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The current study aimed to evaluate the pharmacokinetics and neuroprotective effect of well-characterised berberine-bovine serum albumin (BBR-BSA) nanoparticles. BBR-BSA nanoparticles were generated by desolvation method. Entrapment efficiency, loading capacity, particle size, polydispersity index, surface morphology, thermal stability, and in-vitro release were estimated. In-vitro pharmacokinetic and tissue distribution were conducted. Their neuroprotection was evaluated against lipopolysaccharides-induced neurodegeneration. BBR-BSA nanoparticles showed satisfactory particle size (202.60 ± 1.20 nm) and entrapment efficiency (57.00 ± 1.56%). Results confirmed the formation of spheroid-thermal stable nanoparticles with a sustained drug release over 48 h. Sublingual and intranasal routes had higher pharmacokinetic plasma profiles than other routes, with C max values at 0.75 h (444 ± 77.79 and 259 ± 42.41 ng/mL, respectively). BBR and its metabolite distribution in the liver and kidney were higher than in plasma. Intranasal and sublingual treatment improves antioxidants, proinflammatory, amyloidogenic biomarkers, and brain architecture, protecting the brain. In conclusion, neuroinflammation and neurodegeneration may be prevented by intranasal and sublingual BBR-BSA nanoparticles.

There has been a significant increase in human exposure to heavy metals (HMs) over the course of the previous century, primarily due to the extensive industrial processes. Male infertility is a prominent complication associated with lead exposure, wherein lead has the potential to accumulate within the testes, resulting in oxidative stress and inflammation. In addition, 10-hydroxydecanoic acid (10-HDA) is a component found in the secretions of worker bees and possesses the capacity to mitigate oxidative stress and prevent inflammation. Due to their advantageous properties, zinc oxide nanoparticles (ZnO-NPs) possess a wide range of applications in the field of biomedicine. This study aimed to assess the therapeutic effect of 10-HDA and ZnO-NPs on testicular toxicity in rats induced by lead acetate (PbAc). PbAc was administered orally for a period of 3 months. Following that, 10-HDA and/or ZnO-NPs were administrated for 1 month. PbAc deformed seminal analysis, decreased seminal fructose and sex hormonal levels, and resulted in the development of histopathological complications. Additionally, PbAc increased MDA and decreased Nrf2 and HO-1 expression, confirmed by the declined antioxidant defense system. Furthermore, an increase in testicular inflammatory markers and the Bax/Bcl-2 ratio was observed subsequent to the administration of PbAc. The administration of 10-HDA and ZnO-NPs demonstrated significant efficacy in the restoration of semen quality, pituitary/gonadal hormones, antioxidants, and  testicular histoarchitecture. Moreover, 10-HDA and ZnO-NPs decreased testicular inflammatory markers and apoptotic proteins (caspase-3 and Bax expression levels). In conclusion, combining 10-HDA and ZnO-NPs demonstrated synergistic potential in treating PbAc-induced testicular toxicity, thereby presenting a promising approach in nanomedicine and natural drugs., (© 2024. The Author(s).)

