Cedrol supplementation ameliorates memory deficits by regulating neuro-inflammation and cholinergic function in lipopolysaccharide-induced cognitive impairment in rats.

Background: Cedrol, a sesquiterpene alcohol, is found in a high amount in several conifers. It possess several beneficial health effects, including antioxidant and anti-inflammatory properties. Objective: This study evaluates the neuroprotective role of cedrol against lipopolysaccharide (LPS)-induced neuroinflammation and memory loss in rats. Methods: Wistar rats were treated with cedrol (7.5, 15, and 30 mg/kg, oral, two weeks). During the last week, the rats (except for the control group) were treated with LPS (intraperitoneal injection, 1 mg/kg) to induce memory impairment. After that, the animals were subjected to behavioral studies (Morris water maze and passive avoidance) and biochemical assessments. Results: Our results showed a significant decrease in learning and memory function-in LPS-induced rats which were reversed by cedrol. Also, there was a significant increase in the cerebral levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and malondialdehyde (MDA) as well as acetylcholinesterase (AChE) activity in LPS-treated rats. Besides, a significant reduction in total thiol and superoxide dismutase levels was observed in LPS-treated rats. However, cedrol significantly decreased the brain level of AChE, TNF-α, and IL-1ß. Administration of cedrol also restored the oxidative stress markers. Conclusion: the beneficial effects of cedrol against LPS-induced memory impairment could be due to antioxidant activities and modulation of neuro-inflammatory mediators.

Carvacrol improved learning and memory and attenuated the brain tissue oxidative damage in aged male rats.

Introduction: Aging is an unavoidable process in the body that is accompanied by impaired tissue homeostasis and various changes. Carvacrol has attracted considerable attention for its wide range of pharmacological activities. Therefore, this study attempted to explore the protective effect of carvacrol in aged rats.Materiel and methods: The aged rats were given carvacrol (15 or 30 mg/kg/day) for 4 weeks. Morris water maze and passive avoidance tests were used to determine the learning and memory abilities of the rats. The hippocampus and cortex samples were taken for biochemical analysis.Results: In comparison to young control rats, aged control rats showed learning and memory deficits. There was improvement in the Morris water navigation test and passive avoidance test performance in the treatment groups versus the aged control group. An increment in malondialdehyde (MDA) and a decrease in total thiol groups in the hippocampus and cortex samples of aged control rats in comparison to the young control group were observed. Carvacrol decreased MDA levels and increased total thiol groups in the hippocampus and cortex samples of aged rats.Conclusion: Carvacrol improved learning and memory in aged rats, probably through its anti-oxidation effects.

Vitamin D alleviates hypothyroidism associated liver dysfunction: Histological and biochemical evidence.

There is a complex correlation between thyroid hormones (THs) and liver function. Hypothyroidism as a failure of the thyroid gland to produce adequate thyroid hormones to fulfill the metabolic requirements of the body, may perturb liver structure and function. Emerging evidence suggests the protective effects of vitamin D against liver damage. Herein, this study aimed to investigate the role of vitamin D in hypothyroidism-associated liver injury. Forty male Wistar rats were classified into 4 groups: control, hypothyroid (Hypo) group received 0.05% PTU, Hypo- Vitamin D groups were given 100 and 500 IU/kg vitamin D orally via gavage for 6 weeks. Serum level of liver function including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured. Malondialdehyde (MDA) level, superoxide dismutase (SOD) enzyme activity, and total thiol content were measured as oxidative stress indicators in the liver tissue. Furthermore, to estimate liver tissue fibrosis, Masson's trichrome staining was done. Our findings showed that hypothyroidism-induced liver fibrosis was associated with increased levels of ALT, AST and ALP. Though, vitamin D administration could significantly reduce the ALT, AST and ALP in the serum and suppress the accumulation of collagen fibers. Moreover, the activity of SOD and total thiol content was notably reduced, while the MDA content was significantly increased in the PTU- induced hypothyroid rats compared to the control group. Nonetheless, treatment with vitamin D improved mentioned oxidative stress markers in the Hypo-vitamin D groups. In conclusion, vitamin D due to its potential antioxidant and anti-fibrotic properties could be effective in the decrease of hypothyroidism-associated liver injury.

Minocycline alleviated scopolamine-induced amnesia by regulating antioxidant and cholinergic function.

Background and aim: Minocycline, a tetracycline derivative, has been found to exert neuroprotective properties. The current project aimed to assess the antioxidant status and cholinergic function in the amnesia induced by scopolamine. Methods: We evaluated the passive avoidance performance, acetylcholine esterase (AChE) enzyme activity, and the oxidative stress indicators in the following groups: Normal control, scopolamine, and the treatment groups (the animals were given minocycline (10-30 mg/kg)). Results: Scopolamine (intraperitoneal) injection was associated with impairment of passive avoidance performance and neurotoxicity. Minocycline pronouncedly ameliorated scopolamine injury as presented by the increased latency time to darkness and stay time in lightness along with the decreased darkness entry. Moreover, minocycline decreased lipid peroxidation, while it elevated the levels of superoxide dismutase, AChE enzymes, and thiol groups in both the cortex and hippocampus. Conclusion: Our data suggested that minocycline modulated the antioxidant status and AChE in the brains, which may contribute to its protective effects against scopolamine-induced amnesia.

