Inflammatory and Metabolic Biomarker Assessment in a Randomized Presurgical Trial of Curcumin and Anthocyanin Supplements in Patients with Colorectal Adenomas.

Colorectal cancer prevention is crucial for public health, given its high mortality rates, particularly in young adults. The early detection and treatment of precancerous lesions is key to preventing carcinogenesis progression. Natural compounds like curcumin and anthocyanins show promise in impeding adenomatous polyp progression in preclinical models. We conducted a randomized, double-blind, placebo-controlled, phase II presurgical trial in 35 patients with adenomatous polyps to explore the biological effects of curcumin and anthocyanins on circulating biomarkers of inflammation and metabolism. No significant difference in biomarker changes by treatment arm was observed. However, the network analysis before treatment revealed inverse correlations between adiponectin and BMI and glycemia, as well as direct links between inflammatory biomarkers and leptin and BMI. In addition, a considerable inverse relationship between adiponectin and grade of dysplasia was detected after treatment (corr = -0.45). Finally, a significant increase in IL-6 at the end of treatment in subjects with high-grade dysplasia was also observed (p = 0.02). The combined treatment of anthocyanins and curcumin did not result in the direct modulation of circulating biomarkers of inflammation and metabolism, but revealed a complex modulation of inflammatory and metabolic biomarkers of colon carcinogenesis.

Multifunctional nanoparticles encapsulating methotrexate and curcumin for holistic management of rheumatoid arthritis: in-vitro and pre-clinical assessment.

PURPOSE: Bovine serum albumin (BSA) nanoparticles (BSA-MTX-CUR-NPs) encapsulating methotrexate (MTX) and curcumin (CUR) was developed with an aim to co-deliver the drugs at the inflamed joint so as to maximize the therapeutic efficacy and alleviate toxic side effects associated with MTX. METHODS: Nanoparticle albumin-bound technology was used to formulate nanoparticles, followed by characterization for its particle size, polydispersity index, encapsulation efficiency, zeta potential, surface morphology, in-vitro drug release and drug release kinetics. Further, we investigated the pharmacokinetics and pharmacodynamics of the developed nanoparticles in the adjuvant-induced arthritis model. RESULTS: BSA-MTX-CUR-NPs exhibited particle size of 163.05 ± 1.708 nm, polydispersity index of 0.195 ± 0.0024 and % encapsulation efficiency of 68.23 ± 0.640% for MTX and 75.71 ± 0.216% for CUR with controlled release pattern for both the drugs. The scanning electron microscopy revealed nanoparticles exhibited a spherical shape. DSC study confirmed the absence of incompatibility between the drugs and the excipients. Half-life and area under the curve were significantly higher for MTX in the nanoparticulate form in comparison to free MTX. Pharmacodynamic studies revealed that BSA-MTX-CUR-NPs possessed better disease-modifying effects in comparison to free MTX. CONCLUSION: Hence, it can be concluded that albumin nanoparticles constitute a viable method for delivering MTX and CUR to inflamed joints simultaneously, because of the strong affinity of albumin and enhanced permeability and retention effect at the inflamed joint. This combinational therapy of MTX & CUR in nanoparticulate form has the potential for the holistic management of rheumatoid arthritis.

Assessment of the Anti-inflammatory Effects of NORFLO® ORO in Acute Relapses of HLA-B27-associated Autoimmune Uveitis: A Multicenter, Randomized, Placebo-controlled, Double-blind Clinical Study.

BACKGROUND: An effective therapy to reduce the number and severity of HLA-B27-related acute anterior uveitis (AAU) recurrences represents a clinical need. Curcumin is a promising therapeutic option in various inflammatory eye diseases. To enhance its absorption and eye tissue selectivity, a phospholipidic-curcumin complex (PHBC) has been formulated (Iphytoone®, Eye Pharma S.p.A.). AIMS: This study investigates if PHBC is effective and safe to decrease the number and intensity of HLA-B27-related AAU relapses. METHODS: HLA-B27-related AAU patients were randomly divided to receive PHBC or placebo for 12 months (NCT03584724). RESULTS: Compared with the previous year, the number of relapses decreased in both groups. The proportion of responders was significantly higher in the PBHC group. The severity of attacks was comparable. The study drug was well tolerated. CONCLUSIONS: A beneficial effect of PHBC treatment is suggested because the proportion of responders was significantly higher in this group of patients.

Curcumin/H2O2 photodynamically activated: an antimicrobial time-response assessment against an MDR strain of Candida albicans.

