Combination Of Curcumin Research Articles

A current Research on the Green Synthesis of Copper Nanoparticles from Herbal Extract

The study aims to find out the effectiveness of the combination of citral and curcumin as antifungal compounds. Lemongrass (Cymbopogon citratus) is a valuable family of grass known due to its flavoring, medicinal, and fragrance application. Haldi (Turmeric) scientifically known as Curcuma longa belongs to familthey Zingiberaceae. Its polyphenolic compound curcumin has been showing a variety of antifungal investigations due to extensive traditional uses and very low side effects.Turmeric has beenutilized in traditional medicine for various diseases counting diabetes, hepatitis, hemorrhoids, hysteria, indigestion, skin disease, inflammation, anorexia, hepatic disorders, cough, and sinusitis. In this formulation substudy combination of two bioactive oils is considered to form an effective antifungal spray preparation. The spray preparation is helpful to achieve fast absorption of the drugs through the transdermal way of drug administration. The effectiveness and activity rate of spray preparation is more beneficial. Lemongrass oil and curcumin are dissolved in ethanol to form a stable, safe, and effective spray formulation.

Liposomes Co-Delivering Curcumin and Colistin to Overcome Colistin Resistance in Bacterial Infections.

Antibiotic colistin is the last line of defense against multidrug-resistant (MDR) Gram-negative bacterial infections. Emergence of colistin resistance in microbes is a critical challenge. Herein, curcumin is discovered, for the first time, to reverse the resistance phenotype of colistin-resistant bacteria via a checkerboard assay. For the co-delivery of curcumin and colistin, negatively charged poly(ethylene glycol)-functionalized liposomes encapsulating both drugs (Lipo-cc) are prepared. Killing kinetics and live/dead assays confirm the antibacterial activity of Lipo-cc against colistin-resistant bacteria, which is more potent than that of the free curcumin and colistin combination. Mechanistical studies reveal that Lipo-cc restores the affinity of colistin for the bacterial membrane and improves the uptake of curcumin, which leads to reduced efflux pump activity, achieving a synergistic effect of colistin and curcumin. At the effective antibacterial dose, Lipo-cc does not exhibit any toxicity. The therapeutic efficacy of Lipo-cc is further demonstrated in an intestinal bacterial infection model induced with colistin-resistant Escherichia coli. Lipo-cc reduces the bacterial burden with over 6-log reduction and alleviated inflammation caused by infection. Importantly, unlike colistin, Lipo-cc does not affect the homeostasis of the intestinal flora. Taken together, Lipo-cc successfully overcame colistin resistance, indicating its potential for the treatment of colistin-resistant bacterial infections.

An Overview of the Enhanced Effects of Curcumin and Chemotherapeutic Agents in Combined Cancer Treatments.

Due to the progressive ageing of the human population, the number of cancer cases is increasing. For this reason, there is an urgent need for new treatments that can prolong the lives of cancer patients or ensure them a good quality of life. Although significant progress has been made in the treatment of cancer in recent years and the survival rate of patients is increasing, limitations in the use of conventional therapies include the frequent occurrence of side effects and the development of resistance to chemotherapeutic agents. These limitations are prompting researchers to investigate whether combining natural agents with conventional drugs could have a positive therapeutic effect in cancer treatment. Several natural bioactive compounds, especially polyphenols, have been shown to be effective against cancer progression and do not exert toxic effects on healthy tissues. Many studies have investigated the possibility of combining polyphenols with conventional drugs as a novel anticancer strategy. Indeed, this combination often has synergistic benefits that increase drug efficacy and reduce adverse side effects. In this review, we provide an overview of the studies describing the synergistic effects of curcumin, a polyphenol that has been shown to have extensive cytotoxic functions against cancer cells, including combined treatment. In particular, we have described the results of recent preclinical and clinical studies exploring the pleiotropic effects of curcumin in combination with standard drugs and the potential to consider it as a promising new tool for cancer therapy.

