• Cancer chemoprevention
• Dose-response
• Pharmacodynamics
• Plant flavonoids
• ROS

• Humans
• Flavonoids/pharmacology
• Flavonoids/administration & dosage
• Neoplasms/drug therapy
• Animals
• Dose-Response Relationship, Drug
• Dietary Supplements
• Antioxidants/pharmacology
• Antioxidants/administration & dosage
• Reactive Oxygen Species/metabolism
• Antineoplastic Agents, Phytogenic/pharmacology
• Antineoplastic Agents, Phytogenic/administration & dosage
• Plants/chemistry

• hepatocellular carcinoma
• mTOR signaling pathway
• natural products

• Sichuan Administration of Traditional Chinese Medicine
• Chengdu University of Traditional Chinese Medicine Affiliated Hospital

• curcumin
• endothelial dysfunction
• menopause
• ovariectomy
• turmeric
• vascular function

• FF-2024-167 Faculty of Medicine, Universiti Kebangsaan Malaysia

• anti-inflammatory
• cachexia
• gastric cancer
• natural products

• Humans
• Cachexia/drug therapy
• Cachexia/etiology
• Stomach Neoplasms/complications
• Anti-Inflammatory Agents/therapeutic use
• Biological Products/therapeutic use
• Biological Products/pharmacology
• Animals
• Probiotics/therapeutic use

• PI3K
• cancer
• curcumin
• glioblastoma

• AFM-Telethon

• Animals
• Humans
• Neoplasms/prevention & control
• Chemoprevention
• Dietary Supplements

• National Cancer Institute (NCI)

• HPLC-MS/MS
• curcumin
• curcuminoids
• piperine
• tetrahydrocurcumin
• β-glucuronidase

• clinical trials
• curcumin
• molecular targets
• preclinical studies
• therapeutic potential

• Humans
• Curcumin/pharmacology
• Curcumin/therapeutic use
• Signal Transduction
• Oxidative Stress
• NF-kappa B/metabolism
• Curcuma
• Cytokines/metabolism

• CCL2
• IL-15
• Theracurmin
• Trypanosoma cruzi
• cardiac tissue
• inflammation

• APQ-02511-22 Fundação de Amparo à Pesquisa do Estado de Minas Gerais
• BPD-00754-22 Fundação de Amparo à Pesquisa do Estado de Minas Gerais
• 405946/2021-0 National Council for Scientific and Technological Development
• 305634/2017-8 National Council for Scientific and Technological Development

• cancer
• curcumin
• signalling pathways

• turmeric
• curcumin
• chronic diseases
• natural compounds
• clinical trials

• Department of Biotechnology , Ministry of Science and Technology
• Ministry of Education, India
• Science and Engineering Research Board

• Department of Biotechnology , Ministry of Science and Technology
• Science and Engineering Research Board

• Curcumin
• Neuroprotective Mechanisms
• Spinal Cord Injury

• ascorbate
• curcumin
• hyperthermia
• irreversible electroporation
• microenvironment
• mistletoe
• nanocarriers
• pancreatic carcinoma
• paricalcitol

• Multi-target
• NF-κB
• Prodrug
• Reactive oxgen species
• β-Glucuronidase

• Animals
• Mice
• Cell Line, Tumor
• CRISPR-Cas Systems/genetics
• Curcumin/pharmacology
• Glucuronidase/metabolism
• Glucuronides/metabolism
• Glucuronides/pharmacology
• Glucuronides/therapeutic use
• NF-kappa B/metabolism
• Prodrugs/pharmacology
• Prodrugs/therapeutic use
• Reactive Oxygen Species/metabolism

• Alzheimer's disease
• amyloid
• biomarker
• curcumin
• retina

• Co-delivery
• Drug combination
• Drug resistance
• Nanosystem
• Phytochemicals

• Atomic Force Microscopy
• Brewster Angle Microscopy
• Cell membrane model
• Compressibility
• Curcumin
• Langmuir monolayers

• Curcumin
• clinical trials
• drug-resistant cancer
• signaling pathways

• Antineoplastic Agents, Phytogenic/adverse effects
• Antineoplastic Agents, Phytogenic/pharmacokinetics
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Curcumin/adverse effects
• Humans
• Irinotecan/therapeutic use
• Maximum Tolerated Dose
• Neoplasms/drug therapy
• Neoplasms/metabolism