Punica granatum peel supplementation attenuates cognitive deficits and brain injury in rat by targeting the Nrf2-HO-1 pathway.

The critical role of nutrition to prevent neurodegenerative disorders is well documented. Punica granatum fruit is identified as a highly nutritional food for alleviating various ailments. The ameliorating properties of P. granatum peel on memory dysfunction and the possible roles of oxidative stress, acetylcholinesterase (AchE), and nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase (HO)-1 pathway in the scopolamine-treated rats were assessed. The hydroethanolic extract was standardized using high-performance liquid chromatography (HPLC). The animal groups were as follows: Control, scopolamine (2 mg/kg), and treatment groups (the extract at doses of 200-800 mg/kg). The behavioral performance was evaluated using the Morris water maze (MWM) and passive avoidance equipment. Various biochemical parameters were then measured. Rats received the extract properly found on the platform location, indicated by a shorter traveling time and distance during 5 days of learning MWM. Moreover, the extract increased the delay and light time, while decreasing dark time and the frequency of entries to the dark in the passive avoidance test. The extract also exerted a significant increase in superoxide dismutase activity and thiol content, while decreasing AchE activity and lipid peroxidation in the brain of scopolamine-injured rats. Our results demonstrated the neuroprotective effects of P. granatum peel in minimizing scopolamine injury possibly through targeting the Nrf2-HO-1 pathway.

Ellagic Acid Prevents Oxidative Stress and Memory Deficits in a Rat Model of Scopolamine-induced Alzheimer's Disease.

BACKGROUND: Ellagic acid (EA) has various pharmacological effects such as antiinflammatory and anti-oxidant effects. OBJECTIVE: This study aimed to investigate the effects of EA on learning and memory dysfunction as well as oxidative stress in scopolamine-induced amnesic rats. METHODS: The studied rats were treated according to the following protocol: Control (group 1) and scopolamine (group 2) groups received saline (intraperitoneal injection (i.p.)) while the treatment groups (group 3-5) were given EA (25, 50, and 100 mg/kg, i.p.) for 3 weeks. Thereafter, their behavioral performance was evaluated using Morris water maze (MWM) and passive avoidance (PA) tasks. Notably, scopolamine was injected (into groups II-V at a dose of 2 mg/kg, i.p.) before conducting the tasks. Finally, the oxidative stress indicators in the brain were measured. RESULTS: EA reduced the escape latencies and distances during the learning phase of MWM. The results of probe trials also indicated that EA improved memory retrieval and helped animals recall the platform. Moreover, EA increased delay and light time, while decreasing the frequency of entries to the dark area of PA. In the EA-treated groups, the level of malondialdehyde was decreased, while the levels of total thiol groups, superoxide dismutase, and catalase were increased. CONCLUSION: EA prevented the negative effects of scopolamine on learning and memory which is probably mediated via modulating oxidative stress. Hence, EA could be considered as a potential alternative therapy for dementia.

Minocycline attenuates cholinergic dysfunction and neuro-inflammation-mediated cognitive impairment in scopolamine-induced Alzheimer's rat model.

OBJECTIVE: Minocycline, a semisynthetic tetracycline-derived antibiotic, has various pharmacological effect such as anti-inflammatory, anti-oxidative stress, and anti-apoptotic effects. The current study investigated the involvement of neuro-inflammatory, oxidative stress, and cholinergic markers in neuroprotection by minocycline against scopolamine-induced brain damage. METHODS: Minocycline was administered (oral, 10, 15, and 30 mg/kg, daily) to groups of amnesic rats for 21 days. Passive avoidance memory and spatial learning and memory were assessed. Following that, oxidative stress, cholinergic function, and neuro-inflammation markers were evaluated in the brain tissue. RESULTS: According to our biochemical data, treatment of the scopolamine-injured rats with minocycline decreased the levels of malondialdehyde and acetylcholinesterase (AChE) as well as mRNA expression of AChE and neuro-inflammation markers (tumor necrosis factor-α, interleukin (IL)-1ß, IL-6). It also increased the total thiol levels and superoxide dismutase activity as well as mRNA expression of cholinergic receptor M1 (ChRM1). Moreover, minocycline modified distance and latencies in Morris water maze, prolonged latency to enter the black zone and light time while decreasing time spent and frequency of entries to darkness. CONCLUSION: Taken together, the data indicate that treatment with minocycline improved memory dysfunction mediated possibly through restoring AChE and ChRM1 levels, oxidant/antioxidant balance, as well as inhibiting inflammatory responses.