OBJECTIVE: Human candidiasis is typically treated with antifungal drugs, but the rise of drug-resistant strains of Candida spp. poses a serious problem, making treatment difficult. At the same time, photodynamic therapy (PDT) has drawn increasing attention from researchers for its potential to effectively inhibit multidrug-resistant pathogenic fungi and for its low tendency to induce drug resistance. This study's goal was to examine how a multidrug-resistant oral isolate of Candida albicans responded to a PDT that used a curcumin/H202 formulation as a photosensitizer and was exposed to various light sources. MATERIALS AND METHODS: A commercial product containing curcumin/H2O2 3% was used as a photosensitizer and evaluated in a PDT treatment that can use two different light sources: traditional irradiation with 7 W light at λ = 460 nm or a new, never evaluated, polarized light source of 25 W with a wavelength range of λ = 380-3,400 nm. The antimicrobial activity of these procedures was assessed on a clinical oral isolate of Candida albicans, in terms of agar susceptibility test, growth curve behavior, and biofilm inhibition. RESULTS: Both light sources were able to activate the photosensitizer formulation, suggesting a fungistatic activity vs. this C. albicans MDR strain. An interesting difference was observed in the cell-generation-time (CGTOD) after PDT treatment, where the polarized light was more active compared to the source of 460 nm. In fact, CGTOD was 16 and 8 hours, respectively. CONCLUSIONS: The PDT evaluated here presented an inhibition window time, a crucial point for clinicians, who could activate an additional prophylactic treatment to resolve the clinical management of Candida infections in the oral cavity.

Curcumin-Based Treatment for Macular Edema from Uncommon Etiologies: Efficacy and Safety Assessment.

The aim of this study was to investigate the efficacy and safety of curcumin formulation with a polyvinylpyrrolidone-hydrophilic carrier (CHC*; Diabec®-AlfaIntes, Italy) for the treatment of macular edema (ME) from uncommon etiologies. We conducted retrospective interventional case series, reviewing the medical records of patients referred to the Eye Center, Humanitas Hospital, Bergamo due to persistent ME related to uncommon causes and treated by oral administration of CHC. The main outcomes assessed were best-corrected visual acuity (BCVA), central macular thickness (CMT), and the presence of intraretinal and/or subretinal fluid (SRF). Only patients with a minimum follow-up (f/u) of 6 months were included. The occurrence of any adverse effect was registered. Thirty-one eyes of 30 patients were included, with a mean f/u of 8.32 ± 1.77 months. Of them, 9 patients (10 eyes) were affected by postoperative ME and 21 by chronic central serous chorioretinopathy. Median BCVA significantly improved after treatment, changing from 0.3 [0.16-0.5] to 0.1 [0-0.3] logarithm of the minimum angle of resolution (P < .001). Also CMT was significantly improved, as it decreased from 400 [364-438] µm before treatment to 280 [242-307] µm at the last f/u visit (P < .001). The complete absorption of intraretinal/SRF was detected in 23 of 31 eyes (74%) at the final f/u. No adverse effects were registered. In conclusion, treatment with CHC was effective and safe for eyes affected by ME of various uncommon etiologies, resulting in significant improvement of both functional and anatomical outcomes, with the complete resolution of the edema in the majority of cases (74%).

Coadministration of Polypeptide-k and Curcumin Through Solid Self-Nanoemulsifying Drug Delivery System for Better Therapeutic Effect Against Diabetes Mellitus: Formulation, Optimization, Biopharmaceutical Characterization, and Pharmacodynamic Assessment.

An attempt has been made to prepare solid self-nanoemulsifying drug delivery system (SNEDDS) of polypeptide-k (PPK) and curcumin (CRM) using Labrafil M1944 CS as oil, Tween-80 as surfactant, Transcutol P as cosurfactant and Aerosil-200 (A-200) as porous hydrophobic carrier for improving their antidiabetic potential through oral delivery. Box-Behnken Design was used to optimize the liquid formulation based on the results of the mean droplet size, polydispersity index, percentage drug loading, and zeta potential. The formulation was adsorbed on Aerosil-200 through spray drying. The formulation showed desirable micromeritic, disintegration, and dissolution properties. About fivefold rise in the dissolution and permeation rate for drugs was observed from formulations vis a vis their unprocessed forms. The formulation was found to be stable with variation in pH, dilution, and temperature. The individual solid SNEDDS formulation of PPK and CRM and their combination were evaluated for antidiabetic potential and the results were compared with their naive forms on streptozotocin-induced diabetic rats. The results revealed better control of serum glucose level and other biochemical tests, such as liver parameters, lipid profiles, and antioxidant levels, as well as histological evaluation of pancreatic tissues in all the solid SNEDDS formulation as compared with their naive forms.

Prostate Cancer Disparity, Chemoprevention, and Treatment by Specific Medicinal Plants.

