Folic acid improved memory and learning function in a rat model of neuroinflammation induced by lipopolysaccharide.

Folic acid (FA) plays an important role in the maintenance of normal neurological functions such as memory and learning function. Neuroinflammation contributes to the progression of cognitive disorders and Alzheimer's disease. Thus, this study aimed to investigate the effect of FA supplementation on cognitive impairment, oxidative stress, and neuro-inflammation in lipopolysaccharide (LPS)-injured rats. For this purpose, the rats were given FA (5-20 mg/kg/day, oral) for 3 weeks. In the third week, LPS (1 mg/kg/day; intraperitoneal injection) was given before the Morris water maze (MWM) and passive avoidance (PA) tests. Finally, the brains were removed for biochemical assessments. In the MWM test, LPS increased the escape latency and traveled distance to find the platform compared to the control group, whereas all doses of FA decreased them compared to the LPS group. The findings of the probe trial showed that FA increased the traveling time and distance in the target area. LPS impaired the performance of the rats in the PA test. FA increased delay and light time while decreasing the frequency of entry and time in the dark region of PA. LPS increased hippocampal levels of interleukin (IL)-6 and IL-1ß. The hippocampal level of malondialdehyde was also increased but thiol content and superoxide dismutase activity were decreased in the LPS group. However, treatment with FA restored the oxidative stress markers along with a reduction in the levels of pro-inflammatory cytokines. In conclusion, FA could ameliorate the memory and learning deficits induced by LPS via normalizing the inflammatory response and oxidative stress markers in the brain.

B lymphocytes in COVID-19: a tale of harmony and discordance.

B lymphocytes play a vital role in the human defense against viral infections by producing specific antibodies. They are also critical for the prevention of infectious diseases by vaccination, and their activation influences the efficacy of the vaccination. Since the beginning of coronavirus disease 2019 (COVID-19), which became the main concern of the world health system, many efforts have been made to treat and prevent the disease. However, for the development of successful therapeutics and vaccines, it is necessary to understand the interplay between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, and the immune system. The innate immune system provides primary and nonspecific defense against the virus, but within several days after infection, a virus-specific immune response is provided first by antibody-producing B cells, which are converted after the resolution of disease to memory B cells, which provide long-term immunity. Although a failure in B cell activation or B cell dysfunction can cause a severe form of the disease and also lead to vaccination inefficiency, some individuals with B cell immunodeficiency have shown less production of the cytokine IL-6, resulting in a better disease outcome. In this review, we present the latest findings on the interaction between SARS-CoV-2 and B lymphocytes during COVID-19 infection.

Ameliorative effects of thiamin on learning behavior and memory dysfunction in a rat model of hypothyroidism: implication of oxidative stress and acetylcholinesterase.

Hypothyroidism causes learning and memory impairment. Considering the neuroprotective properties of thiamine (Vitamin B1), this study was conducted to investigate the effects of thiamine on acetylcholinesterase (AChE) activity, oxidative damage, and memory deficits in hypothyroid rats.In this study, 50 rats (21 days old) were randomly divided into 5 groups and treated with propylthiouracil (0.05% in drinking water) and thiamine (50, 100, and 200 mg/kg, oral) for 7 weeks. Following that, Morris water maze (MWM) and passive avoidance (PA) tests were performed. Finally, oxidative stress indicators and AChE activity were measured in brain tissue.Treatment of hypothyroid rats with thiamine, especially at 100 and 200 mg/kg, alleviated the ability to remember the location of the platform as reflected by less time spent and distance to reach the platform, during the MWM test (P < 0.05 to P < 0.001). In the PA test, the latency to enter the dark chamber and light stay time were increased in rats who received thiamine compared to the hypothyroid group (P < 0.05 to P < 0.001). In addition, thiamine increased the levels of total thiol groups and superoxide dismutase while decreasing the levels of malondialdehyde and AChE.Our results suggest that thiamine supplementation could effectively improve memory loss in a rat model of hypothyroidism. The positive effects of thiamin on the learning and memory of hypothyroid rats may be due to amelioration of redox hemostasis and cholinergic disturbance.

The possible mechanism of Datura stramonium on pentobarbital-induced sleep in mice.

