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•Curcumin-nicotinamide cocrystal was formed.•Cocrystallization was performed with carbon dioxide as supercritical solvent.•Cocrystal showed 2 times greater dissolution rate in water ...than pure curcumin.•Cocrystal presented greater antinociceptive activity than curcumin.
Curcumin is a bioactive polyphenol, which presents several medicinal benefits such as antinociceptive, anti-inflammatory, anti-carcinogenic, antimalarial, and antioxidant activity. Despite the benefits, the main barrier in curcumin use by pharmaceutical industry is its low solubility in water medium and hence low bioavailability. The cocrystallization process is characterized by the incidence of molecular interactions between the active pharmaceutical ingredient and coformer that enables improvements in physicochemical properties such as solubility and bioavailability. The main objective of this work is to produce a curcumin-nicotinamide cocrystal by Cocrystallization with Supercritical Solvent (CSS) technique in order to increase curcumin water dissolution rate as well as antinociceptive/anti-inflammatory activities. Curcumin-nicotinamide cocrystal dissolution rate were about 2 times greater than pure curcumin in water medium. The cocrystallization process increased curcumin antinociceptive/anti-inflammatory potency probably due to alterations in its bioavailability. These results open new possibilities of use for curcumin cocrystals in pharmaceutical industries.
The increase in proinflammatory cytokine expression causes behavioral changes consistent with sickness behavior, and this led to the suggestion that depression might be a psychoneuroimmunological ...phenomenon. Here, we evaluated the effects of the pretreatment with fluoxetine (10 mg/kg, i.p.) and curcumin (0.5 mg/kg, i.p.) on the immune response elicited by the inoculation of an Aeromonas hydrophila bacterin in zebrafish. Non-pretreated but A. hydrophila-inoculated and sham-inoculated groups of fish served as controls. The social preference, locomotor, exploratory activities, and cerebral expression of il1b, il6, tnfa, and bdnf mRNA were compared among the groups. Behavioral changes characteristic of sickness behavior and a significant increase in the expression of il1b and il6 cytokines were found in fish from the immunostimulated group. The behavioral alterations caused by the inflammatory process were different between males and females, which was coincident with the increased expression of cerebral BDNF. Fluoxetine and curcumin prevented the sickness behavior induced by A. hydrophila and the increased expression of proinflammatory cytokines. Our results point to the potential of zebrafish as a translational model in studies related to neuroinflammation and demonstrate for the first time the effects of fluoxetine and curcumin on zebrafish sickness behavior.
•Curcumin+resveratrol cocrystal was prepared using supercritical technology.•Cocrystal exhibited higher water solubility compared to raw compounds.•Antioxidant activity and dissolution rate were ...improved after cocrystallization.•Cocrystal presented greater antinociceptive activity than raw components.
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Bioactive compounds curcumin and resveratrol have been appointed to have potential for prevention and treatment of several diseases, replacing synthetic compounds with limited action. However, both present low aqueous solubility and bioavailability. Cocrystallization aims to modify physicochemical properties of active compounds by occurrence of intermolecular forces between them and possible modifications in the crystalline matrix. This research aimed to synthesize a curcumin-resveratrol cocrystal by the Cocrystallization with Supercritical Solvent (CSS) technique intending to improve the components solubility and dissolution rate. Characterization by Differential Scanning Calorimetry, X-Ray Powder Diffraction and Fourier Transform-Infrared Spectroscopy confirmed cocrystal formation. Comparing to raw components, cocrystal antioxidant activity was improved as well as dissolution rate. Curcumin and resveratrol solubility were improved 1.5 and 2 times, respectively. Behavioral tests in mice showed that curcumin-resveratrol antinociceptive/anti-inflammatory potency was increased probably due to alterations in its bioavailability, which gives the cocrystal good potential of use in the pharmaceutical industry.
