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Development of AS1411aptamer-conjugated liposomes for targeted delivery of arsenic trioxide is the primary goal of this study. AS1411aptamer was used as ligand to target nucleolin, which is highly expressed on the surface of melanoma cancer cells. The targeted liposomes were constructed by the thin film method, and arsenic trioxide was loaded as cobalt (II) hydrogen arsenite (CHA) to increase the loading efficiency and stability of the liposomes. The liposomal structure was characterized by Fourier Transform Infrared Spectroscopy (FT-IR) and field emission scanning electron microscopy (FESEM). In addition, particle sizes and zeta potential of the CHA-loaded liposomes (CHAL) and aptamer-functionalized CHA-loaded liposomes (AP-CHAL) were determined. In vitro cytotoxicity of CHAL and AP-CHAL were evaluated using MTT assay in murine melanoma (B16) and mouse embryonic fibroblast (MEF) cell lines. The encapsulation efficiency of CHAL and AP-CHAL was reported as 60.2 ± 6.5% and 58.7 ± 4.2%, respectively. In vivo antitumor activity of CHAL and AP-CHAL in the B16 tumor-xenograft mouse model was dramatically observed. All mice of both groups survived until the end of treatment and showed body weight gain. The tumor protrusion completely disappeared in 50% of the mice in these groups. Furthermore, histopathology studies demonstrated that CHAL and AP-CHAL did not induce significant toxicity in healthy mice tissues. However, unlike the CHAL group, which showed an initial increase in tumor volume, a specific antitumor effect was observed in the AP-CHAL group from the beginning of treatment. The results showed that AP-CHAL can be used as an effective drug delivery system with high potential in the treatment of solid tumors.
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Neonatal seizures commonly caused by hypoxia can lead to long-term neurological outcomes. Early inflammation plays an important role in the pathology of these outcomes. Therefore, in the current study, we explored the long-term effects of Fingolimod (FTY720), an analog of sphingosine and potent sphingosine 1-phosphate (S1P) receptors modulator, as an anti-inflammatory and neuroprotective agent in attenuating anxiety, memory impairment, and possible alterations in gene expression of hippocampal inhibitory and excitatory receptors following hypoxia-induced neonatal seizure (HINS). Seizure was induced in 24 male and female pups (6 in each experimental group) at postnatal day 10 (P10) by premixed gas (5% oxygen/ 95% nitrogen) in a hypoxic chamber for 15 minutes. Sixty minutes after the onset of hypoxia, FTY720 (0.3 mg/kg) or saline (100 µl) was administered for 12 days (from P10 up to P21). Anxiety-like behavior and hippocampal memory function were assessed at P90 by elevated plus maze (EPM) and novel object recognition (NOR), respectively. Long-term potentiation (LTP) was recorded from hippocampal dentate gyrus region (DG) following stimulation of perforant pathway (PP). In addition, the hippocampal concentration of superoxide dismutase activity (SOD), malondialdehyde (MDA), and thiol as indices of oxidative stress were evaluated. Finally, the gene expression of NR2A subunit of N-Methyl-D-aspartic acid (NMDA) receptor, GluR2 subunit of (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) AMPA receptor and γ2 subunit of γ-Aminobutyric acid (GABAA) receptor were assessed at P90 by the quantitative real-time PCR. FTY720 significantly reduced later-life anxiety-like behavior, ameliorated object recognition memory and increased the amplitude and slope of the field excitatory postsynaptic potential (fEPSP) in the rats following HINS. These effects were associated with restoration of the hippocampal thiol content to the normal values and the regulatory role of FTY720 in the expression of hippocampal GABA and glutamate receptors subunits. In conclusion, FTY720 could restore the dysregulated gene expression of excitatory and inhibitory receptors. It also increased the reduced hippocampal thiol content, which was accompanied with attenuation of HINS-induced anxiety, reduced the impaired hippocampal related memory, and prevented hippocampal LTP deficits in later life following HINS.
