Results: The RCTs included in this study involved dietary supplementation with eight polyphenols (curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein) and 2,173 participants. This systematic review and meta-analysis found that 1) curcumin may decrease body mass index (BMI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Triglycerides (TG) total cholesterol (TC), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) compared to placebo; and curcumin does not increase the occurrence of adverse events. 2) Although the meta-analysis results of all randomized controlled trials (RCTs) did not reveal significant positive changes, individual RCTs showed meaningful results. 3) Naringenin significantly decreased the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) but had no significant effect on AST and ALT, and it is a safe supplementation. 4) Only one team presents a protocol about anthocyanin (from Cornus mas L. fruit extract) in the treatment of NAFLD. 5) Hesperidin may decrease BMI, AST, ALT, TG, TC, HOMA-IR, and so on. 6) Catechin may decrease BMI, HOMA-IR, and TG level, and it was well tolerated by the patients. 7) Silymarin was effective in improving ALT and AST and reducing hepatic fat accumulation and liver stiffness in NAFLD patients. Conclusion: Based on current evidence, curcumin can reduce BMI, TG, TC, liver enzymes, and insulin resistance; catechin can reduce BMI, insulin resistance, and TG effectively; silymarin can reduce liver enzymes. For resveratrol, naringenin, anthocyanin, hesperidin, and catechin, more RCTs are needed to further evaluate their efficacy and safety.

Complementary and alternative therapies in skin cancer a literature review of biologically active compounds.

Complementary and alternative medicine or therapies (CAM) are frequently used by skin cancers patients. Patient's self-administration of CAM in melanoma can reach up to 40%-50%. CAMs such as botanical agents, phytochemicals, herbal formulas ("black salve") and cannabinoids, among others, have been described in skin cancer patients. The objective of this review article was to acknowledge the different CAM for skin cancers through the current evidence, focusing on biologically active CAM rather than mind-body approaches. We searched MEDLINE database for articles published through July 2022, regardless of study design. Of all CAMs, phytochemicals have the best in vitro evidence-supporting efficacy against skin cancer including melanoma; however, to date, none have proved efficacy on human patients. Of the phytochemicals, Curcumin is the most widely studied. Several findings support Curcumin efficacy in vitro through various molecular pathways, although most studies are in the preliminary phase. In addition, the use of alternative therapies is not exempt of risks physicians should be aware of their adverse effects, interactions with standard treatments, and possible complications arising from CAM usage. There is emerging evidence for CAM use in skin cancer, but no human clinical trials support the effectiveness of any CAM in the treatment of skin cancer to date. Nevertheless, patients worldwide frequently use CAM, and physicians should educate themselves on currently available CAMs.

Natural compounds as safe therapeutic options for ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. Several conventional treatments for UC such as corticosteroids, immunosuppressive agents, tumor necrosis factor antagonist, integrin blockers, and interleukin antagonist, and salicylates are available but are associated with the various limitations and side-effects. None of the above treatments helps to achieve the ultimate goal of the therapy, i.e., maintenance of remission in the long-term. Natural remedies for the treatment of UC show comparatively less side effects as compared to conventional approaches, and affordable. The current review presents details on the role of herbal drugs in the treatment and cure of UC. Google, PubMed, Web of Science, and Scopus portals have been searched for potentially relevant literature to get the latest developments and updated information related to use of natural drugs in the treatment of UC. Natural products have been used over centuries to treat UC. Some of the essential herbal constituents exhibiting antiulcerogenic activity include gymnemic acid (Gymnema sylvestre), shagoal (Zingiber officinale), catechin (Camellia sinensis), curcumin (Curcuma longa), arctigenin (Arctium lappa), and boswellic acid (Boswellia serrata). Although many plant-derived products have been recommended for UC, further research to understand the exact molecular mechanism is still warranted to establish their usefulness clinically.

A phase I evaluation of the effect of curcumin on dose-limiting toxicity and pharmacokinetics of irinotecan in participants with solid tumors.

