BACKGROUND

Curcumin has been investigated as a potential natural solution to prevent or even treat skeletal muscle decline. There are a number of externally sourced finished products (ie, those imported from other countries) containing curcumin, but high cost limits their usage. The emerging research and development of locally sourced curcumin is an opportunity to produce high-quality oral supplements comparable to existing imported products.

The primary purpose of this study is to determine the effects of oral administration of a local curcumin formulation on skeletal muscle using an animal model that similarly demonstrated the course of human sarcopenia.

Purpose-bred 11- to 12-week-old female Sprague Dawley (SD) rats will be used in this study. SD rats are extensively used in animal models of human diseases and conditions such as diabetes, obesity and sarcopenia. Female rats have been selected because they do not demonstrate more temperature or activity variance and have more stable behavior compared to males. To simulate sarcopenia in this animal model, the tail suspension (TS) method was utilized. The TS method involves decreased hind limb function by suspending the animal’s tail for the duration of treatment. The laboratory animals will be randomized to receive any of the four treatments: (1) low-dose curcumin + vehicle; (2) high-dose curcumin + vehicle; (3) vehicle only; and (4) control (distilled water). The interventions will be subdivided into two: 2-week treatment and 4-week treatment. The gastrocnemius muscles on both sides will be excised and weighed, and the muscle tissues subjected to rapid freezing in acetone-dry ice and sliced into 10 μm-thick sections for staining. Examination of muscle architecture and computation of atrophy factors will be performed. The presence of connective tissue, fat tissue and number of atrophic muscle cells will be determined. Accurate quantitative detection of the rat total AMP (adenosine monophosphate)-Activated Protein Kinase will be performed in the gastrocnemius muscle tissue utilizing the enzyme-linked immunosorbent assay kit.

BACKGROUND

Sarcopenia is a multifactorial disease with a progressive decline in skeletal muscle mass, muscle strength, and physical performance. Curcumin is a nutraceutical investigated for its anti-inflammatory and antioxidant properties. It is inexpensive, accessible, and considered a safe and practical approach to help alleviate symptoms of sarcopenia and improve muscle mass and function. Objective: This systematic review aims to obtain more conclusive evidence on the effectiveness of curcumin among adults 40 years and above with sarcopenia in improving muscle pain, strength, performance, and muscle morphology.

This systematic review aims to obtain more conclusive evidence on the effectiveness of curcumin among adults 40 years and above with sarcopenia in improving muscle pain, strength, performance, and muscle morphology.

The review will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. It will focus on any interventional studies on curcumin for adults diagnosed with sarcopenia, with the following outcomes: clinically significant improvement in pain, muscle strength and performance, quality of life, and improvement in muscle morphology. Studies completed until 2024 will be included. The databases to be searched include PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL Plus (EBSCOhost), Embase, and Web of Science. The identified citations will be collated in Zotero and uploaded to Covidence© to be assessed using the eligibility criteria and systematically reviewed by two independent reviewers. The CASP Randomised Controlled Trial Checklist will be utilized to assess the quality of the included studies.

The results will serve as a groundwork for future sarcopenia research among allied health specialists, particularly those in the field of physiotherapy - students, healthcare practitioners, and academicians (PROSPERO registration number: CRD42023448750).

Objective: This study aimed to evaluate the effects of combination of curcumin and piperine supplementation on Fasting Plasma Glucose (FPG), Homeostatic Model of Insulin Resistance (HOMA-IR), Body Mass Index (BMI) in patients with prediabetes and type 2 Diabetes Mellitus (T2DM). This review was done to identify potential herbal remedies that may help improve glycemic parameters, leading to better health outcomes in combination with current antidiabetic treatment. Methodology: This systematic review was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). It was conducted in 2023 with sources and databases from MEDLINE, EBSCO-Host, ScienceDirect and ProQuest. This paper included randomized-controlled trials exploring the effects of the combination of curcumin and piperine on patients with prediabetes and T2DM. Systematic reviews, observational studies, case reports, case series, conference abstracts, book sections, commentaries/editorials, non-human studies and articles with unavailable full-text and written in non-English language, were excluded. The key terms for the literature search were “curcumin,” “piperine,” “prediabetes” and “Type 2 Diabetes Mellitus.” We use Cochrane Risk of Bias (RoB) 2 for quality assessment of the included studies and Review Manager (RevMan) 5.4 to do the meta-analysis. Results: A total of three studies were included in this systematic review. Two studies from Neta et al., and Cicero et al., showed no significant difference in HOMA-IR, BMI and FPG levels between the curcumin, piperine and placebo groups. One study from Panahi et al. demonstrated a significant difference in BMI levels between the curcumin and piperine and placebo groups (p <0.01). The meta-analysis showed that FPG levels, HOMA-IR and BMI improved among patients with diabetes given in curcumin and piperine with reported mean differences (MD) of = -7.61, 95% CI [-15.26, 0.03], p = 0.05, MD = -0.36, 95% CI [-0.77 to 0.05], p = 0.09, and MD = -0.41, 95% CI [-0.85 to 0.03], p = 0.07, respectively). Conclusions The supplementation of curcumin and piperine showed a numerical reduction in FPG, HOMA-IR and BMI, but were not statistically significant. Further research is needed as there is a paucity of studies included in the review.
Curcumin ; Prediabetic State ; Diabetes Mellitus, Type 2

