Doses Of Curcumin Research Articles

Photodynamic inactivation strategies for maximizing antifungal effect against Sporothrix spp. and Candida albicans in an in vitro investigation.

Sporotrichosis is a zoonotic disease caused by the dimorphic fungus Sporothrix spp., leading to skin lesions that can, in some cases, progress and result in the death of infected individuals. Candida albicans is another fungus involved in several skin, oral, and vaginal mucosal infections. Fungal diseases are concerning due to increasing incidence and the limited variety of antifungal classes available for treatment. Furthermore, antifungal medications can cause various side effects, exacerbated by their prolonged use during infection treatment. There is a need to explore alternatives to conventional drugs that are effective, fast, and safe in combating sporotrichosis. This study aimed to achieve in vitro elimination of the fungi Sporothrix brasiliensis and Sporothrix schenckii through Photodynamic Inactivation (PDI), using curcumin as a photosensitizer and in combination with antifungal agents used in the treatment of sporotrichosis. Yeasts of Candida albicans, Sporothrix brasiliensis, and Sporothrix schenckii were subjected to Photodynamic Inactivation (PDI) using light at a wavelength of 450 ± 10 nm, irradiance of 35 mW/cm2, delivering a fluence of 31.5 J/cm2, with curcumin as the photosensitizer at doses ranging from 0.75 to 150 μg/mL. After determining the Minimum Inhibitory Concentration (MIC) values of the antifungal drugs itraconazole, ketoconazole, and potassium iodide, sub-MIC doses of these antifungals were combined with sub-MIC doses of curcumin in a new PDI session. Photodynamic inactivation is a promising technique in the treatment of sporotrichosis, as well as its combination with antifungals. The combination of curcumin in concentrations ranging from 0.75 g/mL a 7.5 g/mL with sub-MIC concentrations of itraconazole, ketoconazole, and potassium iodide was able to completely inactivate the fungi C. albicans, S. brasiliensis and S. schenckii, indicating that PDI may increase the effectiveness of antifungals. However, further studies are needed to establish protocols for future clinical applications.

Curcumin and Vitamin D Reduce HMGB-1 mRNA Levels in Mice Infected with Salmonella typhi.

This study examined the effects of curcumin and vitamin D on high-mobility group box-1 (HMGB-1) mRNA expression in mice infected with Salmonella typhi. The experimental design allocated 40 mice, intraperitoneally infected with S. typhi, to pre- and post-test controls randomly divided into four groups (10 mice per group). Mice in group A were treated with the antibiotic levofloxacin (1.95 mg/kg once daily) as the positive control; group B mice were administered curcumin at a dose of 200 mg/kg body weight; group C mice were treated with a curcumin dose of 200 mg/kg BW and vitamin D; and group D mice received distilled water (placebo) as the negative control. The intervention was performed for 5 days. On day 10, HMGB-1 mRNA expression was measured, and the results were compared to those before the intervention. HMGB-1 mRNA level in group C decreased significantly by 5.76-fold (95% confidence interval: 2.55, 8.98). In contrast, HMGB-1 mRNA levels did not decrease significantly in group B. These results suggest that the combination of curcumin and vitamin D reduced HMGB-1 mRNA levels in infected mice, highlighting the potential of this combination as an antimicrobial and anti-inflammatory agent.

Effect of curcumin and cacao extract on interleukin-6 expression on ribociclib-induced hepatotoxicity in rats

Purpose: To assess the relationship between interleukin-6 (IL-6) expression and the protective effect of curcumin and cacao extract on hepatotoxicity caused by ribociclib. Method: Sixty adult male albino rats (9 – 10 weeks old) were utilized in this experiment. The rats were separated into six groups (n = 10 each). Group 1 (control) rats received 2 mL of normal saline daily. Group 2 rats were administered 5 mg/kg ribociclib and group 3 rats received 5 mg/kg ribociclib with a cacao dose of 200 mg/kg daily. Group 4 rats were administered 5 mg/kg ribociclib treated with curcumin (200 mg/kg) daily. Groups 5 and 6 were administered cacao and curcumin doses of 200 mg/kg daily. All rats were sacrificed and liver immunohistochemical and histological examinations were performed. Result: The findings demonstrated that ribociclib administration caused liver damage and morphological changes at a histological level in liver tissue. The immunohistochemical investigation revealed that IL-6 levels were significantly increased in group 2 and control group (p < 0.05). Furthermore, co-administration of curcumin and cacao with ribociclib suppressed the levels of IL-6 expression in the liver tissue of rats compared to control group 1. Conclusion: Co-administration of curcumin and cacao protects the liver against ribociclib-induced liver damage. It is necessary to determine the effect of long-term administration of these extracts on the functions of some organs such as the liver and kidney.

