Assessing the Influence of Intermittent Alcohol Access on Acrylamide-Induced Neuronal Toxicity in an Experimental Rat Model.

Tobacco and alcohol have been identified as health risk behaviors associated with significant unfavorable health consequences, ranking within the list of the top ten causes of mortality and disability-adjusted life years (DALY). The combustion of tobacco leads to the formation of acrylamide (ACR), which is well known for its neurotoxic effects. Similarly, alcohol consumption has also been widely recognized for its neurotoxic effects. Both substances can affect neurons and neuroglia cells through various pathways. This study sought to examine the impacts of co-administration of ACR and intermittent-access ethanol (IAE) consumption over a period of one month. The experimental group received 20 mg/kg of ACR, administered orally, along with IAE of 20% ethanol sessions lasting 24 h, three times per week. The cognitive outcomes were assessed utilizing the elevated plus maze (EPM), which was employed as a means of assessing the capability to learn and remember, the novel object recognition (NOR) test, which was employed to assess recognition memory, and the Y-maze, which was used to explore a new environment and navigate. Additionally, ELISA assays were performed to examine underlying mechanisms, including markers associated with inflammation (NF-κB, PGE2, and TNF-α), apoptosis (Bcl2, Bax, and Caspase-3), and oxidative stress (MDA, catalase, and GSH). These markers were assessed in the brain homogenate as part of the investigation. Furthermore, a histopathological study was conducted. The findings indicated that NF-κB levels increased significantly in the combination of ACR and IAE groups (ACR + IAE) compared to either the ACR-alone or IAE-alone groups. However, parallel changes were observed in TNF-α, PGE2, Bax, Bcl-2, Caspase-3, GSH, and CAT levels when comparing the ACR + IAE group to the ACR-alone group. Comparable alterations were noted between the ACR + IAE treatment and IAE-alone groups in TNF-α, Bcl-2, MDA, GSH, and CAT levels. Moreover, the histopathological analysis revealed significant changes between the ACR + IAE and the ACR- or IAE-alone groups. Regarding memory parameters assessed using tests including EPM, NOR, and Y-maze, considerable changes were observed across all treatment groups as opposed to the control. Surprisingly, there were no notable differences in the NOR and Y-maze tasks between the alone and combination treatment. Further study is necessary to explore the long-term alteration of co-administering ACR and IAE on behavior, memory, and neurotoxicity-related mechanisms, in order to elucidate their combined effects more clearly.

Beneficial effect of lupeol and metformin in mouse model of intracerebroventricular streptozotocin induced dementia.

This study examines the effectiveness of lupeol and metformin in a mouse model of dementia generated by intracerebroventricular streptozotocin (i.c.v., STZ). Dementia was induced in Swiss mice with the i.c.v. administration of STZ at a dosage of 3 mg/kg on the first and third day. The assessment of dementia involved an examination of the Morris Water Maze (MWM) performance, as well as a number of biochemical and histological studies. STZ treatment resulted in significant decrease in MWM performance; various biochemical alterations (increase in brain acetyl cholinesterase (AChE) activity, thiobarbituric acid reactive species (TBARS), nitrite/nitrate, and reduction in nuclear factor erythroid 2 related factor-2 (Nrf-2), reduced glutathione (GSH) levels) and neuroinflammation [increased myeloperoxidase (MPO) activity & neutrophil infiltration]. The administration of Lupeol (50 mg/kg & 100 mg/kg; p.o.) and Metformin (150 mg/kg & 300 mg/kg; p.o.) demonstrated a considerable reduction in the behavioral, biochemical, and histological alterations produced by STZ. Low dose combination of lupeol (50 mg/kg; p.o.) and Metformin (150 mg/kg; p.o.) produced more pronounced effect than that of high doses of either agent alone. It is concluded that Lupeol and Metformin has shown efficacy in dementia with possible synergism between the two and can be explored as potential therapeutic agents for managing dementia of Alzheimer's disease (AD) type.

An evaluation of knee osteoarthritis pain in the general community-Asir region, Saudi Arabia.

