ROS in diabetic atria regulate SK2 degradation by Atrogin-1 through the NF-κB signaling pathway.

One of the independent risk factors for atrial fibrillation is diabetes mellitus (DM); however, the underlying mechanisms causing atrial fibrillation in DM are unknown. The underlying mechanism of Atrogin-1-mediated SK2 degradation and associated signaling pathways are unclear. The aim of this study was to elucidate the relationship among reactive oxygen species (ROS), the NF-κB signaling pathway, and Atrogin-1 protein expression in the atrial myocardia of DM mice. We found that SK2 expression was downregulated comitant with increased ROS generation and enhanced NF-κB signaling activation in the atrial cardiomyocytes of DM mice. These observations were mimicked by exogenously applicating H2O2 and by high glucose culture conditions in HL-1 cells. Inhibition of ROS production by diphenyleneiodonium chloride or silencing of NF-κB by siRNA decreased the protein expression of NF-κB and Atrogin-1 and increased that of SK2 in HL-1 cells with high glucose culture. Moreover, chromatin immunoprecipitation assay demonstrated that NF-κB/p65 directly binds to the promoter of the FBXO32 gene (encoding Atrogin-1), regulating the FBXO32 transcription. Finally, we evaluated the therapeutic effects of curcumin, known as a NF-κB inhibitor, on Atrogin-1 and SK2 expression in DM mice and confirmed that oral administration of curcumin for 4 weeks significantly suppressed Atrogin-1 expression and protected SK2 expression against hyperglycemia. In summary, the results from this study indicated that the ROS/NF-κB signaling pathway participates in Atrogin-1-mediated SK2 regulation in the atria of streptozotocin-induced DM mice.

Apoptosis antagonizing transcription factor-mediated liver damage and inflammation to cancer: Therapeutic intervention by curcumin in experimental metabolic dysfunction associated steatohepatitis-hepatocellular carcinoma.

In tandem with the expanding obesity pandemic, the prevalence of metabolic dysfunction associated steatohepatitis (MASH, formerly known as NASH)- driven hepatocellular carcinoma (HCC) is predicted to rise globally, creating a significant need for therapeutic interventions. We previously identified the upregulation of apoptosis antagonizing transcription factor (AATF), which is implicated in facilitating the progression from MASH to HCC. The objective of this study was to examine whether the intervention of curcumin could alleviate AATF-mediated MASH, inhibit tumor growth, and elucidate the underlying mechanism. A preclinical murine model mimicking human MASH-HCC was employed, subjecting mice to either a chow diet normal water (CDNW) or western diet sugar water (WDSW) along with very low dose of carbon tetrachloride (CCl4 - 0.2 µL/g, weekly). Mice receiving curcumin (CUR) alongside WDSW/CCl4 exhibited significant improvements, including reduced liver enzymes, dyslipidemia, steatosis, inflammation, and hepatocellular ballooning. Curcumin treatment also suppressed hepatic expression of inflammatory, fibrogenic, and oncogenic markers. Of note, there was a significant reduction in the expression of AATF upon curcumin treatment in WDSW/CCl4 mice and human HCC cells. In contrast, curcumin upregulated Kruppel-like factor 4 (KLF4) in MASH liver and HCC cells, which is known to downregulate sp1 (specificity protein-1) expression. Thus, curcumin treatment effectively inhibited the progression of MASH to HCC by downregulating the expression of AATF via the KLF4-Sp1 signaling pathway. These preclinical findings establish a novel molecular connection between curcumin and AATF in reducing hepatocarcinogenesis, and provide a strong rationale for the development of curcumin as a viable treatment for MASH-HCC in humans.

Interaction of gallium, indium, and vanadyl curcumin complexes with hen egg-white lysozyme (HEWL): Mechanistic aspects and evaluation of antiamyloidogenic activity.

Many proteins and peptides can aggregate into amyloid fibrils with high-ordered and cross-ß rich structure characteristics. Amyloid deposition is a common feature of neurodegenerative diseases called amyloidosis. Various natural polyphenolic compounds such as curcumin exhibited antiamyloidogenic activities, but less researches were focused on the metal complexes of these compounds. In this study, the inhibitory effects of gallium curcumin (Ga(cur)3), indium curcumin (In(cur)3), and vanadyl curcumin (VO(cur)2) on the amyloid fibrillation of hen egg white lysozyme (HEWL) have been investigated. Moreover, the details of binding interactions of these metal complexes with HEWL have been explored. The results of fluorescence quenching analyses revealed that In(cur)3 and VO(cur)2 have much higher binding affinities than Ga(cur)3 toward HEWL. The interactions of these metal complexes were accompanied by partial conformational changes in the tertiary structure of HEWL. The kinetic curves of the fibrillation process demonstrated that In(cur)3 and VO(cur)2 have higher inhibitory effects than Ga(cur)3 on the amyloid fibrillation of HEWL. The strength of binding to HEWL is completely in accordance with inhibitory activities of these metal complexes of curcumin.