Combination of epigallocatechin 3 gallate and curcumin improves d-galactose and normal-aging associated memory impairment in mice

Previously, we observed curcumin improves aging-associated memory impairment in d-galactose (D-gal) and normal-aged (NA) mice. Evidence showed that multiple agents can be used in managing aging-induced memory dysfunction, drawn by the contribution of several pathways. Curcumin and Epigallocatechin 3 gallate (EGCG) combination substantially reduced the oxidative stress that commonly mediates aging. This study examined the combined effect of EGCG and curcumin on memory improvement in two recognized models, D-gal and normal-aged (NA) mice. The co-administration of EGCG and curcumin significantly (p < 0.05) increased retention time detected by passive avoidance (PA) and freezing response determined in contextual fear conditioning (CFC) compared to the discrete administration of EGCG or curcumin. Biochemical studies revealed that the combination of EGCG and curcumin remarkably ameliorated the levels (p < 0.05) of glutathione, superoxide dismutase, catalase, advanced oxidation protein products, nitric oxide, and lipid peroxidation compared to the monotherapy of EGCG or curcumin in mice hippocampi. The behavioral and biochemical studies revealed that the combination of EGCG and curcumin showed better improvement in rescuing aging-associated memory disorders in mice. EGCG and curcumin combination could serve as a better choice in managing aging-related memory disorders.

Macrophage targeted polymeric curcumin nanoparticles limit intracellular survival of Mycobacterium tuberculosis through induction of autophagy and augment anti-TB activity of isoniazid in RAW 264.7 macrophages.

Rapid emergence of antibiotic resistance in tuberculosis has left us with limited resources to treat and manage multi drug resistant (MDR) cases of tuberculosis, prompting the development of novel therapeutics. Mycobacterium tuberculosis (MTB) perturbs the host protective pathways for its survival, therefore host directed therapeutic (HDT) interventions offer an attractive alternative strategy. Curcumin (CMN), the principle curcuminoid from Curcuma longa is known to have anti-TB activity against MDR strains of MTB in macrophages. We discovered that treatment of CMN induced autophagy in uninfected and MTB infected macrophages which was evident by conversion of LC3-I to LC3-II and degradation of p62. Inhibition of autophagy by a pharmacological inhibitor 3-MA resulted in significant inhibition of intracellular killing activity of CMN, suggesting the involvement of autophagy in intracellular clearance of MTB. Moreover, annexin v-FITC/PI staining data suggested induction of apoptosis in uninfected and MTB infected macrophages post CMN treatment. This finding was further corroborated by up-regulated expression of pro-apoptotic proteins, Bax, cleaved caspase-3 and PARP and diminished expression of anti-apoptotic protein Bcl-2 as evaluated by immunoblotting. Using GFP-MTB H37Rv and Lysotracker Red staining we demonstrated co-localization of GFP-MTB H37Rv containing phagosome to lysosome after CMN treatment, indicating enhanced phagosome lysosome fusion. Due to poor bioavailability of CMN, its clinical use is limited, therefore to overcome this issue, CMN was encapsulated in Poly(lactic-co-glycolic) acid (PLGA) shell, resulting in polymeric CMN nano particles (ISCurNP). Flow cytometric evaluation suggested >99% uptake of ISCurNP after 3h of treatment. In BALB/c mice, oral dose of ISCurNP resulted in 6.7-fold increase in the bioavailability compared to free CMN. Moreover, ISCurNP treatment resulted in significant decrease in the intracellular survival of MTB H37Rv through induction of autophagy. Adjunct action of ISCurNP and CMN in combination with isoniazid (INH) revealed >99% decrease in intracellular survival of MTB in macrophage as compared to ISCurNP, CMN or INH alone. In conclusion, our findings suggest the role of ISCurNP as novel host directed formulation to combat both sensitive and MDR strains of MTB by induction of autophagy.

Enhancing the Anticancer and Anti-Inflammatory Properties of Curcumin in Combination with Quercetin, for the Prevention and Treatment of Prostate Cancer.

Prostate cancer is the second most common cancer in men. Although epidemiologic studies show that a higher intake of polyphenols, curcumin (CUR), and quercetin (QRT), in particular, result in lower prostate cancer risk, the chemopreventive mechanisms underlying the effects of CUR and QRT have not been fully understood yet, and most investigations were conducted with individual compounds. Here, we investigated the anticancer and anti-inflammatory effects of CUR in combination with QRT, respectively, in a human prostate cancer cell line, PC-3, and in LPS-stimulated RAW 264.7 cells, and found that their combination significantly inhibited proliferation and arrested the cell cycle, inducing apoptosis, so exhibiting synergic activities stronger than single drug use. Moreover, via their antioxidant effects, the combination of CUR and QRT modulated several inflammation-mediated signaling pathways (ROS, nitric oxide, and pro-inflammatory cytokines) thus helping protect cells from undergoing molecular changes that trigger carcinogenesis. Although additional studies, including in vivo experiments and translational studies, are required, this study raises the possibility of their use as a safe, effective, and affordable therapeutic approach to prostate cancer.