8539 Curcumin a Double Edged Sword: A Case of Curcumin Induced Pituitary Macroadenoma Apoplexy

Abstract Disclosure: P. Balozian: None. D. Alfakara: None. M. Linz: None. <Curcumin, the active component of turmeric, exerts numerous beneficial anti-inflammatory, antiplatelet, and anticoagulant effects. Recent literature has shown however that curcumin inhibits proliferation and induces apoptosis of pituitary cells. Despite these findings, there are limited clinical cases reporting an association between curcumin and pituitary adenoma apoplexy.We report the case of a 39-year old G9P6A3 female with Hashimoto’s disease and class II obesity who presented with a constant bifrontal excruciating headache, blurry vision, photophobia, and nausea. She also had fatigue and amenorrhea for two years. Her exam showed normal vitals, decreased visual acuity, diplopia, and bitemporal hemianopsia. Data showed a serum prolactin of 69 ug/L , plasma IGF-1 of 133 ng/ml (Z score -0.4), TSH of 2.58 with a free T4 of 0.47 ng/dl [0.61-1.12 ng/dL], a random cortisol of 12.7 mcg/dl despite her stress and pain, ACTH of 27 pg/ml, DHEA-S of 46 mcg/dl, an LH of 0.5 IU/L, and an FSH of 4mIU/ml with an estradiol of 25 pg/ml. MRI of the pituitary revealed a 1.8 cm macroadenoma with a mass effect on the overlying optic chiasm and a T1 intrinsic hyperintense signal indicative of a hemorrhagic component. She was given IV dexamethasone for 24 hours then underwent transsphenoidal resection of the hemorrhagic tumor that resulted in rapid resolution of headaches and visual symptoms. She was not given any glucocorticoids during or after surgery. Labs immediately after surgery revealed a prolactin of <1ug/L and a cortisol of 26.7 mcg/dl. Pathology showed corticotroph tumor with hemosiderin deposition with a 4.2% Ki67 and negative ACTH immunostaining. On medication review, patient had been taking large doses of curcumin. In the absence of other recent precipitating factors, it was highly likely that she had curcumin-triggered apoplexy of a pituitary macroadenoma. Most recent bloodwork, about 20 months from presentation, revealed a serum prolactin of 5.0 ug/L, IGF-1 of 123ng/mL (Z score -0.6), TSH of 0.97 mIU/L with a free T4 of 0.85 ng/dL, a random cortisol of 5.3 ug/dL, ACTH of 18.2 pg/mL, DHEA-S of 94 ug/dL, LH of 2.5 IU/L, FSH of 4.3 IU/L, and an estradiol of 45 pg/mL. Regular menstrual cycles had resumed. Headaches, nausea, and vision abnormalities completely resolved.The case illustrates the need to identify any herbal remedies and supplements a patient is taking, particularly turmeric, as supplements may contribute to increased bleeding tendency of an already existing adenoma. The case also emphasizes the potential rapid recovery of pituitary function after surgical resection of an apoplectic pituitary tumor.> Presentation: 6/3/2024