Fluorinated curcumin derivative (Shiga-Y6) modulates the level of thioredoxin-interacting protein (TXNIP) in a mouse model of diabetes.

Thioredoxin interacting protein (TXNIP) has emerged as a significant regulator of ß-cell mass and loss, rendering it an attractive target for treating diabetes. We previously showed that Shiga-Y6, a fluorinated curcumin derivative, inhibited TXNIP mRNA and protein expression in vitro, raising the question of whether the same effect could be translated in vivo. Herein, we examined the effect of Shiga-Y6 on TNXIP levels and explored its therapeutic potential in a mouse model of diabetes, Akita mice. We intraperitoneally injected Shiga-Y6 (SY6; 30 mg/kg of body weight) or vehicle into 8-week-old Akita mice for 28 consecutive days. On day 29, the mice were euthanized, following which the serum levels of glucose, insulin, and glucagon were measured using ELISA, the expression of TXNIP in pancreatic tissue lysates was determined using western blotting, and the level of ß-cell apoptosis was assessed using the TUNEL assay. TXNIP levels in the pancreatic tissue of Akita mice were significantly elevated compared with wild-type (WT) mice. Shiga-Y6 administration for 28 days significantly lowered those levels compared with Akita mice that received vehicle to a level comparable to WT mice. In immunohistochemical analysis, both α- to ß-cell ratio and the number of apoptotic ß-cells were significantly reduced in SY6-treated Akita mice, compared with vehicle-treated Akita mice. Findings from the present study suggest a potential of Shiga-Y6 as an antidiabetic agent through lowering TXNIP protein levels and ameliorating pancreatic ß-cells apoptosis.

Synergistic anticancer effects of co-delivery of linc-RoR siRNA and curcumin using polyamidoamine dendrimers against breast cancer.

Breast cancer resistance to chemotherapy necessitates novel combination therapeutic approaches. Linc-RoR is a long intergenic noncoding RNA that regulates stem cell differentiation and promotes metastasis and invasion in breast cancer. Herein, we report a dual delivery system employing polyamidoamine dendrimers to co-administer the natural compound curcumin and linc-RoR siRNA for breast cancer treatment. Polyamidoamine dendrimers efficiently encapsulated curcumin and formed complexes with linc-RoR siRNA at an optimal N/P ratio. In MCF-7 breast cancer cells, the dendriplexes were effectively internalized and the combination treatment synergistically enhanced cytotoxicity, arresting the cell cycle at the G1 phase and inducing apoptosis. Linc-RoR gene expression was also significantly downregulated. Individual treatments showed lower efficacy, indicating synergism between components. Mechanistic studies are warranted to define the molecular underpinnings of this synergistic interaction. Our findings suggest dual delivery of linc-RoR siRNA and curcumin via dendrimers merits further exploration as a personalized therapeutic approach for overcoming breast cancer resistance.

Antibacterial Photodynamic Therapy by Zn(II)-Curcumin Complex: Synthesis, Characterization, DFT Calculation, Antibacterial Activity, and Molecular Docking.

The increase in antibacterial drug resistance is threatening global health conditions. Recently, antibacterial photodynamic therapy (aPDT) has emerged as an effective antibacterial treatment with high cure gain. In this work, three Zn(II) complexes viz., [Zn(en)(acac)Cl] (1), [Zn(bpy)(acac)Cl] (2), [Zn(en)(cur)Cl] (3), where en=ethylenediamine (1 and 3), bpy=2,2'-bipyridine (2), acac=acetylacetonate (1 and 2), cur=curcumin monoanionic (3) were developed as aPDT agents. Complexes 1-3 were synthesized and fully characterized using NMR, HRMS, FTIR, UV-Vis. and fluorescence spectroscopy. The HOMO-LUMO energy gap (Eg), and adiabatic splittings (ΔS1-T1 and ΔS0-T1 ) obtained from DFT calculation indicated the photosensivity of the complexes. These complexes have not shown any potent antibacterial activity under dark conditions but the antibacterial activity of these complexes was significantly enhanced upon light exposure (MIC value up to 0.025 µg/mL) due to their light-mediated 1 O2 generation abilities. The molecular docking study suggested that complexes 1-3 interact efficiently with DNA gyrase B (PDB ID: 4uro). Importantly, 1-3 did not show any toxicity toward normal HEK-293 cells. Overall, in this work, we have demonstrated the promising potential of Zn(II) complexes as effective antibacterial agents under the influence of visible light.