BACKGROUND: Knee osteoarthritis (KOA) is one of the most common conditions resulting in disability, particularly in the elderly population. Osteoarthritis (OA) is the most common articular disease and the leading cause of chronic disability in the developed world. OBJECTIVE: This study was carried out to evaluate knee pain in the Asir region of Saudi Arabia. An analytical cross-sectional survey design was adopted in the Asir region from April 2023 to August 2023 to assess the knee pain of the adult population using an anonymous online questionnaire. RESULTS: Of 1234, 332 were men (26.90) and 902 were women (73.09). WOMAC index score category 55.34% (n = 683) of the subjects had a low risk (score <60), 28.68% (n = 354) had a moderate risk (score 60-80), and 15.96% (n = 197) had a high risk (score ≥81) for KOA. According to clinical criteria, 79.33% (n = 979) of the study subjects had OA. Age group, gender 2.17 (1. 67-2.82) [OR 2.17; 95% CI 1.67-2.82), family history of OA [OR 0.47; 95% CI 0.37-0.62], diabetes [OR 2.78; 95% CI 2.17-3.56], hypertension [OR 0.35; 95% CI 0.26-0.45] were significantly associated with the percentage of the WOMAC index score using the Chi-square test analysis (P<0.05). Therefore, the WOMAC index showed higher diagnostic precision with a statistically significant association [OR 9.31 CI 6.90-12.81] with a P< 0.0001. CONCLUSION: KOA is more common in older, obese people who have reached the age of 50 in the Asir region, and it is more prevalent in women. Alarms the need for appropriate awareness programs for better disease prevention and health outcomes for the benefit of the community through general public health programs.

Proximate composition, lipid and elemental profiling of eight varieties of avocado (Persea americana).

Eight Moroccan avocado varieties were analyzed for their nutritional composition and physicochemical properties. The nutritional contents of the sample were determined through the evaluation of the moisture, oil, ash, protein, and carbohydrate contents, and energy value calculation. Additionally, macroelements (Ca, Mg, and Na) and microelements (Fe, Zn, Cu, and Mn) were determined in the mineral profile. Oils were examined also for their fatty acid, phytosterol, and tocopherol profiles. As a result of the study, the avocado presents significant differences between the eight studied varieties (p < 0.05), with regard to moisture content (57.88 g/100 g to 84.71 g/100 g), oil content (8.41 g/100 g to 57.88 g/100 g), ash (0.57 g/100 g to 1.37 g/100 g), protein content (5.7 g/100 g to 8.61 g/100 g), carbohydrate content (5.63 g/100 g to 14.61 g/100 g), and energy value (99.9 kcal/100 g to 316.8 kcal/100 g). Sodium (5783.01 mg/kg to 12,056.19 mg/kg) was the predominant macro-element in all varieties, followed by calcium (295.95 mg/kg to 531.67 mg/kg), and magnesium (246.29 mg/kg to 339.84 mg/kg). Copper (85.92 mg/kg to 112. 31 mg/kg) was the main microelement in all varieties, followed by iron (8.5 mg/kg to 20.32 mg/kg), and manganese (7.3 mg/kg to 18.45 mg/kg), while zinc (1.72 mg/kg to 5.66 mg/kg) was detected in small amounts. In addition, significant difference was observed in lipid profiles, according to the eight studied varieties (p < 0.05). Avocado oils were mainly composed of monounsaturated fatty acids (76.89 g/100 g to 84.7 g/100 g), with oleic acid (50.38 g/100 g to 71.49 g/100 g) standing out as particularly characteristic, while ß-sitosterol (l2365.58 mg/kg to 4559.27 mg/kg), and α-tocopherol (30.08 mg/kg to 182.94 mg/kg) were among its major phytosterols and tocopherols. All avocado varieties represented in this study can be consumed as a fruit as an excellent source of energy, minerals, fatty acids, phytosterols, and tocopherols. The regular consumption of this fruit provides the body with several essential nutrients.

Impact of levetiracetam on cognitive impairment, neuroinflammation, oxidative stress, and neuronal apoptosis caused by lipopolysaccharides in rats.