A SYSTEMATIC REVIEW OF THE EFFECTIVENESS OF TURMERIC IN THE TREATMENT OF BREAST CANCER

Breast cancer remains a significant global health concern, necessitating the exploration of innovative therapeutic strategies. Curcumin, a bioactive compound derived from turmeric, has garnered considerable attention due to its diverse pharmacological properties, including anticancer effects. However, the clinical translation of curcumin is hampered by its poor bioavailability. Nanoformulations of curcumin, particularly Cur-NPs, offer a promising solution to this challenge by enhancing drug solubility, stability, and targeted delivery. This in-depth abstract delves into the potential of Cur-NPs as a therapeutic approach for breast cancer treatment. The systematic review included in vivo studies investigating the efficacy and toxicity of Cur-NPs in breast cancer models. Notably, Cur-NPs demonstrated significant antitumoral activity across diverse breast cancer models, attributed to mechanisms such as apoptosis induction, inhibition of proliferation, and suppression of angiogenesis. Moreover, Cur-NPs exhibited minimal toxicity, with no or low adverse effects observed in terms of body weight, organ histopathology, and hematological/biochemical parameters. Characterization of Cur-NPs revealed a diverse array of nanoparticle types, including polymer NPs, micelles, lipid-based NPs, and metal NPs. Poly(ethylene glycol) chains were commonly incorporated into NP compositions, enhancing their biocompatibility and circulation time. Targeting moieties such as folic acid and hyaluronic acid further augmented the specificity of drug delivery to breast cancer cells. Experimental design varied among studies, encompassing different animal models, routes of administration, and treatment durations. Intravenous administration emerged as the predominant route, although alternative routes such as intraperitoneal and intratumoral administration were also explored. The onset of treatment protocols varied based on days after tumour induction or tumour volume, with curcumin doses ranging from 2 to 100 mg/kg and administered with varying frequencies. In conclusion, Cur-NPs represent a promising therapeutic approach for breast cancer treatment, offering enhanced efficacy and safety profiles compared to free curcumin. Further research is warranted to optimize Cur-NP formulations and elucidate their clinical potential in breast cancer patients. The review also identified a diverse array of nanoparticle formulations employed in breast cancer therapy, including liposomes, polymeric nanoparticles, micelles, and dendrimers. These nanoparticles were engineered to encapsulate various anticancer drugs, including chemotherapeutic agents, molecularly targeted therapies, and immunomodulators, with the aim of enhancing their efficacy and reducing systemic toxicity. Targeted drug delivery strategies were employed to selectively deliver therapeutic agents to tumour cells while sparing healthy tissues, thereby minimizing off-target effects and improving treatment outcomes. Preclinical studies provided compelling evidence of the efficacy of nanoparticle-based therapies in inhibiting tumour growth, suppressing metastasis, and overcoming drug resistance in breast cancer models. Nanoparticles demonstrated superior pharmacokinetic properties, enhanced bioavailability, and controlled drug release kinetics, leading to improved therapeutic efficacy compared to conventional formulations. Furthermore, nanoparticle-based therapies exhibited synergistic effects when combined with traditional chemotherapy agents, leading to enhanced antitumor activity and reduced treatment resistance. Clinical studies evaluating the safety and efficacy of nanoparticle-based therapies in breast cancer patients demonstrated promising results, with favourable tolerability profiles and encouraging preliminary efficacy outcomes. However, challenges remain in translating preclinical findings into clinical practice, including issues related to scalability, manufacturing, and regulatory approval. Additionally, further research is needed to optimize nanoparticle formulations, tailor treatment strategies to individual patient profiles, and elucidate long-term safety and efficacy outcomes.

Clinical Assessment of Breast Cancer Resistance Protein (BCRP)-Mediated Drug-Drug Interactions of Sepiapterin with Curcumin and Rosuvastatin in Healthy Volunteers.

Sepiapterin, also known as PTC923 and CNSA-001, is a synthetic form of endogenous sepiapterin being developed as a novel oral treatment for phenylketonuria. Sepiapterin is a natural precursor of tetrahydrobiopterin (BH4) and, when orally administered, is converted to BH4 via the pterin salvage pathway. In vitro studies have demonstrated that both sepiapterin and BH4 are both substrates and inhibitors of the breast cancer resistance protein (BCRP) transporter. This phase I study investigated BCRP-mediated drug-drug interactions of sepiapterin as a victim and as a perpetrator. An open-label, fixed-sequence, four-period, crossover, single-dose study was conducted in adult male and female healthy volunteers (18-55 years of age). In a given treatment period, subjects received a single oral dose of sepiapterin (20 mg/kg), sepiapterin (20 mg/kg) plus curcumin (2 g), rosuvastatin (10 mg), or rosuvastatin (10 mg) plus sepiapterin (60 mg/kg). The pharmacokinetics of sepiapterin, its metabolite BH4, and rosuvastatin were studied, and geometric mean ratios of exposures in the presence and absence of the BCRP inhibitor curcumin or sepiapterin were estimated. The presence of the BCRP c.421C>A polymorphism was evaluated in all subjects. A total of 29 subjects were enrolled and included in the safety analysis. Among them, 26 subjects were included in the pharmacokinetic and drug-drug interaction analyses. Following oral administration20 mg/kg sepiapterin, sepiapterin was rapidly and extensively converted to BH4, and BH4 maximum observed concentration (415.0 ng/mL) was observed 4.95 h (time to maximum observed concentration) post-dose. Sepiapterin maximum observed concentration and area under the concentration-time curve from time 0 to time of the last quantifiable measurement or the last sample collection time (AUClast) were <1% of BH4 values. Coadministration of the BCRP inhibitor curcumin (2 g) increased BH4 maximum observed concentration, AUClast, and area under the concentration-time curve from time 0 extrapolated to infinity by 24%, 21%, and 20%, respectively. When sepiapterin was coadministered with the BCRP substrate rosuvastatin, there was no effect on the pharmacokinetics of rosuvastatin. BCRP c.421C/A carriers (n = 4) had higher plasma exposures of BH4 (1.39 × for AUClast) and rosuvastatin (1.61 × for AUClast) than c.421C/C carriers (n = 22). Greater increases in BH4 exposures (1.33 vs 1.18 for AUClast) were observed in c.421C/A carriers compared with c.421C/C carriers when sepiapterin was coadministered with curcumin. All treatments were well tolerated during the study. Oral coadministration of the BCRP inhibitor curcumin slightly increased the plasma exposure of sepiapterin and its metabolite BH4 in healthy volunteers. This modest increase was deemed not clinically meaningful. Sepiapterin did not alter the pharmacokinetics of the BCRP substrate rosuvastatin.

