Ulcerative colitis is a long-term inflammatory colon illness that significantly affects patients quality of life. Traditional medicines and therapies often come with challenges such as side effects, instability, unpredictability, and high costs. This has captured interest in natural products that have huge health benefits. Various natural compounds, including resveratrol, curcumin, quercetin, berberine, and hesperidin demonstrate immunomodulatory and oxido-inflammatory properties inside the gut epithelium, showing potential in managing ulcerative colitis. These compounds attenuate inflammatory mediators, NF-κB, and TLR4 signaling leading to a reduction in the production of inflammation-related cytokines, including TNF-α and IL-6. They also augment the activity of internal defense compounds, including superoxide radical dismutase enzyme and heme oxygenase-1, thereby alleviating oxidative damage. In addition, natural compounds have a profound effect on the endogenous microbiota and thus, support mucosal healing and intercellular barrier integrity. Both experimental and clinical analyses provide evidence that these bioactive compounds may help reduce clinical manifestations, induce and sustain remission, and improve the well-being of individuals suffering from ulcerative colitis. This review seeks to discuss various aspects of natural compounds in the management of ulcerative colitis, including mechanisms, therapeutic prospects, and hurdles, and hence the basis for future research and practice.

Curcumin has diverse biological functions, especially antioxidant and anti-inflammatory properties, but clinical trials have been hindered by its low bioavailability and pharmacokinetic properties. To achieve therapeutic efficacy, understanding curcumin's in vivo metabolism is crucial. We reviewed current research on curcumin metabolism in PubMed, Google Scholar, and CNKI. This article outlines curcumin's metabolic processes in the body via oral and intravenous injection. It suggests that upon entering the human body, curcumin may undergo oxidation, reduction, binding, and microbial community influence.

Biotransformation is recognised as a green chemistry tool to synthesise diverse natural product analogues for valorisation of their chemistry and bioactivities. It offers significant benefits compared to chemical synthesis, given its cost-effectiveness and greater selectivity. In this work, a curcumin analogue, namely gingerenone A, was yielded from the biotransformation process catalysed by Streptomyces sp. K1-18. The structure of the compound was established by using mass spectrometry/mass spectrometry chemical profiling assisted with in silico fragmentation by MetFrag tool. This biotransformation successfully afforded a reduction reaction on curcumin. This is the first report on utilisation of Streptomyces sp. K1-18 as a biocatalyst for biotransformation of curcumin.

Antipsychotic (AP) medications are the primary treatment for severe mental illnesses, including schizophrenia and severe mood disorders. APs are currently categorized into typical or first-generation APs and atypical or second-generation APs. Although both first-generation and second-generation APs are considered effective in treating psychotic symptoms in severe mental disorders, they differ in their mechanisms, treatment strategies, and side effect profiles. Because of their potential motor and metabolic side effects, which often compromise patient adherence and clinical outcomes, whether and how to use APs remains controversial. The use of dietary interventions in combination with APs is emerging as a viable strategy to reduce AP adverse effects while maintaining their efficacy and enhance patient adherence to treatment. In contrast to drugs that possess a well defined molecular mechanism of action, dietary interventions act in pleiotropic ways by nature. While providing a holistic approach to patient care this pleiotropy needs to be analyzed and systematized to enhance the efficacy and safety of the combination of them with APs. Guidelines for this type of treatment are still needed. In this review, we explore the pharmacological properties, therapeutic applications, and limitations of APs, and discuss the potential benefits and limitations of those dietary interventions that are employed to improve the efficacy and counteract side effects of APs discussing also their mechanisms of action. Finally, we critically discuss the main results of clinical studies combining APs and dietary interventions and provide a view on future directions in terms of research and clinical use of these combinations. SIGNIFICANCE STATEMENT: Antipsychotic drugs are useful in a variety of psychiatric conditions, yet their use is hampered by issues of efficacy and safety. An important step toward therapy optimization is their use in combination with dietary interventions (ie, dietary supplements and nutraceuticals) that have shown promising results in clinical trials.

Tetrahydrocurcumin (THC), a curcumin derivative, shows potential in oncology and neurology. It regulates NF-κB, reduces inflammation, promotes cancer cell apoptosis, inhibits tumor angiogenesis, and enhances antioxidants, aiding in treating inflammation-related cancers. In neurology, THC's anti-inflammatory and antioxidant properties protect neurons, reduce neuroinflammation, and support autophagy for cellular debris clearance, with its blood-brain barrier penetration offering a neuroprotective edge. Research on THC's therapeutic application must focus on improving delivery and bioavailability and confirming its clinical safety and efficacy.