OBJECTIVE: To explore the effect of curcumin on the proliferation of renal cell carcinoma and analyze its regulation mechanism. METHODS: In RCC cell lines of A498 and 786-O, the effects of curcumin (2.5, 5, 10 µ mo/L) on the proliferation were analyzed by Annexin V+PI staining. Besides, A498 was inoculated into nude mice to establish tumorigenic models, and the model mice were treated with different concentrations of curcumin (100, 200, and 400 mg/kg), once daily for 30 days. Then the tumor diameter was measured, the tumor cells were observed by hematoxylin-eosin staining, and the protein expressions of miR-148 and ADAMTS18 were detected by immunohistochemistry. In vitro, after transfection of miR-148 mimics, miR-148 inhibitor or si-ADAMTS18 in cell lines, the expression of ADAMTS18 was examined by Western blotting and the cell survival rate was analyzed using MTT. Subsequently, Western blot analysis was again used to examine the autophagy phenomenon by measuring the relative expression level of LC3-II/LC3-I; autophagy-associated genes, including those of Beclin-1 and ATG5, were also examined when miR-148 was silenced in both cell lines with curcumin treatment. RESULTS: Curcumin could inhibit the proliferation of RCC in cell lines and nude mice. The expression of miR-148 and ADAMTS18 was upregulated after curcumin treatment both in vitro and in vivo (P<0.05). The cell survival rate was dramatically declined upon miR-148 or ADAMTS18 upregulated. However, si-ADAMTS18 treatment or miR-148 inhibitor reversed these results, that is, both of them promoted the cell survival rate. CONCLUSION Curcumin can inhibit the proliferation of renal cell carcinoma by regulating the miR-148/ ADAMTS18 axis through the suppression of autophagy in vitro and in vivo. There may exist a positive feedback loop between miR-148 and ADAMTS18 gene in RCC.
Animals ; Mice ; Carcinoma, Renal Cell/metabolism* ; Curcumin/therapeutic use* ; MicroRNAs/metabolism* ; Mice, Nude ; Cell Line, Tumor ; Kidney Neoplasms/metabolism* ; Autophagy ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; ADAMTS Proteins/metabolism*

OBJECTIVES: This study aims to explore the therapeutic targets of curcumin in periodontitis through network pharmacology and molecular docking technology. METHODS: Targets of curcumin and periodontitis were predicted by different databases, and the protein-protein interaction (PPI) network constructed by String revealed the interaction between curcumin and periodontitis. The key target genes were screened for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was performed to analyze the binding potential of curcumin to periodontitis. RESULTS: A total of 672 periodontitis-related disease targets and 107 curcumin-acting targets were obtained from the databases, and 20 key targets were screened. The GO and KEGG analyses of the 20 targets showed that curcumin might play a therapeutic role through the hypoxia-inducible factor (HIF)-1 and parathyroid hormone (PTH) signaling pathways. Molecular docking analysis showed that curcumin had good binding potential with multiple targets. CONCLUSIONS The potential key targets and molecular mechanisms of curcumin in treating periodontitis provide a theoretical basis for new drug development and clinical applications.
Humans ; Network Pharmacology ; Curcumin/therapeutic use* ; Molecular Docking Simulation ; Periodontitis/drug therapy* ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional

OBJECTIVE: To assess the efficacy of a curcumin supplementation on cognitive abilities in women suffering from premenstrual syndrome (PMS) and dysmenorrhea. METHODS: A randomized, triple-blind, placebo-controlled trial was conducted from December 2019 to March 2020. A total of 124 women who had both PMS and dysmenorrhea were enrolled, and were equally and randomly assigned to the curcumin group or placebo group, 62 cases in each. Each subject received either a capsule containing 500 mg of curcuminoid, or a placebo daily, for 10 days (7 days before and until 3 days after the onset of menstrual bleeding) over 3 menstrual cycles. The cognitive abilities questionnaire was used to measures cognitive functions in 7 specific areas. Adverse reactions were monitored during and after the trial in both groups. RESULTS: Administration of curcumin was associated with a significant increase in memory score (P=0.002), inhibitory control and selective attention (P=0.020), and total cognitive ability task (P=0.024). In addition, significant increments were found in scores of memory (3.5±3.1 vs. 0.4±3.8 in the curcumin and placebo groups, respectively; P=0.035), inhibitory control and selective attention (3.0±3.7 vs. 0.4±3.7; P=0.027) and total cognitive abilities (8.3±12.3 vs. 2.2±12.4; P=0.025) in the curcumin group versus placebo groups. Curcumin was safe and well-tolerable in current clinical trial. CONCLUSION Curcumin has a beneficial efficacy on cognitive function scores in women with PMS and dysmenorrhea, with improvements in memory, inhibitory control and selective attention. (Registration No. IRCT20191112045424N1, available at: https://www.irct.ir ).
Humans ; Female ; Curcumin/therapeutic use* ; Dysmenorrhea/drug therapy* ; Premenstrual Syndrome/psychology* ; Cognition ; Double-Blind Method

OBJECTIVE: To evaluate the effect of curcumin on renal mitochondrial oxidative stress, nuclear factor-κB/NOD-like receptor protein 3 (NF-κB/NLRP3) inflammatory body signaling pathway and tissue cell injury in rats with acute respiratory distress syndrome (ARDS). METHODS: A total of 24 specific pathogen free (SPF)-grade healthy male Sprague-Dawley (SD) rats were randomly divided into control group, ARDS model group, and low-dose and high-dose curcumin groups, with 6 rats in each group. The ARDS rat model was reproduced by intratracheal administration of lipopolysaccharide (LPS) at 4 mg/kg via aerosol inhalation. The control group was given 2 mL/kg of normal saline. The low-dose and high-dose curcumin groups were administered 100 mg/kg or 200 mg/kg curcumin by gavage 24 hours after model reproduction, once a day. The control group and ARDS model group were given an equivalent amount of normal saline. After 7 days, blood samples were collected from the inferior vena cava, and the levels of neutrophil gelatinase-associated lipocalin (NGAL) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The rats were sacrificed, and kidney tissues were collected. Reactive oxygen species (ROS) levels were determined by ELISA, superoxide dismutase (SOD) activity was detected using the xanthine oxidase method, and malondialdehyde (MDA) levels were determined by colorimetric method. The protein expressions of hypoxia-inducible factor-1α (HIF-1α), caspase-3, NF-κB p65, and Toll-like receptor 4 (TLR4) were detected by Western blotting. The mRNA expressions of HIF-1α, NLRP3, and interleukin-1β (IL-1β) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Renal cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). The morphological changes in renal tubular epithelial cells and mitochondria were observed under a transmission electron microscope. RESULTS: Compared with the control group, the ARDS model group exhibited kidney oxidative stress and inflammatory response, significantly elevated serum levels of kidney injury biomarker NGAL, activated NF-κB/NLRP3 inflammasome signaling pathway, increased kidney tissue cell apoptosis rate, and renal tubular epithelial cell damage and mitochondrial integrity destruction under transmission electron microscopy, indicating successful induction of kidney injury. Following curcumin intervention, the injury to renal tubular epithelial cells and mitochondria in the rats was significantly mitigated, along with a noticeable reduction in oxidative stress, inhibition of the NF-κB/NLRP3 inflammasome signaling pathway, and a significant decrease in kidney tissue cell apoptosis rate, demonstrating a certain dose-dependency. Compared with the ARDS model group, the high-dose curcumin group exhibited significantly reduced serum NGAL levels and kidney tissue MDA and ROS levels [NGAL (μg/L): 13.8±1.7 vs. 29.6±2.7, MDA (nmol/g): 115±18 vs. 300±47, ROS (kU/L): 75±19 vs. 260±15, all P < 0.05], significantly down-regulated protein expressions of HIF-1α, caspase-3, NF-κB p65, and TLR4 in the kidney tissue [HIF-1α protein (HIF-1α/β-actin): 0.515±0.064 vs. 0.888±0.055, caspase-3 protein (caspase-3/β-actin): 0.549±0.105 vs. 0.958±0.054, NF-κB p65 protein (NF-κB p65/β-actin): 0.428±0.166 vs. 0.900±0.059, TLR4 protein (TLR4/β-actin): 0.683±0.048 vs. 1.093±0.097, all P < 0.05], and significantly down-regulated mRNA expressions of HIF-1α, NLRP3, and IL-1β [HIF-1α mRNA (2^-ΔΔCt): 2.90±0.39 vs. 9.49±1.87, NLRP3 mRNA (2^-ΔΔCt): 2.07±0.21 vs. 6.13±1.32, IL-1β mRNA (2^-ΔΔCt): 1.43±0.24 vs. 3.95±0.51, all P < 0.05], and significantly decreased kidney tissue cell apoptosis rate [(4.36±0.92)% vs. (27.75±8.31)%, P < 0.05], and significantly increased SOD activity (kU/g: 648±34 vs. 430±47, P < 0.05). CONCLUSIONS Curcumin can alleviate kidney injury in ARDS rats, and its mechanism may be related to the increasing in SOD activity, reduction of oxidative stress, and inhibition of the activation of the NF-κB/NLRP3 inflammasome signaling pathway.
Male ; Rats ; Animals ; Rats, Sprague-Dawley ; NF-kappa B ; Actins ; Caspase 3 ; Curcumin ; Lipocalin-2 ; Toll-Like Receptor 4 ; Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; Reactive Oxygen Species ; Saline Solution ; Kidney ; Superoxide Dismutase

