Therapeutic Efficacy Of Curcumin Research Articles

Integrating Network Pharmacology, Transcriptomics to Reveal Neuroprotective of Curcumin Activate PI3K / AKT Pathway in Parkinson's Disease.

Parkinson's disease (PD) is the most prevalent movement disorder. Curcumin, a polyphenol with hydrophobic properties, has been proved against Parkinson. Our previous study suggested that curcumin's effectiveness in treating Parkinson's disease may be linked to the gut-brain axis, although the specific mechanism by which curcumin exerts neuroprotective effects in the brain remains unknown. The therapeutic efficacy of curcumin was evaluated using behavioral tests, immunofluorescence of tyrosine hydroxylase (TH). Network pharmacology and transcriptomics predicted the mechanisms of curcumin in PD. Activation of the phosphatidylinositol 3-kinase PI3K/AKT pathway was confirmed by quantitative polymerase chain reaction (qPCR) and immunofluorescence. Curcumin restored the dyskinesia and dopaminergic neurons damage of MPTP-induced mice. Curcumin against Parkinson's disease by regulating inflammation, oxidative stress, and aging. The mechanisms of these were associated with activation of PI3K / AKT pathway. In conclusion, the neuroprotective mechanisms of curcumin activate PI3K / AKT pathway in Parkinson's disease was revealed by our study.

Alginate and Chitosan-Based Delivery Systems for Improving the Bioavailability and Therapeutic Efficacy of Curcumin.

One of the major challenges in harnessing the therapeutic benefits of curcumin (an active ingredient from turmeric) is its poor bioavailability due to its short biological half-life. In this regard, nanoformulations have shown tremendous hope for improving the pharmacokinetic and therapeutic behavior of curcumin by altering its biological stability and bioavailability. Biopolymers, especially alginate and chitosan, have received special attention as excipients to prepare nanoformulations of curcumin due to their abundant availability, biocompatibility, and amicability to form different types of self-assembled structures and ease of undergoing chemical modifications. However, there are certain challenges, such as poor water solubility under physiological conditions and heterogeneity with regard to molecular weight and large-scale production of well-preserved nanostructures. Substantial advancement has been achieved towards overcoming these challenges by developing newer derivatives through a chemical modifications approach, and this has ascertained the suitability of alginate and chitosan as excipients for drug delivery systems (DDS). The present minireview briefly discusses curcumin and its limitation as a drug molecule, carbohydrates as DDS, and the recent developments related to the alginate and chitosan-based nanoformulations of curcumin. Special emphasis has been given to highlighting the impact of alginate and chitosan-based nanoformulations in improving the therapeutic efficacy and bioavailability of curcumin.

Precision cardiac targeting: empowering curcumin therapy through smart exosome-mediated drug delivery in myocardial infarction.

Nanoparticle-mediated drug delivery has emerged as a highly promising and effective therapeutic approach for addressing myocardial infarction. However, clinical translation tends to be a failure due to low cardiac retention as well as liver and spleen entrapment in previous therapies. Herein, we report a two-step exosome delivery system, which precludes internalization by the mononuclear phagocyte system before the delivery of therapeutic cardiac targeting exosomes (ExoCTP). Importantly, curcumin released by ExoCTP diminishes reactive oxygen species over-accumulation in ischemic myocardium, as well as serum levels of lactate dehydrogenase, malonyldialdehyde, superoxide dismutase and glutathione, indicating better antioxidant capacity than free curcumin. Finally, our strategy was proven to greatly potentiate the delivery and therapeutic efficacy of curcumin without systemic toxicity. Taken together, our smart exosome-mediated drug delivery strategy can serve either as therapeutics alone or in combination with other drugs for effective heart targeting and subsequent wound healing.

