Numerous dietary phytochemicals such as curcumin, lutein and isoflavones are associated with health beneficial activities, however their application is often limited by their low bioavailability. Therefore, bioenhancers represent a feasible approach to increase the absorption efficiency of bioactive compounds. Here, we combined uptake and transport studies in differentiated Caco-2 cells with high resolution analytics and fractionation to evaluate the impact of spearmint (Mentha spicata) on the cellular uptake of curcumin. Additionally, we utilized mechanistic studies in native and overexpressing cell systems to assess P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) efflux transporter activity as well as in-silico molecular docking simulations. We found significantly elevated intracellular curcuminoid levels mediated by spearmint. Fractionation and functional assays identified (R)-(-)-carvone as a putative candidate for the biologically active compound mediating increased curcumin uptake via BCRP inhibition. Inhibition of P-gp-mediated efflux might additionally be involved. Molecular docking simulations suggest a common binding site of curcumin and (R)-(-)-carvone in BCRP. Further, spearmint significantly increased cellular uptake of lutein and transintestinal transport of isoflavones in-vitro. In summary, spearmint was identified as a novel bioenhancer for curcumin, lutein and isoflavones. Our findings suggest that spearmint increases bioavailability of a wide range of nutrients and drugs at least partially due to interference with BCRP via its active compound (R)-(-)-carvone.

In prion diseases, the cellular prion protein (PrPC) forms an abnormal, infectious, and disease-causing form known as PrPSc. Inhibition of prion propagation is a key approach for the treatment of these diseases. We report on a curcumin-based compound, GT863 (formerly known as PE859) that displays therapeutic efficacy when administered orally. GT863 inhibited abnormal prion protein formation in prion-infected neuroblastoma cells in a prion strain dependent manner: effectively for RML prion and marginally for 22 L prion. Treatment with ad libitum GT863-containing feed prolonged the incubation period of intracerebrally RML prion infected Tga20 mice by 217% increase in mean. Although the 263 K prion-infected Tg7 mice were less sensitive to GT863 than RML prion infected Tga20, treatment with ad libitum GT863-containing feed prolonged the incubation period by 39% increase in mean. The mechanism of the anti-prion effectiveness in vivo needs to be elucidated and managed. Nevertheless, GT863 could inspire the development of oral chemotherapy for prion diseases.

Thiolated chitosan (Cs-SH) nanoparticles were synthesized and incorporated into bacterial cellulose (BC) membranes through vacuum-assisted confinement. Thiolation significantly enhanced the intrinsic adhesion capacity of chitosan (Cs) as well as its solubility in neutral aqueous solutions. Subsequently, Cs-SH nanoparticles were successfully loaded with curcumin (Cur-Cs-SH), with nanoparticle sizes of 121 ± 2 nm for Cs-SH and 152 ± 6 nm for Cur-Cs-SH. Stability assessments revealed improved pH tolerance and colloidal stability due to the introduction of thiol groups and curcumin encapsulation. Notably, the retention yield of nanoparticles in BC was calculated to be 99 % (w/v) within 45 min. Nanoparticle and curcumin in vitro release studies demonstrated pH-dependent profiles, indicating controlled release kinetics influenced by initial loading and environmental acidity. Moreover, the enhanced adhesive properties of the developed BC membranes, verified by mucin disks and porcine skin adhesion tests, suggested their potential for targeted drug delivery to human tissue. Additionally, antimicrobial assays suggested a synergistic effect between Cs-SH and encapsulated curcumin, exhibiting antibacterial activity against S. aureus and E. coli. In this research, the bioavailability of curcumin was increased by encapsulating it in Cur-Cs-SH nanoparticles, which enhanced its antimicrobial properties and improved the adhesion of BC membranes, thereby expanding their applications in biomedicine.

Gastric ulcer is a common disorder of the digestive system. The combination of turmeric and honey is known to treat stomach ulcers. However, curcumin, an active component in turmeric, has limitations, i.e., poor water solubility and low oral bioavailability. Therefore, turmeric and honey were formulated into a nanoemulsion with black pepper to enhance curcumin bioavailability. The study followed a systematic approach to optimize the nanoemulsion formula, determine stability, and evaluate ulcer healing activity in rats with ethanol-induced gastric ulcers. Nanoemulsion was prepared using a low-energy emulsification method called emulsion phase inversion (EPI). Two stability evaluations were carried out, i.e., storage and freeze-thaw stability tests. The organoleptic, droplet size, polydispersity index, pH, viscosity, and curcumin content of the nanoemulsion were evaluated. Male Wistar albino rats were induced with 96% ethanol for six days. The rats were divided into six groups, i.e., healthy control, ulcerated control, omeprazole, two different doses of turmeric, honey, and black pepper nanoemulsion (NTBH1 and NTBH2), and turmeric and honey nanoemulsion (NTH). The antiulcer activity was determined by measuring the ulcer area, ulcer index, curative index, ulcer severity score, and histology. The best formula with the smallest droplet size, i.e., 144.6±3.8 nm, was obtained from the nanoemulsion using Tween 80 as surfactant, glycerin as cosolvent, and sodium alginate as viscosity enhancer. The result showed that the nanoemulsion was stable after being stored at 25 and 40°C for four weeks and after six cycles of freeze-thaw test. The ulcer index of the ulcerated rats from the lowest to the highest, i.e., NTBH2, omeprazole, NTH, and NTBH1. In conclusion, the nanoemulsion developed in this study containing turmeric, honey, and black pepper holds promising potential in treating gastric ulcers, offering a hopeful outlook for future treatments.

Background/Objectives: Individuals with special metabolic demands are at risk of deficiencies in fat-soluble vitamins, which can be counteracted via supplementation. Here, we tested the ability of micellization alone or in combination with selected natural plant extracts to increase the intestinal absorption and bioefficacy of fat-soluble vitamins. Methods: Micellated and nonmicellated vitamins D3 (cholecalciferol), D2 (ergocalciferol), E (alpha tocopheryl acetate), and K2 (menaquionone-7) were tested in intestinal Caco-2 or buccal TR146 cells in combination with curcuma (Curcuma longa), black pepper (Piper nigrum), or ginger (Zingiber officinale Roscoe) plant extracts. The vitamin uptake was quantified via HPLC-MS, and bioefficacy was assessed via gene expression analyses or the Griess assay for nitric oxide generation. Results: Micellization increased the uptake of vitamin D into buccal and intestinal cells, with vitamin D3 being more efficient than vitamin D2 in increasing the expression of genes involved in calcium transport. The micellization of vitamin E acetate increased its uptake and conversion into biologically active free vitamin E in intestinal cells only. The vitamin K2 uptake into buccal and intestinal cells was increased via micellization. Plant extracts increased the uptake of select micellated vitamins, with no plant extract being effective in combination with all vitamins. The curcuma extract increased the uptake of vitamins D2/D3 but not their bioefficacy. Black pepper and ginger extracts increased the uptake of vitamin E acetate into intestinal cells but failed to increase its conversion into free vitamin E. The ginger extract augmented the uptake of vitamin K2 and increased NO generation additively. Conclusions: Our data substantiate the positive effects of micellization on fat-soluble vitamin absorption and bioefficacy in vitro. While the application of plant extracts in addition to micellization to further increase bioefficacy is an interesting approach, further studies are warranted to understand vitamin-specific interactions and translation into increased bioefficacy.