Hexahydrocurcumin (HHC), the primary metabolite of curcumin, shows promising therapeutic potential due to its antioxidant and anti-inflammatory properties. The retinal pigment epithelium (RPE) plays a crucial role in maintaining retinal homeostasis; however, its dysfunction-linked to oxidative stress and chronic inflammation-contributes to the progression of degenerative diseases such as age-related macular degeneration (AMD). This review highlights the therapeutic potential of HHC in protecting and regenerating RPE cells. It explores the effects of oxidative stress on the RPE, the mechanisms underlying its damage, and the involvement of reactive oxygen species (ROS) and inflammatory mediators. HHC has demonstrated the ability to modulate these pathways by activating nuclear factor erythroid 2-related factor 2 (NRF2), enhancing antioxidant defenses, and inhibiting pro-inflammatory cytokine production. Preclinical studies suggest that HHC mitigates vascular remodeling and endothelial dysfunction by reducing the expression of transforming growth factor β (TGF-β1) and matrix metalloproteinase-9 (MMP-9). Moreover, HHC improves nitric oxide bioavailability and promotes nitric oxide synthase expression, thereby counteracting oxidative stress-induced vascular damage. Emerging evidence indicates that HHC may be a promising candidate for the treatment of retinal degenerative diseases, particularly those associated with oxidative stress and inflammation. However, further studies, including clinical trials, are essential to confirm its efficacy and elucidate the precise mechanisms underlying HHC's protective effects on RPE cells.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Conventional treatments such as chemotherapy and radiotherapy are often associated with severe side effects and limited effectiveness. Curcumin, a polyphenol derived from Curcuma longa, has demonstrated anti-inflammatory and anticancer properties. A systematic review of the recent scientific literature followed PRISMA guidelines to evaluate the benefits of a curcumin-enriched diet for adults with colorectal cancer. Articles published between 2018 and 2024 were retrieved from PubMed, SciELO, Google Scholar, and Scopus. Studies meeting the inclusion criteria focused on curcumin, adults, and colorectal cancer outcomes. The administration of curcumin-containing products was associated with improved survival rates, enhanced quality of life, tumor reduction, and anti-inflammatory effects. A curcumin-enriched diet shows potential as an effective adjunct therapy for CRC patients, though its limited bioavailability and potential side effects, such as gastrointestinal discomfort, pose challenges. Addressing these limitations through larger cohorts, extended study durations, and improved formulations to enhance bioavailability is essential. Such efforts could enable the development of personalized dietary recommendations for CRC management.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are targeted for designing drugs against cognitive dysfunction. Curcumin (CUR) and indole-3-propionic acid (IPA) are known for their neuroprotective activity. The clinical application of CUR is hindered due to poor absorption and bioavailability. Hence, CUR was conjugated with IPA to form the CUR-IPA diester. CUR-IPA inhibition against electric eel AChE (eAChE), human AChE (hAChE), and hBChE was carried out. In silico and molecular dynamics (MD) analyses of the interaction of CUR-IPA with hAChE and hBChE were done. UV-visible spectroscopy (λmax at 415 and 276 nm), NMR spectrum, and ESI/MS/MS [m/z = 711 (M + H)] confirmed CUR-IPA formation. CUR-IPA showed in vitro antioxidant activity. The IC50 values of eAChE, hAChE, and hBChE enzyme inhibition were 5.66, 59.30, and 60.66 μM, respectively. MD simulation-based analysis such as RMSD, RMSF, free-energy calculation, PCA, FEL, and DCCM confirmed the stable binding of CUR-IPA with hAChE and hBChE. Further QM/MM analysis confirmed the stable interaction of CUR-IPA with hAChE and hBChE. Since CUR-IPA showed in vitro inhibition against AChE and BChE, a further neuroprotective effect in in vivo could be studied.

Aquatic animals inhabiting marine coastal environments are highly susceptible to environmental fluctuations and pollution, exemplified by widespread mass mortalities induced by marine bacteria or viruses. Enhancing antioxidant defenses presents a promising strategy to mitigate such environmental stressors. We postulated that supplementation of oysters with natural compounds such as flavonoids, exemplified by curcumin (CUR), could effectively bolster their antioxidant protection. Adult Pacific oysters were supplemented with CUR (30 μM) in seawater for 2, 4, 8, and 16 days. CUR metabolites progressively accumulated in gills, mantle, and digestive glands. Notably, oyster antioxidant response was significantly augmented, as evidenced by elevated glutathione (GSH) levels, and enhanced activities of glutathione reductase (GR), thioredoxin reductase (TrxR), and glutathione S-transferase (GST) after 4, 8, and 16 days of CUR supplementation. This response was tissue-specific, with the most pronounced increase in gills, followed by mantle, whereas digestive gland exhibited minimal response. After being supplemented with CUR for 8 days, oysters were subjected to antioxidant-disrupting agents such as N-ethylmaleimide (NEM), 1‑chloro-2,4-dinitrobenzene (CDNB). Both chemicals reduced antioxidant protection in untreated animals. However, CUR supplementation prevented these redox-disrupting effects, suggesting the potential ability of CUR to counteract antioxidant stressors. The effects of 8 days of CUR supplementation were also tested against the lethal effects of the pathogens V. tapetis, V, alginolyticus, and V. anguillarum, but CUR failed to induce immunological protection. The antioxidant protection induced by CUR holds promise for application in aquaculture to bolster animal health and resilience against abiotic stressors. Further research is needed to investigate the long-term impact of CUR supplementation and its role against biotic stressors, such as bacterial and viral infections.

p53 is a critical tumor suppressor protein responsible for regulating the cell cycle and inducing apoptosis. Mutations in the p53 gene, particularly in the DNA-binding domain, are frequently associated with various cancers due to the loss of transcriptional activity. Curcumin and its derivatives have demonstrated potential as p53 enhancers and reactivators of mutant p53. This study employs in silico methods to evaluate the potential of curcumin derivatives to enhance wild-type p53 expression and restore the function of the p53 mutant R273H.

Curcumin and 20 derivatives were selected from PubChem for computational analysis. Their potential as p53 enhancers was assessed using Quantitative Structure-Activity Relationship (QSAR) analysis. Molecular docking was conducted to determine their binding affinities with wild-type and mutant p53 proteins, followed by molecular dynamics (MD) simulations to evaluate ligand-receptor stability. Pharmacokinetics and toxicity assessments were performed using predictive computational models to evaluate their drug-like properties.

QSAR analysis identified hexahydrocurcumin (probable activity [Pa]: 0.837) and tetrahydrocurcumin (Pa: 0.752) as the most potent p53 enhancers. Molecular docking revealed strong binding affinities for curcumin derivatives at key p53 binding residues, particularly through hydrogen bonds with His 273 of the R273H mutant. MD simulations demonstrated that curcumin, bisdemethoxycurcumin, and monodemethylcurcumin stabilized p53 mutant R273H, closely mimicking the structural stability of wild-type p53. Pharmacokinetic analysis indicated favorable absorption, distribution, metabolism, and excretion profiles for most derivatives, with low toxicity predicted for the majority.

Curcumin and its derivatives exhibit dual functions as p53 enhancers and reactivators of the p53 mutant R273H. Hexahydrocurcumin and tetrahydrocurcumin emerged as promising compounds with strong bioactivity and favorable pharmacokinetic properties, suggesting their potential as anticancer agents. Further in vitro and in vivo studies are necessary to validate these findings and explore their therapeutic applications.