Curcuminoid Nanovesicles as Advanced Therapeutics

AbstractTurmeric (Curcuma longa rhizome) is well‐known for its therapeutic properties in traditional Indian and Chinese medicines. It has preventive and therapeutic activity against diseases that target human body systems as well as various cancer types. This review focuses on the mechanism of action of curcumin against various factors involved in the metastatic process. The antimicrobial, antidiabetic, anti‐oxidant, and anti‐HIV activities and mechanism of curcumin‐functionalized nanovesicles are also reviewed. Despite the biocompatibility of curcumins, its medical applications are limited due to its low bioavailability, insolubility in water, and degradation at certain pH levels. Moreover, the low stability and rapid metabolism of curcumin limits its clinical applications. Therefore, it is imperative to design strategies to mitigate this shortfall which include the synthesis of curcumin glycosides or the development of curcumin delivery systems to improve the bioavailability and therapeutic efficacy of curcumin. This review provides insight into the different chemical methods for the synthesis and modification adopted to achieve these compounds.

Novel Drug Delivery System for Curcumin: Implementation to Improve Therapeutic Efficacy against Neurological Disorders

Curcumin, a hydrophobic polyphenolic compound present in Curcuma longa Linn. (Turmeric), has been used to improve various neurodegenerative conditions, including Amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Prion disease, stroke, anxiety, depression, and ageing. However, the Blood-Brain Barrier (BBB) impedes the delivery of curcumin to the brain, limiting its therapeutic potential. This review summarises the recent advances towards the therapeutic efficacy of curcumin along with various novel strategies to overcome its poor bioavailability across the bloodbrain barrier. The data for the compilation of this review work were searched in PubMed Scopus, Google Scholar, and Science Direct. Various approaches have been opted to expedite the delivery of curcumin across the blood-brain barrier, including liposomes, micelles, polymeric nanoparticles, exosomes, dualtargeting nanoparticles, etc. Conclusion: The review also summarises the numerous toxicological studies and the role of curcumin in CNS disorders.

Physicochemical investigation of a novel curcumin diethyl γ-aminobutyrate, a carbamate ester prodrug of curcumin with enhanced anti-neuroinflammatory activity.

Curcumin is a polyphenol compound that alleviates several neuroinflammation-related diseases including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy and cerebral injury. However, the therapeutic efficacy of curcumin is limited by its poor physicochemical properties. The present study aimed to develop a new carrier-linked curcumin prodrug, curcumin diethyl γ-aminobutyrate (CUR-2GE), with improved physicochemical and anti-neuroinflammatory properties. CUR-2GE was designed and synthesized by conjugating curcumin with gamma-aminobutyric acid ethyl ester (GE) via a carbamate linkage. The carbamate linkage was selected to increase stability at acidic pH while GE served as a promoiety for lipophilic enhancement. The synthesized CUR-2GE was investigated for solubility, partition coefficient, stability, and bioconversion. The solubility of CUR-2GE was less than 0.05 μg/mL similar to that of curcumin, while the lipophilicity with log P of 3.57 was significantly increased. CUR-2GE was resistant to chemical hydrolysis at acidic pH (pH 1.2 and 4.5) as anticipated but rapidly hydrolyzed at pH 6.8 and 7.4. The incomplete hydrolysis of CUR-2GE was observed in simulated gastrointestinal fluids which liberated the intermediate curcumin monoethyl γ-aminobutyric acid (CUR-1GE) and the parent curcumin. In plasma, CUR-2GE was sequentially converted to CUR-1GE and curcumin within 1 h. In lipopolysaccharide (LPS)-stimulated BV-2 microglial cells, CUR-2GE effectively attenuated the pro-inflammatory mediators by decreasing the secretion of nitric oxide and cytokines (TNF-α and IL-6) to a greater extent than curcumin due to an increase in cellular uptake. Altogether, the newly developed acid-stable CUR-2GE prodrug is a potential pre-clinical and clinical candidate for further evaluation on neuroprotective and anti-neuroinflammatory effects.