Introduction: Neuroinflammation is associated with the elevation of toxic proinflammatory mediators that promote neurodegeneration and subsequently affect cognition. Causes of inflammation in the neuronal cells are believed to initiate various neurodegenerative disorders, mainly Alzheimer's disease. Levetiracetam is a second-generation antiepileptic drug. There is evidence supporting the memory-enhancing effect of levetiracetam from numerous experimental and clinical studies. Therefore, this research focused on finding its protective effects against lipopolysaccharides prompted cognitive impairment and exploring possible mechanisms underlining their neuroprotection. Methodology: Two doses (100 or 200 mg/kg) of levetiracetam were administrated orally for 30 days. Additionally, four doses (250 µg/kg) of lipopolysaccharide were injected peripherally to induce neurotoxicity. Behavioral tests were carried out using various maze models. At the end of the tests, brain tissues were collected for biochemical evaluations. Cholinergic, neuroinflammatory, apoptosis, and oxidative-related parameters were analyzed in the brain homogenate to explore the possible mechanisms of action of levetiracetam. Results: In lipopolysaccharide-induced rats, levetiracetam indicated a reduction (p < 0.01) in transfer latency using the elevated plus-maze. An improvement (p < 0.01) in novel and familiar objects exploration time using novel object recognition test. A rise (p < 0.05) in novel arm entries and extended time spent in the novel arm using the Y-maze test. In extension, the levels of acetylcholine (p < 0.001), anti-inflammatory factors (transforming growth factor-ß1; p < 0.01 and interleukin-10; p < 0.05), and an antioxidant (catalase; p < 0.01) were elevated in lipopolysaccharide-induced rats after the administration of levetiracetam. In contrast, inflammatory factors (cyclooxygenase-2; p < 0.05, nuclear factor kappa B; p < 0.05, tumor necrosis factor-α; p < 0.01, and interleukin-6 (p < 0.01), apoptosis inducers (BCL2-associated X protein; p < 0.05 and Caspase-3 (p < 0.001), and oxidative stress (malondialdehyde; p < 0.05) were considerably reduced with levetiracetam in lipopolysaccharide-induced rats. Conclusion: The collective results suggested that levetiracetam may be able to treat neuroinflammatory-related memory loss by enhancing cholinergic activity while reducing neuroinflammation, cellular apoptosis, and oxidative stress.

Quetiapine Moderates Doxorubicin-Induced Cognitive Deficits: Influence of Oxidative Stress, Neuroinflammation, and Cellular Apoptosis.

Chemotherapy is considered a major choice in cancer treatment. Unfortunately, several cognitive deficiencies and psychiatric complications have been reported in patients with cancer during treatment and for the rest of their lives. Doxorubicin (DOX) plays an important role in chemotherapy regimens but affects both the central and peripheral nervous systems. Antipsychotic drugs alleviate the behavioral symptoms of aging-related dementia, and the atypical class, quetiapine (QUET), has been shown to have beneficial effects on various cognitive impairments. The present investigation aimed to determine the possible mechanism underlying the effect of thirty-day administrations of QUET (10 or 20 mg/kg, p.o.) on DOX-induced cognitive deficits (DICDs). DICDs were achieved through four doses of DOX (2 mg/kg, i.p.) at an interval of seven days during drug treatment. Elevated plus maze (EPM), novel object recognition (NOR), and Y-maze tasks were performed to confirm the DICDs and find the impact of QUET on them. The ELISA tests were executed with oxidative [malondialdehyde (MDA), catalase, and reduced glutathione (GSH)], inflammatory [cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), and tumor necrosis factor-alpha (TNF-α)], and apoptosis [B-cell lymphoma 2 (Bcl2), Bcl2 associated X protein (Bax), and Caspase-3] markers were assessed in the brain homogenate to explore the related mechanisms. DICD lengthened the transfer latency time in EPM, shortened the exploration time of the novel object, reduced the discrimination ability of the objects in NOR, and lowered the number of arm entries and time spent in the novel arm. QUET alleviated DICD-related symptoms. In addition, QUET reduced neuronal oxidative stress by reducing MDA and elevating GSH levels in the rat brain. Moreover, it reduced neuronal inflammation by controlling the levels of COX-2, NF-κB, and TNF-α. By improving the Bcl-2 level and reducing both Bax and Caspase-3 levels, it protected against neuronal apoptosis. Collectively, our results supported that QUET may protect against DICD, which could be explained by the inhibition of neuronal inflammation and the attenuation of cellular apoptosis protecting against oxidative stress.

Neuroprotective Effect of Methanolic Ajwa Seed Extract on Lipopolysaccharide-Induced Memory Dysfunction and Neuroinflammation: In Vivo, Molecular Docking and Dynamics Studies.