• P50 CA058223 NCI NIH HHS
• S10 RR024595 NCRR NIH HHS

Nutritional habits impinge on the health of the gastrointestinal (GI) tract, contributing to GI disorder progression. GI cancer is a widespread and aggressive tumor sensitive to nutritional changes. Indeed, specific nutritional expedients can be adopted to prevent GI cancer onset and to slow down disease activity. Moreover, the patient’s nutritional status impacts prognosis, quality of life, and chemotherapy tolerance. These patients encounter the highest frequency of malnourishment risk, a condition that can progressively evolve into cachexia. Clinical studies dealing with this topic stressed the importance of nutritional counseling and put under the spotlight nutrient delivery, the type of nutrient supplementation, and timing for the start of nutritional management. A medical practitioner well-prepared on the topic of nutrition and cancer should operate in the clinical team dedicated to these oncological patients. This specific expertise needs to be implemented as soon as possible to adopt nutritional interventions and establish a proper patient-tailored dietary regimen. The nutritional gap closure should be prompt during anticancer treatment to stabilize weight loss, improve treatment tolerability, and ameliorate survival rate. Recently, novel nutritional approaches were investigated to target the bidirectional link between epigenetics and metabolism, whose alteration supports the onset, progression, and therapeutic response of GI cancer patients.

The purpose of this study was to determine the clinical and chondroprotective efficacy and safety of orally administered Theracurmin in patients who underwent mosaicplasty for knee chondral or osteochondral diseases over 12 months of treatment.

We enrolled 50 patients, older than 20 years of age, who underwent mosaicplasty for their knee joint diseases. Theracurmin at 180 mg of curcumin per day or placebo was administered orally every day for 12 months. Because 7 patients dropped out of the study, 43 patients were examined; they included 14 men and 29 women and 24 right and 19 left knees. The mean operative age was 59.5 years (range, 24-84 years). We evaluated the Japanese Orthopaedic Association knee osteoarthritis score (JOA), visual analog scale (VAS), and Japanese Knee Osteoarthritis Measure (JKOM) as clinical symptoms; T2 mapping values using magnetic resonance imaging as an indication of the chondroprotective effect; and blood concentration of curcumin at 0, 3, 6, and 12 months after the operations. We performed intraoperative acoustic evaluation of articular cartilage as a measure of chondroprotective effect during the operations and second-look arthroscopy.

The JOA, VAS and JKOM at 3, 6, and 12 months were significantly better than those during the preoperative period. However, the values of JOA, VAS and JKOM and T2 mapping were not significantly different between the Theracurmin and placebo groups. The blood concentration of curcumin in the Theracurmin group was significantly higher than that in the placebo group at 3, 6, and 12 months after the operations. Cartilage stiffness and surface roughness were significantly better in the Theracurmin group than in the placebo group at second-look arthroscopy.

The oral administration of Theracurmin for 1 year demonstrated significantly better chondroprotective effects and no worse clinical effects and adverse events than the placebo.

Level I, double-blinded, placebo-controlled, prospective study.

Recent evidence in basic science is leading to a growing interest in the possible role of curcumin in treating retinal diseases. Curcumin has been demonstrated to be able to modulate gene transcription and reduce ganglion cell apoptosis, downgrade VEGF, modulate glucose levels and decrease vascular dysfunction. So far, the use of curcumin has been limited by poor bioavailability; to overcome this issue, different types of carriers have been used. Multiple recent studies disclosed the efficacy of using curcumin in treating different retinal conditions. The aim of this review is to comprehensively review and discuss the role of curcumin in retinal diseases from bench to bedside.