Aloysia gratissima is a plant native to America, with applications in folk medicine for a wide range of diseases, such as bronchial infections, lung disorders, nervous system disorders (depression, ...anxiety), and inflammatory processes, among others. However, investigations about this species and its biological actions are still scarce. This literature review was carried out using articles published in the past 30 years on the PubMed, SciELO, and Web of Science platforms, with the focus on the method of extraction, chemical composition, and clinical and preclinical studies on the pharmacological properties of A. gratissima. We noticed that the main constituents of A. gratissima are guaiol, pinocamphone, ß-pinene, and 1,8-cineole. Additionally, preclinical studies reveal that A. gratissima extracts present antidepressant, anti-inflammatory, antinociceptive, antibacterial, antifungal, and virucidal effects. The results also demonstrate that there is a greater interest on the part of researchers from 2012 onwards in studying A. gratissima extracts with potential for possible new drugs.
Background and aim: Campomanesia xanthocarpa Berg. (Myrtaceae) present several pharmacological actions, but there are no reports on its antidepressant-like potential. This study investigated the ...antidepressant-like effect and mechanism of action of Campomanesia xanthocarpa seeds extract obtained from supercritical CO_2 (40℃, 250 bar). Experimental procedure: Mice were orally treated with the extract 1 h before the TST. To investigate the involvement of the monoaminergic system in the antidepressant-like activity of the extract, pharmacological antagonists were administered prior to the acute oral administration of the extract (60 mg/kg). Also, the interaction of the extract with antidepressants was assessed in the tail suspension test (TST). The in vitro inhibitory potential of C. xanthocarpa seeds extract towards MAO A and MAO B enzymes was tested in vitro. Results and conclusion: Animals treated with Campomanesia xanthocarpa seeds extract showed a significant reduction in the immobility time in the TST. Mice pretreatment with SCH23390, sulpiride, prazosin, yohimbine, and p-chlorophenylalanine prevented the anti-immobility effect of the extract in the TST. The combined administration of sub-effective doses of the extract with imipramine, bupropion and fluoxetine significantly reduced mice immobility time in the TST. The extract showed MAO A inhibitory activity (IC_(50) = 151.10 ± 5.75 μg/mL), which was greater than that toward MAO B (IC_(50) ＞ 400 μg/mL). The extract of Campomanesia xanthocarpa seeds obtained by supercritical CO_2 shows antidepressant-like activity, which relies on the activation of the monoaminergic neurotransmission (serotoninergic, dopaminergic and noradrenergic), suggesting that this species might represent a resource for developing new antidepressants.
The antidepressant-like effect of a supercritical CO2 (SCCO2) Valeriana glechomifolia extract enriched in valepotriates was investigated in a mice tail suspension test (TST) and forced swimming test ...(FST). The SCCO2 extract decreased mice immobility in the FST (0.5–20mg/kg p.o.) and elicited a biphasic dose–response relationship in the TST (1–20mg/kg p.o.) with no alterations in locomotor activity and motor coordination (assessed in the open-field and rota-rod tests, respectively). The anti-immobility effect of the SCCO2 extract (5mg/kg, p.o.) was prevented by mice pre-treatment with yohimbine (1mg/kg, i.p., an α2 adrenoceptor antagonist), SCH 23390 (15μg/kg, s.c., D1 dopamine receptor antagonist) and sulpiride (50mg/kg, i.p., D2 dopamine receptor antagonist). However, mice pre-treatments with prazosin (1mg/kg, i.p., α1 adrenoceptor antagonist) and p-chlorophenilalanine methyl ester (4×100mg/kg/day, i.p., a serotonin synthesis inhibitor) were not able to block the anti-immobility effect of the SCCO2 extract. Administration (p.o.) of the SCCO2 extract (0.25mg/kg) and imipramine (10mg/kg), desipramine (5mg/kg) and bupropion (3mg/kg) at sub-effective doses significantly reduced mice immobility time in the FST. These data provide the first evidence of the antidepressant-like activity of V. glechomifolia valepotriates, which is due to an interaction with dopaminergic and noradrenergic neurotransmission.
► V. glechomifolia shows antidepressant-like effect in animal models. ► Sulpiride, SCH 23390 and yohimbine block the anti-immobility V. glechomifolia effect. ► V. glechomifolia potentiates the effect of antidepressants in forced swimming test. ► V. glechomifolia mode of action involves dopaminergic and noradrenergic systems.