Curcumin inhibits UDP-glucuronyltransferases, a primary metabolic pathway for cancer chemotherapeutic agents like irinotecan. Concurrent administration of both agents may exacerbate irinotecan toxicity. We conducted this phase I study to determine the safety of concurrent curcumin and irinotecan administration. Ten participants with advanced solid tumors received one of four doses (1, 2, 3, and 4 g) of a curcumin phosphatidylcholine complex (PC) orally daily, and 200 mg/m2 of i.v. infusion irinotecan on days 1 and 15 of a 28-day cycle, to determine the maximum tolerated dose (MTD) of PC. Thirteen participants received 4 g of PC (MTD) to assess the effect on the pharmacokinetic (PK) properties of irinotecan and its metabolites, SN-38 and SN-38G. Irinotecan, SN-38, and SN-38G exposure equivalence with and without curcumin was assessed using area under the plasma concentration-time curves from 0 to 6 h (AUC0-6h ). Safety assessments and disease responses were also evaluated. The combination of irinotecan and PC was well-tolerated. Because there was no dose limiting toxicity, the maximum dose administered (4 g) was defined as the recommended phase II dose of PC. PC did not significantly alter the plasma exposure and other PK properties of irinotecan and its metabolites. There was no apparent increase in the incidence of irinotecan-associated toxicities. The objective response rate was 3/19 (22%, 95% confidence interval [CI]: 5-39%), median progression free survival and overall survival (n = 23) were 4 months (95% CI: 2.9-8.9 months) and 8.4 months (95% CI: 3.7 - not evaluable [NE]), respectively. Future studies are required to evaluate the efficacy of this combination.

Efficacy and safety of adjuvant curcumin therapy in ulcerative colitis: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumin, an active polyphenol extracted from Traditional Chinese medicine Curcuma longa (turmeric), has shown many health-related benefits and pharmacological effects. Adjuvant curcumin therapy for ulcerative colitis has become increasingly popular, but its efficacy and safety of which is still controversial. The purpose of this study is to evaluate the efficacy and safety of adjuvant curcumin therapy in ulcerative colitis. MATERIALS AND METHODS: The Medline, EMBASE, the Cochrane Library, CNKI, VIP, WanFang, and SinoMed databases were searched from inception to June 2021, to identify all randomized controlled clinical trials with adjuvant curcumin therapy in ulcerative colitis. The primary outcomes were clinical and endoscopic remission, and subgroup analyses were also performed. RESULTS: Six randomized trials with a total of 385 participants were included in this study. Qualified trials recommended that adjuvant curcumin therapy for ulcerative colitis was effective in inducing clinical remission (RR = 2.10, 95% CI 1.13 to 3.89), but not in clinical improvement (RR = 1.62, 95% CI 1.00 to 2.61), endoscopic remission (RR = 4.17, 95% CI 0.63 to 27.71) or endoscopic improvement (RR = 4.13, 95% CI 0.20 to 87.07). Included studies showed that appropriate dosage, formation, longer duration, and topical medication may have a greater potential advantage. No severe adverse effects had been reported. CONCLUSIONS: Available evidence suggested that adjuvant curcumin therapy may be effective for clinical remission in ulcerative colitis patients without causing severe adverse effects. The appropriate methods of administration can achieve better curative effect, which requires further study to verify.

Targeting of cancer cell death mechanisms by curcumin: Implications to cancer therapy.

Cancer is known as a second major cause of death globally. Nowadays, several modalities have been developed for the treatment of cancer. Radiotherapy and chemotherapy are the most common modalities in most countries. However, newer modalities such as immunotherapy and targeted therapy drugs can kill cancer cells with minimal side effects. All anticancer agents work based on the killing of cancer cells. Numerous studies are ongoing to kill cancer cells more effectively without increasing side effects to normal tissues. The combination modalities with low toxic agents are interesting for this aim. Curcumin is one of the most common herbal agents that has shown several anticancer properties. It can regulate immune system responses against cancer. Furthermore, curcumin has been shown to potentiate cell death signalling pathways and attenuate survival signalling pathways in cancer cells. The knowledge of how curcumin induces cell death in cancers can improve therapeutic efficiency. In this review, the regulatory effects of curcumin on different cell death mechanisms and their signalling pathways will be discussed. Furthermore, we explain how curcumin may potentiate the anticancer effects of other drugs or radiotherapy through modulation of apoptosis, mitotic catastrophe, senescence, autophagy and ferroptosis.