• carrier
• curcumin
• diabetic retinopathy
• macular degeneration
• retinitis pigmentosa
• review

• Apoptosis
• Curcumin/pharmacology
• Curcumin/therapeutic use
• Humans
• Retinal Diseases/drug therapy

Background: Breast cancer is the most common cancer in women globally, and diagnosing it early and finding potential drug candidates against multi-drug resistant metastatic breast cancers provide the possibilities of better treatment and extending life. Methods: The current study aimed to evaluate the synergistic anti-metastatic activity of Curcumin (Cur) and Paclitaxel (Pacli) individually, the combination of Curcumin–Paclitaxel (CP), and also in conjugation with gold nanoparticles (AuNP–Curcumin (Au-C), AuNP–Paclitaxel (Au-P), and AuNP–Curcumin–Paclitaxel (Au-CP)) in various in vitro and in vivo models. Results: The results from combination treatments of CP and Au-CP demonstrated excellent synergistic cytotoxic effects in triple-negative breast cancer cell lines (MDA MB 231 and 4T1) in in vitro and in vivo mouse models. Detailed mechanistic studies were performed that reveal that the anti-cancer effects were associated with the downregulation of the expression of VEGF, CYCLIN-D1, and STAT-3 genes and upregulation of the apoptotic Caspase-9 gene. The group of mice that received CP combination therapy (with and without gold nanoparticles) showed a significant reduction in the size of tumor when compared to the Pacli alone treatment and control groups. Conclusions: Together, the results suggest that the delivery of gold conjugated Au-CP formulations may help in modulating the outcomes of chemotherapy. The present study is well supported with observations from cell-based assays, molecular and histopathological analyses.

• Curcumin
• Paclitaxel
• gold nanoparticles
• metastasis
• triple-negative breast cancer cell lines (4T1 and MDA MB 231)

• Animals
• Antineoplastic Agents/pharmacology
• Apoptosis/drug effects
• Carcinogenesis/drug effects
• Cell Line
• Cell Line, Tumor
• Curcumin/pharmacology
• Drug Resistance, Multiple/drug effects
• Female
• Gold/pharmacology
• HEK293 Cells
• Humans
• Metal Nanoparticles/administration & dosage
• Mice
• Mice, Inbred BALB C
• Neoplasm Metastasis/drug therapy
• Paclitaxel/pharmacology
• Triple Negative Breast Neoplasms/drug therapy

• FH deficiency
• case report
• curcumin
• experimental treatment
• lupus
• translational medicine

•

PUREMERIC™ is a standardized turmeric extract containing not less than 95 % curcuminoids.

Turmeric is a culinary spice valued since ancient time for its medicinal properties, mostly attributed to curcumin, the major polyphenol present. The safety of curcumin is well established in humans. However, the tolerability of curcumin is largely determined either in subjects with existing health problems, or in healthy individuals at low doses. More recently the safety of turmeric supplementation is opposed following some case reports on the occurrence of acute hepatitis due to its consumption.

Here we have investigated the safety and tolerability of a standardized turmeric extract containing 95 % curcuminoids (PUREMERIC™) in an open label, single arm, prospective clinical study. Twelve healthy subjects aged 18–50 years received 500 mg PUREMERIC capsules twice daily for 90 days.

After PUREMERIC supplementation, the liver function parameters such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and direct bilirubin, gamma-glutamyl transpeptidase (GGT), and lactate dehydrogenase (LDH) were not significantly altered in the serum compared to baseline. The hematological parameters were within the normal range.

Collectively, these data contradict the turmeric- induced liver damage and establishes the safety of the extract in healthy individuals.

• Cholestatic hepatitis
• Curcumin
• Healthy subjects
• Safety
• Turmeric

• Dietary bioactive compounds
• breast cancer
• in vivo and clinical studies
• mechanism
• therapeutic agents

Hepatocellular carcinoma (HCC) is due to poor prognosis and lack of availability of effective treatment. Novel therapeutic strategies will be the fine tuning of intracellular ROS signaling to effectively deprive cells of ROS-induced tumor-promoting events. This review discusses the generation of ROS, the major signaling their modulation in therapeutics. We explore some of the major pathways involved in HCC, which include the VEGF, MAPK/ERK, mTOR, FGF, and Ser/Thr kinase pathways. In this review, we study cornerstone on natural bioactive compounds with their effect on hepatocarcinomas. Furthermore, we focus on oxidative stress and FDA-approved signaling pathway inhibitors, along with chemotherapy and radiotherapy enhancers which with early evidence of success. While more in vivo testing is required to confirm the findings presented here, our findings will aid future nonclinical, preclinical, and clinical studies with these compounds, as well as inspire medicinal chemistry scientists to conduct appropriate research on this promising natural compound and their derivatives.