Islamic literature has indicated that daily consumption of Ajwa dates heals a variety of chronic diseases and disorders. The current research investigates the neuroprotective effect of methanolic Ajwa seed extract (MASE) on lipopolysaccharide (LPS)-induced cognitive deficits using multiple approaches. For animal studies, MASE (200 and 400 mg/kg, p.o.) was administrated for thirty consecutive days, and four doses of LPS (250 µg/kg, i.p.) were injected to induce neurotoxicity. Memory functions were evaluated using elevated plus-maze and novel object recognition tests. Acetylcholine (ACh) and neuroinflammatory markers (cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-ß1) were estimated in brain tissues. Studies of molecular docking and dynamics were conducted to provide insight into the molecular-level mechanisms. MASE administration resulted in a significant reversal of LPS-induced memory impairment in both maze models. Both doses of MASE elevated the ACh levels in an LPS-treated rat brain. In addition, the extract lowered COX-2 and proinflammatory cytokines (TNF-α and IL-6) while increasing anti-inflammatory cytokines (IL-10 and TGF-ß1) in LPS-treated brain tissues. Molecular modeling results revealed that the compound's ellagic acid, epicatechin, catechin, kaempferol, quercetin, and apigenin have the potential to act as a dual inhibitor of acetylcholinesterase (AChE) and COX-2 and can be responsible for the improvement of both cholinergic and inflammatory conditions, while the cinnamic acid, hesperidin, hesperetin, narengin, and rutin compounds are responsible only for the improvement of cholinergic transmission. The above compounds acted by interacting with the key residues Trp84, Asp72, Gly118, Ser200, Tyr334, and His440, which are responsible for the hydrolysis of ACh in AChE, while the COX-2 is inhibited by interacting with the residues (Val349, Leu352, Tyr355, Tyr385, Ala527, Ser530, and Leu531) of the hydrophobic channel. By promoting cholinergic activity and protecting neuroinflammation in the rat brain, MASE provides neuroprotection against LPS-induced cognitive deficits. Our preliminary findings will help with further drug discovery processes related to neuroinflammation-related neurodegeneration.

Lactobacillus Spp.-Enhanced Memory is Strain-Dependent and Associated, in Part, with Amyloidogenic and anti-Oxidant/Oxidative Stress Interplay in Amyloid Beta Precursor Protein Transgenic Mice.

This study explored mechanisms underpinning enhanced memory in amyloid precursor protein (APP) transgenic mice (male; 10-12 months; n = 6/group) supplemented with Lactobacillus plantarum LAB12 (LAB12)/Lactobacillus casei Shirota (LcS). Morris Water Maze test was performed before brains were harvested for gene expression and biochemical studies. LAB-supplemented mice exhibited reduced escape latency and distance but significant increased time spent in platform zone. This was associated with downregulated beta-site APP cleaving enzyme-1 (BACE1) mRNA and significant reduced nitric oxide in brains. LAB12 also significantly increased glutathione. The LAB-enhanced memory is strain-dependent and could be mediated, in part, through amyloidogenic pathway and anti-oxidant/oxidative stress interplay.

A study on the prevalence of smoking habits among the student community in Aseer Region, Saudi Arabia.

Objectives: A cross-sectional study was aimed to assess the prevalence of smoking habits among students at King Khalid University (KKU), Abha, KSA. Methods: This was a cross-sectional study using a Modified Fagerstrom Tolerance Questionnaire (mFTQ), online survey was carried out among the students of KKU. This tool uses a five-point Likert scale for all seven questions, except one question on smoking during the first 2 h of the day. Results: The prevalence of smoking among male students was 67% (n = 243) and females 33% (n = 122). Of the current cigarette smokers, 19% had a nicotine dependence score of ≥6 (high), 48% scored 4-6 (moderate) and 33% scored <4 (minimal). Association between mFTQ and the number of cigarettes per day (p < 0.001), first smoke of your cigarettes (p < 0.018), smoking in the morning (p < 0.007), and difficulty refraining from smoking in public areas (p < 0.000). The results of the current study recommend that cigarette smoking habits are a significant risk behavior among young students. The strength of this study signifies that most participants (62%) intend to quit if appropriately supported. Conclusion: According to the findings of the current investigation, smoking was quite common among males. It raises the alarm about the critical need for adequate education to support health education initiatives, discourage teen smoking, and enhance health outcomes for the community.

Aripiprazole Attenuates Cognitive Impairments Induced by Lipopolysaccharide in Rats through the Regulation of Neuronal Inflammation, Oxidative Stress, and Apoptosis.