While a balanced diet can fulfill most nutritional needs, optimizing the composition of specific foods like broccoli can amplify their health benefits.

Broccoli (Brassica oleracea L. Italica group) is a widely consumed cruciferous vegetable valued for its gastrointestinal and immune health benefits. However, the individual contributions and interactions of broccoli glucosinolates, as they hydrolyze into bioactive isothiocyanates, remain poorly understood.

This study investigated mixtures of four major aliphatic glucosinolates-glucoraphanin, gluconapin, progoitrin, and sinigrin-in individual and combinational models to assess their effects on human colorectal cell proliferation.

Combination index analysis revealed moderate to strong antagonistic interactions among these glucosinolates, with the most significant antagonism observed during enzymatic hydrolysis by myrosinase. Mixture analysis identified an optimal glucosinolate ratio including glucoraphanin (81-84%), gluconapin (9-19%), and others (0-7%) to maximize their antiproliferative effects (adjusted R2 > 0.80). This optimal profile was achievable within the target broccoli mapping population. Testing the near-optimal VB067 isogenic broccoli line showed a 44% increase in antiproliferative activity compared to the initial breeding parent or an average sister line.

This study highlights the potential of leveraging nutrient-nutrient interactions to guide molecular breeding and produce functional varieties of cruciferous vegetables with optimized health benefits.

This study investigates the potential synergistic effects of extracts from Curcuma longa (turmeric), Coffea arabica (Arabica coffee beans), and Capsicum annuum (chili peppers) in reducing oxidative stress and inflammation, which are associated with metabolic disorders such as obesity, diabetes, and cardiovascular diseases. Using a systematic design of experiment (DoE) optimization approach, an optimal extract ratio of 1:3:4 (turmeric: coffee: chili) was identified. The efficacy of the extract combination was assessed through various antioxidant assays, inhibition of inflammation-related gene expression, and safety testing via the 3-(4,5-dimethylthazolk-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The extract combination showed higher antioxidant activity and comparable anti-inflammatory effects relative to each single extract. Additionally, the extract combination demonstrated effective activity compared with turmeric extract while using a lower concentration, resulting in reduced cytotoxicity. The optimized extract combination was successfully incorporated into nanostructured lipid carriers (NLCs) with a hydrodynamic diameter of 258.0 ± 10.2 nm, which effectively redisperses after the spray-drying process with increased diameter to 349.8 ± 49.6 nm. Under stress conditions, the stability of curcumin and capsaicin in dried-NLCs was maintained. In summary, the optimized extract-loaded NLCs formulation, achieved through a multistage approach, shows promise in mitigating oxidative stress and inflammation, suggesting its potential as a valuable daily dietary supplement.

Cannabidiol (CBD) is one of the major phytochemical constituents of cannabis, Cannabis sativa, widely recognized for its therapeutic potential. While cannabis has been utilized for medicinal purposes since ancient times, its psychoactive and addictive properties led to its prohibition in 1937, with only the medical use being reauthorized in 1998. Unlike tetrahydrocannabinol (THC), CBD lacks psychoactive and addictive properties, yet the name that suggests its association with cannabis has significantly contributed to its public visibility. CBD exhibits diverse pharmacological properties, most notably anti-inflammatory effects. Additionally, it interacts with key drug-metabolizing enzyme families, including cytochrome P450 (CYP) and uridine 5'-diphospho-glucuronosyltransferase (UGT), which mediate phase I and phase II metabolism, respectively. By binding to these enzymes, CBD can inhibit the metabolism of co-administered drugs, which can potentially enhance their toxicity or therapeutic effects. Mild to moderate adverse events associated with CBD use have been reported. Advances in chemical formulation techniques have recently enabled strategies to minimize these effects. This review provides an overview of CBD, covering its historical background, recent clinical trials, adverse event profiles, and interactions with molecular targets such as receptors, channels, and enzymes. We particularly emphasize the mechanisms underlying its anti-inflammatory effects and interaction with drugs relevant to organ transplantation. Finally, we explore recent progress in the chemical formulation of CBD in order to enhance its bioavailability, which will enable decreasing the dose to use and increase its safety and efficacy.

Breast cancer is the most common malignancy in the women. Chemotherapy is a crucial part of breast cancer treatment especially for advanced and metastatic forms of the disease. However, chemotherapy has limitations due to tumor heterogeneity, chemoresistance, and side effects. There is potential in combining chemotherapeutic drugs with natural items to enhance their effectiveness against cancer. In this study, we examined the synergistic effects of combining curcumin: piperine with sorafenib on the progression of breast cancer cells by altering many pathways associated with cancer and regulating the expression of numerous microRNAs. We tested the cytotoxic impact of curcumin: piperine on MCF-7 breast cancer cells using SRB assay. We analyzed the expression levels of selected microRNAs, genes, and proteins related to cancer stem cells, epithelial-mesenchymal transition, apoptosis and cell cycle progression using qPCR, ELISA and flow cytometry techniques. The findings of this study demonstrated that sorafenib and curcumin: piperine together enhances the suppression of MCF-7 cell survival. Molecular genetic analysis revealed that this combination provoked downregulation in oncomirs [miR-21 and miR-155], vimentin, Snail1, Notch, TGF-β1, Smad4, β-catenin1 and Wnt10b genes. Meanwhile, there were upregulation of tumor suppressor miRNAs [miR-28, miR-139 and miR-149] and E-cadherin gene expression level. Also, this combination resulted in a decrease of vimentin, IL-6, STAT3 and MMP-9; an increase of E-cadherin protein levels. Moreover, this combination induced apoptotic cell death and arrested cell cycles at specific phases. This study suggests that the combination of sorafenib and curcumin: piperine can combat breast cancer by modulating several microRNAs and signaling pathways involved in the development and progression of breast cancer.