Lifestyle influences physical and cognitive development during the period of adolescence greatly. The most important of these lifestyle factors are diet and stress. Therefore, the aim of this study was to investigate the impact of high fat diet (HFD) and chronic mild stress on cognitive function and anxiety-like behaviors in young rats and to study the role of caffeic acid as a potential treatment for anxiety and cognitive dysfunction. Forty rats were assigned into 4 groups: control, HFD, HFD + stress, and caffeic acid-treated group. Rats were sacrificed after neurobehavioral testing. We detected memory impairment and anxiety-like behavior in rats which were more exaggerated in stressed rats. Alongside the behavioral changes, there were biochemical and histological changes. HFD and/or stress decreased hippocampal brain-derived neurotrophic factor (BDNF) levels and induced oxidative and inflammatory changes in the hippocampus. In addition, they suppressed Wnt/β-catenin pathway which was associated with activation of glycogen synthase kinase 3β (GSK3β). HFD and stress increased arginase 1 and inducible nitric oxide synthase (iNOS) levels as well. These disturbances were found to be aggravated in stressed rats than HFD group. However, caffeic acid was able to reverse these deteriorations leading to memory improvement and ameliorating anxiety-like behavior. So, the current study highlights an important neuroprotective role for caffeic acid that may guard against induction of cognitive dysfunction and anxiety disorders in adolescents who are exposed to HFD and/or stress., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alzheimer's disease (AD) is an age-related neurodegenerative disorder that causes severe dementia and memory loss. Surface functionalized poly(lactic-co-glycolic acid) nanoparticles have been reported for better transport through the blood-brain barrier for AD therapy. This study investigated the improved therapeutic potential of berberine-loaded poly(lactic-co-glycolic acid)/Tet-1 peptide nanoparticles (BBR/PLGA-Tet NPs) in a rat model of sporadic AD. BBR was loaded into the PLGA-Tet conjugate. BBR/PLGA-Tet NPs were physicochemically and morphologically characterized. AD was achieved by bilateral intracerebroventricular (ICV) injection of streptozotocin (STZ). Cognitively impaired rats were divided into STZ, STZ + BBR, STZ + BBR/PLGA-Tet NPs, and STZ + PLGA-Tet NPs groups. Cognitive improvement was assessed using the Morris Water Maze. Brain acetylcholinesterase and monoamine oxidase activities, amyloid β42 (Aβ42), and brain glycemic markers were estimated. Further, hippocampal neuroplasticity (BDNF, pCREB, and pERK/ERK), Tau pathogenesis (pGSK3β/GSK3β, Cdk5, and pTau), inflammatory, and apoptotic markers were evaluated. Finally, histopathological changes were monitored. ICV-STZ injection produces AD-like pathologies evidenced by Aβ42 deposition, Tau hyperphosphorylation, impaired insulin signaling and neuroplasticity, and neuroinflammation. BBR and BBR/PLGA-Tet NPs attenuated STZ-induced hippocampal damage, enhanced cognitive performance, and reduced Aβ42, Tau phosphorylation, and proinflammatory responses. BBR/PLGA-Tet NPs restored neuroplasticity, cholinergic, and monoaminergic function, which are critical for cognition and brain function. BBR/PLGA-Tet NPs may have superior therapeutic potential in alleviating sporadic AD than free BBR due to their bioavailability, absorption, and brain uptake., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The prolonged use of exogenous glucocorticoids, such as dexamethasone (Dex), is the most prevalent secondary cause of osteoporosis, known as glucocorticoid-induced osteoporosis (GIO). The current study examined the preventative and synergistic effect of aqueous chicory extract (ACE) and ethanolic purslane extract (EPE) on GIO compared with Alendronate (ALN). The phytochemical contents, elemental analysis, antioxidant scavenging activity, and ACE and EPE combination index were evaluated. Rats were randomly divided into control, ACE, EPE, and ACE/EPE MIX groups (100 mg/kg orally), Dex group (received 1.5 mg Dex/kg, Sc), and four treated groups received ACE, EPE, ACE/EPE MIX, and ALN with Dex. The bone mineral density and content, bone index, growth, turnover, and oxidative stress were measured. The molecular analysis of RANK/RANKL/OPG and Nrf2/HO-1 pathways were also evaluated. Dex causes osteoporosis by increasing oxidative stress, decreasing antioxidant markers, reducing bone growth markers (OPG and OCN), and increasing bone turnover and resorption markers (NFATc1, RANKL, ACP, ALP, IL-6, and TNF-α). In contrast, ACE, EPE, and ACE/EPE MIX showed a prophylactic effect against Dex-induced osteoporosis by modulating the measured parameters and the histopathological architecture. In conclusion, ACE/EPE MIX exerts a powerful synergistic effect against GIO by a mode of action different from ALN.