The potential preventive effect of dietary phytochemicals In Vivo

IntroductionChemoprevention refers to using specific substances during oncogenesis. Curcumin and catechins are both polyphenol types of phytochemicals present in curcuma longa and green tea. The effect of curcumin is synergistic with epigallocatechin gallate, the most abundant polyphenol in tea.AimTo evaluate and compares the chemopreventive effect of both green tea and curcumin (each individually and in combination) through induction of hamster buccal pouch carcinoma.Materials and methodsSquamous cell carcinoma was chemically induced in fifty Syrian golden hamsters divided into 5 groups (10 each). The first group was used as a normal control group. The second group received the carcinogenic agent only. The other three groups received green tea, curcumin, and a combination of both, respectively. Flow cytometry, immunofluorescence, and immunohistochemical assays were used to evaluate apoptosis, proliferation, and angiogenesis. ANOVA test was used to analyze the results between the study groups.ResultsThe cells of the positive control group (B) resulted in 11.57% apoptosis. In the study groups, treatment of the cells with green tea (C), and curcumin (D) and both of them (E) showed increased apoptosis. The fluorescent image in group B showed an increase of the red fluorescence in the nucleus and cytoplasm of the squamous cell carcinoma cells while groups C, D, and E showed a decrease of the red fluorescence in the nuclei of the squamous cell carcinoma cells. The microvessel density was higher in the positive control group as compared to the treated groups.ConclusionsThe combination of green tea and curcumin has a significant chemopreventive effect against oral carcinogenesis.

Development and optimization of in-situ gels for vaginal delivery of metronidazole and curcumin via box-behnken design: In vitro characterization and anti-trichomonas activity

The aim of this study was to develop and optimize vaginal poloxamer in-situ gel formulations with metronidazole and curcumin combination for the treatment of infections caused by parasitic protozoa, Trichomonas vaginalis. Protozoan parasite infections cost the globe a colossal burden in terms of human and animal health. Lack of medication in low-income countries and rising drug resistance are posing substantial challenges in control and eradication of this infection. Today there is a tremendous drift in new alternative/synergic treatment strategies. Combination treatment, in particular, appear to be a promising approach against persistent, common, and infectious diseases like T. vaginalis. Poloxamer in-situ gels were prepared and optimized using the Box-Behnken statistical experiment design concept. The effect of critical parameters on critical quality features were evaluated by measuring the Tsol-gel transition temperature, solubilizing capacity of active substances in poloxamer bases, plastic viscosity, dynamic viscosity, and yield values. Optimized formulations (OPT-F1; F2; F3) were also tested for flow and mechanical properties, in-vitro release properties, cytotoxicity against the SK-HEP-1 cell line, and antiparasitic activity. The optimum formulations include properties that make them appropriate for vaginal administration and have been shown to be non-cytotoxic. The candidate gel formulation (OPT-F3) demonstrated statistically significant in-vitro activity against T. Vaginalis viability, demonstrating its antiparasitic effect. Stability studies conducted at 4 °C and 25 °C temperatures revealed that the ideal formulations retained their stability for 90 days. The study found that the gel containing metronidazole and curcumin is an effective and innovative approach to treating trichomoniasis and advances scientific research in this field.