Curcumin suppresses copper accumulation in non-small cell lung cancer by binding ATOX1

BackgroundNon-small cell lung cancer (NSCLC) is associated with intracellular copper accumulation. Antioxidant 1 (ATOX1) is a copper chaperone. This study aimed to analyze the anti-cancer effects of curcumin on the ATOX1-mediated copper pathway in NSCLC.MethodsA binding activity between curcumin and ATOX1 was measured using molecular docking. NSCLC cells, A549 and H1299, were treated with different doses of curcumin (10, 20, 40 µM) or DC-AC50 (5, 10, 20 µM) for 24 h. The cell viability and levels of ATOX1, ATP7A and COX17 proteins were observed in cells. Overexpressing ATOX1 in cells was established by pcDNA3.1-ATOX1 transfection for 24 h. The ATOX1 overexpressing cells were treated with 40 µM curcumin or 20 µM DC-AC50 for 24 h to analyze the mechanism of curcumin in NSCLC treatment. Cell viability was measured by CCK-8, and levels of proteins were measured by western blotting. The copper level in cells was labeled by copper sensor-1. Moreover, nude mice models were induced by injection of A549 cells and treated with 20 mg/kg/d DC-AC50 or 40 mg/kg/d curcumin. Tumor growth was observed by measuring tumor volume and tumor weight. The levels of ATOX1, ATP7A and COX17 in tumors were measured by immunohistochemistry and western blotting.ResultsCurcumin bound to ATOX1 (score = −6.1 kcal/mol) and decreased the levels of ATOX1, ATP7A and COX17 proteins in NSCLC cells. The curcumin or DC-AC50 treatment suppressed cell viability by inhibiting the ATOX1-mediated copper signaling in NSCLC cells. The ATOX1 overexpression in cells significantly weakened the effects of curcumin on suppressing copper accumulation and the ATOX1-mediated copper pathway (p < 0.05). In mice models, curcumin or DC-AC50 treatment also suppressed tumor growth by suppressing the ATOX1-mediated copper pathway in tumors.ConclusionThis study demonstrated that curcumin bound ATOX1 to suppress copper accumulation in NSCLC cells, providing a new mechanism of curcumin for NSCLC treatment.

Curcumin Treatment Ameliorates Hepatic Insulin Resistance Induced by Sub-chronic Oral Exposure to Cadmium LOAEL Dose via NF-κB and Nrf2 Pathways.

Cadmium (Cd) is a global pollutant, and its accumulation in the liver causes oxidative stress, inflammation, insulin resistance (IR), and metabolic complications. This study investigated whether curcumin treatment could alleviate hepatic IR in Wistar rats exposed to sub-chronic cadmium and explored the underlying molecular pathways. Male Wistar rats were divided into a control group (standard normocaloric diet + cadmium-free water) and a cadmium group (standard normocaloric diet + drinking water with 32.5ppm CdCl2) for 30days. Oral glucose tolerance, insulin response, and IR were assessed using mathematical models. Liver tissue was analyzed for markers of oxidative stress, inflammation, and key regulatory pathways, including NF-κB, Nrf2, MAPKs (JNK and p38), and the IRS1-Akt pathway. We established an effective curcumin dose of 250mg/kg for 5days orally. Results demonstrated that after 30days of exposure, cadmium accumulated in the liver, inducing an oxidative and inflammatory state. This was characterized by increased expression of NF-κB, JNK, and p38, along with diminished Nrf2 expression, hepatic IR, hyperglycemia, and hyperinsulinemia. Curcumin treatment effectively alleviated these metabolic disorders by restoring the balance between NF-κB and Nrf2 in the liver, modulating the MAPK pathway, and, consequently, improving oxidative and inflammatory balance. In conclusion, this study suggests that cadmium induces hepatic IR through an imbalance between NF-κB and Nrf2 signaling pathways. Curcumin treatment appears to improve these pathways, thereby ameliorating hepatic IR.

In Vitro Effects of Curcumin in Free and Phytosomal Forms on the Expression of T Helper1 and Regulatory T Cells' Transcription Factors in Collagen-Induced Arthritis.