Diabetes mellitus is a chronic disease, typified by hyperglycemia resulting from failures in complex multifactorial metabolic functions, that requires life-long medication. Prolonged uncontrolled hyperglycemia leads to micro- and macro-vascular complications. Although antidiabetic drugs are prescribed as the first-line treatment, many of them lose efficacy over time or have severe side effects. There is a lack of in-depth study on the patents filed concerning the use of natural compounds to manage diabetes. Thus, this patent analysis provides a comprehensive report on the antidiabetic therapeutic activity of 6 phytocompounds when taken alone or in combinations. Four patent databases were searched, and 17,649 patents filed between 2001 and 2021 were retrieved. Of these, 139 patents for antidiabetic therapeutic aids that included berberine, curcumin, gingerol, gymnemic acid, gymnemagenin and mangiferin were analyzed. The results showed that these compounds alone or in combinations, targeting acetyl-coenzyme A carboxylase 2, serine/threonine protein kinase, α-amylase, α-glucosidase, lipooxygenase, phosphorylase, peroxisome proliferator-activated receptor-γ (PPARγ), protein tyrosine phosphatase 1B, PPARγ co-activator-1α, phosphoinositide 3-kinase and protein phosphatase 1 regulatory subunit 3C, could regulate glucose metabolism which are validated by pharmacological rationale. Synergism, or combination therapy, including different phytocompounds and plant extracts, has been studied extensively and found effective, whereas the efficacy of commercial drugs in combination with phytocompounds has not been studied in detail. Curcumin, gymnemic acid and mangiferin were found to be effective against diabetes-related complications. Please cite this article as: DasNandy A, Virge R, Hegde HV, Chattopadhyay D. A review of patent literature on the regulation of glucose metabolism by six phytocompounds in the management of diabetes mellitus and its complications. J Integr Med. 2023; 21(3): 226-235.
Humans ; PPAR gamma/metabolism* ; Curcumin/therapeutic use* ; Phosphatidylinositol 3-Kinases ; Diabetes Mellitus/drug therapy* ; Hypoglycemic Agents/pharmacology* ; Hyperglycemia/drug therapy* ; Glucose