Asunto(s)
Epilepsia , Potenciación a Largo Plazo , Ratas , Animales , Masculino , Femenino , Potenciación a Largo Plazo/fisiología , Clorhidrato de Fingolimod/farmacología , Hipocampo , Convulsiones , Hipoxia , Trastornos de la Memoria/etiología , Receptores de N-Metil-D-Aspartato , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
Diabetes induces a disorder in mitochondrial activity, which causes damage to the nuclear and mitochondrial DNA and ultimately increases the release of inflammatory cytokines and damages the sciatic nerve and dorsal root ganglion and induces neuropathy. It has been shown that progesterone has anti-inflammatory and antioxidative effects and prevents nerve cell damage. Therefore, the aim of this experiment was to investigate the effect of progesterone receptor neuroprotection on diabetic neuropathy. Forty male Sprague-Dawley rats were divided into four groups, including control group, diabetic control group, diabetic control group + progesterone (30 mg/kg), and diabetic control group + combination of progesterone (30 mg/kg) and RU486 (10 mg/kg). After the induction of diabetes, blood glucose level, body weight, behavioral tests, electrophysiological tests, oxidative and inflammatory factors, and histological parameters were measured. Progesterone treatment significantly reduced the level of sensitivity to hot plate without significant effect on glucose level, and significant changes were also observed in the results of tail flick test. In addition, the results showed that the administration of progesterone can improve MNCV and significantly reduce the serum levels of oxidative stress and inflammatory factors, as well as inflammation and edema around the sciatic nerve. However, RU486 inverted the beneficial effects of progesterone. Progesterone can be considered as a protective agent in reducing DN because of its ability to reduce inflammation and nerve damage. In addition, RU486, a progesterone receptor blocker, inhibits the beneficial effects of progesterone on the DN; thus, progesterone receptors play an important role in the neuroprotective effect of progesterone.
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Diabetes Mellitus Experimental , Neuropatías Diabéticas , Ratas , Animales , Masculino , Neuropatías Diabéticas/tratamiento farmacológico , Antioxidantes/farmacología , Ratas Sprague-Dawley , Progesterona/farmacología , Receptores de Progesterona , Mifepristona/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/patología , Estrés Oxidativo , Inflamación/patología , Nervio CiáticoRESUMEN
Background and objectives: Zingerone is an ingredient of ginger (Zingiber officinale) with different pharmacological activities. Several studies have investigated the effect of zingerone on various gastrointestinal diseases, including irritable bowel syndrome and diarrhea. This study is aimed to evaluate the effect of zingerone on ethanol-induced gastric ulcers in rats. Materials and Methods: Gastric ulcers were induced by ethanol (96%, 5 mL/kg, po) in male wistar rats and zingerone (50, 100, and 200 mg/kg) was administrated orally. Normal saline and ranitidine were used as negative and positive control, respectively. In this study, the number and length of ulcers, and malondialdehyde (MDA) and nitric oxide (NO) levels in stomach tissues were determined. Results: The findings showed that the mean number and length of gastric ulcers were significantly lower in zingerone-received groups than ethanol group (P < 0.05). The level of malondialdehyde was decreased in the stomach of zingerone groups (P < 0.05) compared to the ethanol group. In addition, zingerone treatment prevented the decrease of nitric oxide level by ethanol in the stomach tissue. Conclusions: The present study showed that zingerone has a protective effect on the ethanol-induced gastric ulcer, which may be due to its free radical scavenging activity.
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Antiulcerosos/uso terapéutico , Guayacol/análogos & derivados , Fitoterapia , Extractos Vegetales/uso terapéutico , Sustancias Protectoras/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/patología , Zingiber officinale/química , Animales , Antiulcerosos/administración & dosificación , Antiulcerosos/farmacología , Modelos Animales de Enfermedad , Etanol/administración & dosificación , Etanol/efectos adversos , Etanol/farmacología , Mucosa Gástrica/metabolismo , Guayacol/administración & dosificación , Guayacol/farmacología , Guayacol/uso terapéutico , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/análisis , Malondialdehído/metabolismo , Necrosis , Óxido Nítrico/análisis , Óxido Nítrico/metabolismo , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/farmacología , Ratas , Ratas Wistar , Solventes/administración & dosificación , Solventes/efectos adversos , Solventes/farmacología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/prevención & controlRESUMEN
