Upregulation in calcineurin (CaN) signaling has been implicated in various neurodegenerative disorders. In the present study, we have investigated the effect of FK506--a CaN inhibitor--on streptozotocin (STZ)-induced experimental dementia of the Alzheimer's type in rats. STZ was administered intracerebroventricularly to induce a cognitive deficit and oxidative stress. Nonimmunosuppressive doses (0.5 and 1 mg/kg postoperatively) of FK506 (tacrolimus) were administered for 21 day in STZ-treated rats. Cognitive functions were assessed using the Morris water maze and passive avoidance tasks. Malondialdehyde and nitrite glutathione levels, as well as acetylcholinesterase activity, were determined to evaluate oxidative stress and cholinergic functions. Lactate dehydrogenase levels were estimated and histological analysis of the dentate gyrus and the CA1 region of the hippocampus was carried out to identify degenerative changes. STZ produced significant deterioration of cognitive functions, oxidative stress, and degenerative changes in the cortical and hippocampal brain regions. FK506 dose-dependently attenuated STZ-induced cognitive deficits, oxidative stress, and degenerative changes in the cortex and hippocampus. These results suggest a potential role of CaN signaling in degenerative processes, and that inhibition of CaN may be useful in the treatment of neurodegenerative disorders such as Alzheimer's disease.
Embelin (EMB) (2,5-Dihydroxy-3-undecyl-1,4-benzoquinone) is a natural benzoquinone extracted mainly from Embelia ribes (ER) and appear as vivid orange dots beneath the fruit's pericarp. It is being used to treat various diseases since ancient times in India. It has been ascribed as one of the 32 ayurvedic drugs of national importance in the National Medicinal Plant Board set up by the Government of India under the Ministry of Indian System of Medicine and Homeopathy. Embelin prevents neuronal oxidative damage by decreasing the peroxidation of lipids. Along with having antioxidant properties, it also prevents the production of amyloid-protein-related fibrils and blocks the progression of inflammatory cascades. Due to embelin's ability to cross the blood-brain barrier, its neuroprotective effects have been studied in the past using in vitro models of neuronal disorders such as convulsion and epilepsy, Alzheimer's disease, anxiety and depression, traumatic brain injury, cerebral ischemia, Huntington's disease, and multiple sclerosis. In addition to its neuroprotective effects, its role as an antitubercular, anti-cancer, antioxidant, astringent, anti-inflammatory, anti-bacterial, contraceptive, carminative, diuretic, and anthelmintic agent has also been studied. With docking studies and recent advancements in formulations of embelin including polyethylene and embelin micelles and embelin noisome preparations, embelin can prove to be a promising compound for its therapeutic actions in a wide range of diseases and disorders. The findings of docking studies suggest the binding ability of embelin to be similar to the standard drug in their respective disorders. In this review and docking analysis, we bring an outline of scientific evidence concerning the neuroprotective actions of embelin, still, further research is required for its prospective as a chief compound in clinical approaches.
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