The online version contains supplementary material available at 10.1007/s12291-024-01212-0.

The development of biocompatible wound dressings containing therapeutic agents to accelerate wound healing is an interesting field of study in biomedical sciences. Polyvinyl alcohol (PVA) nanofibers were loaded with zinc oxide nanoparticles (ZnO NPs) and curcumin (Cur) through electrospinning. The dressings were characterized by SEM and XRD and FTIR. The antioxidant, antibacterial, and cytotoxic activities Cur/ZnO/PVA nano dressing were evaluated using DPPH radical scavenging assay, disc diffusion method, and MTT assay, respectively. Cur/ZnO/PVA nano dressing showed sustained Cur release about 19.7% and 61.1% after 8h and 168h, respectively. Cur/ZnO NPs/PVA mixture had higher antioxidant potential than PVA, ZnO NPs, and Cur. The dressing showed a good antibacterial effect. The in vivo wound healing effect of different types of prepared dressings, including PVA, Cur/PVA, Cur/ZnO/PVA, and ZnO/ PVA nanofibers, was also investigated. PVA dressing containing Cur/ZnO NPs resulted in the highest increase of wound contraction in rats. The assembly of Cur and ZnO NPs on PVA nanofibers could propose as an effective delivery method to improve the wound healing process. The investigated wound dressing could be commercialized and used on a large scale after proper further studies, including clinical trials.

Turmeric is a common spice used in traditional Chinese and Ayurvedic medicine for a variety of purported health benefits. Recent concerns have arisen regarding turmeric-induced liver injury linked to formulations with enhanced bioavailability, often including piperine found in black pepper.

We explore a case of a 40-year-old female with increasing fatigue, pruritus, and dark urine following consumption of turmeric and black pepper "wellness shots" leading to a significant drug-induced liver injury.

This case underscores the critical need to recognise herbal remedies, such as turmeric, as potential sources of hepatotoxicity. Despite a reputation of safety, limited regulation and testing of turmeric may mean potential adverse effects are under-recognised. Understanding the mechanisms behind turmeric and black pepper's hepatotoxicity, including the role of potential genetic predispositions, requires further investigation for its safe use.

Neurodegenerative diseases pose a significant health challenge for the elderly. The escalating presence of toxic metals and chemicals in the environment is a potential contributor to central nervous system dysfunction and the onset of neurodegenerative conditions. Transition metals play a crucial role in various pathophysiological mechanisms associated with prevalent neurodegenerative diseases such as Alzheimer's and Parkinson's. Given the ubiquitous exposure to metals from diverse sources in everyday life, the workplace, and the environment, most of the population faces regular contact with different forms of these metals. Disturbances in the levels and homeostasis of certain transition metals are closely linked to the manifestation of neurodegenerative disorders. Oxidative damage further exacerbates the progression of neurological consequences. Presently, there exists no curative therapy for individuals afflicted by neurodegenerative diseases, with treatment approaches primarily focusing on alleviating pathological symptoms. Within the realm of biologically active compounds derived from plants, flavonoids and curcuminoids stand out for their extensively documented antioxidant, antiplatelet, and neuroprotective properties. The utilization of these compounds holds the potential to formulate highly effective therapeutic strategies for managing neurodegenerative diseases. This review provides a comprehensive overview of the impact of abnormal metal levels, particularly copper, iron, and zinc, on the initiation and progression of neurodegenerative diseases. Additionally, it aims to elucidate the potential of fisetin and curcumin to inhibit or decelerate the neurodegenerative process.

Background: Curcumin appears to be well tolerated and effective for managing chronic inflammatory pain, but its poor oral bioavailability has been a hurdle in its use as a therapeutic agent. The current study was performed to characterize a novel co-amorphous compound based on curcumin/L-arginine 1:2 (CAC12). Methods: Stability, solubility and structural characterization of the CAC12 were carried out by spectrometry techniques and in vitro assays, whereas the antinociceptive and anti-inflammatory effects were evaluated by CFA or carrageenan models. The mechanism of action was determined by cytokine quantification, and pharmacokinetic parameters were obtained through UPLC-MS/MS. The co-amorphous compound was prepared by fast solvent evaporation. Powder XRD, 13C-NMR, ATR-FTIR and TGA/DSC thermal analysis showed a 1:2 stoichiometry for the CAC12. Results: CAC12 was 1000 times more soluble than curcumin, and it was stable for 1 month at 40 °C and 75% relative humidity or for 60 min in physiological medium at pH 4.5-6.8. Co-amorphous curcumin/L-arginine, but not curcumin + L-arginine, decreased carrageenan- or CFA-induced inflammation and nociception by decreasing IL-1α, IL-1β, IL-6, TNF-α, MCP-1 and CXCL1 cytokines. The bioavailability of free plasmatic curcumin increased about 22.4 times when it was given as CAC12 relative to a phytosome formulation at the equivalent dose. Conclusions: Results suggest the possible use of CAC12 to treat inflammatory pain disorders in human beings.

Acute kidney injury (AKI) is linked to high rates of mortality and morbidity worldwide thereby posing a major public health problem. Evidences suggest that ferroptosis is the primary cause of AKI, while inhibition of monoamine oxidase A(MAOA) and 5-hydroxytryptamine were recognized as the defender of ferroptosis. Curcumin (Cur) is a natural polyphenol and the main bioactive compound of Curcuma longa, which has been found nephroprotection in AKI. However, the potential mechanism of Cur in alleviating AKI ferroptosis remains unknown.

This study aims to investigate the effects of Cur on AKI ferroptosis.

Folic acid (FA)-induced AKI mouse model and erastin/(rsl-3)-induced HK-2 model were constructed to assess the renoprotection of Cur. The nuclear magnetic resonance (NMR)-based metabolomics coupled network pharmacology approach was used to explore the metabolic regulation and potential targets of Cur. Molecular docking and enzyme activity assay was carried out to evaluate the effects of Cur on MAOA.

Our results showed that in vivo Cur preserved renal functions in AKI mice by lowering levels of serum creatinine, blood urea nitrogen, while in vitro ameliorated the cell viability of HK-2 cells damaged by ferroptosis. Mechanistic studies indicated that Cur protected AKI against ferroptosis via inhibition of MAOA thereby regulating 5-hydroxy-L-tryptophan metabolism.