Background: The use of herbal extracts in recent years has been of great interest to researchers around the world. Quercetin antoxidant properties play an important role in various fields of health. Objective: Due to the low skin permeability and poor solubility in aqua media, quercetin liposome formulation has been used to obtain topical use of this substance. Methods: In this study, liposomal quercetin was prepared by fusion method and the physicochemical characteristics of the formulation, including particle size, incorporation efficiency and in vitro drug release were evaluated. Results: The particle size of formulations were between 7.68 to 58.1 nm. The incorporation efficiency of formulations were in range of 80.55 to 96.80 percent. In vitro drug release of formulations were about 60 to 70 percent. Conclusion: According to the results obtained, it can be said that the use of this substance as a liposomal formulation can improve physicochemical properties of the drug in the laboratory conditions and provide it as a suitable candidate for further in vivo and clinical studies
Antecedentes: el uso de extractos de hierbas en los últimos años ha sido de gran interés para los investigadores de todo el mundo. Las propiedades de la quercetina antoxidante juegan un papel importante en varios campos de la salud. Objetivo: debido a la baja permeabilidad de la piel y la escasa solubilidad en medios acuáticos, se ha utilizado la formulación de liposomas de quercetina para obtener el uso tópico de esta sustancia. Métodos: En este estudio, la quercetina liposomal se preparó mediante el método de fusión y se evaluaron las características fisicoquímicas de la formulación, incluido el tamaño de partícula, la eficacia de incorporación y la liberación de fármacos in vitro. Resultados: El tamaño de partícula de las formulaciones estuvo entre 7,68 y 58,1 nm. La eficiencia de incorporación de las formulaciones estuvo en el rango de 80,55 a 96,80 por ciento. La liberación de fármacos in vitro de formulaciones fue de aproximadamente 60 a 70 por ciento. Conclusión: De acuerdo con los resultados obtenidos, se puede decir que el uso de esta sustancia como una formulación liposomal puede mejorar las propiedades fisicoquímicas del fármaco en las condiciones de laboratorio y proporcionarlo como un candidato adecuado para estudios in vivo y clínicos adicionales
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24965 , Liposomas/análisis , Liposomas/química , Quercetina/análisis , Quercetina/químicaRESUMEN
BACKGROUND: Royal Jelly (RJ), a food item secreted by worker honeybees, is a mixture that contains protein, glucose, lipid, vitamins, and minerals; it is widely used as a commercial medical product. Previous studies have shown that RJ has a number of physiological effects, such as anti-inflammatory, antitumor, antiallergic and antioxidant activities. OBJECTIVES: In the present study, the anti-inflammatory properties of RJ were investigated in formalin-induced rat paw edema. MATERIALS AND METHODS: In this study, 30 male Wistar albino rats were divided into five equal groups (n = 6) as follows: test groups received different doses (25, 50 and 100 mg/kg, ip) of RJ and a negative control group received normal saline (5 mL/kg) and a positive control group received aspirin (300 mg/kg, i.p). Edema was induced on the right hind paw of the rat by a subplantar injection of 100 µL of formalin (2.5%) after 30 minutes. Paw edema was measured in the rats received the drugs, saline and aspirin before and after the formalin injection during 5 hours, using a plethysmometer. RESULTS: The results showed that RJ has a dose-dependent anti-inflammatory effect and the highest anti-inflammatory effect was observed in the doses of 50 and 100 mg/kg. CONCLUSIONS: Royal jelly has potent anti-inflammatory effects compared to aspirin and it could be used in the treatment of inflammation. However, further studies are required to determine the active components in RJ responsible for this effect and its mechanism of action.
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BACKGROUND: Theophylline has been shown to cause heart anomaly in animal and human fetus. OBJECTIVES: The present study aimed to investigate the protective effect of quercetin on theophylline-induced heart disorders in rat embryo. MATERIALS AND METHODS: Theophylline-induced teratogenicity in rats was used as the animal model. Pregnant rats were administered theophylline (259 mg/kg, po) or theophylline plus quercetin (259 mg/kg, po and 100 mg/kg, ip, respectively) on 9th and 10th days of pregnancy. On day 19, cardiac changes were assessed, measuring malondialdehyde (MDA) and glutathione peroxidase (GPx) activity levels in blood samples and also the fetus heart weight. Histopathological examination was also performed on all specimens. RESULTS: Theophylline-treated rats showed MDA level elevation and GPx activity reduction. Quercetin treatment improved heart conditions and resulted in a significant reduction in MDA levels and elevation in GPx activity. Moreover, co-administration of quercetin and theophylline increased the heart weight significantly. Furthermore, histophatological study showed no changes in the treated groups. CONCLUSIONS: This study demonstrated that quercetin have beneficial effects on theophylline-induced-anomalies in rat embryo.