RESUMEN
OBJECTIVES: The incidence of co-occurring alcohol-use disorder (AUD) and post-traumatic stress disorder (PTSD) is high, and the presence of one disorder aggravates the severity of the other. Emerging evidence shows the neuroprotective and anti-inflammation functions of psychobiotics. Hence, the study explored the effects of probiotics and synbiotic inulin on the gut- and liver-oxidative and inflammatory biomarkers in chronic alcohol exacerbation of PTSD symptoms in rats. METHODS: Young adult rats were administered 10% ethanol in a two-bottle choice test for six weeks and were subjected to single prolonged stress. Probiotics and synbiotic intervention followed this. Markers of oxido-inflammatory stress, liver functions, intestinal (faecal) metabolites, occludin expression, and histopathology of the ileum and liver were evaluated. RESULTS: Chronic alcohol drinking and PTSD increased oxido-inflammatory stress, markers of hepatic damage, and reduced faecal metabolites, which were attenuated by probiotic and synbiotic interventions. Furthermore, reduced immunoexpression of gut and liver occludin, with loss of barrier integrity, viable hepatocytes, congestive portal area, and shortened villi and crypt depth, were observed. Probiotic and synbiotic interventions mitigated these effects. CONCLUSIONS: The study demonstrates that psychobiotics mitigate the detrimental effects of co-occurring chronic alcohol intake in the context of PTSD.
Asunto(s)
Probióticos , Trastornos por Estrés Postraumático , Ratas , Animales , Trastornos por Estrés Postraumático/terapia , Ocludina , Hígado , Probióticos/uso terapéutico , Probióticos/farmacología , Etanol , Consumo de Bebidas AlcohólicasRESUMEN
Rapid eye movement sleep deprivation distorts the body's homeostasis and results in oxidative breakdown which may be responsible for a variety of neurological disorders. Some naturally occurring compounds of plant origin with antioxidant and neuroprotective properties are known to attenuate the detrimental effects of REM sleep deprivation. Morin hydrate, a flavonoid from Mulberry has demonstrated antioxidant and neuroprotective activities but its effect in sleep disturbed mice is unknown. The study was designed to explore the neuroprotective effect of Morin hydrate on 48â¯h. REM sleep deprivation-induced behavioural impairments and neuronal damage in mice. Mice were allotted into six treatment groups (nâ¯=â¯6): groups 1 and 2 received vehicle (10â¯ml/kg normal saline), groups 3-5 received Morin hydrate (5, 10, 20â¯mg/kg i.p) while group 6 received ginseng (25â¯mg/kg) which served as the reference drug. Treatment was performed daily for 5 days and animals were sleep-deprived on the last 48â¯h. Various behavioural tests (Elevated plus maze, Y-maze, locomotor activity) followed by oxidative parameters (malondialdehyde, nitric oxide, reduced glutathione) and histolopathological changes in the Cornu ammonis 1 (CA1) region of the hippocampus were assessed. Data were analysed using ANOVA at α0.05. Morin hydrate (5, 10, 20â¯mg/kg) significantly enhanced memory performance, improves anxiolytic-like behaviour, reverses hyperlocomotion, restored depleted reduced glutathione, attenuated raised malondialdehyde and nitric oxide levels as compared to control animals and protects against loss of hippocampal neurons. Results of this present study suggest that Morin hydrate possess neuroprotective effects against sleep deprivation-induced behavioural impairments, oxidative stress and neuronal damage.
Asunto(s)
Antioxidantes/farmacología , Flavonoides/farmacología , Hipocampo/efectos de los fármacos , Privación de Sueño/tratamiento farmacológico , Animales , Ansiolíticos/farmacología , Conducta Animal/efectos de los fármacos , Flavonoides/química , Hipocampo/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacosRESUMEN
Depression is a recurrent neuropsychiatric disorder that affects millions of individuals worldwide and impact negatively on the patients' social functions and quality of life. Studies have shown that i.p injection of lipopolysaccharide (LPS) induces depressive-like behavior in rodents via induction of oxidative stress and neuroinflammation. Methyl jasmonate (MJ), an isolated compound from jasmine plant has gained reputation in aromatherapy for treatment of depression, nervousness and memory deficits. This study was designed to evaluate the effects of MJ on LPS-induced depressive-like behavior in mice. Mice were given MJ (5-20 mg/kg), imipramine (10 mg/kg) or vehicle (10 mL/kg) intraperitoneally for 7 consecutive days. On day 7, treatment was carried out 30 min prior to i.p injection of LPS (830 µg/kg). Twenty four hours after LPS administration, tail suspension, forced swim and sucrose preference tests were carried out. Thereafter, serum corticosterone levels were determined using ELISA. The levels of malondialdehyde (MDA), glutathione (GSH) and tumor necrosis factor-alpha (TNF-α) were determined in brain tissue homogenates. LPS significantly increased immobility time in the tail suspension and forced swim tests when compared with vehicle (p < 0.05), which indicates depressive-like syndromes. However, the increased immobility time was significantly reduced by MJ (5-20 mg/kg) when compared with LPS-treated group. LPS administration also altered the levels of MDA, GSH, corticosterone and TNF alpha in mice, which was significantly reversed by MJ. These findings suggest that attenuation of LPS-induced depressive-like behavior by MJ may be related to suppression of oxidative stress and release of TNF alpha.