Our study for the first time clarified that Cur might acts as a MAOA inhibitor and alleviates ferroptosis in AKI mice, laying a scientific foundation for new insights of clinical therapy on AKI.

This study investigated the preventive effect of curcumin (CUR) on tooth-supporting structures in hypercholesterolemic (HC) rats with periodontitis (P). Wistar rats (8 weeks old) (n = 30) were assigned to six groups based on dietary intake, CUR-piperine combination treatment and P induction. P was induced in four groups using a ligature model. Serum lipid profiles, oxidative stress parameters, radiographic, histological and histomorphometric analyses were performed. HC rats showed elevated serum cholesterol levels (p < 0.001). Moreover, topical administration of CUR did not regulate hypercholesterolemia in this model. The HC diet increased oxidative stress in gingival tissue, exacerbated by P, whereas CUR attenuated reactive species generation (p < 0.001) and reduced catalase (CAT) activity, possibly due to its antioxidant properties. Histological analysis revealed extensive erosive surfaces and osteoclast presence in the P groups, with the HC + P group showing the highest rate of bone resorption. The CUR-treated groups showed less bone resorption and more bone formation, indicating a protective effect. Histomorphometric studies showed a significant increase in bone volume in the CUR groups compared to the P groups (p < 0.001). CUR prevented bone resorption induced by P and HC diet, with larger osteoblastic surfaces and fewer osteoclasts, suggesting inhibition of bone resorption. CUR also prevented collagen fiber destruction caused by the HC diet. Overall, the study suggests a potential therapeutic role for CUR in mitigating periodontal tissue damage associated with hypercholesterolemia and P, due to its antioxidant and anti-inflammatory properties. Further research would be needed to validate its clinical efficacy as an adjunctive treatment for P.

Chronic pruritus, or persistent itching, is a debilitating condition that severely impacts quality of life, especially in palliative care settings. Traditional treatments often fail to provide adequate relief or are associated with significant side effects, prompting interest in alternative therapies. This review investigates the antipruritic potential of eight medicinal plants: chamomile (Matricaria chamomilla), aloe vera (Aloe barbadensis), calendula (Calendula officinalis), curcumin (Curcuma longa), lavender (Lavandula angustifolia), licorice (Glycyrrhiza glabra), peppermint (Mentha piperita), and evening primrose (Oenothera biennis). These plants are analyzed for their traditional applications, active bioactive compounds, mechanisms of action, clinical evidence, usage, dosage, and safety profiles. Comprehensive searches were conducted in databases including PubMed, Web of Science, Scopus, and b-on, focusing on in vitro, animal, and clinical studies using keywords like "plant", "extract", and "pruritus". Studies were included regardless of publication date and limited to English-language articles. Findings indicate that active compounds such as polysaccharides in aloe vera, curcuminoids in turmeric, and menthol in peppermint exhibit significant anti-inflammatory, antioxidant, and immune-modulating properties. Chamomile and calendula alleviate itching through anti-inflammatory and skin-soothing effects, while lavender and licorice offer antimicrobial benefits alongside antipruritic relief. Evening primrose, rich in gamma-linolenic acid, is effective in atopic dermatitis-related itching. Despite promising preclinical and clinical results, challenges remain in standardizing dosages and formulations. The review highlights the necessity of further clinical trials to ensure efficacy and safety, advocating for integrating these botanical therapies into complementary palliative care practices. Such approaches emphasize holistic treatment, addressing chronic pruritus's physical and emotional burden, thereby enhancing patient well-being.

The bioactive components of plant foods and medicinal plants have attracted interest due to their potential impact on the progression of chronic kidney disease (CKD) and outcomes.

This study aimed to conduct a critical and quantitative systematic review of randomized clinical trials (RCTs) investigating the potential effects of selected phytochemicals from plant-based foods and medicinal plants in CKD and dialysis patients.

The review included studies that related plant-based bioactive compounds (curcumin, propolis, sulforaphane, betalain, catechins, rhein, emodin, aloe-emodin, flavonoids, and triptolide) and medicinal plants (green tea, rhubarb, Astragalus membranaceus, and Tripterygium wilfordii Hook F) in CKD and dialysis patients. A literature search was conducted in PubMed, LILACS, Embase, Scopus, and WOS between December 2022 and October 2024. This review was performed according to the PRISMA flowchart and was registered in PROSPERO (595162).

In the eight RCTs conducted with curcumin, anti-inflammatory, antioxidant, and microbiota-modulating properties were reported. As for propolis, in three RCTs, anti-inflammatory, anti-proteinuric, and renal-protective properties were reported. Sulforaphane in one RCT showed antioxidant and cardiovascular benefits, and in another RCT no effects were observed. In one RCT, genistein was shown to be a potential anti-inflammatory agent and improved nutritional status. Allicin in two RCTs showed cardioprotective, antioxidant, anti-inflammatory, and lipid-lowering effects. Finally, beetroot showed a vasodilator effect in one RCT. As for the medicinal plants, green tea, rhubarb, Astragalus membranaceus, and Tripterygium Wilfordii Hook F, in six RCTs they showed antioxidant, anti-inflammatory, cardioprotective, antiproteinuric, and renoprotective properties.

These results suggest that bioactive compounds of plant-based foods and medicinal plants have promising effects in terms of preventing or treating CKD progression and appear to improve inflammation and antioxidant capacity and support cardiovascular benefits and renoprotective effects; however, it is recommended that further studies be carried out.

Herbal medicine, particularly in developing regions, remains highly popular due to its cost-effectiveness, accessibility, and minimal risk of adverse effects. Curcuma longa L., commonly known as turmeric, exemplifies such herbal remedies with its extensive history of culinary and medicinal applications across Asia for thousands of years. Traditionally utilized as a dye, flavoring, and in cultural rituals, turmeric has also been employed to treat a spectrum of medical conditions, including inflammatory, bacterial, and fungal infections, jaundice, tumors, and ulcers. Building on this longstanding use, contemporary biochemical and clinical research has identified curcumin-the primary active compound in turmeric-as possessing significant therapeutic potential. This review hypothesizes that curcumin's antioxidant properties are pivotal in preventing and treating chronic inflammatory diseases, which are often precursors to more severe conditions, such as cancer, and neurological disorders, like Parkinson's and Alzheimer's disease. Additionally, while curcumin demonstrates a favorable safety profile, its anticoagulant effects warrant cautious application. This article synthesizes recent studies to elucidate the molecular mechanisms underlying curcumin's actions and evaluates its therapeutic efficacy in various human illnesses, including cancer, inflammatory bowel disease, osteoarthritis, atherosclerosis, peptic ulcers, COVID-19, psoriasis, vitiligo, and depression. By integrating diverse research findings, this review aims to provide a comprehensive perspective on curcumin's role in modern medicine and its potential as a multifaceted therapeutic agent.