Curcuminoids, including curcumin and its derivatives, show potent inhibition of aromatase (CYP19A1), crucial for estradiol synthesis and breast cancer metastasis. Our study evaluated the efficacy and mechanism of 10 curcuminoids and their metabolites against human and rat CYP19A1 using placental microsomes, revealing species-specific IC50 values. Cyclocurcumin (IC50, 4.43 μM) and curcumin (IC50, 3.49 μM) were the most effective inhibitors for human and rat CYP19A1, respectively. These compounds acted as mixed or competitive inhibitors, reducing estradiol production in human BeWo cells. Docking analysis showed that curcuminoids interact with CYP19A1 active site, forming a hydrogen bond with Met374. 3D-QSAR analysis highlighted the importance of hydrogen bonding in inhibition. A negative correlation was observed between the pKa values and IC50 values for human CYP19A1. A positive correlation was observed between the lowest binding energy and IC50 values for human CYP19A1. These findings underscore the potential of curcuminoids as therapeutic agents against breast cancer.

Curcumin, a bioactive compound derived from the rhizome of Curcuma longa L., has garnered significant attention for its potent anticancer properties. Despite its promising therapeutic potential, its poor bioavailability, rapid metabolism, and low water solubility hinder curcumin's clinical application. Nanotechnology offers a viable solution to these challenges by enabling the development of curcumin-based nanoparticles (CNPs) that enhance its bioavailability and therapeutic efficacy. This review provides a comprehensive overview of the recent advancements in the design and synthesis of CNPs for cancer therapy. We discuss various NP formulations, including polymeric, lipid-based, and inorganic nanoparticles, highlighting their role in improving curcumin's pharmacokinetic and pharmacodynamic profiles. The mechanisms by which CNPs exert anticancer effects, such as inducing apoptosis, inhibiting cell proliferation, and modulating signaling pathways, are explored in details. Furthermore, we examine the preclinical and clinical studies that have demonstrated the efficacy of CNPs in treating different types of tumors, including breast, colorectal, and pancreatic cancers. Finally, the review addresses the current challenges and future perspectives in the clinical translation of CNPs, emphasizing the need for further research to optimize their design for targeted delivery and to enhance their therapeutic outcomes. By synthesizing the latest research, this review underscores the potential of CNPs as a promising avenue for advancing cancer therapy.

Chronic pain remains a treatment challenge. Curcumin, a natural plant product found in the Curcuma genus, has been shown to possess anti-inflammatory, antioxidant, and neuroprotective properties. In this systematic review and meta-analysis, we aimed to evaluate the efficacy of curcumin and nano-curcumin for treating chronic pain in clinical and preclinical studies. A systematic search was performed through PubMed, SCOPUS, Web of Science Core Collection, Cochrane, and Google Scholar up to April 1, 2023, using relevant keywords. Trials that met the inclusion criteria were included in this study. We applied the mean difference (MD) or standardized mean difference (SMD) in random or fixed-effects models to analyze the impact of combined trials. We also evaluated the potential risk of bias using the Higgins method for clinical studies and the SYRCLE Risk of Bias tool for animal studies. Our meta-analysis included 59 studies, comprising 29 animal studies and 30 clinical studies. Curcumin strongly reduced pain in preclinical studies, and both the intraperitoneal (SMD = 1.48; 95% CI, 0.81 to 2.14; p < 0.001, and I2 = 77.9%) and oral (SMD = 1.27; 95% CI, 1.01 to 1.55; p < 0.001, and I2 = 0.0%) administration method of curcumin had pain-relieving effects. However, the subcutaneous method (SMD = 0.24; 95% CI, - 0.89 to 1.38; p = 0.67) had no effect. The drug's efficacy within the 100-250 mg range (SMD = 1.46; 95% CI, 0.76 to 2.15; p < 0.001; and I2 = 73.4%) surpassed that observed above 250 mg (SMD = 1.23; 95% CI, 0.89 to 1.57; p < 0.001; and I2 = 0.0%). In clinical studies, nano-curcumin had a powerful effect on pain reduction compared to placebo (MD =  - 1.197; CI 95% (- 1.94 to - 0.45); p = 0.002; and I2 = 80.9%), and the effects of NSAIDs on pain were not significantly altered when used in combination with Curcuma longa extract (MD =  - 0.23; CI 95% (- 0.99 to 0.53); p = 0.554; and I2 = 92%). In addition, the effect of increased bioavailability of curcumin (MD =  - 1.54; CI 95% (- 2.06 to - 1.02); p < 0.001; and I2 = 89.6%), curcumin (MD =  - 1.35; CI 95% (- 2.451 to - 0.252); p = 0.016; and I2 = 90.8%), and nano-curcumin was greater than placebo. Our meta-analysis suggests that curcumin and nano-curcumin are effective in reducing chronic pain. These findings have important implications for pharmaceutical science and may lead to the development of new treatments for chronic pain. However, further research is needed to confirm these findings.

Introduction Emerging evidence suggests an association between obesity and Functional Gastrointestinal Disorders (FGIDs). Childhood obesity and FGIDs share many common features, such as high prevalence in the pediatric population, risk factors related to diet and lifestyle, gut microbiota impairments, and psychological distress. This narrative review aims to summarize the main evidence regarding FGIDs in childhood obesity, with a specific focus on the role of diet and its impact on the microbiota. Additionally, the review highlights potential common-ground solutions for preventing and managing both obesity and FGIDs. Methods A comprehensive PubMed search was conducted. Keywords used included terms related to children and adolescents, obesity, functional gastrointestinal disorders, and microbiota. Results The review emphasizes the importance of holistic, multidisciplinary approaches to managing symptoms. In addition to nutrition education, physical activity, and medical care, complementary strategies such as psychological interventions and personalized dietary modifications (e.g., low-FODMAP and fiber-enriched diets) are critical. Given the interplay between gut microbiota alterations, obesity, and FGIDs, microbiota modulation through probiotics, prebiotics, and integrative support shows significant promise. However, the variability in current evidence underlines the need for robust longitudinal studies to develop standardized protocols and maximize treatment efficacy. Conclusions Bridging gaps in knowledge and practice with an integrated, evidence-based framework could improve patient outcomes and deepen understanding of the complex relationship between metabolic and gastrointestinal health in children and adolescents.