Background and Objectives: Aripiprazole (APZ), an atypical antipsychotic, is mainly prescribed for conditions such as schizophrenia and bipolar disorder, while ongoing research indicates promising neuroprotective qualities. APZ's mechanism of action, involving the regulation of neurotransmitter levels, appears to contribute to its potential to shield neural tissues from specific forms of harm and degeneration. Materials and Methods: To investigate its neuroprotective mechanisms, groups of rats were orally administered APZ at 1 or 2 mg/kg once daily for a 30-day period. In addition, neuronal toxicity was induced through intraperitoneal injection of four doses of lipopolysaccharide (LPS) at a concentration of 1 mg/kg. To evaluate cognitive function, particularly, short-term recognition memory, the procedure implemented the novel object recognition (NOR) task. Subsequently, brain tissues were gathered to examine markers linked with neuroinflammation, oxidative stress, and apoptosis. Results: The administration of LPS led to a decline in memory performance during the NOR tasks. Simultaneously, this LPS treatment raised inflammatory markers like cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, and nuclear factor kappa B (NF-κB), increased oxidative markers such as malondialdehyde (MDA), and triggered apoptosis markers like Caspase-3 and Bcl2 associated X protein (Bax) within the brain. Furthermore, it decreased levels of antioxidants like reduced glutathione (GSH) and catalase, as well as the anti-apoptotic marker B-cell lymphoma (Bcl)-2 in brain tissue. The use of APZ resulted in enhanced recognition memory performance, as indicated by improved exploration and discrimination abilities of the objects in the NOR task. Moreover, APZ lowered the markers associated with neuronal vulnerability, such as COX-2, NF-κB, MDA, Caspase-3, and Bax. Additionally, it increased the levels of protective markers, including GSH, catalase, and Bcl-2 in LPS-challenged brains. Conclusions: In summary, the findings suggest that APZ exhibits protective properties against neuronal inflammation, oxidative stress, and apoptosis markers in the context of inflammatory-related neurodegeneration. Additional in-depth investigations are needed to further explore potential applications.

Piracetam as a Therapeutic Agent for Doxorubicin-Induced Cognitive Deficits by Enhancing Cholinergic Functions and Reducing Neuronal Inflammation, Apoptosis, and Oxidative Stress in Rats.

Cancer chemotherapy is known to cause cognitive defects in patients. Our study investigated the effect of piracetam (PIRA; 200 or 400 mg/kg) against doxorubicin (DOX)-induced cognitive deficits in a rat model. The cognitive parameters were analyzed using elevated plus-maze, novel object recognition, and Y-maze tests. Acetylcholinesterase (AChE), neuroinflammatory mediators (cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nuclear factor-κB (NF-κB), tumor necrosis factor-alpha (TNF-α)), apoptotic proteins (B-cell lymphoma-2 (Bcl-2), Bcl2 associated X protein (Bax), cysteine aspartate specific protease-3 (caspase-3)), oxidative parameters (malondialdehyde (MDA), catalase (CAT), and glutathione (GSH)) were also determined in the brain. PIRA administration offered significant protection against DOX-induced cognitive deficits in all maze tests and restored cholinergic functions via a significant reduction in AChE levels. Additionally, PIRA suppressed DOX-induced neuroinflammatory mediators (COX-2, PGE2, NF-κB, and TNF-α), pro-apoptotic proteins (Bax and caspase-3), and oxidative stress (MDA). Besides, it facilitated antioxidant (CAT and GSH) levels. Hence, our study highlighted that the neuroprotective activity of PIRA against DOX-induced cognitive deficits can be linked to reductions of AChE levels, neuro-inflammatory mediators, pro-apoptotic proteins, and oxidative stress.

Levetiracetam Ameliorates Doxorubicin-Induced Chemobrain by Enhancing Cholinergic Transmission and Reducing Neuroinflammation Using an Experimental Rat Model and Molecular Docking Study.