An efficient enzyme-triggered controlled release system for colon-targeted oral delivery to combat dextran sodium sulfate (DSS)-induced colitis in mice.

Oral route colon-targeted drug delivery systems (CDDSs) are desirable for the treatment of ulcerative colitis (UC). However, CDDSs are challenging owing to the physiological and anatomical barriers associated with the gastrointestinal tract (GIT). In this study, we developed an effective enzyme-triggered controlled release system using curcumin-cyclodextrin (CD-Cur) inclusion complex as core and low molecular weight chitosan and unsaturated alginate resulting nanoparticles (CANPs) as shell. The formed CD-Cur-CANPs showed a narrow particle-size distribution and a compact structure. In vitro drug release determination indicated that CD-Cur-CANPs showed pH-sensitive and α-amylase-responsive release characteristics. Furthermore, in vivo experiments demonstrated that oral administration of CD-Cur-CANPs had an efficient therapeutic efficacy, strong colonic biodistribution and accumulation, rapid macrophage uptake, promoted colonic epithelial barrier integrity and modulated production of inflammatory cytokines, reshaped the gut microbiota in mice with dextran sodium sulfate (DSS)-induced colitis. Taken together, our synthetic CD-Cur-CANPs are a promising synergistic colon-targeted approach for UC treatment.

The effects of nano-curcumin as a nutritional strategy on clinical and inflammatory factors in children with cystic fibrosis: the study protocol for a randomized controlled trial.

BACKGROUND: Cystic fibrosis (CF) is a genetic disorder, which is caused by the CFTR protein defects. Along with CFTR dysfunction, inflammation plays a key role in the disease outcomes. Inflammation may develop due to the internal dysfunction of the CFTR protein or external factors. Curcumin affects the CFTR protein function primarily as a corrector and potentiator and secondary as an anti-inflammatory and antimicrobial agent. The present study aims to assess the impact of nano-curcumin on clinical and inflammatory markers in children with CF. METHODS: This prospective, double blind control trial will be conducted at the Akbar Children's Hospital in Mashhad, Iran. Children with CF will be enrolled based on the eligibility criteria. Placebo and curcumin with the maximum dose of 80 mg considering the body surface of the patients will be administrated for 3 months. The primary outcome is to evaluate inflammation based on serum interleukin-6, interleukin-10, and hs-CRP, stool calprotectin, and neutrophil count of nasopharyngeal swab. The secondary outcome involved clinical assessment via spirometry, anthropometrics, and quality of life. They will be assessed before and after 3 months. DISCUSSION: Due to the multifarious effects of curcumin on CF disease, it could be proposed as a nutritional strategy in the treatment of cystic fibrosis. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20200705048018N1 . Registered on July 10, 2020.

c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1) attenuates curcumin-induced cell death differently from its family member, JNK-associated leucine zipper protein (JLP).

Curcumin, a major component of turmeric, is known to exhibit multiple biological functions including antitumor activity. We previously reported that the mitogen-activated protein kinase (MAPK) scaffold protein c-Jun NH2-terminal kinase (JNK)-associated leucine zipper protein (JLP) reduces curcumin-induced cell death by modulating p38 MAPK and autophagy through the regulation of lysosome positioning. In this study, we investigated the role of JNK/stress-activated protein kinase-associated protein 1 (JSAP1), a JLP family member, in curcumin-induced stress, and found that JSAP1 also attenuates curcumin-induced cell death. However, JSAP1 knockout showed no or little effect on the activation of JNK and p38 MAPKs in response to curcumin. In addition, small molecule inhibitors of JNK and p38 MAPKs did not increase curcumin-induced cell death. Furthermore, JSAP1 depletion did not impair lysosome positioning and autophagosome-lysosome fusion. Instead, we noticed substantial autolysosome accumulation accompanied by an inefficient autophagic flux in JSAP1 knockout cells. Taken together, these results indicate that JSAP1 is involved in curcumin-induced cell death differently from JLP, and may suggest that JSAP1 plays a role in autophagosome degradation and its dysfunction results in enhanced cell death. The findings of this study may contribute to the development of novel therapeutic approaches using curcumin for cancer.

Systematic Review and Meta-Analysis of Preventative Strategies for Acute Kidney Injury in Patients Undergoing Abdominal Aortic Aneurysm Repair.