Synthesis of curcumin derivatives containing non-steroidal anti-inflammatory drugs

Synthesis and biological evaluation of hybrid molecules combining naturally occurring antioxidant active structures with anti-inflammatory agents has been a strong trend in medicinal chemistry. This study focuses on modulating the structure of curcumin derivatives or their analogues with the use of non-steroidal anti-inflammatory drugs (NSAIDs). The combinations of curcumin, its keto-blocked derivatives and monocarbonyl analogues with selected non-steroidal anti-inflammatory drugs (ibuprofen, naproxen) were obtained and characterized. The pyrazole, isoxazole, benzylidene derivatives as well as curcumin monocarbonyl analogues were used as substrates in the reactions with selected NSAIDs. As a result of the esterification of curcumin-type diphenol, the corresponding mono- and diester-type derivatives were also obtained and characterized. Moreover, the estimated values of binding affinities and the binding sites of docked derivatives were deduced from modeling studies were very favorable. Results obtained show the binding potential of curcumin and its analogs to the host-targeted proteins nucleocapsid phosphoprotein (PDB ID: 6VYO) structure. Additionally, with the use of selected methods of computational chemistry (Molinspiration Cheminformatics and Osiris Property Explorer) the molecular parameters of the relevant molecules were calculated.

Combination of Lycopene and Curcumin Synergistically Alleviates Testosterone-Propionate-Induced Benign Prostatic Hyperplasia in Sprague Dawley Rats via Modulating Inflammation and Proliferation.

Benign prostatic hyperplasia (BPH) is a progressive urological disease occurring in middle-aged and elderly men, which can be characterized by the non-malignant overgrowth of stromal and epithelial cells in the transition zone of the prostate. Previous studies have demonstrated that lycopene can inhibit proliferation, while curcumin can strongly inhibit inflammation. This study aims to determine the inhibitory effect of the combination of lycopene and curcumin on BPH. To induce BPH models in vitro and in vivo, the BPH-1 cell line and Sprague Dawley (SD) rats were used, respectively. Rats were divided into six groups and treated daily with a vehicle, lycopene (12.5 mg/kg), curcumin (2.4 mg/kg), a combination of lycopene and curcumin (12.5 mg/kg + 2.4 mg/kg) or finasteride (5 mg/kg). Histologic sections were examined via hematoxylin and eosin (H&E) staining and immunohistochemistry. Hormone and inflammatory indicators were detected via ELISA. Network pharmacology analysis was used to fully predict the therapeutic mechanism of the combination of lycopene and curcumin on BPH. Combination treatment significantly attenuated prostate hyperplasia, alleviated BPH pathological features and decreased the expression of Ki-67 in rats. The upregulation of the expression of testosterone, dihydrotestosterone (DHT), 5α-reductase, estradiol (E2) and prostate-specific antigen (PSA) in BPH rats was significantly blocked by the combination treatment. The expression levels of inflammatory factors including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were strongly inhibited by the combination treatment. From the network pharmacology analysis, it was found that the main targets for inhibiting BPH are AKT1, TNF, EGFR, STAT3 and PTGS2, which are enriched in pathways in cancer. The lycopene and curcumin combination is a potential and more effective agent to prevent or treat BPH.

Mechanism underlying joint loading and controlled release of β-carotene and curcumin by octenylsuccinated Gastrodia elata starch aggregates

This study aimed to fabricate a novel codelivery system to simultaneously load β-carotene and curcumin in a controlled and synergistic manner. We hypothesized that the aggregates of octenylsuccinated Gastrodia elata starch (OSGES) could efficiently load and control the release of β-carotene and curcumin in combination. Mechanisms underlying the self-assembly of OSGES, coloading, and corelease of β-carotene and curcumin by relevant aggregates were studied. The OSGES could form aggregates with a size of 120.2 nm containing hydrophobic domains surrounded by hydrophilic domains. For coloading, the increased solubilities were attributed to favorable interactions between β-carotene and curcumin as well as interactions with octenyl and starch moieties via hydrophobic and hydrogen-bond interactions, respectively. The β-carotene and curcumin molecules occupied the interior and periphery of hydrophobic domains of OSGES aggregates, respectively, and they did not exist in isolation but interacted with each other. The β-carotene and curcumin combination-loaded OSGES aggregates with a size of 310.5 nm presented a more compact structure than β-carotene-only and curcumin-only loaded OSGES aggregates with sizes of 463.5 and 202.9 nm respectively, suggesting that a transition from a loose cluster to a compact cluster was accompanied by coloading. During in vitro digestion, the joint effect of β-carotene and curcumin prolonged their release and increased their bioaccessibility due to competition between favorable hydrophobic and hydrogen-bond interactions and the unfavorable structure erosion and relaxation of the loaded aggregates. Therefore, OSGES aggregates were designed for the codelivery of β-carotene and curcumin, indicating their potential to be applied in functional foods and dietary supplements.