BACKGROUND: Insomnia leads to the development of mental problems and missing of accuracy in affected persons. Various investigations have previously revealed which medicinal plants play a role in the improvement of insomnia. In this study, we evaluated the effect of hydro-alcoholic extract of Datura stramonium on insomnia in mice. METHODS: The extracts and fractions at different concentrations were injected intraperitoneally (i.p.) to mice 30 min before the sodium pentobarbital (30 mg/kg, i.p.). Additionally, the blood was collected from cardiac and serum separated to measure brain-derived neurotrophic factor (BDNF). The LC-MS was done to identify the active components. Flumazenil or naloxone were also applied to study the possible mechanism of extract. The PC12 cells were then exposed to different doses of extract and fractions, in order to evaluate cytotoxicity by MTT assay and the measured LD50. RESULTS: The hydro-alcoholic extracts of calyx, seed and petal elevated sleep duration and decreased sleep latency. In addition, water, ethyl acetate and n-butanol fractions of hydro-alcoholic extract of petal increased sleep duration. Of note, Naloxone significantly reversed the hypnotic effect of the extract. The extract increased the level of BDNF in serums. As well, the toxicity assessment revealed that the extracts had not toxic on PC12 cells. The LD50 value was obtained as 4.8 g/kg. CONCLUSION: This research demonstrated that D. stramonium (including seed, petal and calyx) increased the hypnotic effect without neurotoxicity on PC12 cells. Sleep induction may be related to its active ingredients as well as the effect on opioid receptors.

Effect of Sanguisorba minor on scopolamine-induced memory loss in rat: involvement of oxidative stress and acetylcholinesterase.

Sanguisorba minor (S. minor) has neuroprotective and antioxidant activities. However, its potential benefits in ameliorating learning and memory functions have been explored in no studies up to now. So, in the current study, rats were treated with S. minor hydro-ethanolic extract (50, 100, and 200 mg/kg, intraperitoneal (i.p.)) as well as rivastigmine (0.5 mg/kg, i.p.) for 21 consecutive days. Thereafter, their behavioral performance was assessed using Morris water maze (MWM) and passive avoidance (PA) tasks. Notably, 30 min before conducting the tasks, scopolamine was injected. Finally, the biochemical assessments were done using the brain tissue. The extract characterization was performed by liquid chromatography-mass spectrometry, which confirmed the presence of quercetin, myricetin, kaempferol, catechin, ellagic acid, and gallic acid derivatives. In the MWM test, the extract reduced both escape latency and the travelled distance, compared to the scopolamine group. Moreover, in the PA test, the latency to enter the dark chamber significantly increased by the extract, compared to the scopolamine group (p < 0.05-p < 0.001). Notably, the beneficial effects of S. minor on cognitive performance of the scopolamine-treated rats appeared to be similar or even better than rivastigmine in behavior performance. Similar to rivastigmine, it was observed that the extract attenuated both AChE activity and oxidative injury in the brain as evidenced by the increased antioxidant enzymes and total thiol content; however, it decreased malondialdehyde level (p < 0.05-p < 0.001). In conclusion, the results suggested the effectiveness of S. minor in preventing cognitive dysfunction induced by scopolamine. Accordingly, these protective effects might be produced by the regulation of cholinergic activity and oxidative stress. S. minor could be considered as a potential alternative therapy in cognition disorders.

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.

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.

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.

3-Acetyl-11-keto-ß-boswellic acid attenuated oxidative glutamate toxicity in neuron-like cell lines by apoptosis inhibition.