Curcumin might exert its therapeutic effects by interacting with gut microbiota. However, the role of gut microbiota in curcumin metabolism in vivo remains poorly understood. To address this, we used antibiotics to deplete gut microbiota and compared curcumin metabolism in control and antibiotic-treated mice. Using Q-TOF and triple quadrupole mass spectrometry, we identified and quantified curcumin metabolites, revealing distinct metabolic pathways in these two mice groups. The novel metabolites, hexahydro-dimethyl-curcumin and hexahydro-didemethyl-curcumin were exclusively derived from gut microbiota. Additionally, gut bacteria deconjugated curcumin metabolites back into their bioactive forms. Moreover, control mice exhibited significantly lower curcumin degradation, suggesting a protective role of gut microbiota against degradation. In conclusion, our results indicated that gut microbiota might enhance the effectiveness of curcumin by deconjugation, production of active metabolites, and protection against degradation in the large intestine. This study enhances our understanding of the interactions between curcumin and gut microbiota.

Finding environmentally friendly, effective and residue-free alternatives to antibiotics has become a research priority. This is due to the ban on antibiotics in animal feed. Curcumin is a polyphenol extracted from the rhizome of turmeric that has antioxidant, anti-inflammatory and immunomodulatory properties. Curcumin has been widely demonstrated as a traditional flavoured agent and herbal medicine in the fight against diseases. In recent years, curcumin has been extensively studied in animal production, especially in poultry production. This article reviews the source, structure, metabolism and biological functions of curcumin and focuses on the application of curcumin in poultry production. In terms of production performance, curcumin can improve the growth performance of poultry, increase the egg production rate of laying hens and alleviate the negative effects of heat stress on the production performance of poultry and livestock. In terms of meat quality, curcumin can improve poultry meat quality by regulating lipid metabolism and antioxidant capacity. In terms of health, curcumin can improve immunity. Since mycotoxins have been a major problem in poultry production, this article also reviews the role of curcumin in helping poultry resist toxins. It is hoped that the review in this article can provide a concrete theoretical basis and research ideas for the research and application of curcumin in the field of poultry.

Curcumin is widely recognized for its health benefits, though the role of gut microbiota in its metabolic transformation was not well studied. In this study, bacterial strains capable of metabolizing curcumin were isolated from human stool samples. Using 16S rRNA and whole-genome sequencing, two novel strains (Clostridium butyricum UMA_cur1 and Escherichia coli UMA_cur2) were identified. In addition, the metabolic products were analyzed using liquid chromatography-mass spectrometry. These strains efficiently converted curcumin into dihydro-curcumin (DHC) and tetrahydro-curcumin (THC). Notably, E. coli UMA_cur2 also produced hexahydro-curcumin (HHC) and octahydro-curcumin (OHC), marking the first identification of a strain capable of such transformations. The absence of the YncB gene (typically involved in curcumin conversion) in C. butyricum UMA_cur1 suggests an alternative metabolic pathway. Curcumin metabolism begins during the stationary growth phase, indicating that it is not crucial for primary growth functions. Furthermore, E. coli UMA_cur2 produced these metabolites sequentially, starting with DHC and THC and progressing to HHC and OHC. These findings identified two novel strains that can metabolize curcumin to hydrogenated metabolites, which enhance our understanding of the interaction between curcumin and gut microbiota.

In parallel with population aging, the prevalence of neurological and neurodegenerative diseases has been dramatically increasing over the past few decades. Neurodegenerative diseases reduce the quality of life of patients and impose a high cost on the health system. These slowly progressive diseases can cause functional, perceptual, and behavioral deficits in patients. Therefore, neurodegenerative impairments have always been an interesting subject for scientists and clinicians. One of these diseases is spinal cord injury (SCI). SCI can lead to irreversible damage and is classified into two main subtypes: traumatic and non-traumatic, each with very different pathophysiological features.

This review aims to gather relevant information about the beneficial effects of curcumin (Cur), with specific emphasis on its anti-inflammatory properties towards spinal cord injury (SCI) patients.

The review collates data from extensive in-vitro, in-vivo, and clinical trials documenting the effects of CUR on SCI. It examines the modulation of pathophysiological pathways and regulation of the inflammatory cascades after CUR administration.

Various pathophysiological processes involving the nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-kB), and transforming growth factor beta (TGF-β) signaling pathways have been suggested to exacerbate damages resulting from SCI. CUR administration showed to modulate these signaling pathways which lead to attenuation of SCI complications.

Anti-inflammatory compounds, particularly CUR, can modulate these pathophysiological pathways and regulate the inflammatory cascades. CUR, a well-known natural product with significant anti-inflammatory effects, has been extensively documented in experimental and clinical trials.

Curcumin's potential to alter key steps in the Nrf2, NF-kB, and TGF-β signaling pathways suggests that it may play a role in attenuating SCI complications.

Natural photosensitizers (PS) are compounds derived from nature, with photodynamic properties. Natural PSs have a similar action to that of commercial PSs, where cancer cell death occurs by necrosis, apoptosis, and autophagy through ROS generation. Natural PSs have garnered great interest over the last few decades because of their high biocompatibility and good photoactivity. Specific wavelengths could cause phytochemicals to produce harmful ROS for photodynamic therapy (PDT). However, natural PSs have some shortcomings, such as reduced solubility and lower uptake, making them less appropriate for PDT. Nanotechnology offers an opportunity to develop suitable carriers for various natural PSs for PDT applications. Various nanoparticles have been developed to improve the outcome with enhanced solubility, optical adsorption, and tumor targeting. Multidrug resistance (MDR) is a phenomenon in which tumor cells develop resistance to a wide range of structurally and functionally unrelated drugs. Over the last decade, several researchers have extensively studied the effect of natural PS-based photodynamic treatment (PDT) on MDR cells. Though the outcomes of clinical trials for natural PSs were inconclusive, significant advancement is still required before PSs can be used as a PDT agent for treating MDR tumors. This review addresses the increasing literature on MDR tumor progression and the efficacy of PDT, emphasizing the importance of developing new nano-based natural PSs in the fight against MDR that have the required features for an MDR tumor photosensitizing regimen.