Dietary phytochemicals, bioactive compounds derived from plants, have gained increasing attention for their potential role in cancer prevention. Among these, NRF2 (nuclear factor erythroid 2-related factor 2) activating dietary phytochemicals such as curcumin, sulforaphane, ursolic acid, and cyanidin have demonstrated significant antioxidant and anti-inflammatory properties, making them promising agents in chemoprevention. This review examines the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of these dietary phytochemicals, with a focus on their NRF2-mediated effects in cancer prevention.

Preclinical studies have highlighted the potential of these dietary phytochemicals to modulate oxidative stress and inflammation, key drivers of carcinogenesis. We explore the complexity of their PK/PD properties, influenced by factors such as bioavailability, metabolism, and drug interactions. While most of these phytochemicals follow two compartmental PK, their anti-oxidant and anti-inflammatory effects follow the indirect response (IDR) model. Furthermore, we discuss the application of physiologically based pharmacokinetic (PBPK) modeling to simulate the behavior of these compounds in humans, providing insights for clinical translation.

The integration of PK-PD analysis into the development of dietary phytochemical-based therapies offers a pathway to optimize dosing strategies, enhance therapeutic efficacy, and improve safety. This review underscores the importance of these compounds as part of cancer interception strategies, particularly in the early stages of cancer development, where they may offer a natural, less toxic alternative to conventional therapies.

Cancer is a leading cause of death worldwide, and imposes a substantial socioeconomic burden with little impact especially on aggressive types of cancer. Conventional therapies have many serious side effects including generalised systemic toxicity which limits their long-term use. Tumour resistance and recurrence is another main problem associated with conventional therapy. Purified or extracted natural products have been investigated as cost-effective cancer chemoprotective agents with the potential to reverse or delaying carcinogenesis. Curcumin (CUR) as a natural polyphenolic component, exhibits many pharmacological activities such as anti-cancer, anti-inflammatory, anti-microbial, activity against neurodegenerative diseases including Alzheimer, antidiabetic activities (type II diabetes), anticoagulant properties, wound healing effects in both preclinical and clinical studies. Despite these effective protective properties, CUR has several limitations, including poor aqueous solubility, low bioavailability, chemical instability, rapid metabolism and a short half-life time. To overcome the pharmaceutical problems associated with free CUR, novel nanomedicine strategies (including polymeric nanoparticles (NPs) such as poly (lactic-co-glycolic acid) (PLGA) NPs have been developed. These formulations have the potential to improve the therapeutic efficacy of curcuminoids. In this review, we comprehensively summarise and discuss recent in vitro and in vivo studies to explore the pharmaceutical significance and clinical benefits of PLGA-NPs delivery system to improve the efficacy of CUR in the treatment of cancer.

Paraquat (PQ), a widely used non-selective herbicide, induces severe lung toxicity by promoting cell death and tissue necrosis through the generation of reactive oxygen species (ROS) and free radicals. This study aimed to develop and evaluate novel niosomal nanoparticles (NPs) encapsulating curcumin and piperine to mitigate PQ-induced acute pulmonary toxicity in Balb/c mice.

The NPs were prepared using non-ionic surfactants and cholesterol via the thin film hydration method.

Characterization revealed high encapsulation efficiency (>85%), proper particle sizes (264-286 nm), narrow polydispersity index (PDI) (0.19 ± 0.04 to 0.23 ± 0.02), and good stability over 90 days. Thermal analysis confirmed successful encapsulation of curcumin and piperine within the niosomal NPs. In vivo studies showed that PQ exposure significantly elevated ROS, lipid peroxidation (LPO), and protein carbonylation (PC) levels, while reducing glutathione (GSH) levels and impairing mitochondrial function (P < 0.001). However, co-treatment with curcumin- and piperine-loaded niosomal NPs effectively reversed these effects (P < 0.001), improving mitochondrial function.

The combined formulation of curcumin and piperine in niosomal NPs offers a promising therapeutic strategy for treating PQ-induced pulmonary toxicity, likely due to enhanced bioavailability and potent antioxidant activity.

KEY POLICY HIGHLIGHTSNanobubbles and nanoparticles may enhance the polyphenols' bioavailabilityNanobubbles may stimulate the activation of Nrf2 and detox enzymesArmoured oxygen nanobubbles may enhance radiotherapy or chemotherapy effects.

Head and neck cancers (HNC) are aggressive, difficult-to-treat tumors that can be caused by genetic factors but mainly by lifestyle or infection caused by the human papillomavirus. As the sixth most common malignancy, it presents a formidable therapeutic challenge with limited therapeutic modalities. Curcumin, a natural polyphenol, is appearing as a promising multitarget anticancer and antimetastatic agent. Numerous studies have shown that curcumin and its derivatives have the potential to affect signaling pathways (NF-κB, JAK/STAT, and EGFR) and molecular mechanisms that are crucial for the growth and migration of head and neck tumors. Furthermore, its ability to interact with the tumor microenvironment and trigger the immune system may significantly influence the organism's immune response to the tumor. Combining curcumin with conventional therapies such as chemotherapy or radiotherapy may improve the efficacy of treatment and reduce the side effects of treatment, thereby increasing its therapeutic potential. This review is a comprehensive overview that discusses both the benefits and limitations of curcumin and its therapeutic effects in the context of tumor biology, with an emphasis on molecular mechanisms in the context of HNC. This review also includes possibilities to improve the limiting properties of curcumin both in terms of the development of new derivatives, formulations, or combinations with conventional therapies that have potential as a new type of therapy for the treatment of HNC and subsequent use in clinical practice.

