Objective: Several factors lead to memory loss, the most important of which is brain aging that is caused mostly by neuroinflammation and oxidative stress. The need of finding preventive treatments of memory impairment in elderly encouraged authors to assess the effect of Acorus calamus on memory loss, anxiety, and antioxidant indices on neuroinflammation rat models. Materials and Methods: Different fractions of A. calamus were prepared. The subject rats were grouped in 11 groups of 10 each. In the nine treated groups, the extract gavage began 1 week before intraperitoneal (i. p. ) injection of lipopolysaccharide (LPS) and continued for 2 weeks after the last injection of LPS. Behavioral tests, including passive avoidance and elevated plus‑ maze (EPM) tests, were run on days 24, 25, and 26 and the subjects were sacrificed on the day after the last behavioral test, and their hippocampus was isolated to measure the oxidative stress markers. Results: Assessment of oxidative stress markers in hippocampus samples revealed that the amounts of endogenous antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and total antioxidant activity) in the groups that received different fractions were less than their equivalent figures in LPS‑ control group, and levels of malondialdehyde (MDA) in treatment groups were less than MDA level in LPS‑ control group. Moreover, the treatment groups with different fractions of A. calamus revealed better performance compared to LPS‑ control group in shuttle‑ box test. In EPM test, the groups with different fractions revealed lower stress level in comparison with LPS‑ control group. The best performance in memory test and the lowest level of stress in EPM was observed in the group with aqueous fraction at 600 mg/kg dose, and the least figures of oxidative stress markers were of the group with aqueous fraction at 600 mg/kg dose. Conclusion: The oral administration of different fractions of A. calamus, especially aqueous fraction, prevented from memory deficits and stress through controlling oxidative stress and inflammation processes.

Objective: This research revealed the biochemical outcomes of metabolic dysregulation in serum associated with physiological sickness behavior following lipopolysaccharide (LPS)-induced neuroinflammation in rats, and treatment with Clinacanthus nutans (CN). Verification of H NMR analysis of the CN aqueous extract proved the existence of bioactive phytochemical constituents’ in extract. Materials and Methods: Twenty-five rats were subjected to unilateral stereotaxic injection of 10 µ L LPS (1 mg/mL), while another ten rats were injected with phosphate-buffered saline (PBS, 10 µ L) as control. Then, 29 parameters of rat behavior related to sickness were tracked by a device software (SMART 3. 0. 1) on days 0 and 14 of CN treatment. The acquired and accumulated data were analyzed using multivariate data analysis with the SIMCA Software package (version 13, Umetrics AB; Umeå , Sweden). The pattern trends of related groups were documented using PCA and OPLS analysis. Results: A similar ameliorated correlation pattern was detected between improvement in physiological sickness behavior and antiinflammatory biomarkers by the 1 H NMR spectra of the sera following treatment with CN (500 and 1000 mg/kg body weight (bw)) and the control drug (dextromethorphan hydrobromide, 5 mg/kg of rats bw) in rats. Here, 21 biomarkers were detected for neuroinflammation. Treatment with the aqueous CN extract resulted in a statistically significant alteration in neuroinflammation metabolite biomarkers, including ethanol, choline, and acetate. Conclusion: This result denotes that the metabolomics approach is a reliable tool to disclose the relationship between central neuroinflammation, and systemic metabolic and physiological disturbances which could be used for future ethno-pharmacological assessments.

Background: Echium amoenum (E. amoenum) is an Iranian medicinal plant with mood-enhancing effects. Objectives: This study was designed to investigate the effect of standardized E. amoenum hydroalcoholic extract on restraint stress (RS)-evoked anxiety-and-depressive-like behaviors in mice. Methods: This experimental study was conducted at the Tabriz University of Medical Sciences, Tabriz, Iran, in 2018. Doses of the hydroalcoholic extract of E. amoenum were optimized for rosmarinic acid (> %2 w/w) concentration of the extract. Other phytochemical indices, including total phenolic and flavonoid contents and radical scavenging activity, were also measured. For behavioral studies, 65 mice were randomly assigned into five groups (n = 13) of control, RS, RS + E75, RS + E150, and RS + E300. Animals in the RS group were subjected to the RS (3 h/day for 14 days) and treated with normal saline, while treatment groups received E. amoenum extract (75, 150, and 300 mg/kg, p. o. ) concomitantly with RS exposure. Anxiety-like behaviors were assessed by Elevated Plus Maze (EPM) and Open Field Test (OFT). Depression was assessed by the forced swim test (FST) and Tail Suspension Test (TST). Western blotting was performed to determine the protein levels of IL-1 , NF- B, TNF- , and IL-6 in the prefrontal cortex (PFC) and hippocampus (HIP). The concentrations of corticosterone, alanine aminotransferase, aspartate aminotransferase, and alanine phosphatase were also measured in serum. Results: Moderate and high doses of the extract ameliorated RS-induced anxiety-(P < 0. 05 in OFT and EPM) and depressive-like (P < 0. 05 and P < 0. 01 in FST; P < 0. 01 and P < 0. 001 in TST) behaviors. These results were approved by decreased serum corticosterone levels (P < 0. 05 and P < 0. 001). Furthermore, E. amoenum reduced the protein expression of neuroinflammatory markers in the HIP and PFC subregions (significant at least at P < 0. 05 for IL-1 , NF- B, and TNF- ). Although RS slightly increased the serum levels of liver enzymes, no histopathological changes were seen in the liver of the RS or E. amoenum-treated groups. Conclusions: E. amoenum can be an effective and safe complementary strategy for the treatment of stress-associated inflammation and behavioral changes.