TB-4 Antitumor effects of a novel curcumin derivative curcumin monoglucuronide on glioblastoma cells in vitro and in vivo

The therapeutic outcome of glioblastomas (GBMs) is still very poor. Therefore, invention of novel therapeutic methods against GBM cases is considered urgent. The antitumor effects of naturally-derived compounds are attracting attention recently, and therapeutic efficacy of curcumin, a plant-derived compound previously used for multiple purpose, has been indicated in many cancer systems; however, clinical application of curcumin is considered difficult because of its poor bioavailability (under 1 %). Curcumin monoglucuronide (CMG), a water-soluble prodrug of curcumin recently developed for overcoming this weakness, has been demonstrated excellent antitumor effects for several malignancies in vitro and in vivo; therefore, we investigated the effects of CMG against GBM cells. CMG induced cell death of human GBM cells lines (T98G, U251MG, and U87MG) by dose dependent manner by triggering multiple forms of cell death such as apoptosis and perthanatos. Immunoblotting of CMG-treated GBM cell lysates demonstrated activation of multiple cell death signaling. Furthermore, immunodeficiency mice harboring intracerebral U87MG cell xenografts systemically treated by CMG showed significantly prolonged survival compared with control mice. These results suggest CMG would be a novel therapeutic agent against GBM cases.

Preparation and Characterization of Curcumin Nanoemulgel Utilizing Ultrasonication Technique for Wound Healing: In Vitro, Ex Vivo, and In Vivo Evaluation.

Hydrogels being a drug delivery system has great significance particularly for topical application in cutaneous open wound. Its specific physicochemical properties such as non-adhesiveness, moisture retention, exudate absorption, and gas permeability make them ideal as a drug delivery vehicle for wound healing application. Further, curcumin (a natural bioactive) was selected as a therapeutic agent to incorporate into the hydrogel system to design and develop nanogel pharmaceutical products for wound healing. Although, curcumin possesses remarkable anti-inflammatory, antioxidant, and anti-infective activity along with hastening the healing process by acting over the different stages of the wound healing process, but its poor biopharmaceutical (low aqueous solubility and skin penetrability) attributes hamper their therapeutic efficacy for skin applications. The current investigation aimed to develop the curcumin-loaded nanogel system and evaluated to check the improvement in the therapeutic efficacy of curcumin through a nanomedicine-based approach for wound healing activity in Wistar rats. The curcumin was enclosed inside the nanoemulsion system prepared through a high-energy ultrasonic emulsification technique at a minimum concentration of surfactant required to nanoemulsify the curcumin-loaded oil system (Labrafac PG) having droplet size 56.25 ± 0.69 nm with polydispersity index 0.05 ± 0.01 and negatively surface charge with zeta potential −20.26 ± 0.65 mV. It was observed that the impact of Smix (surfactant/co-surfactant mixture) ratio on droplet size of generated nanoemulsion is more pronounced at lower Smix concentration (25%) compared to the higher Smix concentration (30%). The optimized curcumin-loaded nanoemulsion was incorporated into a 0.5% Carbopol® 940 hydrogel system for topical application. The developed curcumin nanoemulgel exhibited thixotropic rheological behavior and a significant (p < 0.05) increase in skin penetrability characteristics compared to curcumin dispersed in conventional hydrogel system. The in vivo wound healing efficacy study and histological examination of healed tissue specimen further signify the role of the nanomedicine-based approach to improve the biopharmaceutical attributes of curcumin.

Modulation of proteasome activity by curcumin and didemethylcurcumin

Modulation of proteasome function by pharmacological interventions and molecular biology tools is an active area of research in cancer biology and neurodegenerative diseases. Curcumin (diferuloylmethane) is a naturally occurring polyphenol that affects multiple signaling pathways. Curcumin shows anti-inflammatory, antioxidant, anti-angiogenic, or anti-apoptotic properties. Recent research suggests that the therapeutic efficacy of curcumin may be due to its activity as a potent inhibitor of the proteasome. Using in vitro cell culture and molecular docking methods, here we show that both curcumin and its synthetic polyphenolic derivative (didemethylcurcumin, CUIII) modulated proteasome activity in a biphasic manner. Curcumin and CUIII increased proteasome activity at nanomolar concentrations, but inhibited proteasome activity at micromolar concentrations. Curcumin was more effective than CUIII in increasing relative proteasome activity at nanomolar concentrations. Also, curcumin was more effective than CUIII in inhibiting relative proteasome activity at micromolar concentrations. Docking simulations of curcumin and didemethylcurcumin binding to the 20S proteasome catalytic subunit estimated K d values of 0.0054 µM and 1.3167 µM, respectively. These values correlate well with the results of the effectiveness of modulation by curcumin compared to CUIII. The small size of CUIII allows it to dock to the narrow cavity of the active site, but the binding interaction is not strong compared to curcumin. These results indicate that curcumin and its didemethyl derivative can be used to modulate proteasome activity and suggest that curcumin and its didemethyl derivative may be useful in treating two different disease classes: neurodegeneration and cancer. Communicated by Ramaswamy H. Sarma