Naringenin (NRG) is a flavanone characterized by potential neuroprotective properties, even if low water solubility and poor oral bioavailability limit the ability of this compound to target the ...central nervous system. As an attempt to overcome these limitations, it is here described the synthesis and characterization of a cocrystal obtained with NRG and betaine (BTN) using gas antisolvent (GAS) technique. The ability of NRG, its cocrystal and the parent physical mixture to permeate across the intestinal and the blood-brain (BBB) barriers was simulated in vitro by using monolayers obtained by IEC-6 cells and a model established by ECV 304, respectively. It is evidenced that the NRG: BTN cocrystal improves both the solubility and dissolution rate of NRG, potentially allowing to enhance its oral bioavailability. Moreover, the results of viability studies performed on IEC-6 cells suggest that low doses of cocrystal frequently administered are required for absorption to be efficient and safe. The study also suggests a synergistic effect of NRG and BTN for the cocrystal and physical mixture in enhancing NRG permeation through the BBB. These results indicate that the NRG:BTN cocrystal is potentially useful for the brain targeting of NRG, following its oral administration.
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Uliginosin B is a natural phloroglucinol derivative, obtained from Hypericum species native to South America. Previous studies have shown that uliginosin B presents antidepressant-like and ...antinociceptive effects. Although its mechanism of action is still not completely elucidated, it is known that it involves the activation of monoaminergic neurotransmission. The aim of the current study was to further investigate the antinociceptive mechanism of action of uliginosin B by combining it with different drugs used for treating pain in clinical practice. The intraperitoneal administration of uliginosin B, morphine, amitriptyline and clonidine, alone or in mixture, produced a dose-dependent antinociceptive effect in the hot-plate assay in mice. The effect of the mixtures of drugs was studied using an adapted isobologram analysis at the effect level of 50% of the maximal effect observed. The analysis showed that the interactions between uliginosin B and morphine was synergistic, while the interactions between uliginosin B and amitriptyline or clonidine were additive. These findings point to uliginosin B as a potential adjuvant for pain pharmacotherapy, especially for opioid analgesia.
Valeriana glechomifolia, a native species from southern Brazil, presents antidepressant-like activity and diene valepotriates (VAL) contribute to the pharmacological properties of the genus. It is ...known that depression can develop on an inflammation background in vulnerable patients and antidepressants present anti-inflammatory properties. We investigated the effects of VAL (10 mg/kg, p.o.) on sickness and depressive-like behaviors as well as proinflammatory cytokines (IL-1β and TNF-α) and BDNF expression in the cortex of mice exposed to a 5 min swimming session (as a stressful stimulus) 30 min before the E. coli LPS injection (600 µg/kg, i.p.). The forced swim + LPS induced sickness and depressive-like behaviors, increased the cortical expression of IL-1β and TNF-α, and decreased BDNF expression. VAL was orally administered to mice 1 h before (pretreatment) or 5 h after (posttreatment) E. coli LPS injection. The pretreatment with VAL restored the behavioral alterations and the expression of cortical proinflammatory cytokines in LPS-injected animals but had no effects on BDNF expression, while the posttreatment rescued only behavioral alterations. Our results demonstrate for the first time the positive effects of VAL in an experimental model of depression associated with inflammation, providing new data on the range of action of these molecules.
Naringin is a flavanone glycoside with various pharmacological activities, including neuroprotective and antipsychotic-like effects. However, it has poor solubility in water and oral bioavailability. ...This study aims to investigate the influence of gas antisolvent operational parameters (pressure, temperature, antisolvent flow rate, and initial concentration of solute) on particle diameter using a 24 Central Composite Design. Naringin particles produced were analyzed for dissolution rate and then applied to ketamine-induced hyperlocomotion in mice. Results for run with C= 5 mg∙mL−1, P = 12 MPa, T = 308 K, CO2 flow rate= 15 mL.min−1 showed amorphous particles while run with C= 10 mg.mL−1, P = 8 MPa, T = 318 K, CO2 flow rate= 15 mL.min−1 kept the crystalline structure of naringin. In vivo assays showed promising results for run with crystalline particles, probably due to the increased bioavailability, and amorphous particles had similar effects to commercial naringin because of the recrystallization when in contact with the aqueous medium.
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•After gas antisolvent process, naringin showed amorphous and crystalline features.•Processed naringin showed greater water dissolution rate than commercial naringin.•Naringin processed reduced particle size and increased surface area vs. commercial naringin•In vivo assays showed that processed naringin has antipsychotic potential.
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