Objective: To construct a new co-cultured liver cancer research model composed of activated hepatic stellate cells (aHSC) and liver cancer cells, explore the efficacy difference between it and traditional model, so as to establish a liver cancer research model in vitro and in vivo that can reflect the real clinical efficacy. Methods: A new co-culture model of liver cancer consisting of aHSC and liver cancer cells was constructed. The differences in efficacy between the new co-culture model and the traditional single cell model were compared by cytotoxicity test, cell migration test, drug retention test and in vivo tumor inhibition test. Western blot was used to detect the drug-resistant protein P-gp and epithelial-mesenchymal transition-related proteins. Masson staining was used to observe the deposition of collagen fibers in tumor tissues of tumor-bearing mice. CD31 immunohistochemical staining was used to observe the microvessel density in tumor tissues of tumor-bearing mice. Results: The cytotoxicity of single cell model and co-culture model was dose-dependent. With the increase of curcumin (CUR) concentration, the cell viability decreased, but the cell viability of single cell model decreased faster than that of co-culture model. When the concentration of CUR was 10 μg/ml, the cell viability of the co-culture model was 62.3% and the migration rate was (28.05±3.68)%, which were higher than those of the single cell model [38.5% and (14.91±5.92)%, both P<0.05]. Western blot analysis showed that the expressions of P-gp and vimentin were up-regulated in the co-culture model, which were 1.55 and 2.04 fold changes of the single cell model, respectively. The expression of E-cadherin was down-regulated, and the expression level of E-cadherin in the single cell model was 1.17 fold changes of the co-culture model. Drug retention experiment showed that the co-culture model could promote drug efflux and reduce drug retention. In vivo tumor inhibition experiment showed that the m-HSC+ H22 co-transplantation model had faster tumor growth and larger tumor volume than those of the H22 single cell transplantation model. After CUR treatment, the tumor growths of m-HSC+ H22 co-transplantation model and H22 single cell transplantation model were inhibited. Masson staining showed that the deposition of collagen fibers in tumor tissues of m-HSC+ H22 co-transplantation model mice was more than that of H22 single cell transplantation model. CD31 immunohistochemical staining showed that the microvessel density in tumor tissue of m-HSC+ H22 co-transplantation model was higher than that of H22 single cell transplantation model. Conclusions: The aHSC+ liver cancer cell co-culture model has strong proliferation and metastasis ability and is easy to be resistant to drugs. It is a new type of liver cancer treatment research model superior to the traditional single cell model.
Animals ; Mice ; Tumor Microenvironment ; Coculture Techniques ; Liver Neoplasms/pathology* ; Cadherins ; Curcumin/pharmacology* ; Collagen ; Cell Line, Tumor

: AbstractObjective: To explore the effect and mechanism of curcumin on human T-cell acute lymphoblastic leukemia (T-ALL) cell apoptosis induced by Mcl-1 small molecule inhibitors UMI-77. METHODS: T-ALL cell line Molt-4 was cultured, and the cells were treated with different concentrations of curcumin and Mcl-1 small molecule inhibitor UMI-77 for 24 h. The MTT method was used to detect the cell survival rate after different treatment; According to the results of curcumin and UMI-77, the experimental settings were divided into control group, curcumin group (20 μmol/L curcumin treated cells), UMI-77 group (15 μmol/L Mcl-1 small molecule inhibitor UMI-77 treated cells) and curcumin+ UMI-77 group (20 μmol/L curcumin and 15 μmol/L Mcl-1 small molecule inhibitor UMI-77 treated cells), MTT method was used to detect cell proliferation inhibition rate, Annexin V-FITC/PI double staining method and TUNEL staining were used to detect cell apoptosis, DCFH-DA probe was used to detect cell reactive oxygen species, JC-1 fluorescent probe was used to detect mitochondrial membrane potential, Western blot was used to detect the expression levels of apoptosis-related proteins and Notch1 signaling pathway-related proteins. RESULTS: After the treatment of Molt-4 cells with different concentrations of curcumin and Mcl-1 small molecule inhibitor UMI-77, the cell survival rate was decreased (P<0.05); Compared with the control group, the cell proliferation inhibition rate of the curcumin group and the UMI-77 group were increased, the apoptosis rate of cell was increased, the level of ROS was increased, the protein expression of Bax, Caspase-3 and Caspase-9 in the cells were all increased, and the protein expression of Bcl-2 was reduced (P<0.05); Compared with the curcumin group or UMI-77 group, the cell proliferation inhibition rate and apoptosis rate of the curcumin+UMI-77 group were further increased, and the level of ROS was increased. At the same time, the protein expression of Bax, Caspase-3 and Caspase-9 in the cells were all increased, the protein expression of Bcl-2 was reduced (P<0.05); In addition, the mitochondrial membrane potential of the cells after curcumin treatment was decreased, and the proteins expression of Notch1 and HES1 were reduced (P<0.05). CONCLUSION Curcumin can enhance the apoptosis of T-ALL cells induced by Mcl-1 small molecule inhibitor UMI-77 by reducing the mitochondrial membrane potential, the mechanism may be related to the inhibition of Notch1 signaling pathway.
Apoptosis ; Apoptosis Regulatory Proteins ; Caspase 3/metabolism* ; Caspase 9/pharmacology* ; Cell Line, Tumor ; Curcumin/pharmacology* ; Humans ; Myeloid Cell Leukemia Sequence 1 Protein/metabolism* ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Reactive Oxygen Species/pharmacology* ; Sulfonamides ; Thioglycolates ; bcl-2-Associated X Protein/pharmacology*