The Therapeutic Efficacy of Curcumin vs. Metformin in Modulating the Gut Microbiota in NAFLD Rats: A Comparative Study

Structural disruption of gut microbiota is closely related to the occurrence of non-alcoholic fatty liver disease (NAFLD). Previous research has demonstrated that both curcumin (CUR) and metformin (MET) have a therapeutic effect against NAFLD and play a role in modulating the gut microbiota. However, there is a lack of direct comparison between the two medications in terms of the therapeutic efficacy and the regulatory effect on gut microbiota. In this study, we administered either CUR or MET to rats with high-fat diet (HFD)-induced obesity to observe changes in body parameters, biochemical parameters, liver, and ileum pathology and gut microbiota, and used next generation sequencing and multivariate analysis to evaluate the structural changes of gut microbiota in a NAFLD rat model before and after CUR and MET intervention. It was found that both CUR and MET attenuated hepatic ectopic fat deposition, alleviated inflammatory factors, and improved intestinal barrier integrity in HFD-fed rats. More importantly, CUR and MET reduced the Firmicutes/Bacteroidetes ratio and reverted the composition of the HFD-disrupted gut microbiota. Both CUR and MET treatments effectively modified the gut microbiome, enriched the abundance of beneficial bacteria and reduced opportunistic pathogens in obese rats. The abundance of Butyricicoccus was increased while the abundance of Dorea was decreased in HFD + CUR group. Besides, some beneficial bacteria such as Prevotella were increased in MET-treated animals. Spearman’s correlation analysis showed that Helicobacter, Akkermansia, Desulfovibrio, Romboutsia, Corynebacterium, Lactobacillus, Ruminococcaceae_unclassified, Lachnospiraceae_unclassified, and Clostridiales_unclassified showed significantly positive correlations with TG, TC, LDL-C, GLU, IL-6, IL-1β, and TNF-α, and negative correlations with HDL-C (both p < 0.05). However, Prevotella and Stomatobaculum showed an opposite trend. In summary, CUR and MET showed similar effects in alleviating hepatic steatosis, improving intestinal barrier integrity and modulating gut microbiota in HFD-induced obesity rats, and therefore may prove to be a novel adjunctive therapy for NAFLD.

Therapeutic Effects of Curcumin on Toxicity Induced by Permethrin in Rat Liver and SK-Hep-1 Cells

This investigation aimed to evaluate the toxic effects of permethrin (PMN) on rat liver and the therapeutic efficacy of curcumin (CMN) against PMN-induced alterations in hepatic biomarkers, liver antioxidant enzymes, and SK-Hep-1 cells. The animals were divided into four groups of six as follows: the first group was defined as the control, while the second, the third, and the fourth groups were orally treated with PMN (62.5 mg/kg bw), CMN (120 mg/kg bw), and PMN plus CMN, respectively for three weeks. Biochemical markers in the serum and the levels of lipid peroxidation (LPO) and antioxidant enzyme activity in the liver were determined. PMN exposure stimulated significant changes in animals’ hepatic biomarkers, including alanine and aspartate aminotransferases (ALT and AST) and alkaline phosphatase (ALP). The results indicated that LPO was significantly raised in PMN-treated rats, as evidenced by high liver malondialdehyde (MDA) concentration. The antioxidant system in PMN-treated rats was altered, which confirmed by a significant decline (p&lt;0.05) in the activity of catalase (CAT), glutathione peroxidase (GPX), and glutathione-S-transferase (GST) in the liver. On the other hand, the administration of CMN with PMN significantly (p&lt; 0.05) ameliorated ALT, AST, ALP, MDA, CAT, GPX, and GST activity. In addition, CMN demonstrated protective activity against toxicity induced by PMN in SK-Hep-1 cells. In conclusion, our findings demonstrated that PMN induced hepatic damage in rats and CMN had noticeable therapeutic effects on hepatic injuries, oxidative stress, and cytotoxicity induced by PMN.