Fenpropathrin provoked kidney damage via controlling the NLRP3/Caspase-1/GSDMD-mediated pyroptosis: The palliative role of curcumin-loaded chitosan nanoparticles.

This study assessed the ability of formulated curcumin-loaded chitosan nanoparticles (CU-CS-NPs) to reduce the kidney damage resulting from fenpropathrin (FPN) in rats compared to curcumin (CU) in rats. Sixty male Sprague Dawley rats were separated into six groups and orally administered 1 mL/kg b.wt corn oil, 50 mg CU/kg b.wt, 50 mg CU-CS-NPs /kg b.wt., 15 mg FPN /kg b.wt, CU+ FPN or CU-CS-NPs + FPN for 60 days. Then, serum renal damage products were assessed. Total antioxidant capacity, reactive oxygen species, interleukin 1ß (IL-1ß), malondialdehyde, NF-κB P65, cleaved-Caspase-1, and Caspase-8 were estimated in kidney homogenates. The cleaved Caspase-3 and TNF-α immunoexpression and pyroptosis-related genes were determined in renal tissues. The results showed that CU-CS-NPS significantly repressed the FPN-induced increment in kidney damage products (urea, uric acid, and creatinine). Moreover, the FPN-associated hypo-proteinemia, renal oxidative stress and apoptotic reactions, and impaired renal histology were considerably repaired by CU and CU-CS-NPs. Additionally, compared to FPN-exposed rats, CU, and CU-CS-NPs-treated rats had considerably lower immunoexpression of cleaved Caspase-3 and TNF-α in renal tissue. The pyroptosis-related genes NLRP3, GSDMD, IL-18, Caspase-3, Caspase-1, IL-1ß, Caspase-8, TNF-α, and NF-κB dramatically upregulated by FPN exposure in the renal tissues. Yet, in CU and CU-CS-NPs-treated rats, the gene above expression deviations were corrected. Notably, CU-CS-NPs were superior to CU in preventing oxidative damage and inflammation and regulating pyroptosis in the renal tissues of the FPN-exposed group. The results of the present study conclusively showed the superior favorable effect of CU-CS-NPs in counteracting renal impairment linked to environmental pollutants.

Mechanism by which HDAC3 regulates manganese induced H3K27ac in SH-SY5Y cells and intervention by curcumin.

Long-term excessive exposure to manganese can impair neuronal function in the brain, but the underlying pathological mechanism remains unclear. Oxidative stress plays a central role in manganese-induced neurotoxicity. Numerous studies have established a strong link between abnormal histone acetylation levels and the onset of various diseases. Histone deacetylase inhibitors and activators, such as TSA and ITSA-1, are often used to investigate the intricate mechanisms of histone acetylation in disease. In addition, recent experiments have provided substantial evidence demonstrating that curcumin (Cur) can act as an epigenetic regulator. Given these findings, this study aims to investigate the mechanisms underlying oxidative damage in SH-SY5Y cells exposed to MnCl2·4H2O, with a particular focus on histone acetylation, and to assess the potential therapeutic efficacy of Cur. In this study, SH-SY5Y cells were exposed to manganese for 24 h, were treated with TSA or ITSA-1, and were treated with or without Cur. The results suggested that manganese exposure, which leads to increased expression of HDAC3, induced H3K27 hypoacetylation, inhibited the transcription of antioxidant genes, decreased antioxidant enzyme activities, and induced oxidative damage in cells. Pretreatment with an HDAC3 inhibitor (TSA) increased the acetylation of H3K27 and the transcription of antioxidant genes and thus slowed manganese exposure-induced cellular oxidative damage. In contrast, an HDAC3 activator (ITSA-1) partially increased manganese-induced cellular oxidative damage, while Cur prevented manganese-induced oxidative damage. In summary, these findings suggest that inhibiting H3K27ac is a possible mechanism for ameliorating manganese-induced damage to dopaminergic neurons and that Cur exerts a certain protective effect against manganese-induced damage to dopaminergic neurons.