Objective(s): Cerebral ischemia/reperfusion causes complex pathological mechanisms that lead to brain tissue damage. Usnic acid is a lichen secondary metabolite that has many different biological properties including anti-inflammatory and anti-oxidant activities. Therefore, the objective of the current study was to investigate the neuroprotective effects of usnic acid on apoptotic cell death, neuroinflammation, anti-oxidant enzyme activities, and oxidative stress levels after transient cerebral ischemia/reperfusion. Materials and Methods: Forty-two male Wistar rats were randomly assigned to three groups (sham, ischemia/reperfusion, and ischemia/reperfusion+usnic acid). Ischemia was induced by 20 min occlusion of common carotid arteries. Injection of usnic acid (25 mg/kg, intraperitoneally) and saline was done at the beginning of reperfusion time. Morris water maze was applied to assess spatial memory. The protein expression amount was measured using immunohistochemical and immunofluorescence staining. Spectrophotometric assay was performed to determine the levels of anti-oxidant enzymes. Results: Usnic acid significantly reduced caspase-3, glial fibrillary acidic proteinpositive and ionized calcium-binding adaptor molecule 1-positive cells (P<0. 001) and enhanced spatial memory disorders (P<0. 05) due to brain ischemia. In addition, treatment with usnic acid improves effects in the antioxidant system following cerebral ischemia (P<0. 05). Conclusion: Our findings indicate that usnic acid has neuroprotective properties, which possibly is applicable as a promising candidate for cerebral injuries caused by ischemia.

Objective(s): The human apolipoprotein E4 (APOE4) is associated with various brain injuries and neurodegenerative changes. Curcumin is an active ingredient isolated from the root of turmeric and is believed to have therapeutic effects on neurodegenerative diseases. The aim of this study was to investigate the effects of curcumin on APOE4-induced neurological damage and explore its molecular mechanisms. Materials and Methods: SH-SY5Y cells were pretreated with curcumin for 24 hr and transfected with human APOE4 gene using Lipofectamine 2000. Then, the effect of curcumin on the transfected cells was detected by ELISA, immunofluorescence staining and Western blot. Results: The production or expression of proinflammatory cytokines and proteins, including tumor necrosis factor-α (TNF-α ), interleukin-1β (IL-1β ), nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was significantly increased in SH-SY5Y cells transfected with APOE4, and curcumin inhibited APOE4-induced cellular inflammatory damage. Western blot analysis showed that, after transfection with APOE4, the expression of total nuclear factor kappa B (NF-κ B) p65 and p-NF-κ B p65 in the nucleus was increased, and curcumin inhibited the nuclear translocation of p65. The overexpression of APOE4 inhibited the expression of peroxisome proliferator-activated receptor-γ (PPARγ ), whereas curcumin reversed and increased the expression of PPARγ protein. Down-regulating PPAR-γ with the inhibitor GW9662 and the shPPARγ gene confirmed that the NF-κ B signaling pathway was inhibited by PPARγ . Conclusion: This study suggests that APOE4 overexpression can induce cellular inflammatory damage, and pretreatment of curcumin could exert an anti-inflammatory effect by upregulating the expression of PPARγ to inhibit the activation of NF-κ B signaling pathway.

Background: Parkinson’ s disease (PD) isoneof themostcommonneurodegenerative movement-related disturbance characterized by the degeneration of dopaminergic neurons with uncertain underlying mechanisms, which can be modeled by the rotenone (ROT). neuroinflammation and oxidative stress (OS) are the most possible hypotheses to create this condition. Objectives: The aim of this study was to evaluate the effects of celecoxib (CLX) on ROT-induced rat model of PD. To this aim, the suppression of neuroinflammation and oxidative stress-mediated apoptosis was surveyed. Methods: In this experimental study, thirty-two male Sprague-Dawley rats randomly classified into 4 groups (n = 8 rats/group) in the following order: control, sham, PD (2. 5 mg/kg/48 hours ROT subcutaneously), CLX + PD (20 mg/kg/24 daily orally CLX + 2. 5 mg/kg/48 hours ROT). After 28 days of the experiment, the rats were sacrificed and their brain was removed. Then histological (Nissl staining) and biochemical assessments (total antioxidant capacity (TAC) were carried out and malondialdehyde (MDA) levels were measured. The data were analyzed by ANOVA test. Results: The biochemical assessments showed TAC was significantly increased in CLX + PD group compared with PD group, whereas MDA was decreased in CLX + PD group compared with PD group (P < 0. 01). We found a significant decrease in the number of dopaminergic cells in substantia nigra pars compacta (SNc) in PD group (P < 0. 001), and treatment with CLX markedly increased dopaminergic neurons in CLX + PD compare to PD group (P < 0. 01). Conclusions: The findings of this study revealed that CLX treatment can effectively improve the antioxidant defense system and attenuates striatum insults on ROT-induced rat model of PD. These findings suggest that CLX plays a neuroprotective role in the inhibition of oxidative stress and neuroinflammation.