Amelioration of oxidative stress, cholinergic dysfunction, and neuroinflammation in scopolamine-induced amnesic rats fed with pomegranate seed.

OBJECTIVE: This study aimed to investigate the effects of pomegranate (Punica granatum L.) seed hydro-ethanolic extract (PSE) on cholinergic dysfunction, neuroinflammation, and oxidative stress in the scopolamine-induced amnesic rats. METHODS: The rats were given PSE (200, 400, and 800 mg/kg, gavage) for 3 weeks. In the third week, scopolamine was administered 30 min before the Morris water maze (MWM) and passive avoidance (PA) tests. Oxidative stress indicators, acetylcholinesterase (AChE) activity, and mRNA expression of necrosis factor (TNF)-α, interleukin (IL)-1ß, AChE, and M1 acetylcholine receptor (CHRM1) in the brain, were measured. RESULTS: PSE reduced the time (maximum 173%) and distance (maximum 332%) required to reach the platform during MWM learning (P < 0.001). In the prob test (P < 0.001), it increased the target area time (maximum 44%) and distance (maximum 30%). PSE also increased delay and light time (maximums of 86 and 48%, respectively) (P < 0.001), while decreasing the time in dark region of PA (maximums 727%) (P < 0.001). PSE also reduced malondialdehyde and AChE in the cortex (maximum 168 and 171%, respectively) and hippocampus (maximum 151 and 182%, respectively) (P < 0.001). In the PSE-treated groups, the levels of thiol and superoxide dismutase were increased in the cortex (maximum 54 and 65%, respectively) and hippocampus (maximum 90 and 51%, respectively) (P < 0.001). TNF-α, IL-1ß, and AChE expressions in the hippocampus were reduced by PSE (maximum 114, 137, and 106%, respectively, P < 0.01). Meanwhile, CHMR expression was increased (66%). CONCLUSION: PSE successfully alleviated scopolamine-induced memory and learning deficits in rats which is probably via modulating cholinergic system function, oxidative stress, and inflammatory cytokines.

Folic acid attenuated learning and memory impairment via inhibition of oxidative damage and acetylcholinesterase activity in hypothyroid rats.

Hypothyroidism has been reported to be associated with cognitive decline. Considering the role of folic acid (FA) in cognitive performance, the present study was designed to investigate the effects of FA on hypothyroidism-induced cognitive impairment, oxidative damage, and alterations in acetylcholinesterase (AChE) activity in rat model of propylthiouracil (PTU)-induced hypothyroidism. In this study, PTU (0.05% in drinking water) and FA (5, 10, and 15 mg/kg, oral gavage) were administered for the rats during 7 weeks. Then, behavioral performance was tested using Morris water maze (MWM) and passive avoidance (PA) tasks. Finally, oxidative stress indicators and AChE activity were assayed in the brain tissues. The impairing effect of hypothyroidism on cognitive performance was markedly alleviated by FA especially at higher doses. In the MWM test, FA reduced escape latency and travelled distance, compared to the non-treated hypothyroid group. In the PA test, latency to enter dark chamber was significantly enhanced by FA compared to the non-treated hypothyroid group (p < 0.05-p < 0.001). Besides, FA attenuated AChE activity and malondialdehyde level but it increased activity of superoxide dismutase enzyme and total thiol content (p < 0.05-p < 0.001). In conclusion, our findings revealed that FA could improve learning and memory ability in hypothyroid rats. The observed protective effects may have been mediated through regulation of oxidative stress and AChE activity.

A spatial-epidemiological dataset of subjects infected by SARS-CoV-2 during the first wave of the pandemic in Mashhad, second-most populous city in Iran.

OBJECTIVE: In March 2020, Iran tackled the first national wave of COVID-19 that was particularly felt in Mashhad, Iran's second-most populous city. Accordingly, we performed a spatio-temporal study in this city to investigate the epidemiological aspects of the disease in an urban area and now wish to release a comprehensive dataset resulting from this study. DATA DESCRIPTION: These data include two data files and a help file. Data file 1: "COVID-19_Patients_Data" contains the patient sex and age + time from symptoms onset to hospital admission; hospitalization time; co-morbidities; manifest symptoms; exposure up to 14 days before admission; disease severity; diagnosis (with or without RT-PCR assay); and outcome (recovery vs. death). The data covers 4000 COVID-19 patients diagnosed between 14 Feb 2020 and 11 May 2020 in Khorasan-Razavi Province. Data file 2: "COVID-19_Spatiotemporal_Data" is a digital map of census tract divisions of Mashhad, the capital of the province, and their population by gender along with the number of COVID-19 cases and deaths including the calculated rates per 100,000 persons. This dataset can be a valuable resource for epidemiologists and health policymakers to identify potential risk factors, control and prevent pandemics, and optimally allocate health resources.