Turmeric is a spice widely used in China, Southeast Asia, and in traditional Ayurvedic medicine. Its safety profile and efficacy as an antioxidant, anti-inflammatory, antimicrobial, antitumor, antidiabetic, and anti-obesity agent have led to extensive research into its potential role in preventing and treating metabolic diseases. The active compound in turmeric is curcumin, which exhibits low systemic bioavailability after oral administration. However, it is detectable in the gut, where it bidirectionally interacts with the gut microbiota (GM), which plays a crucial role in maintaining host health. The favorable effects of curcumin, particularly its hypoglycemic properties, are linked to alteration in intestinal dysbiosis observed in type 2 diabetes mellitus and metabolic syndrome patients. Restoration of the eubiotic GM may contribute to glycemic homeostasis. Preclinical and clinical studies have demonstrated the involvement of the GM in the regulation of glucose and lipid metabolism. Although the underlying mechanism remains incompletely understood, intestinal dysbiosis is associated with insulin resistance, hyperglycemia, and low-grade inflammation. In the present overview, we summarize the biological properties of curcumin, focusing on its link with GM and, therefore, on its potential role in metabolic diseases.

In recent decades, natural compounds derived from herbal medicine or dietary sources have played important roles in prevention and treatment of various diseases and have attracted more and more attention. Curcumin, extracted from the Curcumae Longae Rhizoma and widely used as food spice and coloring agent, has been proven to possess high pharmacological value. However, the pharmacological application of curcumin is limited due to its poor systemic bioavailability. As a major active metabolite of curcumin, tetrahydrocurcumin (THC) has higher bioavailability and stability than curcumin. Increasing evidence confirmed that THC had a wide range of biological activities and significant treatment effects on diseases. In this paper, we reviewed the research progress on the biological activities and therapeutic potential of THC on different diseases such as neurological disorders, metabolic syndromes, cancers, and inflammatory diseases. The extensive pharmacological effects of THC involve the modulation of various signaling transduction pathways including MAPK, JAK/STAT, NF-κB, Nrf2, PI3K/Akt/mTOR, AMPK, Wnt/β-catenin. In addition, the pharmacokinetics, drug combination and toxicology of THC were discussed, thus providing scientific basis for the safe application of THC and the development of its dietary supplements and drugs.

Curcumin, a polyphenol derived from Curcuma longa, used as a dietary spice, has garnered attention for its therapeutic potential, including antioxidant, anti-inflammatory, and antimicrobial properties. Despite its known benefits, the precise mechanisms underlying curcumin's effects on consumers remain unclear. To address this gap, we employed the genetic model Drosophila melanogaster and leveraged two omics tools-transcriptomics and metabolomics. Our investigation revealed alterations in 1043 genes and 73 metabolites upon supplementing curcumin into the diet. Notably, we observed genetic modulation in pathways related to antioxidants, carbohydrates, and lipids, as well as genes associated with gustatory perception and reproductive processes. Metabolites implicated in carbohydrate metabolism, amino acid biosynthesis, and biomarkers linked to the prevention of neurodegenerative diseases such as schizophrenia, Alzheimer's, and aging were also identified. The study highlighted a strong correlation between the curcumin diet, antioxidant mechanisms, and amino acid metabolism. Conversely, a lower correlation was observed between carbohydrate metabolism and cholesterol biosynthesis. This research highlights the impact of curcumin on the diet, influencing perception, fertility, and molecular wellness. Furthermore, it directs future studies toward a more focused exploration of the specific effects of curcumin consumption.

The golden spice turmeric with its main bioactive component curcumin is one of the most popular and extensively studied nutraceuticals. Despite numerous pre-clinical studies reporting positive pharmacodynamics of turmeric extracts and curcumin, the main issues in translating the pharmacological effects to clinical efficacy have been to overcome its poor pharmacokinetics and to deliver significant amounts of the biologically relevant forms of the actives to various tissues. This review is aimed at providing a first critical evaluation of the current published literature with the novel curcumagalactomannoside (CGM) formulation of curcumin using fenugreek galactomannan dietary fibre, specifically designed to address curcumin poor pharmacokinetics. We describe CGM and its technology as a food-grade formulation to deliver 'free' unconjugated curcuminoids with enhanced bioavailability and improved pharmacokinetic properties. The therapeutic relevance of improving bioavailability of 'free' curcuminoids and some of the technical challenges in the measurement of the 'free' form of curcuminoids in plasma and tissues are also discussed. A total of twenty-six manuscripts are reviewed here, including fourteen pre-clinical and twelve clinical studies that have investigated CGM pharmacokinetics, safety and efficacy in various animal models and human conditions. Overall current scientific evidence suggests CGM formulation has improved bioavailability and tissue distribution of the biologically relevant unconjugated forms of turmeric actives called 'free' curcuminoids that may be responsible for the superior clinical outcomes reported with CGM treatments in comparison with unformulated standard curcumin across multiple studies.

Curcumin, an extensively utilized natural pigment in the food industry, has attracted considerable attention due to its potential therapeutic effects, such as anti-tumorigenic and anti-inflammatory activities. The enzyme 17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) holds a crucial position in oestradiol production and exhibits significant involvement in oestrogen-responsive breast cancers and endometriosis. This study investigated the inhibitory effects of curcuminoids, metabolites, and analogues on 17β-HSD1, a key enzyme in oestradiol synthesis. Screening 10 compounds, including demethoxycurcumin (IC50, 3.97 μM) and dihydrocurcumin (IC50, 5.84 μM), against human and rat 17β-HSD1 revealed varying inhibitory potencies. These compounds suppressed oestradiol secretion in human BeWo cells at ≥ 5-10 μM. 3D-Quantitative structure-activity relationship (3D-QSAR) and molecular docking analyses elucidated the interaction mechanisms. Docking studies and Gromacs simulations suggested competitive or mixed binding to the steroid or NADPH/steroid binding sites of 17β-HSD1. Predictive 3D-QSAR models highlighted the importance of hydrophobic regions and hydrogen bonding in inhibiting 17β-HSD1 activity. In conclusion, this study provides valuable insights into the inhibitory effects and mode of action of curcuminoids, metabolites, and analogues on 17β-HSD1, which may have implications in the field of hormone-related disorders.