BACKGOUND: To assess the effect of various preventative interventions for reducing the incidence of postoperative acute kidney injury (AKI) in patients undergoing elective abdominal aortic aneurysm (AAA) repair. METHODS: We included randomized controlled trials of 10 patients or more which tested a preventative intervention versus standard therapy or placebo in patients undergoing elective AAA repair using the open or endovascular approach. Studies including mixed patient populations such as those with aortic occlusive disease, thoracoabdominal aneurysms or ruptured aneurysms were ineligible for review. We searched Medline (1966-2019), EMBASE (1947-2019), CINAHL (1961-2019), Web of Science (1945-2019), Scopus (1966-2019), and The Cochrane Library (1996-2019) for trials available as published manuscripts in English. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Where possible we pooled the results of similar interventions using random effects meta-analysis. RESULTS: We included 17 trials involving 1443 participants. Most trials were small, single-center studies, with varying definitions of AKI and a high or moderate risk of bias. The preventative strategies with possible protective effects were mannitol, a composite of antioxidant supplements, an open extraperitoneal approach, and human atrial natriuretic peptide (hANP). Curcumin, methylprednisolone, carbon dioxide contrast medium, hemodynamic monitoring and N-acetylcysteine were found to be ineffective. Six trials with a total of 355 participants reported on remote ischemic preconditioning (RIPC) and our meta-analysis showed no statistically significant difference between RIPC and standard treatment (OR 1.20, 95% CI 0.37, 3.89); although the results should be interpreted with caution due to considerable statistical heterogeneity (I2 = 70%). None of the interventions studied significantly reduced receipt of renal replacement therapy (RRT). CONCLUSIONS: Interventions that have shown some potential to reduce AKI after AAA repair include mannitol, a composite of antioxidant supplements, an open extraperitoneal approach and hANP. These conclusions are limited by the small size, high risk of bias and inconsistency of the included trials. Large, high quality, multi-center randomized trials will help determine which interventions are effective in reducing the incidence of postoperative AKI among patients undergoing elective AAA repair.

Preparation and characterization of nanocurcumin based hybrid virosomes as a drug delivery vehicle with enhanced anticancerous activity and reduced toxicity.

The present study represents a formulation of nanocurcumin based hybrid virosomes (NC-virosome) to deliver drugs at targeted sites. Curcumin is a bioactive component derived from Curcuma longa and well-known for its medicinal property, but it exhibits poor solubility and rapid metabolism, which led to low bioavailability and hence limits its applications. Nanocurcumin was prepared to increase the aqueous solubility and to overcome all the limitations associated with curcumin. Influenza virosomes were prepared by solubilization of the viral membrane with 1,2-distearoyl-sn-glycerol-3-phosphocholine (DSPC). During membrane reconstitution, the hydrophilic nanocurcumin was added to the solvent system, followed by overnight dialysis to obtain NC-virosomes. The same was characterized using a transmission electron microscope (TEM) and scanning electron microscope (SEM), MTT assay was used to evaluate it's in vitro-cytotoxicity using MDA-MB231 and Mesenchyme stem cells (MSCs). The results showed NC-virosomes has spherical morphology with size ranging between 60 and 90 nm. It showed 82.6% drug encapsulation efficiency. The viability of MDA-MB231 cells was significantly inhibited by NC-virosome in a concentration-dependent manner at a specific time. The IC50 for nanocurcumin and NC-virosome was 79.49 and 54.23 µg/ml, respectively. The site-specific drug-targeting, high efficacy and non- toxicity of NC-virosomes proves its future potential as drug delivery vehicles.

The role of curcumin in aging and senescence: Molecular mechanisms.

