Comparative analysis of protective effects of curcumin, curcumin-β-cyclodextrin nanoparticle and nanoliposomal curcumin on unsymmetrical dimethyl hydrazine poisoning in mice.
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ABSTRACT: The aim of this study was to compare the protective effects of curcumin, curcumin-β-cyclodextrin nanoparticle curcumin (BCD-CUR) and nanoliposomal curcumin (NLC) on unsymmetrical dimethylhydrazine (UDMH) induced poison in mice. Curcumin, BCD-CUR, and NLC were prepared and their properties of zeta potential, particle size, encapsulation efficiency, and loading capacity were characterized. Eighty-eight male ICR mice on normal chow diet were randomly divided into 11 groups, and intraperitoneally injected with UDMH alone, or together with different doses of curcumin, BCD-CUR or NLC daily for up to 10 d. Enzyme activities of serum alanine transaminase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were analyzed by fully-automatic analyzer and neurotransmitter levels were determined with high performance liquid chromatography (HPLC). 150 mg/kg curcumin treatment alone significantly reduced levels of serum ALT and LDH that were induced by UDMH and markedly increased level of γ-amino butyric acid (GABA) that were reduced by UDMH in the hippocampus. 150 mg/kg BCD-CUR not only decreased significantly the increase of ALT, LDH and glutamate (Glu) but also recovered levels of AST and GABA. 150 mg/kg NLC recovered profoundly levels of AST and GABA while decreased remarkably the UDMH induced increase of ALT, LDH, Glu and 5-hydroxytryptamine (5-HT). In addition, treatments with all tested doses of NLC significantly reduced the UMDH induced dopamine (DA), the monoamine neurotransmitter. NLC had more profound protective effects against liver and central nervous system injury induced by UDMH than a suspension of BCD-CUR or curcumin did in mice.
Project description:Cyclodextrin polymers and cyclodextrin-based nanosponges have been widely investigated for increasing drug bioavailability. This study examined curcumin's complexation stability and solubilization with β-cyclodextrin and β-cyclodextrin-based nanosponge. Nanosponges were prepared through the cross-linking of β-cyclodextrin with different molar ratios of diphenyl carbonate. Phase solubility experiments were conducted to evaluate the formed complexes and evaluate the potential of using β-cyclodextrin and nanosponge in pharmaceutical formulations. Furthermore, physicochemical characterizations of the prepared complexes included PXRD, FTIR, NMR, and DSC. In addition, in vitro release studies were performed for the prepared formulations. The formation of β-cyclodextrin complexes enhanced curcumin solubility up to 2.34-fold compared to the inherent solubility, compared to a 2.95-fold increment in curcumin solubility when loaded in β-cyclodextrin-based nanosponges. Interestingly, the stability constant for curcumin nanosponges was (4972.90 M-1), which was ten times higher than that for the β-cyclodextrin complex, where the value was 487.34 M-1. The study results indicated a decrease in the complexation efficiency and solubilization effect with the increased cross-linker amount. This study's findings showed the potential of using cyclodextrin-based nanosponge and the importance of studying the effect of cross-linking density for the preparation of β-cyclodextrin-based nanosponges to be used for pharmaceutical formulations.
Project description:Quercetin (QUE) is a well-known natural product that can exert beneficial properties on human health. However, due to its low solubility its bioavailability is limited. In the present study, we examine whether its formulation with two cyclodextrins (CDs) may enhance its pharmacological profile. Comparative interaction studies of quercetin with 2-hydroxyl-propyl-β-cyclodextrin (2HP-β-CD) and 2,6-methylated cyclodextrin (2,6Me-β-CD) were performed using NMR spectroscopy, DFT calculations, and in silico molecular dynamics (MD) simulations. Using T1 relaxation experiments and 2D DOSY it was illustrated that both cyclodextrin vehicles can host quercetin. Quantum mechanical calculations showed the formation of hydrogen bonds between QUE with 2HP-β-CD and 2,6Μe-β-CD. Six hydrogen bonds are formed ranging between 2 to 2.8 Å with 2HP-β-CD and four hydrogen bonds within 2.8 Å with 2,6Μe-β-CD. Calculations of absolute binding free energies show that quercetin binds favorably to both 2,6Me-β-CD and 2HP-β-CD. MM/GBSA results show equally favorable binding of quercetin in the two CDs. Fluorescence spectroscopy shows moderate binding of quercetin in 2HP-β-CD (520 M-1) and 2,6Me-β-CD (770 M-1). Thus, we propose that both formulations (2HP-β-CD:quercetin, 2,6Me-β-CD:quercetin) could be further explored and exploited as small molecule carriers in biological studies.