Diabetes mellitus (DM) is a collection of metabolic disorder that is characterized by chronic hyperglycemia. Recent studies have demonstrated the crucial involvement of oxidative stress (OS) and inflammatory reactions in the development of DM. Curcumin (CUR), a natural compound derived from turmeric, exerts beneficial effects on diabetes mellitus through its interaction with the nuclear factor kappa B (NF-κB) pathway. Research indicates that CUR targets inflammatory mediators in diabetes, including tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), by modulating the NF-κB signaling pathway. By reducing the expression of these inflammatory factors, CUR demonstrates protective effects in DM by improving pancreatic β-cells function, normalizing inflammatory cytokines, reducing OS and enhancing insulin sensitivity. The findings reveal that CUR administration effectively lowered blood glucose elevation, reinstated diminished serum insulin levels, and enhanced body weight in Streptozotocin -induced diabetic rats. CUR exerts its beneficial effects in management of diabetic complications through regulation of signaling pathways, such as calcium-calmodulin (CaM)-dependent protein kinase II (CaMKII), peroxisome proliferator-activated receptor gamma (PPAR-γ), NF-κB, and transforming growth factor β1 (TGFB1). Moreover, CUR reversed the heightened expression of inflammatory cytokines (TNF-α, Interleukin-1 beta (IL-1β), IL-6) and chemokines like MCP-1 in diabetic specimens, vindicating its anti-inflammatory potency in counteracting hyperglycemia-induced alterations. CUR diminishes OS, avert structural kidney damage linked to diabetic nephropathy, and suppress NF-κB activity. Furthermore, CUR exhibited a protective effect against diabetic cardiomyopathy, lung injury, and diabetic gastroparesis. Conclusively, the study posits that CUR could potentially offer therapeutic benefits in relieving diabetic complications through its influence on the NF-κB pathway.

Oral cancer is the 16th most common malignant tumor worldwide. The risk of recurrence and mortality is high, and the survival rate is low over the following five years. Recent studies have shown that curcumin causes apoptosis in tumor cells by affecting FoF1-ATP synthase (ATP synthase) activity, which, in turn, hinders cell energy production, leading to a loss of cell viability. Additionally, irradiation of curcumin within cells can intensify its detrimental effects on cancer cell viability and proliferation (photodynamic therapy). We treated the OHSU-974 cell line, a model for human head and neck squamous cell carcinoma (HNSCC), and primary human fibroblasts. The treatment involved a 1 h exposure of cells to 0.1, 1.0, and 10 μM curcumin, followed or not by irradiation or the addition of the same concentration of pre-irradiated curcumin. Both instances involved a diode laser with a wavelength of 450 nm (0.25 W, 15 J, 60 s, 1 cm2, continuous wave mode). The treatment with non-irradiated 1 and 10 µM curcumin caused ATP synthase inhibition and a consequent reduction in the oxygen consumption rate (OCR) and the ATP/AMP ratio, which was associated with a decrement in lipid peroxidation accumulation and a slight increase in glutathione reductase and catalase activity. By contrast, 60 s curcumin irradiation with 0.25 W-450 nm caused a further oxidative phosphorylation (OxPhos) metabolism impairment that induced an uncoupling between respiration and energy production, leading to increased oxidative damage, a cellular growth and viability reduction, and a cell cycle block in the G1 phase. These effects appeared to be more evident when the curcumin was irradiated after cell incubation. Since cells belonging to the HNSCC microenvironment support tumor development, curcumin's effects have been analyzed on primary human fibroblasts, and a decrease in cell energy status has been observed with both irradiated and non-irradiated curcumin and an increase in oxidative lipid damage and a slowing of cell growth were observed when the curcumin was irradiated before or after cellular administration. Thus, although curcumin displays an anti-cancer role on OHSU-974 in its native form, photoactivation seems to enhance its effects, making it effective even at low dosages.

To assess the efficacy of curcuminoids (curcumin, demethoxycurcumin, bisdemethoxycurcumin [BDC]) and their analogs (tetrahydrocurcumin [THC], tetrahydrodemethoxycurcumin [THDC], tetrahydrobisdemethoxycurcumin) in reducing inflammatory cytokines and their toxicity to primary human corneal limbal epithelial cells, these cells were cultured and exposed to these compounds.

The PrestoBlue assay assessed cell viability after treatment. Anti-inflammatory effects on hyperosmotic cells were determined using real-time polymerase chain reaction and significance was gauged using one-way analysis of variance and Tukey's tests, considering p-values < 0.05 as significant.

Curcuminoids and their analogs, at 1, 10, and 100 µM, exhibited no effect on cell viability compared to controls. However, cyclosporin A 1:500 significantly reduced cell viability more than most curcuminoid treatments, except 100 µM curcumin and BDC. All tested curcuminoids and analogs at these concentrations significantly decreased mRNA expression levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-17 A, matrix metallopeptidase-9, and intercellular adhesion molecule-1 after 90 mM NaCl stimulation compared to untreated cells. Furthermore, proinflammatory cytokine levels from hyperosmotic cells treated with 1, 10, and 100 µM curcumin, 100 µM BDC, 100 µM THC, 1 and 100 µM THDC mirrored those treated with cyclosporin A 1:500.

The anti-inflammatory efficiency of 1 and 10 µM curcumin, 100 µM THC, 1 and 100 µM THDC was comparable to that of cyclosporin A 1:500 while maintaining cell viability.