Turmeric (Curcuma longa L.) is valued for its coloring properties, flavor enhancement, functionality, as well as antioxidant and anti-inflammatory effects, which help prevent various diseases. This study aimed to evaluate the levels of curcumin and trace elements (Cr, Co, Ni, As, Mo, Cd, Sb, Ba, Hg, and Pb) in 30 samples of turmeric capsules. The quantification of curcumin was performed by spectrophotometry, with results ranging from 0.03 g/100 g to 37.6 g/100 g. The concentration of trace elements was determined by ICP-MS after acid digestion of the samples. Except for the elements Sb and Hg, which showed levels below the quantification limits (0.002 and 0.008 mg/kg, respectively), the results were: Cr (<0.008-0.083 mg/kg), Co (<0.003-0.78 mg/kg), Ni (<0.008-1.61 mg/kg), As (<0.003-0.083 mg/kg), Mo (<0.008-1.21 mg/kg), Cd (<0.002-0.076 mg/kg), Ba (<0.008-23.48 mg/kg), and Pb (<0.008-0.619 mg/kg). The interaction between curcumin and the trace elements was complex, with no direct relationship found between them. The estimated daily intake (EDI) of curcumin varied from 0.004 to 2.684 mg/kg of body weight, with 13 samples below 10 % of the acceptable daily intake (ADI), 12 samples between 10 % and 50 % of the ADI, and three samples above 50 %. For trace elements, Co showed the highest contribution, corresponding to 2.72 % of the health-based guidance value established by EFSA. A careful approach in marketing turmeric-based products is fundamental to ensure their quality, efficacy, and safety for consumers.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with insulin resistance and ensuing dysglycemia, dyslipidemia, and inflammation. Owing to the putative metabolic benefits of curcumin-piperine combination, we explored the efficacy of this combination in improving cardiometabolic indices of patients with T2DM and hypertriglyceridemia. In this double-blind clinical trial, 72 patients with T2DM and hypertriglyceridemia were randomized to receive either a tablet containing 500 mg of curcuminoids plus 5 mg of piperine, or a matched placebo for 12 weeks. Anthropometric indices, blood pressure, glycemic indices, lipid profile, C-reactive protein (CRP), quality of life, and mood were evaluated at baseline and end of the study. After 12 weeks of intervention, the levels of triglycerides (p-value = 0.001) and fasting blood glucose (p-value = 0.004) were significantly reduced in the curcumin-piperine compared with the placebo group. CRP levels were marginally reduced in the curcumin-piperine compared with the placebo group (p-value = 0.081). In addition, energy/fatigue significantly increased in the curcumin-piperine group compared to the control group (p-value = 0.024). However, between-group comparisons showed no significant change in other parameters, including anthropometric indices (waist circumference and body mass index (BMI)), biochemical parameters (low-density lipoprotein (LDL-c), high-density lipoprotein (HDL-c), and insulin), HOMA-IR, blood pressure, quality of life, and DASS-21 items between the studied groups (p-value >0.05). The current study showed that curcumin-piperine supplementation can improve serum CRP, triglycerides, and glucose concentrations in patients with T2DM and hypertriglyceridemia.

Among cancer-related deaths worldwide, colorectal cancer ranks second, accounting for 1.2% of deaths in those under 50 years and 0.6% of deaths in those between 50 and 54 years. The anticancer drug 5-fluorouracil is widely used to treat colorectal cancer. Due to a better understanding of the drug's mechanism of action, its anticancer activity has been increased through a variety of therapeutic alternatives. Clinical use of 5-FU has been severely restricted due to drug resistance. The chemoresistance mechanism of 5-FU is challenging to overcome because of the existence of several drug efflux transporters, DNA repair enzymes, signaling cascades, classical cellular processes, cancer stem cells, metastasis, and angiogenesis. Curcumin, a potent phytocompound derived from Curcuma longa, functions as a nuclear factor (NF)-κB inhibitor and sensitizer to numerous chemotherapeutic drugs. Piperine, an alkaloid found in Piper longum, inhibits cancer cell growth, causing cell cycle arrest and apoptosis. This review explores the mechanism of 5-FU-induced chemoresistance in colon cancer cells and the role of curcumin and piperine in enhancing the sensitivity of 5-FU-based chemotherapy. CLINICAL TRIAL REGISTRATION: Not applicable.

The initiation of colorectal cancer is controlled by various factors, including random occurrences and genetic alterations affecting oncogenes and tumor suppressor genes.Curcumin, a significant compound extracted from turmeric, has attracted interest for its robust anticancer properties, particularly regarding its analogs, 2, 6-bisdifurfurylidene cyclohexanone (DFC) and 2, 6-bis (2, 6-dichlorobenzylidene) cyclohexanone (DCC), which were synthesized and assessed for their anticancer efficacy. A combination of spectroscopic techniques and molecular docking methods was utilized to comprehensively evaluate the interaction behaviors of DFC and DCC. The application of density functional theory (DFT) using the B3LYP/6-311G (d, p) basis set facilitated the prediction of spectroscopic properties. The molecular docking investigations conducted using the Glide docking program from Schrodinger Maestro elucidated the interactions of these drugs at the molecular level. In vitro investigations were performed to evaluate the cytotoxic efficacy of the synthesized curcumin analogs. The determined IC50 values revealed that DFC displayed an IC50 of approximately 82 μM, and DCC exhibited a significantly lower IC50 of around 10 μM. This notable disparity highlights the potential of DFC and DCC as a more efficacious cytotoxic agent and further research be conducted on the produced chemicals in the future.

Piperine has been reported to inhibit the enzyme activity of cytochrome P450 (CYP) 3A4. The aim of this study was to develop and validate a physiologically based pharmacokinetic (PBPK) model for piperine and to predict potential food-drug interactions (FDIs) between piperine and CYP3A4 substrate drugs using these models. The PBPK model for piperine was successfully developed and validated. Using this model, FDIs with ten CYP3A4 substrate drugs were simulated. The predicted area under the curve (AUC) ratios (with and without piperine, following a 7-day intake of 20 mg/day) for six drugs were found to exceed 1.25, with significant increases in AUC observed for ritonavir (31%), nifedipine (34%), cyclosporine (35%), triazolam (36%), alfentanil (39%), and simvastatin (59%) in humans. These findings suggest that caution should be exercised when consuming amounts of black pepper equivalent to a daily intake of 20 mg piperine during treatment with CYP3A4 substrate drugs, as it may significantly alter their pharmacokinetics.