Cancer chemotherapy-induced cognitive impairment (chemobrain) is a major complication that affects the prognosis of therapy. Our study evaluates the nootropic-like activity of levetiracetam (LEVE) against doxorubicin (DOX)-induced memory defects using in vivo and molecular modelling. Rats were treated with LEVE (100 and 200 mg/kg, 30 days) and chemobrain was induced by four doses of DOX (2 mg/kg, i.p.). Spatial memory parameters were evaluated using an elevated plus maze (EPM) and Y-maze. Additionally, acetylcholinesterase (AChE) and the neuroinflammatory biomarkers cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nuclear factor-κB (NF-κB), and tumor necrosis factor-alpha (TNF-α) were analyzed using brain homogenate. PharmMapper was used for inverse docking and AutoDock Vina was used for molecular docking. LEVE treatment significantly diminished the DOX-induced memory impairment parameters in both the EPM and Y-maze. In addition, the drug treatment significantly reduced AChE, COX-2, PGE2, NF-κB, and TNF-α levels compared to DOX-treated animals. The inverse docking procedures resulted in the identification of AChE as the potential target. Further molecular modelling studies displayed interactions with residues Gly118, Gly119, and Ser200, critical for the hydrolysis of ACh. Analysis of the results suggested that administration of LEVE improved memory-related parameters in DOX-induced animals. The 'nootropic-like' activity could be related to diminished AChE and neuroinflammatory mediator levels.

Sukkari dates seed improves type-2 diabetes mellitus-induced memory impairment by reducing blood glucose levels and enhancing brain cholinergic transmission: In vivo and molecular modeling studies.

Cognitive decline is one of the serious complications associated with diabetes mellitus (T2DM) of type-2. In this reported work, the effect of aqueous sukkari dates seed extract (ASSE) was evaluated in T2DM-induced rats. T2DM was induced using intraperitoneal injection of nicotinamide and streptozocin (STZ) administration. The diabetic rats were then treated orally with 200 mg/kg and 400 mg/kg of dates seed extract for 30 days and results were compared with metformin-treated groups. The memory functions were assessed using three maze models. Glucose and insulin levels in the blood and acetylcholine, acetylcholinesterase brain homogenates were estimated. The results showed a significant reduction in transfer latency (TL) (p < 0.001) during the elevated plus maze (EPM) test. The novel object recognition (NOR) test revealed a longer exploration time (p > 0.05) with novel objects and a higher discrimination index (p > 0.05). The Y-maze test also showed a significant increase in the number of entries to the novel arm (p > 0.05) and the total number of entries in the trial (p > 0.01) as well as in test (p > 0.05) sessions. Reduction in blood glucose (p > 0.05) and improvement in blood insulin (p > 0.05) levels were also noted. Improvement in ACh levels (p > 0.001) with 400 mg/kg of ASSE and reduction in AChE (p > 0.001) with both doses of ASSE were also observed in the brain homogenates. The results of ASSE were found comparable with the metformin-treated rats. The estimation of phytochemical constituents displayed a significant presence of phenolic content. Further, molecular modeling studies showed ellagic acid, catechin, and epicatechin as the potential molecule interacting with GSK-3ß, α-amylase, and AChE and may be responsible for observed bioactivity. In conclusion, ASSE has the ability to alleviate T2DM-related cognitive impairments.

Aqueous Ajwa dates seeds extract improves memory impairment in type-2 diabetes mellitus rats by reducing blood glucose levels and enhancing brain cholinergic transmission.

Diabetes is a metabolic disorder prevalent across the globe and is known to cause brain dysfunction, especially memory and cognitive decline. The current study investigates the effect of aqueous Ajwa seeds extract (AASE) on type-2 diabetes mellitus (T2DM)-induced memory deficits using a rat model. T2DM was induced by an administration of nicotinamide (120 mg/kg, i.p.) and streptozotocin (STZ) (60 mg/kg, i.p.). AASE (200 and 400 mg/kg, p.o.) were treated to T2DM rats for 30 days and the results were compared with the metformin (200 mg/kg). Elevated plus maze (EPM), Y-maze, and novel object recognition (NOR) tests were performed to assess the memory functions. The blood glucose and plasma insulin levels were estimated to assess the anti-diabetic effects of AASE. Acetylcholine (ACh) and acetylcholinesterase (AChE) levels were estimated from brain homogenates to assess cholinergic transmission. Treatment with AASE resulted in the reversal of behavioral deficits. EPM showed, a significant reduction in transfer latency (TL) among T2DM rats. High exploration time with a novel object and improvement in discrimination index were observed among treated groups during the NOR test. The Y-Maze test improved the entries and also time spent in the novel arm. Moreover, treatment of AASE reversed hyperglycemic and enhanced plasma insulin levels (200 mg/kg: 3.81 ± 0.08 ng/ml and 400 mg/kg: 4.09 ± 0.10 ng/ml) among T2DM rats (2.81 ± 0.15 ng/ml). Improved ACh levels (200 mg/kg: 186.6 ± 9.51 pg/mg protein and 400 mg/kg: 165.5 ± 9.25 pg/mg protein) and reduced AChE levels (200 mg/kg: 0.29 ± 0.02 ng/mg protein and 400 mg/kg: 0.32 ± 0.03 ng/mg protein) were also noted in the brain of AASE treated groups as referred to diabetic group (ACh: 107.1 ± 7.16 pg/mg protein and AChE: 0.51 ± 0.03 ng/mg protein). The above results were found to be comparable with the metformin-treated groups. From the results, it can be concluded that AASE has the potential to improve T2DM associated cognitive deficits.