Cancer is one of the leading causes of death globally. The development of drug resistance is the main contributor to cancer-related mortality. Cancer cells exploit multiple mechanisms to reduce the therapeutic effects of anticancer drugs, thereby causing chemotherapy failure. Natural products are accessible, inexpensive, and less toxic sources of chemotherapeutic agents. Additionally, they have multiple mechanisms of action to inhibit various targets involved in the development of drug resistance. In this review, we have summarized the basic research and clinical applications of natural products as possible inhibitors for drug resistance in cancer. The molecular targets and the mechanisms of action of each natural product are also explained. Diverse drug resistance biomarkers were sensitive to natural products. P-glycoprotein and breast cancer resistance protein can be targeted by a large number of natural products. On the other hand, protein kinase C and topoisomerases were less sensitive to most of the studied natural products. The studies discussed in this review will provide a solid ground for scientists to explore the possible use of natural products in combination anticancer therapies to overcome drug resistance by targeting multiple drug resistance mechanisms.

• anticancer natural products
• drug detoxification
• drug efflux
• plants derived natural products

Tay-Sachs disease (TSD) is a progressive neurodegenerative disorder that occurs due to a deficiency of a β hexosaminidase A (HexA) enzyme, resulting in the accumulation of GM₂ gangliosides. In this work, we analyzed the effect of umbilical cord blood cell transplantation (UCBCT) and curcumin administration on the course of the disease in a patient with adult TSD. The patient’s serum cytokine profile was determined using multiplex analysis. The level of GM₂ gangliosides in plasma was determined using mass spectrometry. The enzymatic activity of HexA in the plasma of the patient was assessed using a fluorescent substrate assay. The HexA α-subunit (HexA) concentration was determined using ELISA. It was shown that both UCBCT and curcumin administration led to a change in the patient’s cytokine profile. The UCBCT resulted in an increase in the concentration of HexA in the patient’s serum and in an improvement in the patient’s neurological status. However, neither UCBCT nor curcumin were able to alter HexA activity and the level of GM₂ in patient’s plasma. The data obtained indicate that UCBCT and curcumin administration can alter the immunity of a patient with TSD, reduce the level of inflammatory cytokines and thereby improve the patient’s condition.

• GM2 gangliosidosis
• Tay-Sachs disease
• cord blood cell transplantation
• curcumin
• cytokine profile
• lysosomal storage diseases
• β hexosaminidase A

• cancer
• clinical trial
• colon
• curcumin
• formulation
• nanoparticle delivery
• outcome measures
• systematic review

• bioavailability
• chronic diseases
• clinical trials
• curcumin

Orbital fibrosis, a hallmark of tissue remodeling in Graves’ ophthalmopathy (GO), is a chronic, progressive orbitopathy with few effective treatments. Orbital fibroblasts are effector cells, and transforming growth factor β1 (TGF-β1) acts as a critical inducer to promote myofibroblast differentiation and subsequent tissue fibrosis. Curcumin is a natural compound with anti-fibrotic activity. This study aims to investigate the effects of curcumin on TGF-β1-induced myofibroblast differentiation and on the pro-angiogenic activities of orbital fibroblasts. Orbital fibroblasts from one healthy donor and three patients with GO were collected for primary cell culture and subjected to myofibroblast differentiation under the administration of 1 or 5 ng/mL TGF-β1 for 24 h. The effects of curcumin on TGF-β1-induced orbital fibroblasts were assessed by measuring the cellular viability and detecting the expression of myofibroblast differentiation markers, including connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA). The pro-angiogenic potential of curcumin-treated orbital fibroblasts was evaluated by examining the transwell migration and tube-forming capacities of fibroblast-conditioned EA.hy926 and HMEC-1 endothelial cells. Treatment of orbital fibroblasts with curcumin inhibited the TGF-β1 signaling pathway and attenuated the expression of CTGF and α-SMA induced by TGF-β1. Curcumin, at the concentration of 5 μg/mL, suppressed 5 ng/mL TGF-β1-induced pro-angiogenic activities of orbital fibroblast-conditioned EA hy926 and HMEC-1 endothelial cells. Our findings suggest that curcumin reduces the TGF-β1-induced myofibroblast differentiation and pro-angiogenic activity in orbital fibroblasts. The results support the potential application of curcumin for the treatment of GO.