3-Acetyl-11-keto-ß-boswellic acid (AKBA), a pentacyclic triterpenic acid present in gum resin of Boswellia serrata, has been found to possess antioxidant and neuroprotective properties. In this study, we aimed to examine protective properties of AKBA against glutamate-induced neuronal injury. To investigate the effects of AKBA (2.5-10 µM) on glutamate injury in neuron-like cells PC12 and N2a, two treatment regimens (incubation for 2 or 0 hours before glutamate exposure) were used. Then, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method was used to determine viability of the cells. Cellular redox status was evaluated using fluorimetry and comet assays. Annexin V/propidium iodide double staining and Western blot analysis of relative apoptotic proteins were conducted. Based on the results, 24 hours incubation with glutamate (8 mM) increased the cell mortality of PC12 and N2a (P < .001). However, AKBA (2.5-10 µM) enhanced the cell viability in both treatment regimens (P < .001). Also co- and pretreatment with AKBA significantly attenuated lipid peroxidation, reactive oxygen species production, and DNA injury (P < .05 and P < .001). AKBA also restored the activity of cellular superoxide dismutase under glutamate toxicity; this effect was seen to be more significant during the pretreatment regimen (P < .001). Moreover, Western blot analysis indicated that AKBA inhibited glutamate-induced programmed cell death through depressing the elevation of the expression ratio of Bax/Bcl-2 and cleaved-caspase-3 proteins, concentration-dependently. Overall, the present findings suggest the neuroprotective activities of AKBA against glutamate-induced cell injury probably by inhibiting oxidative damage and reducing apoptotic cell death.

Cholinergic agonists inhibit proliferation of human fibroblast-like synoviocytes and monocytic cell lines and reduce VEGF and MMPs expression by these cells.

Background and purpose: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint destruction. Excessive proliferation of fibroblast-like synoviocytes (FLS) and over-expression of angiogenic factors play a crucial role in pannus formation and joint destruction in RA. Clarification of the role of cholinergic agonists in modulation of inflammation and immune system reactions is progressively ongoing. In this study, the anti-angiogenic effect of two cholinergic agonists, nicotine and ARR17779, on human FLS, and monocytic cell lines (U937) was evaluated.Experimental approach: The cells were cultured in DMEM supplemented with 10% FBS and treated with different doses of nicotine and ARR17779 in the presence of TNF-α, LPS, and IFN-γ. After 48 h, cell number was counted in different groups. After RNA extraction, cDNA was synthesized and the expression of VEGF and MMPs has been evaluated by real-time PCR using specific primers and probes. VEGF was assayed in U937 cell line supernatant using ELISA method.Key results: Both nicotine and ARR17779 inhibited FLS and U937 cell proliferation. Cholinergic agonists reduced the expression of MMPs and VEGF. VEGF level in supernatant of U937 cells treated with cholinergic agonists was also reduced.Conclusion and implications: Our results suggest that cholinergic agonists can modulate pathological conditions related to pannus formation in in-vitro conditions. Based on these results, cholinergic agonists can be considered as novel therapeutic options in RA. Further animal studies are needed before introducing these agents into clinical uses.

PROTECTIVE EFFECT OF POMEGRANATE SEED OIL AGAINST MERCURIC CHLORIDE-INDUCED HEPATOTOXICITY IN RAT.

Mercuric chloride (HgCL2) is an environmental and industrial toxicant that affects many tissues. Considering oxidative stress is an important component of mercury induced hepatotoxicity, antioxidants are expected to play a protective role against it. The present study was designed to investigate the probable effects of pomegranate seed oil (PSO) on hepatotoxicity induced by HgCL2, administration in rats. Rats were divided into five groups. Group 1 and 2 received corn oil (1 mL/kg, i.p.) and PSO (0.8 mL/kg, i.p.), respectively. Group 3 was treated with HgCl, (5 mg/kg, i.p.) for 3 days. In groups 4 and 5 PSO (0.4 and 0.8 mL/kg i.p., respectively) was given 1 h before HgCl2 administration. Twenty four hours after last injection of HgCl2, blood samples and specimens of liver were taken. HgCl2 administration led to significant increase in liver malondialdehyde level, significant reduction in total sulfhydryl content and significant changes in serum alanine aminotransferase (ALT) and aspartate aminotransferase activity (AST), compared to control group. The histopathological changes such as necrosis, inflammatory cell infiltration and hepatocellular vacuolization were observed. PSO administration (0.8 mL/kg i.p.) improved the liver function in HgCL2 intoxicated animals as indicated by the significant decline in increased levels of AST, ALT in serum, MDA level and significant elevation in decreased total sulfhydryl content. Histological studies revealed milder hepatic lesions in PSO treated samples. The results indicated that oxidative stress may be an important mechanism of HgCl2 induced hepatic injury and dysfunction and PSO may be a useful agent for the prevention of HgCl2 induced oxidative damage in rat liver.

Protective effect of pomegranate seed oil against cisplatin-induced nephrotoxicity in rat.