Biotechnological Innovations from Ocean: Transpiring Role of Marine Drugs in Management of Chronic Disorders.

Marine drugs are abundant in number, comprise of a diverse range of structures with corresponding mechanisms of action, and hold promise for the discovery of new and better treatment approaches for the management of several chronic diseases. There are huge reserves of natural marine biological compounds, as 70 percent of the Earth is covered with oceans, indicating a diversity of chemical entities on the planet. The marine ecosystems are a rich source of bioactive products and have been explored for lead drug molecules that have proven to be novel therapeutic targets. Over the last 70 years, many structurally diverse drug products and their secondary metabolites have been isolated from marine sources. The drugs obtained from marine sources have displayed an exceptional potential in the management of a wide array of diseases, ranging from acute to chronic conditions. A beneficial role of marine drugs in human health has been recently proposed. The current review highlights various marine drugs and their compounds and role in the management of chronic diseases such as cancer, diabetes, neurodegenerative diseases, and cardiovascular disorders, which has led to the development of new drug treatment approaches.

Natural and Synthetic Agents Targeting Reactive Carbonyl Species against Metabolic Syndrome.

Reactive carbonyl species (RCS) may originate from the oxidation of unsaturated fatty acids and sugar in conditions of pathology. They are known to have high reactivity towards DNA as well as nucleophilic sites of proteins, resulting in cellular dysfunction. It has been considered that various pathological conditions are associated with an increased level of RCS and their reaction products. Thus, regulating the levels of RCS may be associated with the mitigation of various metabolic and neurodegenerative disorders. In order to perform a comprehensive review, various literature databases, including MEDLINE, EMBASE, along with Google Scholar, were utilized to obtain relevant articles. The voluminous review concluded that various synthetic and natural agents are available or in pipeline research that hold tremendous potential to be used as a drug of choice in the therapeutic management of metabolic syndrome, including obesity, dyslipidemia, diabetes, and diabetes-associated complications of atherosclerosis, neuropathy, and nephropathy. From the available data, it may be emphasized that various synthetic agents, such as carnosine and simvastatin, and natural agents, such as polyphenols and terpenoids, can become a drug of choice in the therapeutic management for combating metabolic syndromes that involve RCS in their pathophysiology. Since the RCS are known to regulate the biological processes, future research warrants detailed investigations to decipher the precise mechanism.

Exploring the focal role of LRRK2 kinase in Parkinson's disease.

The major breakthroughs in our knowledge of how biology plays a role in Parkinson's disease (PD) have opened up fresh avenues designed to know the pathogenesis of disease and identify possible therapeutic targets. Mitochondrial abnormal functioning is a key cellular feature in the pathogenesis of PD. An enzyme, leucine-rich repeat kinase 2 (LRRK2), involved in both the idiopathic and familial PD risk, is a therapeutic target. LRRK2 has a link to the endolysosomal activity. Enhanced activity of the LRRK2 kinase, endolysosomal abnormalities and aggregation of autophagic vesicles with imperfectly depleted substrates, such as α-synuclein, are all seen in the substantia nigra dopaminergic neurons in PD. Despite the fact that LRRK2 is involved in endolysosomal and autophagic activity, it is undefined if inhibiting LRRK2 kinase activity will prevent endolysosomal dysfunction or minimise the degeneration of dopaminergic neurons. The inhibitor's capability of LRRK2 kinase to inhibit endolysosomal and neuropathological alterations in human PD indicates that LRRK2 inhibitors could have significant therapeutic usefulness in PD. G2019S is perhaps the maximum common mutation in PD subjects. Even though LRRK2's well-defined structure has still not been established, numerous LRRK2 inhibitors have been discovered. This review summarises the role of LRRK2 kinase in Parkinson's disease.