Preparation of Curcumin-Liposomes using pH-Driven Method to Enhance Stability and Encapsulation Efficiency

Curcumin, a hydrophobic polyphenol, derived from turmeric, has numerous pharmacological activities, including hepatoprotective, antioxidant, anti-inflammatory, antimicrobial, and anticarcinogenic. However, the therapeutic efficacy of curcumin is limited due to its poor oral bioavailability and high susceptibility to degradation. The poor oral bioavailability of curcumin has been attributed to its poor aqueous solubility and extensive first past metabolism. Curcumin dissolves in alkaline conditions but it is highly unstable undergoing rapid hydrolytic degradation in neutral or alkaline condition. To solve these problems, liposome-based encapsulation technology is applied to improve the bioavailability of curcumin. The existing method to prepare curcumin-liposome, thin-film method, is complex and usually required the use of organic solvents. In this study, pH-driven method, an organic solvent-free and easily encapsulation technique utilizing the pH-dependent solubility of curcumin was proposed to improve the stability and bioavailability. Curcumin-liposomes were prepared using phospholipon 90 H and soya lecithin as phospholipid sources. The characterizations of curcumin-liposomes include particle size, microstructure, encapsulation efficiency, infrared spectra, salt stability and storage stability. The particle size measured was 77.85 ± 0.39 nm. It was found that curcumin-liposomes prepared by the pH-driven method was stable during storage for 30 days and gave encapsulation efficiency of 60.71 ± 0.20%, higher as compared to the ones prepared by thin-film method. In conclusion, pH-driven is a promising method for the preparation of curcumin-liposomes to enhance stability and encapsulation efficiency

Different Approaches for Enhancement of Curcumin Aqueous Solubility and Dissolution rate

Curcumin (CUR) is a nature polyphenolic phytoingredient. CUR showed anti-inflammatory, anti-oxidant, anti-fungal and anti-cancer activities. The therapeutic efficacy of CUR was limited due to its poor aqueous solubility, poor oral bioavailability. Poor solubility of drugs is the major challenge associated with formulation development. Therefore, the aim of present work was to enhance CUR aqueous solubility and dissolution rate using Physical mixture and its solid dispersion. CUR solid dispersions were prepared by solvent evaporation and Freeze drying techniques using different polymers, such as cyclodextrins, polyvinyl pyrrolidone (PVP K30), polyethylene glycol 6000 and Pluronic®F-127. The prepared physical mixtures, solid dispersions were characterized using different techniques such as (DSC), (FTIR) and (XRD). Furthermore, the solubility and the dissolution rate of the drug in its different systems were explored. The results of physical characterization of the different systems show no interaction between them. Dissolution studies of CUR solid dispersions showed that the highest drug dissolution rate was achieved at CUR/ Pluronic®F-127 weight ratio of 1:3. Also, complete drug dissolution was obtained for CUR/Pluronic F-127 solid dispersion after 30 min compared to 35% dissolution for CUR alone after the same time. Also, CUR permeability coefficient through rat skin for Pluronic®F-127 micelles and solid dispersion were two times higher than that of the CUR alone. The obtained results concluded that, the preparation of solid dispersion of Pluronic®F-127 solid dispersions by freeze drying method is a promising one to overcome CUR shortcomings through enhancing its aqueous solubility, dissolution rate and skin permeability.