Curcuminoids have many pharmacological effects. They or their metabolites may have side effects by suppressing 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3). Herein, we investigated the inhibition of curcuminoids and their metabolites on human and rat 17β-HSD3 and analyzed their structure-activity relationship (SAR) and performed in silico docking. Curcuminoids and their metabolites ranked in terms of IC50 values against human 17β-HSD3 were bisdemethoxycurcumin (0.61 μM) > curcumin (8.63 μM) > demethoxycurcumin (9.59 μM) > tetrahydrocurcumin (22.04 μM) > cyclocurcumin (29.14 μM), and those against rat 17β-HSD3 were bisdemethoxycurcumin (3.94 μM) > demethoxycurcumin (4.98 μM) > curcumin (9.62 μM) > tetrahydrocurcumin (45.82 μM) > cyclocurcumin (143.5 μM). The aforementioned chemicals were mixed inhibitors for both enzymes. Molecular docking analysis revealed that they bind to the domain between the androstenedione and NADPH active sites of 17β-HSD3. Bivariate correlation analysis showed a positive correlation between LogP and pKa of curcumin derivatives with their IC50 values. Additionally, a 3D-QSAR analysis revealed that a pharmacophore model consisting of three hydrogen bond acceptor regions and one hydrogen bond donor region provided a better fit for bisdemethoxycurcumin compared to curcumin. In conclusion, curcuminoids and their metabolites possess the ability to inhibit androgen biosynthesis by directly targeting human and rat 17β-HSD3. The inhibitory strength of these compounds is influenced by their lipophilicity and ionization characteristics.

The number of elderly people is projected to double in the next 50 years worldwide, resulting in an increased prevalence of neurodegenerative diseases. Aging causes changes in brain tissue homeostasis, thus contributing to the development of neurodegenerative disorders. Current treatments are not entirely effective, so alternative treatments or adjuvant agents are being actively sought. Antioxidant properties of phenolic compounds are of particular interest for neurodegenerative diseases whose psychopathological mechanisms strongly rely on oxidative stress at the brain level. Moreover, phenolic compounds display other advantages such as the permeability of the blood-brain barrier (BBB) and the interesting molecular mechanisms that we reviewed in this work. We began by briefly outlining the physiopathology of neurodegenerative diseases to understand the mechanisms that result in irreversible brain damage, then we provided an overall classification of the phenolic compounds that would be addressed later. We reviewed in vitro and in vivo studies, as well as some clinical trials in which neuroprotective mechanisms were demonstrated in models of different neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), ischemia, and traumatic brain injury (TBI).

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.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multifactorial condition characterized by insulin resistance, oxidative stress, chronic low-grade inflammation, and sometimes fibrosis. To date, no effective pharmacological therapy has been approved for the treatment of metabolic-associated steatohepatitis (MASH), the progressive form of MASLD. Recently, numerous in vitro and in vivo studies have described the efficacy of nutraceutical compounds in the diet has been tested. Among them, curcumin is the most widely used polyphenol in the diet showing potent anti-inflammatory and antifibrotic activities. This review aims to summarize the most important basic studies (in vitro and animal models studies), describing the molecular mechanisms by which curcumin acts in the context of MASLD, providing the rationale for its effective translational use in humans.

Curcuminoids are functional food additives, and the effect on gonadal hormone biosynthesis remains unclear. Gonads contain 3β-hydroxysteroid dehydrogenase isoforms, h3β-HSD2 (humans) and r3β-HSD1 (rats), which catalyse pregnenolone into progesterone. The potency and mechanisms of curcuminoids to inhibit 3β-HSD activity were explored. The inhibitory potency was bisdemethoxycurcumin (IC₅₀, 1.68 µM) >demethoxycurcumin (3.27 µM) > curcumin (13.87 µM) > tetrahydrocurcumin (109.0 µM) > dihydrocurcumin and octahydrocurcumin on KGN cell h3β-HSD2, while that was bisdemethoxycurcumin (1.22 µM) >demethoxycurcumin (2.18 µM) > curcumin (4.12 µM) > tetrahydrocurcumin (102.61 µM) > dihydrocurcumin and octahydrocurcumin on testicular r3β-HSD1. All curcuminoids inhibited progesterone secretion by KGN cells under basal and forskolin-stimulated conditions at >10 µM. Docking analysis showed that curcuminoids bind steroid-active site with mixed or competitive mode. In conclusion, curcuminoids inhibit gonadal 3β-HSD activity and de-methoxylation of curcumin increases inhibitory potency and metabolism of curcumin by saturation of carbon chain losses inhibitory potency.

Oral cancer is one of the leading causes of death worldwide. Oral precancerous lesions (OPL) are the precursors of oral cancer, with varying degrees of progression. Tetrahydrocurcumin (THC) is a major metabolite of curcumin with superior anticancer properties against various types of cancer. However, THC's clinical outcome is limited by its poor aqueous solubility. Herein, we developed novel mucoadhesive biopolymer-based composite sponges for buccal delivery of THC, exploiting nanotechnology and mucoadhesion for efficient prevention and treatment of oral cancer. Firstly, THC-nanocrystals (THC-NC) were formulated and characterized for subsequent loading into mucoadhesive composite sponges. The anticancer activity of THC-NC was assessed on a human tongue squamous carcinoma cell line (SCC-4). Finally, the chemopreventive activity of THC-NC loaded sponges (THC-NC-S) was examined in DMBA-induced hamster OPL. The selected THC-NC exhibited a particle size of 532.68 ± 13.20 nm and a zeta potential of -46.08 ± 1.12 mV. Moreover, THC-NC enhanced the anticancer effect against SCC-4 with an IC50 value of 80 µg/mL. THC-NC-S exhibited good mucoadhesion properties (0.24 ± 0.02 N) with sustained drug release, where 90% of THC was released over 4 days. Furthermore, THC-NC-S had a magnificent potential for maintaining high chemopreventive activity, as demonstrated by significant regression in the dysplasia degree and a decline in cyclin D1 (control: 40.4 ± 12.5, THC-NC-S: 12.07 ± 5.2), culminating in significant amelioration after 25 days of treatment. Conclusively, novel THC-NC-S represent a promising platform for local therapy of OPL, preventing their malignant transformation into cancer.