Interleukin-4 from curcumin-activated OECs emerges as a central modulator for increasing M2 polarization of microglia/macrophage in OEC anti-inflammatory activity for functional repair of spinal cord injury.

Microglia/macrophages are major contributors to neuroinflammation in the central nervous system (CNS) injury and exhibit either pro- or anti-inflammatory phenotypes in response to specific microenvironmental signals. Our latest in vivo and in vitro studies demonstrated that curcumin-treated olfactory ensheathing cells (aOECs) can effectively enhance neural survival and axonal outgrowth, and transplantation of aOECs improves the neurological outcome after spinal cord injury (SCI). The therapeutic effect is largely attributed to aOEC anti-inflammatory activity through the modulation of microglial polarization from the M1 to M2 phenotype. However, very little is known about what viable molecules from aOECs are actively responsible for the switch of M1 to M2 microglial phenotypes and the underlying mechanisms of microglial polarization. Herein, we show that Interleukin-4 (IL-4) plays a leading role in triggering the M1 to M2 microglial phenotype, appreciably decreasing the levels of M1 markers IL­1ß, IL­6, tumour necrosis factor-alpha (TNF-α) and inducible nitric oxide synthase (iNOS) and elevating the levels of M2 markers Arg-1, TGF-ß, IL-10, and CD206. Strikingly, blockade of IL-4 signaling by siRNA and a neutralizing antibody in aOEC medium reverses the transition of M1 to M2, and the activated microglia stimulated with the aOEC medium lacking IL-4 significantly decreases neuronal survival and neurite outgrowth. In addition, transplantation of aOECs improved the neurological function deficits after SCI in rats. More importantly, the crosstalk between JAK1/STAT1/3/6-targeted downstream signals and NF-κB/SOCS1/3 signaling predominantly orchestrates IL-4-modulated microglial polarization event. These results provide new insights into the molecular mechanisms of aOECs driving the M1-to-M2 shift of microglia and shed light on new therapies for SCI through the modulation of microglial polarization.

Folic Acid-Decorated Nanocrystals as Highly Loaded Trojan Horses to Target Cancer Cells.

The nanocrystal (NC) technology has become one of the most commonly used strategies for the formulation of poorly soluble actives. Given their large specific surface, NCs are mainly used to enhance the oral absorption of poorly soluble actives. Differently from conventional nanoparticles, which require the use of carrier materials and have limited drug loadings, NCs' drug loading approaches 100% since they are formed of the pure drug and surrounded by a thin layer of a stabilizer. In this work, we report the covalent decoration of curcumin NCs with folic acid (FA) using EDC/NHS chemistry and explore the novel systems as highly loaded "Trojan horses" to target cancer cells. The decorated NCs demonstrated a remarkable improvement in curcumin uptake, exhibiting enhanced growth inhibition in cancer cells (HeLa and MCF7) while sparing healthy cells (J774A.1). Cellular uptake studies revealed significantly heightened entry of FA-decorated NCs into cancer cells compared to unmodified NCs while also showing reduced uptake by macrophages, indicating a potential for prolonged circulation in vivo. These findings underline the potential of NC highly loaded nanovectors for drug delivery and, in particular, for cancer therapies, effectively targeting folate receptor-overexpressing cells while evading interception by macrophages, thus preserving their viability and offering a promising avenue for precise and effective treatments.

Regulatory effects of curcumin on nitric oxide signaling in the cardiovascular system.

The continuously rising prevalence of cardiovascular disease (CVD) globally substantially impacts the economic growth of developing countries. Indeed, one of the leading causes of death worldwide is unfavorable cardiovascular events. Reduced nitric oxide (NO) generation is the pathogenic foundation of endothelial dysfunction, which is regarded as the first stage in the development of a number of CVDs. Nitric oxide exerts an array of biological effects, including vasodilation, the suppression of vascular smooth muscle cell proliferation and the functional control of cardiac cells. Numerous treatment strategies aim to increase NO synthesis or upregulate downstream NO signaling pathways. The major component of Curcuma longa, curcumin, has long been utilized in traditional medicine to treat various illnesses, especially CVDs. Curcumin improves CV function as well as having important pleiotropic effects, such as anti-inflammatory and antioxidant, through its ability to increase the bioavailability of NO and to positively impact NO-related signaling pathways. In this review, we discuss the scientific literature relating to curcumin's positive effects on NO signaling and vascular endothelial function.