Curcumin nanoparticle-incorporated collagen/chitosan scaffolds for enhanced wound healing

Curcumin is a naturally derived active agent of the perennial herb Curcuma longa with anti-inflammatory, antimicrobial, antioxidant and wound healing properties. Because curcumin has very low aqueous solubility and quick degradation, its use is difficult. Incorporation of curcumin nanoparticles (CNs) into a biocompatible scaffold conquers this difficulty and improves the topical drug delivery and therapeutic efficacy of curcumin. In this study, the authors synthesized and characterized three scaffolds made with CNs and using biocompatible polymers, namely, collagen (C) and chitosan (Ch), with ratios of 2:1 (C2Ch1), 1:1 (C1Ch1) and 1:2 (C1Ch2). Then, the scaffolds were applied as wound dressing to enhance the cutaneous wound healing. Since C1Ch2 and CN-incorporated C1Ch2 (CN-C1Ch2) scaffolds demonstrated the best physicochemical characteristics, these samples were used for further biological evaluations through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide detection of viable cells and evaluation of wound healing activity by excision wound model using male Wistar rats. The in vivo and in vitro wound healing studies presented a greater closure of wounds with enhanced histological parameters in the wounds treated with CN-C1Ch2 scaffolds compared to the other samples. The obtained results indicated that the CN-incorporated C1Ch2 scaffolds could significantly improve the wound healing activity.

Comparison of therapeutic response of lycopene and curcumin in oral submucous fibrosis: A randomized controlled trial.

To evaluate and compare the therapeutic response of lycopene and curcumin with placebo in patients suffering from oral submucous fibrosis (OSMF) and to correlate the habit variables of smoked and smokeless tobacco products in OSMF. A randomized placebo-controlled parallel clinical study was conducted on ninety OSMF patients, who were divided into three treatment groups using computer-generated randomization. Group A patients (n=30) were given curcumin tablet (300mg) twice daily, Group B patients (n=30) received lycopene capsules (8mg) twice daily, and for Group C (n=30), placebo capsules were given once daily for a period of six months. Both the participant and outcome assessor were blinded. Pre- and post-treatment comparison of mouth opening, burning sensation, tongue protrusion, and cheek flexibility was analyzed at periodic follow-up of 9months. The overall improvement in mouth opening, burning sensation, tongue protrusion, and cheek flexibility was 3.9±4.9mm, 4.8±2.6, 5.0±7.2mm, & 0.36±0.71mm, respectively, for curcumin and 4.1±4.2mm, 5.0±2.3, 2.4±3.5mm, & 0.66±0.80mm, respectively, for lycopene with the p value <0.05. Statistically significant improvement in clinical findings was observed in both curcumin and lycopene treatment groups in comparison with placebo. However, the therapeutic efficacy of curcumin and lycopene was found to be almost equal in OSMF patients.

Polymeric Nano-Encapsulation of Curcumin Enhances its Anti-Cancer Activity in Breast (MDA-MB231) and Lung (A549) Cancer Cells Through Reduction in Expression of HIF-1α and Nuclear p65 (Rel A).

The anti-cancer potential of curcumin, a natural NFκβ inhibitor, has been reported extensively in breast, lung and other cancers. In vitro and in vivo studies indicate that the therapeutic efficacy of curcumin is enhanced when formulated in a nanoparticulate carrier. However, the mechanism of action of curcumin at the molecular level in the hypoxic tumour micro-environment is not fully understood. Hence, the aim of our study was to investigate the mechanism of action of curcumin formulated as nanoparticles in in vitro models of breast and lung cancer under an hypoxic microenvironment. Biodegradable poly(lactic-co-glycolic acid) PLGA nanoparticles (NP), loaded with curcumin (cur-PLGA-NP), were fabricated using a solvent evaporation technique to overcome solubility issues and to facilitate intracellular curcumin delivery. Cytotoxicity of free curcumin and cur-PLGA-NP was evaluated in MDA-MB-231 and A549 cell lines using migration, invasion and colony formation assays. All treatments were performed under an hypoxic micro-environment and whole cell lysates from controls and test groups were used to determine the expression of HIF-1α and p65 levels using ELISA assays. A ten-fold increase in solubility, three-fold increase in anti-cancer activity and a significant reduction in the levels of cellular HIF-1α and nuclear p65 (Rel A) were observed for cur-PLGA-NP, when compared to free curcumin. Our findings indicate that curcumin can effectively lower the elevated levels of HIF-1α and nuclear p65 (Rel A) in breast and lung cancer cells under an hypoxic tumour micro-environment when delivered in nanoparticulate form. This applied means of colloidal delivery could explain the improved anti-cancer efficacy of curcumin and has further potential applications in enhancing the activity of anti-cancer agents of low solubility.