Curcumin as a polyphenolic compound has a potential capacity to reduce autoimmune reactions by skewing the balance of Thelper1 (Th1)/regulatory T cells (Treg) toward Treg cells. However, the low absorption and bioavailability of this agent have prompted researchers to use various drug delivery systems such as phytosomes to reduce these drawbacks. To date, few studies have evaluated the effects of phytosomal curcumin (nano-curcumin) on immune responses. Hence, we compared the modulatory effects of curcumin in free and phytosomal form on the expression of Th1 and Treg transcription factors, T-bet (T-box-containing protein) and Foxp3 (forkhead box p3), respectively, in a collagen-induced arthritis model (CIA). Following the induction of CIA, splenocytes were isolated and re-stimulated with collagen in the absence or presence of two different doses of curcumin in free and phytosomal form. Then, expression of T-bet and Foxp3 was assessed by real-time PCR. The expression of T-bet was reduced in curcumin and phytosomal curcumin groups rather than in the untreated group. The level of T-bet was not significantly different between free and phytosomal groups. Moreover, mRNA expression of Foxp3 enhanced after treatment with curcumin, while phytosomal curcumin groups showed no difference in comparison with the untreated group. curcumin in nano/free form showed a modulatory effect on the expression of T-bet. However, only free-form enhanced Foxp3 expression, which could be owing to the low amount of curcumin in the phytosomal complex rather than free-form at the same dose or due to leakage of curcumin from the complex.

Assessment of metabolic interaction between curcumin and tramadol using the isolated perfused rat liver

IntroductionThe presence of phytochemicals in herbal medicines can lead to herb-drug interactions, altering the levels of these compounds and conventional drugs in the bloodstream by influencing CYP450 activity. Considering curcumin's effect on the CYP enzymes responsible for tramadol metabolism, it is essential to assess the potential interaction between curcumin and tramadol when administered together. Materials and methodsThe pharmacokinetics of tramadol were examined in rats receiving either single or multiple doses of curcumin (80 mg/kg) compared to rats without curcumin treatment. Tramadol liver perfusion was conducted on all rat groups and perfusate samples were collected at specified intervals. Tramadol and its main metabolite were detected using an HPLC system coupled with a fluorescence detector. ResultsTramadol concentrations were notably higher in the co-administered group compared to both the control and treatment groups. Conversely, lower concentrations of M1 were observed in the co-administered and treatment groups compared to the control group. The AUC0-60 parameters for tramadol were as follows: 32944.8 ± 1355.5, 22925.7 ± 1650.1, and 36548.0 ± 2808.4 ng⋅min/ml for the control, treatment, and co-administered groups, respectively. Both the co-administered and treatment groups exhibited a lower AUC0-60 of M1 compared to the control group. The lack of significant difference in Cmax and AUC0-60 of M1 between the treatment and co-administered groups suggests that single and multiple doses of curcumin have comparable effects on CYP2D6. ConclusionsThese results indicate a potential for drug interactions when curcumin and tramadol are taken together. Furthermore, the influence of curcumin on tramadol metabolism varied between single and multiple oral administrations of curcumin. Hence, it is vital to highlight this interaction in clinical settings and conduct additional research to fully understand the clinical implications of combining curcumin and tramadol.

Inhibitory effect of Curcumin on a cervical cancer cell line via the RAS/RAF signaling pathway.

Cervical cancer has a very important place in female infertility and ranks fourth among cancers affecting women. Curcumin (CUR) is closely associated with the expression and activity of various regulatory proteins. It is also known that curcumin has preventive and therapeutic effects on various types of cancer. In this study, the anticancer activities of curcumin were demonstrated in the human cervical cancer cell line (HeLa). qRT-PCR and western blot analyses were used to evaluate mRNA and protein expression of curcumin in HeLa and immortalized human skin keratinocyte cell lines (HaCaT) (proliferation and apoptosis regulatory markers of the RAS/RAF signaling pathway). MTT analysis was performed, showing HeLa and HaCaT cell proliferation depending on the dose and duration of curcumin and doxorubicin. A wound scratch healing assay was applied to examine cell migration and invasion of HeLa after curcumin application. To determine the role of curcumin and doxorubicin in the apoptosis of HeLa cells, the mRNA levels of caspase-3 were examined by qRT-PCR. The results were analyzed with a one-way ANOVA SPSS 20.0 program. CUR (IC50: 242.8 μM) and DOX (IC50: 92.1 μM) were determined to have the ability to inhibit the proliferation of HeLa cells and induce apoptosis over a 72-hour period and dose-dependently. Moreover, the results revealed that the mRNA and protein expression levels of RAF and RAS in HeLa cells were downregulated by CUR and DOX. The findings show that an alternative treatment method for cervical cancer can be developed with the application of CUR and DOX. Alternative methods for cervical cancer treatment may be developed using different methods in future studies.