Curcumin can improve spinal cord injury by inhibiting DNA methylation.

Spinal cord injury (SCI) is a serious central nervous system disease. Traumatic SCI often causes persistent neurological deficits below the injury level. Epigenetic changes occur after SCI. Studies have shown DNA methylation to be a key player in nerve regeneration and remodeling, and in regulating some pathophysiological characteristics of SCI. Curcumin is a natural polyphenol from turmeric. It has anti-inflammatory, antioxidant, and neuroprotective effects, and can mitigate the cell and tissue damage caused by SCI. This report analyzed the specific functions of DNA methylation in central nervous system diseases, especially traumatic brain injury and SCI. DNA methylation can regulate the level of gene expressions in the central nervous system. Therefore, pharmacological interventions regulating DNA methylation may be promising for SCI.

Superoxide dismutase: a key target for the neuroprotective effects of curcumin.

Over the past few years, the prevalence of neurodegenerative diseases (NDD) has increased dramatically. The community health system is burdened by the high healthcare costs associated with NDD. Superoxide dismutase (SOD) is a type of metalloenzyme that possesses a distinct characteristic of protecting the body from oxidative stress through antioxidants. In this way, SOD supplementation may activate the endogenous antioxidant mechanism in various pathological conditions and could be used to neutralize free radical excess. Several factors are responsible for damaging DNA and RNA in the body, including the overproduction of reactive species, particularly reactive oxygen species (ROS) and reactive nitrogen species (RNS). Excessive ROS/RNS have deleterious effects on mitochondria and their metabolic processes, mainly through increased mitochondrial proteins, lipids and DNA oxidation. Studies have shown that oxidative stress is implicated in the etiology of many diseases, including NDD. It is thought that anti-inflammatory compounds, particularly phytochemicals, can interfere with these pathways and regulate inflammation. Extensive experimental and clinical research has proven that curcumin (Cur) has anti-inflammatory and anti-neurologic properties. In this review, we have compiled the available data on Cur's anti-inflammatory properties, paying special attention to its therapeutic impact on NDD through SOD.

Supramolecular Organo/hydrogel-Fabricated Long Alkyl Chain α-Amidoamides as a Smart Soft Material for pH-Responsive Curcumin Release.

Low-molecular-mass gelators, due to their excellent biocompatibility, low toxicological profile, innate biodegradability and ease of fabrication have garnered significant interest as they self-assemble through non-covalent interactions. In this study, we have designed and synthesized a series of six α-amidoamides by varying the hydrophobic alkyl chain length (C12-C22), which were well characterized using different spectral techniques. These α-amidoamides formed self-assembled aggregates in a DMSO/water solvent system affording organo/hydrogels at 0.66% w/v, which is the minimum gelation concentration (MGC) making them as remarkable supergelators. The various functionalities present in these gelators such as amides and alkyl chain length pave the way toward excellent gelation mechanism through hydrogen bonding and van der Waals interaction as evidenced from FTIR spectroscopy. Notably, as the chain length increased, organo/hydrogels became more thermally stable. Rheological results showed that the stability and strength of these gelators were considerably impacted by variations in chain length. The SEM morphology revealed dense sheet architectures of the organo/hydrogel samples. Organo/hydrogels have a significant impact on the advancement of innovative drug delivery systems that respond to various stimuli, ushering in a new era in pharmaceutical technology. Inspired by this, we encapsulated curcumin, a chemopreventive medication, into the gel core and further released via gel-to-sol transition induced by pH variation at 37 °C, without any alteration in structure-activity relationship. The drug release behavior was observed by UV-vis spectroscopy. Moreover, cell viability and cell invasion experiments demonstrate that the gel formulations exhibit high biocompatibility and low cytotoxicity. Among the tested formulations, 5e+Cur exhibited remarkable efficacy in controlling A549 cell migration, suggesting significant potential for applications in the pharmaceutical industry.

Multifunctional Hydrogel Enhances Inflammatory Control, Antimicrobial Activity, and Oxygenation to Promote Healing in Infectious Wounds.