PURPOSE: Clinical use of cisplatin is limited by its nephrotoxicity. Cisplatin-induced nephrotoxicity is associated with an increase in oxidative stress, leading ultimately to kidney dysfunction. The aim of this study was to investigate the effect of pomegranate seed oil against nephrotoxicity induced by cisplatin in adult rats. METHODS: Animals were divided into four groups. Group I received corn oil (1 mL/kg). Group II received cisplatin (8 mg/kg). Group III and IV received pomegranate seed oil (PSO) 0.4 mL/kg and 0.8 mL/kg one hour before cisplatin injection for 3 days, respectively. Blood samples were collected by cardiac puncture and used for measuring urea and creatinine concentration. Twenty-hour urine samples were collected to measure protein and glucose concentration. The right kidney fixed in formalin for histological examination and the left kidney was homogenized for measurement of malondialdehyde and total sulfhydryl groups. RESULTS: A significant elevation of serum creatinine, urea, urinary glucose, protein concentrations, and non-significant decrease in total thiol content and increase in MDA level in kidney homogenates were observed in cisplatin-treated rats. Also cisplatin reduced animal's body weight. Mild-to-moderate tubular cell necrosis, hyaline casts, and vascular congestion were observed in group II. PSO pre-treatment significantly decreased urinary protein, glucose, and serum creatinine concentration. PSO also caused a decrease in serum urea, renal MDA, and increase in thiol content, but the level of these parameters were not significant. CONCLUSION: The present results suggest that PSO is an effective agent for the prevention of cisplatin-induced renal dysfunction and oxidative damage in rat.

Protective effect of pomegranate seed oil against cisplatin-induced nephrotoxicity in rat.

PURPOSE: Clinical use of cisplatin is limited by its nephrotoxicity. Cisplatin-induced nephrotoxicity is associated with an increase in oxidative stress, leading ultimately to kidney dysfunction. The aim of this study was to investigate the effect of pomegranate seed oil against nephrotoxicity induced by cisplatin in adult rats. METHODS: Animals were divided into four groups. Group I received corn oil (1 mL/kg). Group II received cisplatin (8 mg/kg). Group III and IV received pomegranate seed oil (PSO) 0.4 mL/kg and 0.8 mL/kg one hour before cisplatin injection for 3 days, respectively. Blood samples were collected by cardiac puncture and used for measuring urea and creatinine concentration. Twenty-hour urine samples were collected to measure protein and glucose concentration. The right kidney fixed in formalin for histological examination and the left kidney was homogenized for measurement of malondialdehyde and total sulfhydryl groups. RESULTS: A significant elevation of serum creatinine, urea, urinary glucose, protein concentrations, and non-significant decrease in total thiol content and increase in MDA level in kidney homogenates were observed in cisplatin-treated rats. Also cisplatin reduced animal's body weight. Mild-to-moderate tubular cell necrosis, hyaline casts, and vascular congestion were observed in group II. PSO pre-treatment significantly decreased urinary protein, glucose, and serum creatinine concentration. PSO also caused a decrease in serum urea, renal MDA, and increase in thiol content, but the level of these parameters were not significant. CONCLUSION: The present results suggest that PSO is an effective agent for the prevention of cisplatin-induced renal dysfunction and oxidative damage in rat.

Protective effect of pomegranate seed oil against mercuric chloride-induced nephrotoxicity in rat.

PURPOSE: Heavy metals such as mercury can induce the generation of free radicals and oxidative stress which are associated with tissue injury. The present study was designed to evaluate the protective effect of pomegranate seed oil against HgCl2-induced nephrotoxicity. METHODS: Twenty-four W/A adult rats were randomly divided into four groups. Group I received corn oil (1 mL/kg). Group II received HgCl2 (5 mg/kg) for 3 days. Group III and IV received PSO 0.4 mL/kg and 0.8 mL/kg, respectively one hour before HgCl2 administration for 3 days. Blood samples were taken by cardiac puncture and used for the measurement of urea and creatinine concentration. Twenty-hour-hour urine samples were collected to measure protein and glucose. The right kidney was fixed in formalin for histological examination and the left kidney was homogenized for measuring malondialdehyde (MDA) and total sulfhydryl groups. RESULTS: Significant elevation of serum creatinine and urea levels as well as urine glucose and protein concentrations, a significant decrease in total thiol content and a significant increase in MDA levels in kidney homogenate samples were observed after administration of HgCl2 as compared with control group. PSO pretreatment resulted in a significant decrease in serum creatinine and urea levels as well as urine glucose and protein concentrations when compared with HgCl2 treated (group II). PSO also significantly reversed the HgCl2-induced depletion in thiol content and elevation in MDA content. Histological studies revealed milder kidney lesions in PSO treated groups (groups III and IV) compared to HgCl2 treated group. CONCLUSION: Our results suggest that PSO has a protective effect against HgCl2-induced nephrotoxicity in rats.