Therapeutic Effects of Curcumin Nanoparticles against Monosodium Iodoacetate Induced Osteoarthritis in Rats

The experiment involved thirty male rats divided into six groups. One group received saline as a control, another received monosodium iodoacetate (MIA) to induce OA, and the remaining four groups received MIA alongside various treatments: chitosan NPs, curcumin-loaded chitosan at two different doses (150 mg/kg and 300 mg/kg), or ibuprofen, a common pain medication. The researchers monitored changes in the knee joints by measuring their diameter and examining X-ray images throughout the experiment. The results revealed that curcumin nanoparticles, particularly at the higher dose (300 mg/kg), were significantly more effective than chitosan or the lower curcumin dose (150 mg/kg) in reducing joint swelling and preventing cartilage degeneration. Interestingly, this higher dose of curcumin nanoparticles demonstrated effectiveness comparable to ibuprofen. These findings suggest that curcumin nanoparticles have the potential to be a valuable therapeutic agent for OA. Their anti-inflammatory properties may offer relief from pain and swelling in the joints, while the nanoparticle delivery system may improve curcumin's bioavailability and effectiveness compared to traditional curcumin. The study paves the way for curcumin nanoparticles as a potential alternative to NSAIDs for OA patients who experience side effects or intolerance to these medications.

Meta-analysis of the effect of curcumin supplementation on skeletal muscle damage status.

Meta-analysis was conducted to examine the effect of supplemental curcumin intake on skeletal muscle injury status and to propose an optimal intervention program. In accordance with the procedures specified in the PRISMA statement for systematic reviews and meta-analyses of randomized controlled trials, the Review Manager 5.3 was used to analyze the results of creatine kinase (CK), muscle soreness, interleukin-6 (IL-6), and range of motion (ROM) as outcome indicators in the 349 subjects included in the 14 articles. The effect size of curcumin supplementation on muscle soreness, mean difference (MD) = -0.61; the relationship between curcumin supplementation and muscle soreness for time of measurement (I2 = 83.6%)、the relationship between curcumin supplementation and muscle soreness for period of intervention (I2 = 26.2%)、the relationship between whether one had been trained (I2 = 0%) and supplementation dose (I2 = 0%) were not heterogeneous for the relationship between curcumin supplementation and muscle soreness; The effect size on CK, MD = -137.32; the relationship between curcumin supplementation and CK (I2 = 79.7%)、intervention period (I2 = 91.9%)、whether or not trained (I2 = 90.7%)、and no heterogeneity in the relationship between curcumin supplementation and CK for the time of measurement (I2 = 0%); The effect size MD = 4.10 for the effect on ROM; The effect size for IL-6 was MD = -0.33. This meta-analysis highlights that curcumin supplementation significantly mitigates skeletal muscle damage, with notable improvements in CK levels, muscle soreness, IL-6 levels, and ROM. The results highlight the importance of curcumin dosage and timing, revealing that prolonged supplementation yields the best results, especially for untrained individuals or those less exposed to muscle-damaging exercise. For muscle soreness and ROM enhancement, a pre-emptive, low-dose regimen is beneficial, while immediate post-exercise supplementation is most effective at reducing CK and IL-6 levels.

Curcumin ameliorates pyroptosis in diabetic seminal vesicles by upregulating TRPV6.

Diabetes damages the seminal vesicle tissues leading to a decrease in seminal fluid secretion, so investigations are ongoing to identify specific therapeutic approaches to address diabetes-induced damage to seminal vesicles. This study investigated the secretory dysfunction of seminal vesicles and how curcumin can ameliorate this dysfunction. First, 40 diabetic males (DM group) and 40 nondiabetic males (control group) underwent seminal vesicle ultrasound evaluation and ejaculate volume measurements. Then, the effects of curcumin on seminal vesicle function were investigated in a diabetic rat model. Fifty 8-week-old SPF-grade SD rats were categorized into five groups: control, DM (diabetes mellitus), low-dose CUR (curcumin 50mg/kg/d), medium-dose CUR (curcumin 100mg/kg/d), and high-dose CUR (curcumin 150mg/kg/d). After a month-long diet with varying curcumin doses, key parameters such as body weight, blood glucose levels, seminal vesicle volume, and seminal fluid secretion were measured. Transcriptome sequencingwas performed to assess differences in gene expression and structural changes in rat seminal vesicle tissues were examined by HE staining. Finally, human seminal vesicle cell lines were cultured and divided into five groups (HG-CON, HG-CUR-5µM, HG-CUR-10µM, HG-CUR-20µM, and HG-CUR-50µM) to measure the fructose levels in the seminal vesicle cell culture fluids and evaluate the expression of CASP1, GSDMD, and TRPV6. Post TRPV6 interference, variations in the gene expression of CASP1, GSDMD, and TRPV6 were monitored. Diabetic patients exhibited a notable reduction in seminal vesicle volume and ejaculate volume compared with the control group, with a direct correlation between the decrease in ejaculate and seminal vesicle volume. Animal studies demonstrated that curcumin supplementation significantly augmented seminal vesicle volume in diabetic rats and notably improved their seminal vesicle secretory dysfunction, particularly in the high-dose curcumin group. Transcriptome sequencing and experimental verification pinpointed the differential expression of TPRV6 and pyroptosis-associated genes (CASP1, GSDMD), with reduced TRPV6 expression but increased markers of pyroptosis (CASP1 and GSDMD) in diabetic rats. Curcumin treatment reversed these effects with an increase in TRPV6 and a decrease in GSDMD and CASP1. Cell transfection experiments indicated that TRPV6 downregulation increased GSDMD and CASP1 gene expression. Curcumin effectively activates TRPV6, thereby diminishing pyroptosis in the seminal vesicle tissues of diabetic rats. This activation not only leads to an increase in the seminal vesicle volume but also significantly ameliorates the seminal vesicle secretory dysfunction in diabetic rats.

