Background and Objective: Lipolysaccharide (LPS) is a large molecule isolated from bacteria such as the enterobacteriaceae family with a negative effect on memory and learning through disturbing the balance of free radicals and creating oxidative stress conditions. In this study, we evaluated the effect of quercetin on oxidative stress and LPS-induced memory impairment in the rat. Materials and Methods: Male rats (n=40) were randomly divided into 5 groups: control, control under treatment with quercetin at a dose of 50 mg/kg, LPS, and LPS groups treated with quercetin at doses of 10 or 50 mg/kg. For induction of inflammation, LPS dissolved in normal saline (500 μ g/kg) was injected intraperitoneally. After one week, the passive avoidance behavior was tested in the shuttle box and hippocampal homogenate was prepared. Acetylcholinesterase (AChE) activity and lipid peroxidation (malondialdehyde, MDA) were measured using specific kits. Data were analyzed by SPSS software (version 16). Results: Step-through latency (STL) in quercetin50-treated LPS group was significantly greater than control group (p<0. 05). In addition, AChE activity and level of MDA was significantly lower in quercetin50-treated LPS group versus LPS group (p<0. 05). Meanwhile, quercetin at a dose of 10 mg/kg did not have such a significant effect. Conclusion: Quercetin at a dose of 50 mg/kg has a protective effect on learning and memory impairment due to LPS and part of its beneficial effect is mediated via attenuation of lipid peroxidation and AChE.

Objective(s): Parkinson’ s disease (PD) is a common progressive neurodegeneration disease. Its incidence increases with age and affects about 1% of people over 60. Incidentally, transient receptor potential V1 (TRPV1) and its relation with neuroinflammation in mouse brain has been widely reported. Materials and Methods: We used 6-hydroxydopamine (6-OHDA) to induce PDD in mice. We then used the Morris water maze and Bio-Plex to test learning and inflammatory mediators in mouse plasma. Western blotting and immunostaining were used to examine TRPV1 pathway in the hippocampus and medial prefrontal cortex (mPFC). Results: On acquisition days 3 (Control = 4. 40 ± 0. 8 sec, PDD = 9. 82 ± 1. 52 sec, EA = 5. 04 ± 0. 58 sec, Riva = 4. 75 ± 0. 87 sec; P=0. 001) and 4, reversal learning days 1, 2, 3 (Control = 2. 86 ± 0. 46 sec, PDD = 9. 80 ± 1. 83 sec, EA = 4. 6 ± 0. 82 sec, Riva = 4. 6 ± 1. 03 sec; P=0. 001) and 4, PDD mice showed significantly longer escape latency than the other three groups. Results showed that several cytokines were up-regulated in PDD mice and reversed by EA and rivastigmine. TRPV1 and downstream molecules were up-regulated in PDD mice and further reversed by EA and rivastigmine. Interestingly, α 7 nicotinic receptors and parvalbumin levels in both the hippocampus and prefrontal cortex increased in EA-treated mice, but not in rivastigmine-treated mice. Conclusion: Our results showed that TRPV1 played a role in the modulation of neuroinflammation of PDD, and could potentially be a new target for treatment.

Background: Alzheimer disease (AD) is the most common age‑, dependent dementia. The complex natural accumulation of amyloid beta (Aβ, ) precursor protein in hippocampus neurons is regarded as the earliest pathological feature of AD, although there are cholinergic assumptions and effective inflammation in AD. In this animal experimental study, we evaluated the preventive effect of hyoscyamoside (Hyo) and donepezil (Dz) on plaque formation and improvement of neurogenic inflammation in AD rats. Methods: Dz was prepared and Hyo (steroidal saponin) was isolated from Hyoscymus niger. Then, Wistar rats divided into five groups including negative and positive controls, AD, Dz, and Hyo treatment groups based on the drug exposure and their behavioral alternation was examined using Morris water maze (MWM) test. Bielschowsky staining was used to detect the nerve fibers. Serum levels of interleukin (IL)‑, 4 and IL‑, 6 were evaluated by ELISA. The RNA expression of cyclin‑, dependent kinase CDK11-P58 in peripheral blood lymphocytes was performed using quantitative PCR. Results: The MWM test showed significant changes in time the models spent to find the hidden platform. The Hyo treatment group showed a notable speed change (P < 0. 01). The histopathological analysis of the hippocampal tissue revealed the inhibition of Aβ,formation in the treatment groups. The treatment groups had a significant decline in the serum level of IL‑, 6, and the IL‑, 4 serum level was increased in the Hyo and Dz treated groups. The expression levels of CDK11-P58 was significantly decreased in the treatment groups. Conclusions: In sum, the therapeutic effects of Hyo is comparable with that of Dz in AD rats by suppressing neuroinflammation. Thus, these compounds could be considered as a preventive agent in the AD therapy.

Objective: Sustained inflammation, which could be promoted by AB aggregation and tau hyperphosphorylation, is a critical player in Alzheimer's disease (AD) pathogenesis. In the first phase, this study was designed to evaluate the anti-inflammatory properties of Ecballium elaterium (EE), as a Mediterranean therapeutic plant, and its effects on biochemical and behavioral signs of nucleus basalis of Meynert lesioned (NBML) rats, as an approved model of AD. In the second phase, we investigated the effect of EE on nuclear factor (NF)-KB pathway which is responsible for encoding proteins involved in the inflammatory cascade. Materials and Methods: Animals were divided randomly into four groups as following: control, NBML rats (AD), AD rats that were treated by high-and low-dose EE. Prostaglandins (PGs) levels were measured by enzyme-linked immunosorbent assay (ELISA) kits. Cyclooxygenase-2 (COX-2) and acetylcholinesterase (AChE) levels were assessed by fluorometric kit and Elman method, respectively. Behavioral signs were evaluated by Morris Water Maze (MWM) test and inflammatory proteins content was analyzed by immunoblotting method. Results: According to the results, treatment of NBML rats with EE fruit juice reduced PGs and cytokines more than 2-fold in comparison with AD rats through inhibition of COX-2 enzyme. Attenuation of inflammatory response in NBML rats was accompanied by reduced AChE activity (about 3-fold) and improved learning ability. Interestingly, EE reduced NF-KB expression for about 3-fold which resulted in a more than 10-fold increase in IKBa/P-IKBa ratio. Conclusion: Our results confirmed the TNF-a/cytokines/NFKB/COX-2 pathway involves as the main inflammatory response in NBML rats. We also provided biochemical and behavioral evidence which introduces EE as an anti-inflammatory adjuvant to improve pathophysiological signs in patients suffering from AD and related dementia.