Ameliorating effects of selenium nanoparticle coated by gallic acid on histological and biochemical parameters of testis in azoospermic rat model.

This study was designed to examine the effects of selenium nanoparticles (SeNPs) coated with gallic acid (GA) on testis in azoospermic rats. Thirty-six adult Wistar rats were assigned to six groups: control (1 ml intraperitoneal (i.p.) phosphate-buffered saline (PBS) for 7 consecutive days), SHAM (single i.p. injection of 1 ml of 8 % dimethyl sulfoxide (DMSO)), BUS (single i.p. injection of busulfan (BUS) 30 mg/kg body weight), GA (single i.p. injection of BUS 30 mg/kg on day 1, 100 mg/kg body weight GA from days 2-7), SeNPs (single i.p. injection of BUS 30 mg/kg on day 1, 0.5 mg/kg body weight SeNPs from days 2-7), and SeNPs-GA (single i.p. injection of BUS 30 mg/kg on day 1, 0.5 mg/kg body weight SeNPs-GA from days 2-7). Subsequently, serum levels of testosterone and insulin-like growth factor-1 (IGF-1), antioxidant markers, sperm parameters, and histological parameters were evaluated. The results showed that BUS injection induced azoospermia in rats by causing oxidative stress and testicular tissue damage. In contrast, co-administration of SeNPs and GA showed significant improvements in testosterone and IGF-1 levels, antioxidant status, testicular tissue characteristics, and sperm parameters. Overall, the findings suggest that GA-coated SeNPs offer therapeutic potential in BUS-induced azoospermic models.

Oligoprotective Activity of Levetiracetam Against Glutamate Toxicity: An in vitro Study.

INTRODUCTION: The role of glutamate in the development of some brain pathological conditions, such as multiple sclerosis, has been well described. Levetiracetam (LEV), a new broad-spectrum antiseizure medicine, is widely used to control certain types of seizures. METHOD: Apart from its anti-seizure activity, LEV exerts neuroprotection via anti-inflammatory, antioxidant, and antiapoptotic effects. The current study was designed to evaluate the protective potential of LEV against glutamate-induced injury in OLN-93 oligodendrocytes. METHOD: At first, the potential negative impact of LEV on OLN-93 viability was evaluated. After that, the cells were concurrently treated with LEV (0-100 µM) and glutamate (8 mM) for 24 h. The viability, redox status, and the rate of apoptosis of OLN-93 cells were then assessed using 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyl-2H-tetrazolium bromide (MTT), 2',7' dichlorodihydrofluorescein diacetate (H2DCFDA), 2-thiobarbituric acid reactive substances (TBARS) and annexin V/propidium iodide (PI) assays, respectively. Moreover, caspase-3 expression, as a marker of cell apoptosis, was evaluated by western blotting. RESULTS: LEV at 1-800 µM did not have any negative effect on cell survival. Treatment with LEV (50 and 100 µM) substantially enhanced the cell viability following glutamate insult. The cytoprotective activity of LEV (50 and 100 µM) against glutamate toxicity was accompanied by reduced Reactive Oxygen Species (ROS) accumulation and Malondialdehyde (MDA) level. Moreover, 100 µM of LEV inhibited apoptosis and decreased the expression level of cleaved caspase-3 following glutamate exposure. CONCLUSION: Taken together, the results suggested that LEV has protective effects against glutamate-mediated cytotoxicity in OLN-93 cells. The oligoprotective action of LEV was shown to be exerted via inhibition of oxidative stress and cellular apoptosis.