Combination of Curcumin and Zerumbone Improves VEGF-A Inhibition in Colorectal Cancer In Vivo and In Vitro Model

Combination of Curcumin and Zerumbone Improves VEGF-A Inhibition in Colorectal Cancer In Vivo and In Vitro Model

Synthesis, Cytotoxicity and Molecular Docking of New Hybrid Compounds by Combination of Curcumin with Oleanolic Acid.

Curcumin and oleanolic acid are natural compounds with high potential in medicinal chemistry. These products have been widely studied for their pharmacological properties and have been structurally modified to improve their bioavailability and therapeutic value. In the present study, we discuss how these compounds are utilized to develop bioactive hybrid compounds that are intended to target cancer cells. Using a bifunctional linker, succinic acid, to combine curcumin and triterpenoic oleanolic acid, several hybrid compounds were prepared. Their cytotoxicity against different cancer cell lines was evaluated and compared with the activity of curcumin (the IC50 value (24 h), for MCF7, HeLaWT and HT-29 cancer cells for KS5, KS6 and KS8 compounds was in the range of 20.6-94.4 µM, in comparison to curcumin 15.6-57.2 µM). Additionally, in silico studies were also performed. The computations determined the activity of the tested compounds towards proteins selected due to their similar binding modes and the nature of hydrogen bonds formed within the cavity of ligand-protein complexes. Overall, the curcumin-triterpene hybrids represent an important class of compounds for the development of effective anticancer agents also without the diketone moiety in the curcumin molecule. Moreover, some structural modifications in keto-enol moiety have led to obtaining more information about different chemical and biological activities. Results obtained may be of interest for further research into combinations of curcumin and oleanolic acid derivatives.

Curcumin Enhances the Abscopal Effect in Mice with Colorectal Cancer by Acting as an Immunomodulator.

Radiotherapy (RT) is an effective cancer treatment. The abscopal effect, referring to the unexpected shrinkage observed in non-irradiated tumors after radiation therapy, is thought to be mediated by systemic immune activation. However, it has low incidence and is unpredictable. Here, RT was combined with curcumin to investigate how curcumin affects RT-induced abscopal effects in mice with bilateral CT26 colorectal tumors. Indium 111-labeled DOTA-anti-OX40 mAb was synthesized to detect the activated T cell accumulations in primary and secondary tumors correlating with the changes in protein expressions and tumor growth to understand the overall effects of the combination of RT and curcumin. The combination treatment caused the most significant tumor suppression in both primary and secondary tumors, accompanied by the highest 111In-DOTA-OX40 mAb tumor accumulations. The combination treatment elevated expressions of proapoptotic proteins (Bax and cleaved caspase-3) and proinflammatory proteins (granzyme B, IL-6, and IL-1β) in both primary and secondary tumors. Based on the biodistribution of 111In-DOTA-OX40 mAb, tumor growth inhibition, and anti-tumor protein expression, our findings suggest that curcumin could act as an immune booster to augment RT-induced anti-tumor and abscopal effects effectively.

Pro-Osteogenic and Anti-Inflammatory Synergistic Effect of Orthosilicic Acid, Vitamin K2, Curcumin, Polydatin and Quercetin Combination in Young and Senescent Bone Marrow-Derived Mesenchymal Stromal Cells.

During aging, bone marrow mesenchymal stromal cells (MSCs)-the precursors of osteoblasts-undergo cellular senescence, losing their osteogenic potential and acquiring a pro-inflammatory secretory phenotype. These dysfunctions cause bone loss and lead to osteoporosis. Prevention and intervention at an early stage of bone loss are important, and naturally active compounds could represent a valid help in addition to diet. Here, we tested the hypothesis that the combination of two pro-osteogenic factors, namely orthosilicic acid (OA) and vitamin K2 (VK2), and three other anti-inflammatory compounds, namely curcumin (CUR), polydatin (PD) and quercetin (QCT)-that mirror the nutraceutical BlastiMin Complex® (Mivell, Italy)-would be effective in promoting MSC osteogenesis, even of replicative senescent cells (sMSCs), and inhibiting their pro-inflammatory phenotype in vitro. Results showed that when used at non-cytotoxic doses, (i) the association of OA and VK2 promoted MSC differentiation into osteoblasts, even when cultured without other pro-differentiating factors; and (ii) CUR, PD and QCT exerted an anti-inflammatory effect on sMSCs, and also synergized with OA and VK2 in promoting the expression of the pivotal osteogenic marker ALP in these cells. Overall, these data suggest a potential role of using a combination of all of these natural compounds as a supplement to prevent or control the progression of age-related osteoporosis.