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Acetatos/farmacología , Antidepresivos/farmacología , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Corticosterona/sangre , Ciclopentanos/farmacología , Depresión/tratamiento farmacológico , Depresión/metabolismo , Jasminum , Lipopolisacáridos/farmacología , Estrés Oxidativo/efectos de los fármacos , Oxilipinas/farmacología , Extractos Vegetales/farmacología , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Acetatos/administración & dosificación , Animales , Antidepresivos/administración & dosificación , Antidepresivos Tricíclicos/farmacología , Ciclopentanos/administración & dosificación , Depresión/sangre , Depresión/inducido químicamente , Modelos Animales de Enfermedad , Imipramina/farmacología , Infusiones Parenterales , Masculino , Ratones , Oxilipinas/administración & dosificación , Extractos Vegetales/administración & dosificaciónRESUMEN
This present study was carried out to investigate the likely mechanisms by which methyl jasmonate (MJ), 'an agent widely used in aromatherapy for neurological disorders, attenuates lipopolysaccharide (LPS)-induced memory deficits in mice. Mice were given intraperitoneal administration of LPS (250 µg/kg) alone or in combination with MJ (10-40 mg/kg), donepezil, DP (1 mg/kg), or vehicle for 7 successive days. Thereafter, memory was assessed using object recognition test (ORT). Acetylcholinesterase and myeloperoxidase activities were estimated in brain tissue homogenates. Brain levels of nitric oxide and markers of oxidative stress as well as histopathologic changes of the prefrontal cortex and cornu ammonis 1 (CA1) of the hippocampal region were also assessed. MJ (10-40 mg/kg) attenuated LPS-induced memory impairment in ORT. Moreover, the increased brain activities of acetylcholinesterase and myeloperoxidase enzymes were suppressed by MJ when compared with control (p < 0.05). Increased brain oxidative stress and nitric oxide levels in LPS-treated mice were significantly decreased by MJ. It offers protection against LPS-induced neuronal degeneration of the prefrontal cortex and CA1 of the hippocampus, suggesting neuroprotective effect. Taken together, these findings showed that MJ offers protection against LPS-induced memory deficits via mechanisms related to inhibition of acetylcholinesterase, myeloperoxidase, oxidative stress and neuronal degeneration.
Asunto(s)
Acetatos/farmacología , Ciclopentanos/farmacología , Lipopolisacáridos/farmacología , Trastornos de la Memoria/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Oxilipinas/farmacología , Acetatos/uso terapéutico , Acetilcolinesterasa/metabolismo , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Ciclopentanos/uso terapéutico , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/psicología , Ratones , Fármacos Neuroprotectores/uso terapéutico , Nitritos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Oxilipinas/uso terapéutico , Reconocimiento en Psicología/efectos de los fármacosRESUMEN
Abstract Background: This study presents the results of the pharmacological evaluation of the analgesic and anxiolytic potentials of Jobelyn®, a potent antioxidant African herbal formulation, in mice. The analgesic effect was assessed utilizing acetic acid-induced writhing, tail immersion and formalin-induced paw licking pain models. The anxiolytic activity was evaluated using elevated-plus maze (EPM) and light/dark box. Methods: Mice (5/group) were treated with JB (10-200 mg/kg, p.o.) 1 h before the tests were carried out. In the writhing test, the number of abdominal constrictions was recorded for a period of 30 min after induction of nociception with 0.6% acetic acid, i.p. In the tail immersion test, the latency to tail withdrawal responses to noxious heat was measured. The duration of paw licking (s) was measured as an index of nociception in the formalin test. In the anxiolytic test, the patterns of transition in the two arms of the EPM and in the light/dark box were assessed. Results: JB (10-200 mg/kg, p.o.) significantly inhibited the inflammatory pain produced by acetic acid as evidenced by decreased number of abdominal constrictions in comparison with the control. It also shows higher potency in suppressing the inflammatory pain associated with the second phase of the formalin test. However, JB did not exhibit anxiolytic properties nor modify the pain behavior in the tail immersion test. Conclusions: The results obtained from this study suggest that Jobelyn® might be efficacious against inflammatory pain and further support its recommendation for the management of pain with inflammation as the underlying factor.