Chronic infected wounds often fail to heal through normal repair mechanisms, and the persistent response of reactive oxygen species (ROS) and inflammation is a major contributing factor to the difficulty in their healing. In this context, we developed an ROS-responsive injectable hydrogel. This hydrogel is composed of ε-polylysine grafted (EPL) with caffeic acid (CA) and hyaluronic acid (HA) grafted with phenylboronic acid (PBA). Before the gelation process, a mixture CaO2@Cur-PDA (CCP) consisting of calcium peroxide (CaO2) coated with polydopamine (PDA) and curcumin (Cur) is embedded into the hydrogel. Under the conditions of chronic refractory wound environments, the hydrogel gradually dissociates. HA mimics the function of the extracellular matrix, while the released caffeic acid-grafted ε-polylysine (CE) effectively eliminates bacteria in the wound vicinity. Additionally, released CA also clears ROS and influences macrophage polarization. Subsequently, CCP further decomposes, releasing Cur, which promotes angiogenesis. This multifunctional hydrogel accelerates the repair of diabetic skin wounds infected with Staphylococcus aureus in vivo and holds promise as a candidate dressing for the healing of chronic refractory wounds.

Curcumin inhibits propofol-induced autophagy of MN9D cells via Akt/mTOR/p70S6K signaling pathway.

The rapid rise in propofol dependency and abuse has highlighted limited resources for addressing substance abuse-related cognitive impairment, prompting the development of novel therapies. Dysregulated autophagy flow accelerates neuronal cell death, and interventions countering this dysregulation offer an appealing strategy for neuronal protection. Curcumin, a potent natural polyphenol derived from turmeric rhizomes, is renowned for its robust antineurotoxic properties and enhanced cognitive function. Utilizing CCK-8 and Ki67 fluorescent staining, our study revealed that curcumin treatment increased cell viability and proliferative potential in MN9D cells exposed to propofol-induced neurotoxicity. Furthermore, enzyme-linked immunosorbent assay and western blot analysis demonstrated the partial restoration of dopamine synthesis, secretion levels, and TH expression in damaged MN9D cells treated with curcumin. Scanning electrode microscope images displayed reduced autolysosomes and phagosomes in curcumin-treated cells compared to the propofol group. Immunoblotting revealed that curcumin mitigated the degradation of LC3I to LC3II and p62 induced by propofol stimulation, with green fluorescence expression of LC3 postcurcumin treatment resembling that following autophagy inhibitor HCQ treatment, indicating that modulating autophagy flow can alleviate propofol's toxic effects. Moreover, curcumin treatment upregulated the Akt/mTOR/p70S6K signaling pathway, suggesting that curcumin potentially curtails autophagy dysregulation in nerve cells by activating Akt/mTOR/p70S6K. In conclusion, our findings suggest that curcumin can ameliorate propofol abuse-induced neurotoxicity, partially through autophagy regulation and Akt/mTOR/p70S6K signaling activation.

Curcumin relieves oxaliplatin-induced neuropathic pain via reducing inflammation and activating antioxidant response.

Oxaliplatin (OXA) has shown high effectiveness in the treatment of cancers, but its anticancer clinical effects often induce neurotoxicity leading to neuropathic pain. Oxidative damage and NLRP3 inflammasome play important roles in neuropathic pain development. Here, neuropathic pain mouse model was constructed by continuous intraperitoneal injection of OXA. OXA administration induced mechanical pain, spontaneous pain, thermal hyperalgesia and motor disability in mice. The spinal cord tissues of OXA mice exhibited the suppressed antioxidative response, the activated NLRP3 inflammasome mediated inflammatory responses, and the increased GSK-3ß activity. Next, we injected curcumin (CUR) intraperitoneally in OXA mice for seven consecutive days. CUR-treated mice showed increased mechanical pain thresholds, reduced number of spontaneous flinches, increased paw withdrawal latency, and restored latency to fall. While in the spinal cord, CUR treatment inhibited the NLRP3 inflammasome mediated inflammatory response, increased Nrf2/GPX4-mediated antioxidant responses, and decreased mitochondrial oxidative generation. Additionally, CUR combined with GSK-3ß through four covalent bonds and reduced GSK-3ß activity. In conclusion, our findings suggest that CUR treatment inhibits GSK-3ß activation, increases Nrf2 mediated antioxidant responses, inhibits oxidative damage and inflammatory reaction, and alleviates OXA-induced neuropathic pain.

Integration of Ethanol and the Immune Modulator Curcumin for Immunoablation of Hepatocellular Carcinoma.