Does curcumin improve liver enzymes levels in nonalcoholic fatty liver disease? A systematic review, meta-analysis, and meta-regression.

The aim of this meta-analysis is to investigate the sources of heterogeneity in randomized clinical trials examining the effects of curcumin supplementation on liver aminotransferases in subjects with nonalcoholic fatty liver disease (NAFLD). We conducted a systematic search of the PubMed, SCOPUS, and Web of Science databases for randomized clinical trials and identified 15 studies (n = 835 subjects). We used random-effects models with DerSimonian-Laird methods to analyze the serum levels of alanine aminotransferase and aspartate aminotransferase enzymes. Our results indicate that curcumin did not affect serum alanine aminotransferase, but it did reduce aspartate aminotransferase levels. Notably, both outcomes showed high heterogeneity (p < 0.01). Subgroup analysis revealed that adding piperine to curcumin did not benefit aminotransferase levels in NAFLD patients. Additionally, we found a negative correlation between the duration of the intervention and the relative (mg/kg/day) curcumin dose with the reduction in liver aminotransferases. In summary, the sources of heterogeneity identified in our study are likely attributed to the duration of the intervention and the relative dose of curcumin. Consequently, longer trials utilizing high doses of curcumin could diminish the positive impact of curcumin in reducing serum levels of aminotransferases in patients with NAFLD.

Folate-Modified Curcumin-Loaded Nanoparticles for Overcoming Delivery Challenges in Cancer Treatment: A Narrative Review.

Curcumin, as an anti-tumor agent, is not widely used in cancer treatment due to the lack of effective levels of its metabolites in cancerous tissue. Addressing the barriers to the carrier and delivery of drugs to the specific sites of therapeutic action while reducing side effects is a priority. Folate receptor expression is high in malignant and low in normal cells. Folate as a targeted ligand could selectively target cancer cells. Thus, this narrative review aimed to provide an overview of the studies that have investigated the different types of folate-modified curcumin as a carrier and deliverer and their structural properties that enhance therapeutic drug efficacy. A literature search was performed using PubMed, Scopus, Web of Science, and Google Scholar databases. Thirty-eight preclinical studies addressing this topic were identified. The findings of the current review have shown that folate-modified nanoparticles containing curcumin as a promising therapeutic approach can be effective in improving different types of cancers. In vitro studies have shown a higher cellular uptake and cytotoxicity effect, higher cell inhibition, and anti-proliferation with a lower dosage of curcumin. In vivo studies have shown more tumor suppression and smaller tumor volume without toxicity after the administration of folate-modified nanoparticles containing curcumin. Future clinical trials are needed to confirm the beneficial effect of folate-modified curcumin as a new drug delivery platform for cancer treatment.

Mitigation of Karenia brevis Cells and Brevetoxins Using Curcumin, a Natural Supplement

Curcumin, a natural plant product, was investigated as a mitigation tool against Karenia brevis, the toxic dinoflagellate responsible for Florida red tides. A series of laboratory bench-top studies were conducted with additions of 0.1, 1, 2, 3, 5, 10, 20, 30, and 40 mg/L curcumin to K. brevis at an average of 1.0 × 106 cells/L to determine the efficacy of curcumin against K. brevis cells and brevetoxins and to optimize treatment dosage. Treatment with 5 mg/L of curcumin reduced K. brevis cell abundance by 89% and total brevetoxins by 60% within 24 h. Lower concentrations of curcumin (0.1–3 mg/L) exhibited between a 2 and 45% reduction in K. brevis and a reduction in brevetoxins of between 2 and 44% within 24 h. At the highest curcumin doses, 30 and 40 mg/L, a 100% reduction in cell abundance was observed by 6 h, with reduction in total brevetoxins by at least 64% in 48 h. These results suggest that curcumin, used alone or potentially in combination with other technologies, is a promising K. brevis bloom mitigation option.

Curcumin’s effects on growth indices, histological scores, blood metabolites, redox state, immunity, and antioxidant-related genes of red tilapia (Oreochromis sp.)