The health benefits of curcumin have been demonstrated by several clinical studies, but its low bioavailability compromises its functionality. In this regard, emulsions have proven to be effective encapsulation systems for curcumin. Nevertheless, emulsions with a high oil content (50%) may offer some advantages due to the large amount of compound they can incorporate. Therefore, the aim of this work was to study the pharmacokinetics and biodistribution of curcumin when carried in optimized emulsions containing 50% MCT oil and a plant-based emulsifier (soybean lecithin) at 2 h or 4 h post-oral administration to rats. The most stable emulsion was obtained using 50% of oil and a surfactant-oil-ratio 0.1, through a microfluidization process. After the oral administration of the systems (150 mg curcumin/kg body weight), curcumin glucuronide was the main compound present in plasma (AUC0-t = 1556.3 ng·h·ml-1), especially at 2-4 h post-administration. The total curcuminoid bioavailability was increased by 10.6-fold when rats were fed with the curcumin emulsion rather than with a control suspension. Moreover, rats fed with the emulsion showed the highest accumulation of free curcuminoids, which present the highest biological activity, in the liver (129 ng curcumin/g tissue) and brown adipose tissue (193 ng curcumin/g tissue). The obtained results are of great interest since the presence of curcumin in the brown adipose tissue has been shown to play a relevant role in the prevention of obesity and its related metabolic disorders.

The purpose of this review is to summarize the most recent findings investigating the impact of several natural sirtuin (SIRT) activators, particularly SIRT1, on atherosclerosis.

Sirtuins that belong to a family of class III histone deacetylases are believed to be novel therapeutic targets to treat age-related and chronic diseases. SIRT expression is regulated by small molecules called SIRT-activating compounds that can be found in natural food products. SIRT1 may exert protective effects in atherosclerosis, which is said to be a major cause of cardiovascular diseases. Most of the evidence supporting the beneficial effects of these natural compounds comes from in vitro or animal-based studies, while there have been particularly few or inconsistent human-based studies evaluating their long-term impact in recent years. SIRT1 activation has been demonstrated to mitigate or prevent atherosclerosis through various mechanisms. However, further research is required to determine the optimal SIRT activator dosage and to establish a stronger correlation between health effects and the administration of bioactive compounds. Additionally, conducting more human clinical trials is necessary to ensure the safety of these compounds for preventing atherosclerosis development.

Obesity is a major cause of morbidity and mortality globally, increasing the risk for chronic diseases. Thus, the need to identify more effective anti-obesity agents has spurred significant interest in the health-promoting properties of natural compounds. Of these, curcumin, the most abundant and bioactive constituent of turmeric, possesses a variety of health benefits including anti-obesity effects. However, despite its anti-obesity potential, curcumin has demonstrated poor bioavailability, which limits its clinical applicability. Synthesizing curcumin derivatives, which are structurally modified analogs of curcumin, has been postulated to improve bioavailability while maintaining therapeutic efficacy. This review summarizes in vitro and in vivo studies that assessed the effects of curcumin derivatives against obesity and its associated metabolic complications. We identified eight synthetic curcumin derivatives that were shown to ameliorate obesity and metabolic dysfunction in diet-induced obese animal models, while five of these derivatives also attenuated obesity and associated metabolic complications in cell culture models. These curcumin derivatives modulated adipogenesis, lipid metabolism, insulin resistance, steatosis, lipotoxicity, inflammation, oxidative stress, endoplasmic reticulum stress, apoptosis, autophagy, fibrosis, and dyslipidemia to a greater extent than curcumin. In conclusion, the findings from this review show that compared to curcumin, synthetic curcumin derivatives present potential candidates for further development as therapeutic agents to modulate obesity and obesity-associated metabolic complications.

Metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease that has no viable treatment. Curcumin (Cur) and resveratrol (Res) are two natural products that have been studied for their potential to ameliorate MAFLD. However, while these compounds have been investigated individually, their combined use and the potential for a synergistic or augmented effect remain unexplored. This study aims to investigate the effect of curcumin (Cur) and resveratrol (Res) as a potential combination therapy on MAFLD. Cur, Res and Cur+Res were tested in palmitic acid (PA)-induced-HepG2 cells. MAFLD model was established using Goto-Kakizaki rats. The animals were treated with vehicle control (model group), Cur (150 mg/kg), Res (150 mg/kg), Cur+Res (150 mg/kg, 8:2, w/w), or metformin (Met, positive control, 400 mg/kg/day) via oral gavage for 4 weeks. Wistar rats were used as the control group. Network pharmacology was conducted to elucidate the molecular actions of Cur and Res, followed by q-PCR and immunoblotting in vivo. Cur+Res exhibited synergistic effects in reducing triglyceride, total cholesterol and lipid accumulation in PA-induced HepG2 cells. The combination also markedly attenuated hepatic steatosis in the MAFLD rats. Network pharmacology illustrated that the interaction of Cur and Res was associated with the modulation of multiple molecular targets associated with the PI3K/AKT/mTOR and HIF-1 signaling pathways. Experimental results confirmed that Cur+Res nomalised the gene targets and protein expressions in the PI3K/AKT/mTOR and HIF-1 signaling pathways, including PI3K, mTOR, STAT-3, HIF-1α, and VEGF. The present study demonstrated an advanced effect of Cur and Res in combination to attenuate MAFLD, and the mechanism is at least partly associated with the modulation of the PI3K/AKT/mTOR and HIF-1 signaling pathways.

Dihydrocurcumin (DHCUR), a natural product and reductive metabolite of curcumin (CUR), is limitedly explored owing to its low bioavailability and limited accessibility due to lack of straightforward synthetic routes and poor yields with known methods. Herein, we report a concise and straightforward route to synthesize DHCUR and its analogs in excellent yields. Dihydroferuloylacetone is condensed with aldehydes to obtain desired DHCURs/1,7-diarylheptanoids in 81-90% yields. The developed protocol facilitates easy access to bioactive natural products, 1,7-diarylheptanoids and DHCUR, for therapeutic study.