Project description:Curcumin is a polyphenolic compound with anti-oxidative and anti-cancer properties that is obtained from turmeric plants. Several studies have demonstrated that cancer cells are not killed unless they are exposed to 5-50 mM of curcumin. Consequently, it is vital to control the concentration of curcumin in cancer therapy. In this study, a sensitive electrochemical sensor was fabricated based on a beta-cyclodextrin-reduced graphene oxide (β-CD-rGO) nanocomposite for measuring curcumin concentration. The effects of experimental factors were investigated and the optimum parametric conditions were determined using the Taguchi optimization method. The β-CD-rGO modified electrode exhibited good electrochemical properties for curcumin detection. The results of differential pulse voltammetry experiments unveiled that the sensor shows a linear response to curcumin concentration over the range of 0.05-10 mM with a detection limit of 33 nM and sensitivity of 4.813 μA μM-1. The fabricated sensor exhibited selectivity in the presence of other electroactive species, e.g., propranolol, clomipramine and clonazepam.
Project description:The title compound, 3C(14)H(12)N(2)O(2)·C(3)H(7)NO, was synthesized by reaction of benzoyl chloride with hydrazine hydrate under microwave irradition. The asymmetric unit comprises three 1,2-dibenzoyl-hydrazine mol-ecules and one dimethyl-formamide mol-ecule. The 1,2-dibenzoyl-hydrazine mol-ecules are linked by pairs of N-H⋯O hydrogen bonds into chains propagating along [010].
Project description:Scrotal hyperthermia leads to oxidative stress and apoptosis in spermatogenic cells, which subsequently causes male infertility. In this study, we examined the effects of β-carotene and/or curcumin on heat-stress- (HS-) induced testicular injuries in mice. ICR male mice (8 weeks old) were consecutively treated with β-carotene (10 mg/kg) and/or curcumin (20 mg/kg) orally once a day for 14 days and then subjected to single exposure with scrotal HS at 43°C for 15 min on day 7. HS induced a significant reduction in testicular weight, appearance of multinucleated giant cells, and desquamation of germ cells in destructive seminiferous tubules, as well as degenerative Leydig cells. Moreover, HS reduced the superoxide dismutase (SOD) activity and mRNA levels of mitochondrial SOD, phospholipid hydroperoxide glutathione peroxidase, B-cell lymphoma-extra-large, and 3β-hydroxysteroid dehydrogenase, with increases in lipid peroxidation levels and mRNA levels of BCL2-associated X protein and caspase-3 relative to those of the control group. However, these changes were significantly recovered by combined treatment with β-carotene and curcumin after HS. These findings indicate that the combined treatment with β-carotene and curcumin might be a valuable protective agent to ameliorate hyperthermic spermatogenic disorders via its potent antioxidative, antiapoptotic, and androgen synthetic effects.
Project description:Ionizable cyclodextrins have attracted increasing attention in host-guest chemistry and pharmaceutical industry, mainly due to the introduction of favorable electrostatic interactions. The ionizable cyclodextrins could not only enhance its own solubility but also induce oppositely charged guests to form more stable complex. However, the aggregation induced by charged cyclodextrins has rarely been reported. In this work, guided by the concept of molecular-induced aggregation, a series of carboxyl modified cyclodextrins were synthesized via "click" and hydrolysis reaction. Then, UV-vis spectrum was used to investigate the aggregating behaviors induced by these cyclodextrins towards the cationic guest molecules. The results showed that only the hepta-carboxyl-β-cyclodextrin could induce the guest molecules to self-assemble into supramolecular spherical nanoparticles. Meanwhile, it could form stable inclusion complex with amantadine, a drug for anti-Parkinson and antiviral. The assembly behaviors were investigated by dynamic light scattering, scanning electron microscope, atomic force microscope, transmission electron microscope and NMR spectroscopy. The supramolecular nanoparticles induced by hepta-carboxyl-β-CD and its inclusion with amantadine could be used to encapsulate the model drug and achieve its controlled releasing behaviors.