Prostate cancer (PC) is one of the most common cancers in men. The global burden of this disease is rising. Its incidence and mortality rates are higher in African American (AA) men compared to white men and other ethnic groups. The treatment decisions for PC are based exclusively on histological architecture, prostate-specific antigen (PSA) levels, and local disease state. Despite advances in screening for and early detection of PC, a large percentage of men continue to be diagnosed with metastatic disease including about 20% of men affected with a high mortality rate within the African American population. As such, this population group may benefit from edible natural products that are safe with a low cost. Hence, the central goal of this article is to highlight PC disparity associated with nutritional factors and highlight chemo-preventive agents from medicinal plants that are more likely to reduce PC. To reach this central goal, we searched the PubMed Central database and the Google Scholar website for relevant papers. Our search results revealed that there are significant improvements in PC statistics among white men and other ethnic groups. However, its mortality rate remains significantly high among AA men. In addition, there are limited studies that have addressed the benefits of medicinal plants as chemo-preventive agents for PC treatment, especially among AA men. This review paper addresses this knowledge gap by discussing PC disparity associated with nutritional factors and highlighting the biomedical significance of three medicinal plants (curcumin, garlic, and Vernonia amygdalina) that show a great potential to prevent/treat PC, as well as to reduce its incidence/prevalence and mortality, improve survival rate, and reduce PC-related health disparity.

Curcumin restores rotenone induced depressive-like symptoms in animal model of neurotoxicity: assessment by social interaction test and sucrose preference test.

Environmental toxin rotenone has been associated to with increased Parkinson's disease (PD) prevalence in population. Depression is one of the main non-motor symptoms of PD. Curcumin exhibits neuroprotective action in neurodegenerative diseases. In the study we investigated the effect of pre- and post-treatment of curcumin on rotenone-induced depressive-like behaviors and neurotransmitter alterations in rat model of PD. In pre-treatment phase rats were administered with curcumin (100 mg/kg/day, p.o.) for 2 weeks. After curcumin treatment rotenone (1.5 mg/kg/day, s.c.) was administered in Pre-Cur + Rot group and rotenone alone group for 8 days. Meanwhile, in Post-Cur + Rot group rotenone was injected for 8 days in order to develop PD-like symptoms. After rotenone administration curcumin (100 mg/kg/day, p.o.) was administered in Post-Cur + Rot group for 2 weeks. Depressive-like behaviors were monitored by the forced swim test (FST), open field test (OFT), sucrose preference test (SPT) and social interaction test (SIT). Animals were decapitated after behavioral analysis, striatum and hippocampus were dissected out for neurochemical estimations. Results showed that the rotenone administration significantly (p < 0.01) produced depressive-like symptoms in all depression-related behavioral test. All these behavioral deficits were accompanied by the reduction of striatal and hippocampal neurotransmitter levels following rotenone administration. Pre- and post-treatment with curcumin significantly (p < 0.01) reversed the depressive-like behavior induced by rotenone and significantly (p < 0.01) improved neurotransmitter levels as compared to rotenone injected rats. Our results strongly suggest that normalization of neurotransmitter levels particularly highlights the antidepressant effect of curcumin against rotenone-induced depressive behavior.

A Quality by Design (QbD) approach to the development of a gradient high-performance liquid chromatography for the simultaneous assay of curcuminoids and doxorubicin from long-circulating liposomes.

The present study highlights the advantages of using an Analytical Quality by Design (AQbD) approach to the optimization of a high-performance liquid chromatography method for the simultaneous assay of curcumin (CUR), demetoxycurcumin (DMC), bisdemetoxycurcumin (BDMC) and doxorubicin (DOX) co-encapsulated in long circulating liposomes. Within the QbD paradigm, the present study aimed to establish the method operable design region (MODR) for the optimization of the high-performance liquid chromatography-fluorescence (HPLC-FLD) assay by means of Design of Experiments (DOE) and response surface methodology, in order to achieve a good separation and quantification of all analyzed compounds along to an acceptable analysis time. A deep understanding of the quality target product profile (QTPP) and of the analytical target profile (ATP), followed by a risk assessment for variables that affect the efficiency of the method led to the development of a precise, accurate and cost-effective method. The assay was linear over the range of 2-20 µg/ml for all investigated compounds. The intra-and inter-day precision were less than 2%, with accuracies between 97-104% of the true values. The method was successfully applied to the quantification of curcuminoids and DOX from long-circulating liposomes.

Alzheimer's disease in the retina: imaging retinal aß plaques for early diagnosis and therapy assessment.