Dipeptide Nitrile CD34 with Curcumin: A New Improved Combination Strategy to Synergistically Inhibit Rhodesain of Trypanosoma brucei rhodesiense.

Rhodesain is the main cysteine protease of Trypanosoma brucei rhodesiense, the parasite causing the acute lethal form of Human African Trypanosomiasis. Starting from the dipeptide nitrile CD24, the further introduction of a fluorine atom in the meta position of the phenyl ring spanning in the P3 site and the switch of the P2 leucine with a phenylalanine led to CD34, a synthetic inhibitor that shows a nanomolar binding affinity towards rhodesain (Ki = 27 nM) and an improved target selectivity with respect to the parent dipeptide nitrile CD24. In the present work, following the Chou and Talalay method, we carried out a combination study of CD34 with curcumin, a nutraceutical obtained from Curcuma longa L. Starting from an affected fraction (fa) of rhodesain inhibition of 0.5 (i.e., the IC50), we observed an initial moderate synergistic action, which became a synergism for fa values ranging from 0.6 to 0.7 (i.e., 60-70% inhibition of the trypanosomal protease). Interestingly, at 80-90% inhibition of rhodesain proteolytic activity, we observed a strong synergism, resulting in 100% enzyme inhibition. Overall, in addition to the improved target selectivity of CD34 with respect to CD24, the combination of CD34 + curcumin resulted in an increased synergistic action with respect to CD24 + curcumin, thus suggesting that it is desirable to use CD34 and curcumin in combination.

Curcumin reduces paclitaxel resistance in ovarian carcinoma cells by upregulating SNIP1 and inhibiting NFκB activity

The therapeutic activity of paclitaxel against ovarian carcinoma is relatively low due to the frequent occurrence of chemoresistance and disease recurrence. We found earlier that a combination of curcumin and paclitaxel reduces cell viability and promotes apoptosis in paclitaxel-resistant (i.e., taxol-resistant, Txr) ovarian cancer cells. In the present study, we first used RNA sequencing (RNAseq) analysis to identify genes that are upregulated in Txr cell lines but downregulated by curcumin in ovarian cancer cells. The nuclear factor kappa B (NFκB) signaling pathway was shown to be upregulated in Txr cells. Furthermore, based on the protein interaction database BioGRID, we found that Smad nuclear interacting protein 1 (SNIP1) may be involved in regulating the activity of NFκB in Txr cells. Accordingly, curcumin upregulated SNIP1 expression, which in turn downregulated the pro-survival genes Bcl-2 and Mcl-1. Using shRNA-guided gene silencing, we found that SNIP1 depletion reversed the inhibitory effect of curcumin on NFκB activity. Moreover, we identified that SNIP1 enhanced NFκB protein degradation, thereby suppressing NFκB/p65 acetylation, which is involved in the inhibitory effect of curcumin on NFκB signaling. The transcription factor early growth response protein 1 (EGR1) was shown to represent an upstream transactivator of SNIP1. Consequently, we show that curcumin inhibits NFκB activity by modulating the EGR1/SNIP1 axis to attenuate p65 acetylation and protein stability in Txr cells. These findings provide a new mechanism to account for the effects of curcumin in inducing apoptosis and reducing paclitaxel resistance in ovarian cancer cells.