Project description:This study was designed to investigate the protective effect of curcumin against d-galactose (d-gal)-induced premature ovarian failure (POF) in mice. A mouse POF model was induced by subcutaneous injection of d-gal (200 mg/kg/day) daily for 42 days. Mice in the curcumin group received both d-gal treatment and intraperitoneal injection of curcumin (100 mg/kg/day) for 42 days. Ovarian function, oxidative stress and apoptosis were evaluated. The P, E2 and SOD levels were higher, and the FSH, LH and MDA levels were significantly lower in the curcumin group than those in the d-gal group. The proportion of primordial follicles was also significantly higher in the curcumin group than that in the d-gal group. In addition, curcumin treatment after d-gal administration resulted in significantly lower Sod2, Cat, 8-OhdG, 4-HNE, NTY and senescence-associated protein P16 expression levels, higher Amh expression levels and less apoptosis in granulosa cells than was observed in the d-gal group. Moreover, the p-Akt, Nrf2 and HO-1 protein expression levels were significantly higher and the apoptosis-related cleaved caspase-3 and -9 protein expression levels were markedly lower in the curcumin group than in the d-gal group. In conclusion, curcumin effectively inhibited d-gal-induced oxidative stress, apoptosis and ovarian injury via a mechanism involving the Nrf2/HO-1 and PI3K/Akt signaling pathways, suggesting that curcumin is a potential protective agent against POF.
Project description:The water-soluble β-cyclodextrin-curcumin (CDC) is used in pharmaceutical applications and as a natural food colorant. The previous study revealed that curcumin potentially impacted the reproductive system. The present study investigated the possible roles of the CDC in testosterone secretion in Leydig cells and mice. Primary Leydig cells were treated with the CDC to determine their effect on cell proliferation, testosterone levels, the protein and mRNA expression of the transcription factor, and steroidogenic enzymes. Our data showed that CDC stimulated testosterone production via upregulating transcription factor steroidogenic factor-1 (NR5A1), cAMP-response element-binding protein (CREB), and steroidogenic enzymes steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (CYP11A1), 17-alpha-hydroxylase/17,20-lyase (CYP17A1), 3β-/17β-hydroxysteroid dehydrogenase type 1 (3β/17β-HSD, HSD3b1/HSD17b1). CDC could significantly stimulate H89-suppressed StAR and CREB expression but not reverse melatonin-suppressed StAR expression. We further detected the hormonal activity with transgenic yeast, and CDC showed potential androgenic antagonistic activity. Meanwhile, we investigated its aphrodisiac effect on hydrocortisone-induced mice. Exposure to hydrocortisone decreased the mating ability, reproductive organs, and testosterone level and disrupted testicular histology. However, all of these effects were significantly improved by CDC treatment. In conclusion, these results indicated that mechanisms of CDC in stimulating testosterone production involve upregulating the cAMP-PKA pathway.
Project description:Drug delivery systems are used to improve the biopharmaceutical properties of curcumin. Our aim was to investigate the effect of a water-soluble 'two in one' polymer containing covalently bonded PEG and βCD moieties (βCPCD) on the solubility and bioavailability of curcumin and compare it to a polymeric β-cyclodextrin (βCDP) cross-linked with epichlorohydrin. Phase-solubility and dynamic light scattering (DLS) experiments showed that the solubility of curcumin increased significantly in 10 m/m % βCPCD and βCDP solutions, but βCPCD-curcumin particles had higher hydrodynamic volume. The formation of the βCPCD-curcumin complex in solution and sedimented phase was confirmed by NMR spectroscopy. Biocompatibility and permeability experiments were performed on Caco-2 cells. Polymers did not show cytotoxicity up to 10 m/m % and βCPCD significantly increased the permeability of curcumin. DLS measurements revealed that among the interaction of polymers with mucin, βCPCD formed bigger aggregates compared to βCDP. Curcumin complexes were lyophilized into capsules and structurally characterized by micro-CT spectroscopy. Drug release was tested in a pH 1.2 medium. Lyophilized complexes had a solid porous matrix and both βCPCD and βCDP showed rapid drug release. βCPCD provides an opportunity to create a swellable, mucoadhesive matrix system for oral drug delivery.
Project description:The asymmetric unit of the title compound, C(21)H(20)N(2), contain two mol-ecules, both of them showing an E configuration of the C=N bond. The dihedral angles between the phenyl rings in the phenyl-hydrazone groups are 86.84 (10) and 84.85 (8)° for the two mol-ecules. Inter-molecular C-H⋯π inter-actions are observed in the crystal structure.