PURPOSE: To investigate immuno-ethanol ablation using an ethanol and immune adjuvant formulation as a potent immunoablation approach that can achieve an enhanced anticancer effect in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Ethanol concentration- and exposure time-dependent cellular responses were investigated. Curcumin was combined with ethanol as an immunoablation agent. Cellular uptake of curcumin, cancer cell killing, and inflammatory markers of ethanol-curcumin treatment were characterized. To evaluate the potential in vivo anticancer immunity of ethanol-curcumin treatment, each right and left lobe of rat liver was concurrently inoculated with N1S1 HCC cells and a mixture of treated N1S1 cells (ethanol only or ethanol-curcumin) in Sprague Dawley rats (each group: 5 rats; control: nontreated N1S1 cells). Tumor growth and immune response were characterized with 7T magnetic resonance (MR) imaging, flow cytometry analysis, and immunohistology. RESULTS: An optimized ethanol-curcumin (10% ethanol and 0.5% weight/volume (w/v) curcumin solution) treatment contributed to an enhanced cellular uptake of curcumin, increased cancer cell killing, and decreased inflammatory reaction. Ethanol-curcumin-treated N1S1 cell implantation in the rat liver demonstrated N1S1 HCC tumor rejection. The secondary tumor growth by nontreated N1S1 cell inoculation was significantly suppressed at the same time. Activated anticancer immunity was evidenced by significantly increased CD8+ T cell infiltration (3.5-fold) and CD8+-to-regulatory T cell ratio (4.5-fold) in the experimental group compared with those in the control group. CONCLUSIONS: Enhanced anticancer effect of immuno-ethanol ablation could be achieved with ethanol-curcumin agent. The results underscore the importance of optimized immunoablation therapeutic procedures for enhanced therapeutic outcomes.

The effect of curcumin supplementation on circulating adiponectin and leptin concentration in adults: a GRADE-assessed systematic review and meta-analysis of randomised controlled trials.

Curcumin is a phytocompound found in the root of turmeric, a common herbal ingredient in many Asian cuisines. The compound contains anti-inflammatory activity, which is mediated through an upregulation of adiponectin and reduction of leptin. Results of randomised controlled trials (RCT) have shown that the effects of curcumin on adipokines are conflicting. Therefore, the current systematic review and meta-analysis of RCT were conducted with the aim of elucidating the role of curcumin supplementation on serum adiponectin and leptin. The search included PubMed, Embase, Cochrane Library, Scopus, Web of Science and Google Scholar from inception to August 2023. For net changes in adipokines, standardised mean differences (SMD) were calculated using random effects models. Thirteen RCT with fourteen treatment arms were eligible for inclusion in this meta-analysis. Curcumin supplementation was effective in increasing serum adiponectin (SMD = 0·86, 95 % CI (0·33, 1·39), P < 0·001; I2 = 93·1 %, P < 0·001) and reducing serum leptin (SMD = -1·42, 95 % CI (-2·29, -0·54), P < 0·001; I2 = 94·7 %, P < 0·001). In conclusion, curcumin supplementation significantly increased circulating adiponectin and decreased leptin levels in adults.

Rational design and comparison of three curcumin-based fluorescent probes for viscosity detection in living cells and zebrafish.

Viscosity is a crucial indicator of the cellular microenvironment, which can affect the normal level of cellular metabolism. Aberrant levels of viscosity can result in the emergence of a variety of physiological problems including diabetes, Parkinson's disease, inflammation, etc. Therefore, it is crucial to exploit effective assays that can detect viscosity levels in living cells and organisms. Three new nitrogen-containing heterocyclic fluorescent probes, CNO, CNN and CNNB, were designed and prepared by coupling curcumin with isoxazole, pyrazole, and phenylpyrazole rings, respectively. The fluorescence response properties of these probes to the viscosity level were analyzed in parallel. All the probes, CNO, CNN and CNNB, exhibited a significantly enhanced fluorescence response to viscosity in a broad pH range with excellent photostability, sensitivity and anti-interference ability. The sensing mechanisms of these probes for viscosity were verified by DFT calculations. In addition, these probes were successfully employed for detecting viscosity levels in living HeLa cells and zebrafish. This research compares the viscosity-responsive capabilities of curcumin-based fluorescent probes containing different nitrogen-containing heterocyclic structures, and provides a new design strategy and guidance for developing curcumin-based fluorescent probes for viscosity analysis.