Beneficial effect of 5-HT1b/1d agonist on Parkinson's disease by modulating glutamate and reducing deposition of α-synuclein.

The given investigation examined the neuroprotection role of 5-HT1b/1d agonist in reserpine induced Parkinson's disease (PD) in male Wistar rats. PD was induced in rats by reserpine at 5 mg/kg ip for 3 days and thereafter the rats were provided with the following treatments for 4 days, zolmitriptan (ZLM) group (30 mg/kg ip); STD group (levodopa + carbidopa, 200 + 5 mg/kg ip); ZLM + GA group (zolmitriptan, 30 mg/kg ip and glutamic acid, 1.5 mg/kg); ZLM + DX group (zolmitriptan, 30 mg/kg ip and dextromethorphan, 20 mg/kg ip). All the groups were then assessed for cognitive and motor functions at the end of the protocol. Moreover, oxidative stress parameters and histopathological changes were observed in rats of all treatment groups. Deposition of α-synuclein in the brain tissue was observed by silver staining. Data of this investigation revealed that motor and cognitive functions were improved in the ZLM-treated group compared with the negative control group, which was observed to be reversed in ZLM + GA group. Treatment with ZLM ameliorated oxidative stress and histopathological changes in the brain tissue of PD rats. Further, ZLM reduced the deposition of α-synuclein in PD rats, which reversed in ZLM + GA-treated group. This study concludes by stating that 5-HT1b/1d agonist can prevent neurodegeneration and reduce oxidative stress in PD rats. The probable underlying mechanism of such an effect of 5-HT1b/1d agonist could be by regulating the deposition of α-synuclein and reducing the expression of NMDA receptor.

Geraniol reverses obesity by improving conversion of WAT to BAT in high fat diet induced obese rats by inhibiting HMGCoA reductase.

OBJECTIVES: Present report evaluates the protective effect of geraniol on high fat diet (HFD) induced obesity in rats and also determines the molecular mechanism of it. METHODS: Rats were induced with obesity with administration of HFD for four weeks and geraniol 200 and 400 mg/kg p.o. was administered for the next four week in the respective groups. Blood glucose and oral glucose tolerance test (OGTT), lipid profile was estimated in the geraniol treated HFD induced obesity in rats. Moreover, docking study was performed to determine the specific mechanism of geraniol by targeting HMG-CoE A reductase (in silico). RESULTS: There was significant increase in body weight and amelioration in altered serum glucose and lipid profile were observed in the geraniol treated group than negative control group. Weight of organs and adipose tissue isolated from different regions of the body was reduced in geraniol treated group than negative control. Moreover, geraniol interact with HMG-CoA reductase having binding energy -5.13. CONCLUSIONS: In conclusion, data of the report reveals that geraniol reduces obesity by promoting the conversion of white adipose tissue (WAT) to brown adipose tissue (BAT), as it interacts with HMG-CoA reductase in HFD induced obesity in rats.

Immunosenescence as a convergence pathway in neurodegeneration.

Immunity refers to the body's defense mechanism to protect itself against illness or to produce antibodies against pathogens. Senescence is a cellular phenomenon that integrates a sustainable growth restriction, other phenotypic abnormalities and including a pro-inflammatory secretome. It is highly involved in regulating developmental stages, tissue homeostasis, and tumor proliferation monitoring. Contemporary experimental reports imply that abolition of senescent cells employing evolved genetic and therapeutic approaches augment the chances of survival and boosts the health span of an individual. Immunosenescence is considered as a process in which dysfunction of the immune system occurs with aging and greatly includes remodeling of lymphoid organs. This in turn causes fluctuations in the immune function of the elderly that has strict relation with the expansion of autoimmune diseases, infections, malignant tumors and neurodegenerative disorders. The interaction of the nervous and immune systems during aging is marked by bi-directional influence and mutual correlation of variations. The enhanced systemic inflammatory condition in the elderly, and the neuronal immune cell activity can be modulated by inflamm-aging and peripheral immunosenescence resulting in chronic low-grade inflammatory processes in the central Nervous system known as neuro-inflammaging. For example, glia excitation by cytokines and glia pro-inflammatory productions contribute significantly to memory injury as well as in acute systemic inflammation, which is associated with high levels of Tumor necrosis factor -α and a rise in cognitive decline. In recent years its role in the pathology of Alzheimer's disease has caught research interest to a large extent. This article reviews the connection concerning the immune and nervous systems and highlights how immunosenescence and inflamm-aging can affect neurodegenerative disorders.

Protective effect of vanillin on the management of cecal ligation and puncture induced sepsis rat model.

Present investigation evaluates the protective effect of vanillin against sepsis. Sepsis was induced by cecal ligation and puncture (CLP) in rat and vanillin was administered at dose of 100 and 200 mg/kg p.o. for five days after induction of sepsis. Effect of vanillin was observed on the percentage of survival, body weight and food intake were determined in CLP induced sepsis rats. Level of liver enzymes in the serum and organ weight was also observed in vanillin treated CLP induced rats. Moreover, histopathological changes were also observed in liver and lung tissue of hematoxylin and eosin (H&E) staining. There was significant improvement in bodyweight and food intake in vanillin treated group than negative control group after the sepsis induction. Moreover, vanillin improves the percentage of survival rate and reduces the level of liver enzymes and spleen weight in CLP induced sepsis rat. It also improves the level of glutathione (GSH) compared to negative control group. In conclusion, data of investigation reveals that vanillin ameliorates the survival rate and oxidative stress in CLP induced sepsis rat model.

Is Regular Probiotic Practice Safe for Management of Sepsis?

For decades, the gut has been thought to play an important role in sepsis pathogenesis. Sepsis is a serious life-threatening, chronic condition of an infection caused by dysregulated host immune response in most of the intensive care unit patients. Probiotics have dual roles in polymicrobial sepsis i.e. probiotics may induce sepsis in many cases and may prevent its prognosis in many cases. Experimental evidence from both pre-clinical and clinical studies have demonstrated that probiotic therapy ameliorates various inflammatory mediators such as tumor necrosis factor, interleukin-10 (IL-10), IL-6, etc., in septicemia. In addition, probiotic use was also found to reduce the severity of pathological conditions associated with irritable bowel disorder and prevent development of endocarditis in septicemia. On contrary, probiotic therapy in neonatal and athymic adult mice fail to provide any beneficial effects on mortality and sepsis-induced inflammation. Importantly, in few clinical trials probiotic use was found to aggravate sepsis by promoting inflammatory cascade rather than suppressing it. This review discusses various studies regarding the beneficial or harmful effects associated with probiotic therapy in sepsis.