Curcumin, a polyphenol, targets multiple signaling molecules and shows activity at the cellular level, supporting its various health benefits. Thereafter, the present study examines the effects of different doses of dietary curcumin on growth indices, feed efficiency, serum metabolites, redox (oxidation) status, immunity, histological assessment, and antioxidant-related genes in red tilapia (Oreochromis sp, Oreochromis aureus x O. mossambicus). A total of 1200 red tilapia with an average weight of 19.1±0.03 g were distributed in 12 cement ponds (3×3.5×1m). Each treatment was assigned three pounds (n=100 replicates). For 60 days, fish were fed baseline diets containing 0, 0.4, 0.6, and 0.8 g of curcumin/kg of diet. The treated fish showed increased body weight and SGR (specific growth rate) compared to the T0 group (P<0.05). Curcumin in the diet significantly improved weight gain, percentages, and FCR (feed conversion ratio), with a dose-dependent effect (P < 0.05). Curcumin supplementation showed no influence on feed intake, fish mortality, or survival rate (P >0.05). The curcumin-treated fish groups improved tissue structure in hepatocytes, pancreatic lumens, hepatic blood sinusoids, and intestine tissue layers, particularly the mucosal layer. The T0.8 group had reduced liver enzymes (AST and ALT) and greater total protein and albumin levels (P<0.05). The T0.6 and T0.8 groups showed significantly lower MDA levels than the other groups (P < 0.05). Curcumin groups demonstrated significantly higher antioxidant indices (CAT, GPx, and SOD) compared to the basal diet (P<0.05). Curcumin administration resulted in significant improvements in IgM and lysosome levels (P<0.05). All supplemented groups had considerably (P<0.05) higher levels of SOD, CAT, and GPx mRNA than the control group. Consequently, administering 0.6–0.8 g/kg of curcumin to red tilapia (Oreochromis sp.) diets may improve the fish’s growth, health, tissue composition, and antioxidant response.

A low dose of curcumin-PDA nanoparticles improves viability and proliferation in endoneurial fibroblasts and Schwann cell cultures

Curcumin is a polyphenol extracted from Curcuma longa’s roots. Low doses of curcumin are related to anti-inflammatory, antioxidant, and neuroprotective effects, while high doses are used for their lethality. This diversity of behaviors allows us to understand curcumin as a compound with hormetic action. Due to its strongly hydrophobic character, curcumin is often solubilized in organic compounds. In this way, we have recently reported the undesirable and occasionally irreversible effects of alcohol and DMSO on the viability of primary Schwann cell cultures. In this scenario, the use of nanoparticles as delivery systems has become a successful alternative strategy for these compounds. In the present work, we describe the structure of Polydopamine (PDA) nanoparticles, loaded with a low dose of curcumin (Curc-PDA) without the use of additional organic solvents. We analyzed the curcumin released, and we found two different forms of curcumin. Small increased cell viability and proliferation were observed in endoneurial fibroblast and Schwann cell primary cultures when Curc-PDA was steadily supplied for 5 days. The increased bioavailability of this natural compound and the impact on cells in culture not only confirm the properties of curcumin at very low doses but also provide a glimpse of a possible therapeutic alternative for PNS conditions in which SCs are involved.

Curcumin as a Multifunctional Spice Ingredient against Mental Disorders in Humans: Current Clinical Studies and Bioavailability Concerns.

Mental disorders in terms of depression, anxiety, and stress are one of the major causes of burden globally. Over the last two decades, the use of plant-based substances in the treatment of mental disorders in combination or not with medication has increasingly attracted the interest of the scientific research community. However, even if there is a plethora of naturally occurring bioactive compounds, most of them have low bioavailability, rendering them unable to insert into the bloodstream to exert their biological activities. This is a comprehensive narrative review that critically summarizes and scrutinizes the new approaches to the treatment of mental disorders using curcumin, also highlighting its bioavailability properties. The most accurate were searched using effective and relevant keywords. This narrative review reveals substantial evidence that curcumin can exert significant effects on several mental disorders. However, despite the low cost, the extensive and confirmed potency of curcumin and its involvement in signaling pathways and the scientifically confirmed data regarding its molecular mechanisms of action against mental disorders, this naturally occurring compound presents low oral bioavailability. Pharmaceutical technology has provided solutions to increase the bioavailability of curcumin. Combination with piperine, galactomannosides, liposomal formulation or nanoformulation overcomes the bioavailability and solubility disadvantages. Although curcumin demonstrates anti-anxiety, anti-depressive and anti-stress properties, studies on humans are limited and heterogeneous. Further research is highly recommended to determine the most functional formula, dose, duration, and possible side effects of curcumin on mental disorders in humans. Based on the current knowledge, the curcumin nanoformulation and Theracurmin, a form of colloidal submicroscopic particles, seem to be the most effective bioavailable formulations, which may be examined in future clinical human studies.