Retraction: Creation of ultrasound and temperature-triggered bubble liposomes from economical precursors to enhance the therapeutic efficacy of curcumin in cancer cells.

Retraction of ‘Creation of ultrasound and temperature-triggered bubble liposomes from economical precursors to enhance the therapeutic efficacy of curcumin in cancer cells’ by Santanu Patra et al., RSC Adv., 2016, 6, 85473–85485.

Improvement of intestinal absorption of curcumin by cyclodextrins and the mechanisms underlying absorption enhancement

Curcumin is known to possess a wide range of pharmacological activities for the treatment of chronic or inflammatory diseases, Alzheimer’s disease, and various cancers. However, the therapeutic efficacy of curcumin is restricted by its poor bioavailability after oral administration. In this study, the effects of various cyclodextrins on the intestinal absorption of curcumin were evaluated in rat intestine by an in situ closed-loop method. Among the tested cyclodextrins, 50 mM α-cyclodextrin significantly enhanced the absorption of curcumin without inducing any intestinal toxicity. The analysis of cellular transport across Caco-2 cell monolayers showed that 50 mM α-cyclodextrin reduced the transepithelial electrical resistance value of cell monolayers and improved the permeability of 5(6)-carboxyfluorescein, a poorly absorbable drug, which is mainly transported via a paracellular pathway. Furthermore, the western blotting analysis showed that α-cyclodextrin decreased the expression of claudin-4, a tight junction-associated protein, in brush border membrane vesicles. Additionally, α-cyclodextrin increased the membrane fluidity of lipid bilayers in brush border membrane vesicles and may also have promoted the permeation of drug molecules via a transcellular pathway. These results suggested that α-cyclodextrin might enhance the intestinal absorption of curcumin via both paracellular and transcellular pathways.

Neuroprotective effect of curcumin-I in copper-induced dopaminergic neurotoxicity in rats: A possible link with Parkinson's disease.

Numerous findings indicate an involvement of heavy metals in the neuropathology of several neurodegenerative disorders, especially Parkinson's disease (PD). Previous studies have demonstrated that Copper (Cu) exhibits a potent neurotoxic effect on dopaminergic neurons and triggers profound neurobehavioral alterations. Curcumin is a major component of Curcuma longa rhizomes and a powerful medicinal plant that exerts many pharmacological effects. However, the neuroprotective action of curcumin on Cu-induced dopaminergic neurotoxicity is yet to be investigated. The aim of the present study was to evaluate the impact of acute Cu-intoxication (10mg/kg B.W. i.p) for 3days on the dopaminergic system and locomotor performance as well as the possible therapeutic efficacy of curcumin I (30mg/kg B.W.). Intoxicated rats showed a significant loss of Tyrosine Hydroxylase (TH) expression within substantia nigra pars compacta (SNc), ventral tegmental area (VTA) and the striatal outputs. This was correlated with a clear decrease in locomotor performance. Critically, curcumin-I co-treatment reversed these changes and showed a noticeable protective effect; both TH expression and locomotor performance was reinstated in intoxicated rats. These results demonstrate altered dopaminergic innervations following Cu intoxication and a new therapeutic potential of curcumin against Cu-induced dopaminergic neurotransmission failure. Curcumin may therefore prevent heavy metal related Parkinsonism.

Niosome, a novel drug delivery system, for improving therapeutic efficacy of curcumin (review)

Niosome, a novel drug delivery system, for improving therapeutic efficacy of curcumin (review)