Designing and evaluation of dermal targeted combinatorial nanostructured lipid carrier gel loaded with curcumin and resveratrol for accelerating cutaneous wound healing

A nanostructured lipid carrier containing combined curcumin (CUR) and resveratrol (RSV) was prepared and tested for its potential to accelerate wound healing through topical administration. Prepared nano lipid carrier (NLC) formulation had a particle size of 132.3 ± 4.54 nm, polydispersity index (PDI) of 0.478, and zeta potential of −16.6 mV. Entrapment efficiency (EE) for CUR and RSV was found to be 94.21 ± 0.28% and 84.61 ± 0.15%, respectively. Drug loading was found to be 8.560 ± 0.948% (for CUR) and 7.602 ± 0.452% (for RSV). NLC formulation was converted to NLC gel by incorporation of Carbopol 934 for enhancing its dermal applicability. Flux and permeability coefficient for CUR and RSV in NLC gel was found to be 22.087 µg/cm2/h, 11.299 µg/cm2/h, and 0.2208, 0.1129, respectively, through goat ear skin and 19.213 µg/cm2/h, 22.66 µg/cm2/h and 0.1921, 0.2266, respectively, through Strat-MTM membrane. Dermatokinetic study revealed significant enhancement in Cskin max and AUC0–12h in skin sample treated with NLC gel in comparison with plain gel. Also, NLC gel showed longer retention time which indicates prolonged drug action at targeted site thus, NLC gel may show better therapeutic efficacy than plain gel.

Clinical effectiveness and tolerability of UC-II, sodium hyaluronate, and curcumin in osteoarthritis of the knee – CAPE Study: A multicentre, Prospective, real-world evidence study

Background: Osteoarthritis (OA) is a degenerative joint disease that results in the breakdown of cartilage, causing pain, stiffness, and decreased range of motion in the affected joints. It is a common form of arthritis, particularly in older adults. Undenatured type II collagen (UC-II) is a nutritional supplement which has been found to be effective in treating OA.Objective: To determine the efficacy and safety of UC-II, sodium hyaluronate, and curcumin in treating knee OA.Materials and Methods: 813 patients with knee OA were enrolled in the study. Subjects received a capsule containing 40 mg UC-II, 80 mg sodium hyaluronate and 200 mg curcumin once daily for three months. The Western Ontario and McMaster Osteoarthritis Index (WOMAC) evaluated pain, joint stiffness, and physical functions. A Visual Analog Scale (VAS) was used to assess the severity of the initial pain. Moreover, clinical symptom scores and patient and physician global assessments were evaluated. The patients were assessed before the treatment and three months after the initiation of the treatment. Results: The WOMAC scores for pain, stiffness, and function, as well as the VAS score, were significantly improved (P< 0.05) in subjects after three months compared to the baseline. There was a 73.51% improvement in the total WOMAC scores and a 69.92% improvement in the VAS scores. There was a significant reduction in clinical symptoms, and global assessments of treatment by patients and physicians based on overall efficacy were favourable after the three-month treatment.Conclusion: The study showed that UC-II, sodium hyaluronate and curcumin in combination effectively improve the symptoms of OA and should be positively considered for the symptomatic management of OA.

The Combination of Natural Molecules Naringenin, Hesperetin, Curcumin, Polydatin and Quercetin Synergistically Decreases SEMA3E Expression Levels and DPPIV Activity in In Vitro Models of Insulin Resistance.

Type 2 diabetes mellitus (T2DM) is a disease characterized by a prolonged hyperglycemic condition caused by insulin resistance mechanisms in muscle and liver, reduced insulin production by pancreatic β cells, and a chronic inflammatory state with increased levels of the pro-inflammatory marker semaphorin 3E. Phytochemicals present in several foods have been used to complement oral hypoglycemic drugs for the management of T2DM. Notably, dipeptidyl peptidase IV (DPPIV) inhibitors have demonstrated efficacy in the treatment of T2DM. Our study aimed to investigate, in in vitro models of insulin resistance, the ability of the flavanones naringenin and hesperetin, used alone and in combination with the anti-inflammatory natural molecules curcumin, polydatin, and quercetin, to counteract the insulin resistance and pro-inflammatory molecular mechanisms that are involved in T2DM development. Our results show for the first time that the combination of naringenin, hesperetin, curcumin, polydatin, and quercetin (that mirror the nutraceutical formulation GliceFen®, Mivell, Italy) synergistically decreases expression levels of the pro-inflammatory gene SEMA3E in insulin-resistant HepG2 cells and synergistically decreases DPPIV activity in insulin-resistant Hep3B cells, indicating that the combination of these five phytochemicals is able to inhibit pro-inflammatory and insulin resistance molecular mechanisms and could represent an effective innovative complementary approach to T2DM pharmacological treatment.