Healthy aging and human longevity are intricate phenotypes affected by environmental factors such as physical exercise, diet, health habits, and psychosocial situations as well as genetic factors. Diet and caloric restriction have a crucial role in healthy aging. Curcumin, a polyphenolic compound isolated from the Curcuma longa, has been shown to exert anti-aging characteristics. Recently, investigations on curcumin with regard to aging and age-associated disease in model organisms has described that curcumin and its metabolites, prolong the mean lifespan of some aging model organisms such as C. elegans, D. melanogaster, yeast, and mouse. It has been proposed to have several biological activities, such as antioxidative, anti-inflammatory, anticancer, chemopreventive, and anti-neurodegenerative characteristics. In several studies on various model organisms it has been shown that the lifespan extension via curcumin treatment was connected with enhanced superoxide dismutase (SOD) activity, and also declined malondialdehyde (MDA) and lipofuscin levels. As well as the pivotal role of curcumin on the modulating of major signaling pathways that influence longevity of organisms like IIS, mTOR, PKA, and FOXO signaling pathways. This review defines the use of curcumin in traditional and modern medicine, its biochemistry and biological functions, such as curcumin's anti-aging, anti-cancer, anti-microbial, anti-inflammatory, and anti-oxidant characteristics. Also, the review further describes the role of curcumin in a pharmacological context and new insights on its therapeutic capacity and restrictions. Particularly, the review emphasizes in-depth on the efficiency of curcumin and its mechanism of action as an anti-aging compound and also treating age-related disease.

Suppressive effects of curcumin on milk production without inflammatory responses in lactating mammary epithelial cells.

BACKGROUND: Curcumin is a naturally occurring polyphenol found in Curcuma longa with multiple therapeutic properties, such as anti-inflammatory, wound healing and anti-cancer effects. Curcuma longa is also used as a galactagogue to improve milk production during lactation. PURPOSE: To assess curcumin could have therapeutic potential for breastfeeding mothers, we investigated whether and how curcumin influences milk production in lactating mammary epithelial cells (MECs) at the cellular and molecular levels. METHODS: We prepared a lactating MEC culture model that produced milk components and formed less-permeable tight junctions (TJs) to investigate the molecular mechanism of curcumin on milk production, TJs, and inflammation in vitro. RESULTS: Curcumin downregulated milk production in lactation MECs concurrently with inactivation of lactogenesis-relating signaling (STAT5 and glucocorticoid receptor). The maintenance of a less-permeable TJ barrier was also confirmed, although the TJ protein claudin-4 increased. Curcumin inactivated NFκB and STAT3 signaling, which are closely involved in inflammatory responses in weaning and mastitis mammary glands. The expression levels of IL-1ß and TNF-α were also decreased by curcumin treatment. Furthermore, curcumin blocked activation of inflammatory signaling by lipopolysaccharide treatment in MECs, similar to those in MECs that were treated with diclofenac sodium. The drastic phosphorylation of ERK was induced by curcumin treatment in the absence of EGF. U0126, an inhibitor of ERK phosphorylation, attenuated the adverse effects of curcumin on lactating MECs. CONCLUSION: The results of the present study suggests that curcumin downregulates milk production via inactivation of STAT5 and GR signaling with concurrent suppression of inflammatory responses via STAT3 and NFκB signaling in MECs. These findings provide new insights into the role of curcumin as a mild suppressor of milk production without inflammatory damages in breastfeeding mothers.

The Effects of Curcumin on the Side Effects of Anticancer Drugs in Chemotherapy: A Randomized Controlled Trial.

Curcumin, the active ingredient of the spice turmeric, has been shown to have anticancer activities in several preclinical and clinical studies. The prophylactic effect of curcumin against chemotherapy-induced damage and side effects was evaluated in a double-blind, placebo-controlled randomized trial. Eighty cancer patients on standard chemotherapy regimens were randomly assigned to receive curcumin as adjuvant therapy (500 mg per 12 hours) and matched control group to receive placebo for 9 weeks. Pre- and post-intervention, the changes in the health-related quality-of-Life (QoL) score (based on the University of Washington Quality-of-Life (UW-QoL) questionnaire, version 3), clinical symptoms, and hematological and biochemical parameters were assessed. Comparison between groups based on total QoL score showed that curcumin supplementation was not associated with improved QoL (P = 0.102). Hematological and biochemical analysis showed no statistical differences between the groups at the end of the trial (P > 0.05). However, during the trial, significant differences were observed in hemoglobin (Hb), hematocrit (HCT), lactic acid dehydrogenase (LDH), serum glutamic-oxaloacetic transaminase (SGOT), and anaplastic lymphoma kinase (ALK) between the groups (P < 0.05). Future studies in a larger homogenous population of cancer patients are required to confirm the adjuvant effect of curcumin on chemotherapy-induced QoL.