Minocycline mitigated enduring neurological consequences in the mice model of sepsis.

AIM: Sepsis-associated encephalopathy is a frequently observed consequence of sepsis, often resulting in chronic brain inflammation and injury, ultimately leading to a range of behavioral abnormalities. This study explores the potential preventive effects of minocycline on the long-lasting outcome of sepsis in a mice model of sepsis. METHODS: Adult male C57 mice were subjected to experimental sepsis through a single intraperitoneal injection of 5 mg/kg lipopolysaccharide (LPS). Minocycline administration via oral gavage (12.5, 25, and 50 mg/kg) commenced three days before sepsis induction and continued on the day of induction. Mice underwent behavioral assessments one month post-sepsis, with subsequent brain tissue analysis to investigate oxidative stress markers and cholinergic function. KEY FINDINGS: One month following sepsis induction, mice exhibited significant anxiety- and depressive-like behaviors as determined by assessments in the elevated plus maze (EPM), open field, and tail suspension test (TST). Additionally, they displayed impaired recognition memory in the novel object recognition (NOR) test. Brain tissue analysis revealed a notable increase in oxidative stress markers and acetylcholinesterase (AChE) activity in septic mice. Notably, minocycline treatment effectively mitigated the long-term behavioral abnormalities resulting from sepsis, attenuated oxidative stress markers, and reduced AChE activity. SIGNIFICANCE: These findings underscore the potential of minocycline as a therapeutic intervention during sepsis induction to prevent the enduring behavioral and neurological consequences of experimental sepsis.

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.

Minocycline mitigates sepsis-induced neuroinflammation and promotes recovery in male mice: Insights into neuroprotection and inflammatory modulation.

Sepsis is associated with brain injury and acute brain inflammation, which can potentially transition into chronic inflammation, triggering a cascade of inflammatory responses that may lead to neurological disorders. Minocycline, recognized for its potent anti-inflammatory properties, was investigated in this study for its protective effects against sepsis-induced brain injury. Adult male C57 mice pretreated with minocycline (12.5, 25, and 50 mg/kg) 3 days before sepsis induction. An intraperitoneal injection of 5 mg/kg LPS was used to induce sepsis. Spontaneous locomotor activity (SLA) and weight changes were assessed over several days post-sepsis to monitor the recovery of the mice. The expression of inflammatory mediators and oxidative stress markers was assessed 24 h post sepsis. Septic mice exhibited significant weight loss and impaired SLA. Initially, minocycline did not attenuate the severity of weight loss (1 day) or SLA (4 h post-sepsis), but it significantly accelerated the recovery of the mice in later days. Minocycline dose-dependently mitigated sepsis-induced brain inflammation and oxidative stress. Our findings demonstrate that pretreatment with minocycline has the potential to prevent brain tissue damage and accelerate recovery from sepsis in mice, suggesting that minocycline may serve as a promising therapeutic intervention to protect against sepsis-induced neurological complications.

The Effects of Curcumin Plus Piperine Co-administration on Inflammation and Oxidative Stress: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: The beneficial effects of curcumin against various chronic disorders have been shown in the last few decades. However, due to its low bioavailability, therapeutic effects are less than expected. Piperine has been used in scientific evaluations as an effective compound to increase the bioavailability of curcumin. The present review investigated the impact of curcumin plus piperine intake on oxidative stress and inflammatory markers of Randomized Clinical Trials (RCTs). METHODS: Using relevant keywords, we searched Cochrane Library, Scopus, PubMed, and Web of Science between January 1st, 1970, and September 30th, 2022. A comprehensive search for RCTs was performed. Continuous data were pooled by Standard Mean Difference (SMD) and 95% confidence interval. All related statistical analyses were performed using Comprehensive Meta-Analysis (CMA) software. RESULTS: A total of 13 articles were incorporated into the final meta-analysis. According to the current meta-analysis, curcumin plus piperine administration showed a significantly increased SOD activity and GSH levels while significantly decreased MDA concentrations. In addition, our study revealed that curcumin plus piperine significantly decreased TNF-α and IL-6 concentrations. CONCLUSION: These results indicated that curcumin plus piperine administration could effectively reduce oxidative stress and inflammation.