Curcumin, a polyphenolic compound derived from the widely used spice Curcuma longa, has shown anti-atherosclerotic effects in animal models and cultured vascular cells. Inflammation is a major contributor to atherosclerosis development and progression. We previously reported that the induction of the proinflammatory molecule TRAF3IP2 (TRAF3 Interacting Protein 2) or inhibition of the matrix metallopeptidase (MMP) regulator RECK (REversion Inducing Cysteine Rich Protein with Kazal Motifs) contributes to pro-oxidant, proinflammatory, pro-mitogenic and pro-migratory effects in response to external stimuli in vascular smooth muscle cells. Here we hypothesized that EF24, a curcumin analog with a better bioavailability and bioactivity profile, reverses interleukin (IL)-18-induced TRAF3IP2 induction, RECK suppression and the proinflammatory phenotype of primary human aortic smooth muscle cells (ASMC). The exposure of ASMC to functionally active recombinant human IL-18 (10 ng/mL) upregulated TRAF3IP2 mRNA and protein expression, but markedly suppressed RECK in a time-dependent manner. Further investigations revealed that IL-18 inhibited both miR-30a and miR-342 in a p38 MAPK- and JNK-dependent manner, and while miR-30a mimic blunted IL-18-induced TRAF3IP2 expression, miR-342 mimic restored RECK expression. Further, IL-18 induced ASMC migration, proliferation and proinflammatory phenotype switching, and these effects were attenuated by TRAF3IP2 silencing, and the forced expression of RECK or EF24. Together, these results suggest that the curcumin analog EF24, either alone or as an adjunctive therapy, has the potential to delay the development and progression of atherosclerosis and other vascular inflammatory and proliferative diseases by differentially regulating TRAF3IP2 and RECK expression in ASMC.

Reprogrammed glucose metabolism is considered as the hallmark of cancer with therapeutic implications. Phytocompounds have potential to inhibit cancer metabolism. Here, we tested the ability of Withaferin A (WA), a withanolide derived from Withania somnifera, in modulating cancer metabolism. The assessed effect of WA on aerobic glycolysis in breast cancer cell lines showed that WA decreases the glucose uptake, lactate production and ATP generation by inhibiting the expression of key glycolytic enzymes i.e., GLUT1, HK2 and PKM2. We also identified that WA induced inhibition of cancer glycolysis by targeting c-myc as validated by silencing experiments followed by metabolic readouts. Decreased glycolysis resulted in reduced cell viability, biomass and colony forming ability of breast cancer cells. To further validate our in vitro findings in breast cancer patients, we analyzed 90 metabolic pathways in ~ 2000 breast tumors and observed that glycolysis is the most deregulated pathway in breast tumors. Deregulated glycolysis also predicted poor prognosis in breast cancer patients. In addition, patient data showed correlation between c-myc expression and glycolytic deregulation in breast cancer. Taken together, our results highlight the role of WA in inhibiting breast cancer metabolism via c-myc/glycolysis axis.

Obesity is defined as an abnormal accumulation of adipose tissue in the body and is a major global health problem due to increased morbidity and mortality. Adipose tissue is made up of adipocytes, which are fat-storing cells, and the differentiation of these fat cells is known as adipogenesis. Several transcription factors (TFs) such as CEBPβ, CEBPα, PPARγ, GATA, and KLF have been reported to play a key role in adipogenesis. In this study, we report one more TF AP-1, which is found to be involved in adipogenesis. Human mesenchymal stem cells  were differentiated into adipocytes, and the expression pattern of different subunits of AP-1 was examined during adipogenesis. It was observed that C-FOS was predominantly expressed at an early stage (Day 2), whereas FRA2 expression peaked at later stages (Days 6 and 8) of adipogenesis. Chromatin immunoprecipitation-sequencing analysis revealed that C-FOS binds mainly to the promoters of WNT1, miR-30a, and ANAPC7 and regulates their expression during mitotic clonal expansion. In contrast, FRA2 binds to the promoters of CIDEA, NOTCH1, ARAF, and MYLK, regulating their expression and lipid metabolism. Data obtained clearly indicate that the differential expression of C-FOS and FRA2 is crucial for different stages of adipogenesis. This also raises the possibility of considering AP-1 as a therapeutic target for treating obesity and related disorders.

Despite significant advancements in chemotherapy, effective treatments for advanced cancer stages remain largely elusive due to chemoresistance. Resistance to anticancer agents in cancer cells can arise through various mechanisms, including multi-drug resistance, inhibition of apoptosis, modification of drug targets, and enhancement of DNA repair capabilities. Consequently, there is a critical need for agents that can suppress the molecular signatures responsible for drug resistance. Piperine, an active alkaloid extracted from Piper nigrum L. (black pepper), is one such agent that has been extensively studied for its potential in addressing chronic diseases, including cancer. Piperine's antineoplastic properties are mediated through the regulation of numerous key cellular signaling pathways and the modulation of various biological processes. Its capability to enhance drug bioavailability and counteract mechanisms of drug resistance, such as the inhibition of P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP-1), emphasizes its potential as an adjunct in cancer therapy. Research across various cancer types has demonstrated piperine's role in chemosensitization by targeting P-gp and MRP-1 and altering drug-metabolizing enzymes. This review provides a comprehensive analysis of piperine's pharmacological characteristics and its capacity to modulate several cellular signaling pathways involved in drug resistance. Furthermore, the review emphasizes how piperine, when used in conjunction with other chemotherapeutic agents or natural compounds, can enhance therapeutic effects, leading to improved outcomes in cancer treatment.

The aim of this review is to explore how diet and dietary supplements influence the activity of key multidrug resistance (MDR) transporters-MRP2, BCRP, and P-gp. These transporters play a crucial role in drug efflux from cancer cells and significantly affect chemotherapy outcomes. This review focuses on how dietary phytochemicals, such as catechins and quercetin, impact the expression and function of these transporters. Both in vitro and in vivo experiments were examined to assess changes in drug bioavailability and intracellular drug accumulation. The findings show that certain dietary components-such as catechins, flavonoids, resveratrol, curcumin, terpenoids, sterols, and alkaloids-can either inhibit or induce MDR transporter activity, thus influencing the effectiveness of chemotherapy. These results highlight the importance of understanding diet-drug interactions in cancer therapy to improve treatment outcomes and reduce side effects. In conclusion, dietary modifications and supplements should be carefully considered in cancer treatment plans to optimize therapeutic efficacy.

Neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function, posing a tremendous burden on health systems worldwide. Although the underlying pathological mechanisms for various neurodegenerative diseases are still unclear, a common pathological hallmark is the abundance of neuroinflammatory processes, which affect both disease onset and progression. In this review, we explore the pathways and role of neuroinflammation in various neurodegenerative diseases and further assess the potential use of curcumin, a natural spice with antioxidant and anti-inflammatory properties that has been extensively used worldwide as a traditional medicine and potential therapeutic agent. Following the examination of preclinical and clinical studies that assessed curcumin as a potential therapeutic agent, we highlight the bioavailability of curcumin in the body and discuss both the challenges and benefits of using curcumin as a therapeutic compound for treating neurodegeneration. Although elucidating the involvement of curcumin in aging and neurodegeneration has great potential for developing future CNS-related therapeutic targets, further research is required to elucidate the mechanisms by which Curcumin affects brain physiology, especially BBB integrity, under both physiological and disease conditions.