• Graves’ ophthalmopathy
• curcumin
• orbital fibrosis
• thyroid eye disease

• Cell Differentiation/drug effects
• Cells, Cultured
• Curcumin/pharmacology
• Endothelial Cells/metabolism
• Graves Ophthalmopathy/etiology
• Graves Ophthalmopathy/metabolism
• Graves Ophthalmopathy/pathology
• Humans
• Myofibroblasts/cytology
• Myofibroblasts/drug effects
• Myofibroblasts/metabolism
• Neovascularization, Physiologic/drug effects
• Reactive Oxygen Species
• Signal Transduction/drug effects
• Transforming Growth Factor beta1/metabolism
• Transforming Growth Factor beta1/pharmacology

• Curcumin
• bioavailability
• biological applications
• commercial nanoproducts
• nanoformulations
• therapeutic mechanisms

• H. pylori
• HER2
• VDAC
• curcumin
• drug-delivery
• gastric cancer
• photodynamic therapy

• Cancer
• curcumin
• exosomes
• liposomes
• nanoformulations
• niosomes
• pro-niosomes
• vesicular

• Antioxidants
• Apoptosis
• Curcumin
• Human periodontal ligament stem cells
• Osteogenesis
• Stem cell transplantation

• Animals
• Apoptosis/drug effects
• Bone and Bones/metabolism
• Cell Differentiation/drug effects
• Cell Proliferation/drug effects
• Cells, Cultured
• Curcumin/metabolism
• Curcumin/pharmacology
• Female
• Humans
• Ligaments/metabolism
• Male
• Molar/metabolism
• Osteogenesis/drug effects
• Oxidative Stress/physiology
• Periodontal Ligament/metabolism
• Rats, Sprague-Dawley
• Stem Cell Transplantation/methods
• Stem Cells/cytology
• Stem Cells/drug effects
• Stem Cells/metabolism
• Young Adult
• Rats

Cancer is a major burden of disease globally. Each year, tens of millions of people are diagnosed with cancer worldwide, and more than half of the patients eventually die from it. Significant advances have been noticed in cancer treatment, but the mortality and incidence rates of cancers are still high. Thus, there is a growing research interest in developing more effective and less toxic cancer treatment approaches. Curcumin (CUR), the major active component of turmeric (Curcuma longa L.), has gained great research interest as an antioxidant, anticancer, and anti-inflammatory agent. This natural compound shows its anticancer effect through several pathways including interfering with multiple cellular mechanisms and inhibiting/inducing the generation of multiple cytokines, enzymes, or growth factors including IκB kinase β (IκKβ), tumor necrosis factor-alpha (TNF-α), signal transducer, and activator of transcription 3 (STAT3), cyclooxygenase II (COX-2), protein kinase D1 (PKD1), nuclear factor-kappa B (NF-κB), epidermal growth factor, and mitogen-activated protein kinase (MAPK). Interestingly, the anticancer activity of CUR has been limited primarily due to its poor water solubility, which can lead to low chemical stability, low oral bioavailability, and low cellular uptake. Delivering drugs at a controlled rate, slow delivery, and targeted delivery are other very attractive methods and have been pursued vigorously. Multiple CUR nanoformulations have also been developed so far to ameliorate solubility and bioavailability of CUR and to provide protection to CUR against hydrolysis inactivation. In this review, we have summarized the anticancer activity of CUR against several cancers, for example, gastrointestinal, head and neck, brain, pancreatic, colorectal, breast, and prostate cancers. In addition, we have also focused on the findings obtained from multiple experimental and clinical studies regarding the anticancer effect of CUR in animal models, human subjects, and cancer cell lines.

• Curcuma longa
• anticancer
• cellular mechanisms
• curcumin
• mechanism of action
• nanoformulations

• Cancer
• Colon
• Curcumin
• Esophagus
• Gastrointestinal
• Oral cavity

• bioavailability
• cytokine inhibition
• inflammatory bowel disease

• Chemo therapy
• Combination therapy
• Phytochemicals
• Repurposed drug