Exploring the role of neuropeptides in depression and anxiety.

Depression is one of the most prevalent forms of mental disorders and is the most common cause of disability in the Western world. Besides, the harmful effects of stress-related mood disorders on the patients themselves, they challenge the health care system with enormous social and economic impacts. Due to the high proportion of patients not responding to existing drugs, finding new treatment strategies has become an important topic in neurobiology, and there is much evidence that neuropeptides are not only involved in the physiology of stress but may also be clinically important. Based on preclinical trial data, new neuropharmaceutical candidates may target neuropeptides and their receptors and are expected to be essential and valuable tools in the treatment of psychiatric disorders. In the current article, we have summarized data obtained from animal models of depressive disorder and transgenic mouse models. We also focus on previously published research data of clinical studies on corticotropin-releasing hormone (CRH), galanin (GAL), neuropeptide Y (NPY), neuropeptide S (NPS), Oxytocin (OXT), vasopressin (VP), cholecystokinin (CCK), and melanin-concentrating hormone (MCH) stress research fields.

Piracetam-induced neuroprotection in lipopolysaccharides-challenged EOC-20 cells and mouse brain via attenuating oxidative stress

Abstract Therapeutically, piracetam has been used for decades as a cognitive enhancer for memory- related neuronal disorders. The present study aimed to investigate the neuroprotective potential of piracetam on lipopolysaccharides (LPS)-induced neuronal deficit using both in-vitro and in-vivo experimental models. For the in-vitro analysis, EOC-20 murine microglial cells were induced with a neuronal toxicity of 100 µg/ml of LPS, and the formation of intracellular reactive oxygen species (ROS) and nitric oxide (NO) productions were determined. For in-vivo neuroprotective analysis, groups of mice were treated orally with two doses of piracetam (200 and 400 mg/kg) for 30 days. Neuronal toxicity was induced by four intraperitoneal injections of LPS (250 µg/kg/day). The malondialdehyde (MDA) level was measured for oxidative stress, and catalase reduced glutathione (GSH), glutathione reductase (GRD), and superoxide dismutase (SOD) levels were determined as the antioxidant parameters. The result of the cell viability study was that pre-treatment with piracetam significantly protected the LPS-induced cell loss, and attenuated the ROS generation and NO production in LPS-induced EOC-20 cells. Moreover, the treatment of piracetam significantly reduced the MDA levels and improved catalase, GSH, GRD, and SOD activities in LPS-induced mice brains. The overall results from this study supported the neuroprotective effects of piracetam against LPS-induced neuronal toxicity.

Neuroprotective Effect of Clobenpropit against Lipopolysaccharide-Induced Cognitive Deficits via Attenuating Neuroinflammation and Enhancing Mitochondrial Functions in Mice.

Clobenpropit (CLO), an antagonist on histamine H3 receptors (HH3R), has been shown to protect NMDA-induced neuronal necrosis in cortical neuronal cell culture from rats. In this work, we explored its potential on lipopolysaccharide (LPS)-induced memory deficits, neuroinflammation, and mitochondrial dysfunction in mice. CLO (1 and 3 mg/kg, p.o.) was treated continually for 30 days, and neurotoxicity was induced by four doses of LPS (250 µg/kg, i.p.). The radial arm maze (RAM) was used to access memory behaviors. After the REM test, brain tissue was collected from each mouse to estimate pro-inflammatory cytokines (TNFα and IL6), anti-inflammatory cytokines (TGF-ß1 and IL-10), cyclooxygenase-2 (COX 2), and mitochondrial respiratory chain complex (MRCC- I, II and IV) enzymes. CLO treatment reversed the LPS-induced behavioral deficits by a significant reduction in time taken to consume all five bites (TTB), working memory error (WME), and reference memory error (REM) in the REM test. Regarding neuroinflammation, it attenuated the release of COX, TNF-α, and IL-6, and augmented TGF-ß1 and IL-10 levels in the brain. Reversal of LPS-induced brain MRCC (I, II, and IV) levels also resulted with CLO treatment. From these findings, CLO promises neuroprotection against LPS-induced cognitive deficits by ameliorating neuroinflammation and restoring the MRCC enzymes in mice.