In many cultures, "food as medicine" has existed for centuries as the foundation of health. It is a practice built on the knowledge that food and diet play important roles in disease prevention and management. Foods possessing therapeutic properties are often referred to as functional foods. Many herbs and spices contain numerous nutritional and non-nutritional components that can interact with pharmacologically relevant receptors, either directly or indirectly via their metabolites, to regulate cellular biochemical processes. Although opinions are changing, the concept of food as a therapeutic intervention goes against conventional Western medicine. To provide guidance to clinicians interested in using these products, members of the Food as Medicine working group of the Nutrition Committee NASPGHAN, as part of a two-part review series, have identified frequently used foods, supplements, herbs, and spices that are utilized for therapeutic intent and have created summaries of commonly used indications, doses, and caveats. In this review, the focus is the use of select herbs and spices for medicinal purposes. Gaps in our knowledge in how to effectively use these agents in pediatric patients are discussed. Evidence supporting their use for management of gastrointestinal conditions, especially in the pediatric population, is provided when available. Circumstances in clinical settings and patient indications may require actions different from those recommended in this review and professional judgment should prevail.

Combining two or more chemicals in chemotherapy is rapidly increasing because of its higher efficacy, lower toxicity, lower dosages, and lower drug resistance. Here, we identified a novel combination of luteolin (LUT) and curcumin (CUR), two bioactive compounds from foods, synergistically suppressed triple-negative breast cancer (TNBC) cell proliferation (LUT 30 µM + CUR 20 µM), colony formation (LUT 1 µM + CUR 2 µM), and tumor growth in xenograft mice (LUT 10 mg/kg body weight/day + CUR 20 mg/kg body weight/day, i.p. injection every other day, 5 weeks), while the individual chemical alone did not show these inhibitory effects significantly at the selected concentrations/dosages. Our total RNA transcriptome analysis in xenograft tumors revealed that combining LUT and CUR synergistically activated type I interferon (IFN) signaling and suppressed transforming growth factor-beta (TGF-β) signaling pathways, which was further confirmed by the expression/activity of several proteins of the pathways in tumors. In addition, this combination of LUT and CUR also synergistically decreased oncoprotein levels of c-Myc and Notch1, the critical molecules required to maintain stem cell properties, tumor clonal evolution, and drug resistance. These results suggest that the combination of LUT and CUR synergistically inhibits TNBC by suppressing multiple cellular mechanisms, such as proliferation, colony formation, and transformation, as well as tumor migration, invasion, and metastasis, via regulating IFN and TGF-β signaling pathways. Therefore, combining LUT and CUR may be an effective therapeutic agent to treat highly aggressive, drug-resistant TNBC patients after clinical trials.

The acute manifestations of coronavirus disease 2019 (COVID-19) exhibit the hallmarks of sepsis-associated complications that reflect multiple organ failure. The inflammatory cytokine storm accompanied by an imbalance in the pro-inflammatory and anti-inflammatory host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to severe and critical septic shock. The sepsis signature in severely afflicted COVID-19 patients includes cellular reprogramming and organ dysfunction that leads to high mortality rates, emphasizing the importance of improved clinical care and advanced therapeutic interventions for sepsis associated with COVID-19. Phytochemicals of functional foods and nutraceutical importance have an incredible impact on the healthcare system, which includes the prevention and/or treatment of chronic diseases. Hence, in the present review, we aim to explore the pathogenesis of sepsis associated with COVID-19 that disrupts the physiological homeostasis of the body, resulting in severe organ damage. Furthermore, we have summarized the diverse pharmacological properties of some potent phytochemicals, which can be used as functional foods as well as nutraceuticals against sepsis-associated complications of SARS-CoV-2 infection. The phytochemicals explored in this article include quercetin, curcumin, luteolin, apigenin, resveratrol, and naringenin, which are the major phytoconstituents of our daily food intake. We have compiled the findings from various studies, including clinical trials in humans, to explore more into the therapeutic potential of each phytochemical against sepsis and COVID-19, which highlights their possible importance in sepsis-associated COVID-19 pathogenesis. We conclude that our review will open a new research avenue for exploring phytochemical-derived therapeutic agents for preventing or treating the life-threatening complications of sepsis associated with COVID-19.

Curcumin, a polyphenol natural product derived from turmeric, possesses diverse pharmacological effects due to its interactions with various cells and molecules. Recent studies have highlighted its immunomodulatory properties, including its impact on immune cells and mediators involved in immune responses. Th17 cells play a crucial role in promoting immune responses against extracellular pathogens by recruiting neutrophils and inducing inflammation. These cells produce inflammatory cytokines such as TNF-α, IL-21, IL-17A, IL-23, IL-17F, IL-22, and IL-26. Curcumin has been shown to significantly inhibit the proliferation of Th17 cells and reduce the production of inflammatory cytokines, including TNF-α, IL-22, and IL-17. This review aims to assess the effectiveness of curcumin and its underlying mechanisms in modulating Th17 cells.

Colorectal cancer (CRC) development and progression, one of the most common cancers globally, is supported by specific mechanisms to escape cell death despite chemotherapy, including cellular autophagy. Autophagy is an evolutionarily highly conserved degradation pathway involved in a variety of cellular processes, such as the maintenance of cellular homeostasis and clearance of foreign bodies, and its imbalance is associated with many diseases. However, the role of autophagy in CRC progression remains controversial, as it has a dual function, affecting either cell death or survival, and is associated with cellular senescence in tumor therapy. Indeed, numerous data have been presented that autophagy in cancers serves as an alternative to cell apoptosis when the latter is ineffective or in apoptosis-resistant cells, which is why it is also referred to as programmed cell death type II. Curcumin, one of the active constituents of Curcuma longa, has great potential to combat CRC by influencing various cellular signaling pathways and epigenetic regulation in a safe and cost-effective approach. This review discusses the efficacy of curcumin against CRC in vitro and in vivo, particularly its modulation of autophagy and apoptosis in various cellular pathways. While clinical studies have assessed the potential of curcumin in cancer prevention and treatment, none have specifically examined its role in autophagy. Nonetheless, we offer an overview of potential correlations to support the use of this polyphenol as a prophylactic or co-therapeutic agent in CRC.