BACKGROUND: Definite Alzheimer's disease (AD) diagnosis at early stages is vital for targeting intervention, yet currently unavailable. Noninvasive detection of the pathological hallmark, amyloid-ß protein (Aß) plaques, is limited in the brain. However, the existence of Aß plaques in the retina, possibly at presymptomatic stages, may improve early detection of AD. OBJECTIVE: To summarize clinical and preclinical evidence showing that the retina, an accessible part of the central nervous system, displays abnormalities in AD, especially Aß plaque pathology. The ability to monitor in vivo retinal plaque dynamics in response to immunotherapy is also assessed. METHODS: Literature analysis of retinal AD pathology and imaging is provided. In our studies, systemic curcumin is administered to enable monitoring of retinal Aß plaques in live APP(SWE)/PS1(Δ)(E9) transgenic mice by optical imaging. RESULTS: Visual and retinal abnormalities, including early manifestation of retinal Aß plaque pathology, have been documented in AD patients and animal models. In mouse models, retinal Aß plaques accumulate with age and decrease in response to immunotherapy, consistent with brain pathology. Here, we demonstrate that retinal plaques can be individually monitored in real time following glatiramer acetate immunization. CONCLUSION: Translation of noninvasive retinal-plaque imaging to humans could eventually facilitate early and accurate AD diagnosis and therapy assessment.

Targeting metabolic syndrome: candidate natural agents.

Following on from impressive economic development and urbanization, China is currently experiencing a high prevalence of metabolic syndrome. Patients with metabolic syndrome suffer from the "The Deadly Quartet" of hyperglycemia, hypertriglyceridemia, hypertension, and central (or upper body) obesity. Current treatment strategies directed towards metabolic syndrome tend to be limited to just one of these four conditions, so developing novel drugs to target multiple metabolic abnormalities could be preferable to current approaches. New insights suggest benefits of natural agents as treatments for metabolic syndrome. Herein, we review the evidence for using nine such agents developed on the basis of traditional medicine or herbal preparations.

The ovariectomized, mature rat model of postmenopausal osteoporosis: an assessment of the bone sparing effects of curcumin.

Identification of natural health products that might benefit skeletal health could reduce the negative impact of osteoporotic bone fractures upon society. The objectives of this study were to evaluate an animal model of postmenopausal osteoporosis and to search for evidence that curcumin reduces bone mineral losses in a dose-dependent manner when endogenous estrogen levels are reduced. Bone mineral density was measured at the spine, femur and whole body before and at 2, 4 and 6 months after ovariectomy in each of 40 mature rats. Serum osteocalcin and C-telopeptide were measured as indicators of bone formation and resorption rates. Femoral compressive strength was measured at 6 months. Ovariectomy alone resulted in loss of mineral from the spine (p<0.005) and an increase in osteocalcin levels (p<0.05). At the same time, there was an increase in energy to fracture (p<0.01) due to an increased bone size. When ovariectomized animals were given etidronate there was no loss of mineral from the spine, the size of the femur increased (p<0.005), C-telopeptide levels were reduced (p<0.001) and femoral compressive strength increased (p<0.025). Administration of curcumin to ovariectomized animals resulted in changes that were intermediate between those produced by etidronate and by ovariectomy alone. The increase in femur size produced by the highest dose of curcumin was statistically significant (p< 0.01) and curcumin administration resulted in a significant, dose dependent, increase in energy to fracture. Curcumin produces beneficial changes in bone turnover and increases in bone strength using the ovariectomized mature rat model of postmenopausal osteoporosis.

From exotic spice to modern drug?

The global demand for more affordable therapeutics and concerns about side effects of commonly used drugs are refocusing interest on Eastern traditional medicines, particularly those of India and China.

Review. Facts and fiction of phytotherapy for prostate cancer: a critical assessment of preclinical and clinical data.

The objective of this work was to substantially review all preclinical and clinical data on phytochemicals, such as genistein, lycopene, curcumin, epigallocatechin-gallate, and resveratrol, in terms of their effects as a potential treatment of prostate cancer. It is known, that prostate cancer patients increasingly use complementary and alternative medicines in the hope of preventing or curing cancer. The preclinical data for the phytochemicals presented in this review show a remarkable efficacy against prostate cancer cells in vitro, with molecular targets ranging from cell cycle regulation to induction of apoptosis. In addition, well-conducted animal experiments support the belief that these substances might have a clinical activity on human cancer. However, it is impossible to make definite statements or conclusions on the clinical efficacy in cancer patients because of the great variability and differences of the study designs, small patient numbers, short treatment duration and lack of a standardised drug formulation. Although some results from these clinical studies seem encouraging, reliable or long-term data on tumor recurrence, disease progression and survival are unknown. At present, there is no convincing clinical proof or evidence that the cited phythochemicals might be used in an attempt to cure cancer of the prostate.