RESUMO
Alzheimer's Disease is a degenerative neurological condition which leads to a decline in memory and cognitive function. Chlorogenic Acid (CGA) presents properties including neuroprotective, antioxidant and anti-inflammatory. The aim of this study was to examine the impact of CGA on cognitive impairments, neuroinflammation and neuronal damage in mice submitted to an experimental model of Sporadic Alzheimer Disease (SAD) induced by intracerebroventricular administration of streptozotocin (ICV-STZ). Male Swiss mice received bilateral ICV-STZ injections (3 mg/Kg) on days 1 and 3. The treatment with CGA (5 mg/Kg, orally) or vehicle (water, orally), was initiated and continued for 26 days, starting 2 h after the second induction procedure. At first, there was no change in serum glucose levels after SAD induction. ICV-STZ induces impairments in aversive, recognition, and spatial memory, while CGA treatment significantly alleviated these memory deficits. Furthermore, locomotor activity, working memory, and anxiety-related activities remained unaffected by the treatments. CGA treatment protects against ICV-STZ-induced increase in the nitrite/nitrate and TBARS levels. ICV-STZ induced a reduction in viable cells, depletion of BDNF, and triggered astrogliosis and microgliosis in the cortex and hippocampus. Treatment with CGA preserves viable cell count in the prefrontal cortex, CA1, and CA3 regions of the hippocampus. Additionally, it prevented BDNF depletion in the prefrontal cortex and hippocampus (CA1, CA3, and DG regions), and mitigated astrogliosis and microgliosis in the prefrontal cortex and hippocampus (CA1, CA3, and DG regions). These findings indicate the neuroprotective effects of CGA, underscoring their potential as therapeutic agents or adjuncts in the treatment of SAD.
RESUMO
Ischemic stroke is one of the major causes of human morbidity and mortality. The pathophysiology of ischemic stroke involves complex events, including oxidative stress and inflammation, that lead to neuronal loss and cognitive deficits. Palmatine (PAL) is a naturally occurring (Coptidis rhizome) isoquinoline alkaloid that belongs to the class of protoberberines and has a wide spectrum of pharmacological and biological effects. In the present study, we evaluated the impact of Palmatine on neuronal damage, memory deficits, and inflammatory response in mice submitted to permanent focal cerebral ischemia induced by middle cerebral artery (pMCAO) occlusion. The animals were treated with Palmatine (0.2, 2 and 20 mg/kg/day, orally) or vehicle (3% Tween + saline solution) 2 h after pMCAO once daily for 3 days. Cerebral ischemia was confirmed by evaluating the infarct area (TTC staining) and neurological deficit score 24 h after pMCAO. Treatment with palmatine (2 and 20 mg/kg) reduced infarct size and neurological deficits and prevented working and aversive memory deficits in ischemic mice. Palmatine, at a dose of 2 mg/kg, had a similar effect of reducing neuroinflammation 24 h after cerebral ischemia, decreasing TNF-, iNOS, COX-2, and NF- κB immunoreactivities and preventing the activation of microglia and astrocytes. Moreover, palmatine (2 mg/kg) reduced COX-2, iNOS, and IL-1ß immunoreactivity 96 h after pMCAO. The neuroprotective properties of palmatine make it an excellent adjuvant treatment for strokes due to its inhibition of neuroinflammation.