Blood-brain barrier (BBB) efflux transporters' overexpression hinders antiepileptic drug brain entry. Breast cancer resistance protein (BCRP) is a major BBB efflux transporter. In the present work, BCRP's role as a mechanism that might contribute to drug-resistant epilepsy (DRE) in a mouse model of acute seizures was studied with further assessment of the effect of its inhibition by ko143 and metformin (MET) on lamotrigine (LTG) bioavailability and efficacy. 42 male mice divided into 6 groups: G1: Normal control, G2: LTG-injected healthy mice: LTG 20 mg/kg i.p., G3: Acute seizures (A.S) mice: Pentylenetetrazole (PTZ) 50 mg/kg i.p., G4: LTG-treated A.S mice: LTG 20 mg/kg + PTZ 50 mg/kg i.p., G5: Ko143 + LTG treated A.S mice: Ko143 15 mg/kg i.p. before LTG + PTZ, G6: MET + LTG treated A.S mice: MET 200 mg/kg i.p. before LTG + PTZ. Seizures severity, serum, brain LTG, and brain BCRP were assessed. PTZ group experienced the highest seizure frequency and brain BCRP expression. Ko143 and MET groups showed a significant decrease in brain BCRP with subsequent improvement in brain LTG level and better seizure control. BCRP has a significant role in epilepsy resistance and its inhibition with ko143 or MET adds value to DRE management., (© 2023. The Author(s).)

Resveratrol is known to exhibit neuroprotective effects in many neurological disorders via autophagy modulation. However, controversial results have been reported about the therapeutic potential of resveratrol and the implication of autophagy in demyelinating diseases. This study aimed to evaluate the autophagic changes in cuprizone-intoxicated C57Bl/6 mice and explore the effect of autophagy activation by resveratrol on the demyelination and remyelination processes. Mice were fed with chow containing 0.2% cuprizone for 5 weeks, followed by a cuprizone-free diet for 2 weeks. Resveratrol (250 mg/kg/day) and/or chloroquine (an autophagy inhibitor; 10 mg/kg/day) were given for 5 weeks starting from the third week. At the end of the experiment, animals were tested on rotarod and then sacrificed for biochemical assessment, luxol fast blue (LFB) staining, and transmission electron microscopy (TEM) imaging of the corpus callosum. We observed that cuprizone-induced demyelination was associated with impaired degradation of autophagic cargo, induction of apoptosis, and manifest neurobehavioral disturbances. Oral treatment with resveratrol promoted motor coordination and improved remyelination with regular compacted myelin in most axons without a significant impact on myelin basic protein (MBP) mRNA expression. These effects are mediated, at least in part, via activating autophagic pathways that may involve SIRT1/FoxO1 activation. This study verified that resveratrol dampens cuprizone-induced demyelination, and partially enhances myelin repair through modulation of the autophagic flux, since interruption of the autophagic machinery by chloroquine reversed the therapeutic potential of resveratrol., (© 2023. The Author(s).)

Ultraviolet C (UVC) devices are an effective means of disinfecting surfaces and protecting medical tools against various microbes, including coronavirus. Overexposure to UVC can induce oxidative stress, damage the genetic material, and harm biological systems. This study investigated the prophylactic efficacy of vitamin C and B12 against hepatotoxicity in UVC-intoxicated rats. Rats were irradiated with UVC (725.76, 967.68, and 1048.36 J/cm 2 ) for 2 weeks. The rats were pretreated with the aforementioned antioxidants for two months before UVC irradiation. The prophylactic effect of vitamins against UVC hepatotoxicity was evaluated by monitoring the alteration of liver enzyme activities, antioxidant status, apoptotic and inflammatory markers, DNA fragmentation, and histological and ultrastructural alterations. Rats exposed to UVC showed a significant increase in liver enzymes, oxidant-antioxidant balance disruption, and increased hepatic inflammatory markers (TNF-α, IL-1β, iNOS, and IDO-1). Additionally, obvious over-expression of activated caspase-3 protein and DNA fragmentation were detected. Histological and ultrastructural examinations verified the biochemical findings. Co-treatment with vitamins ameliorated the deviated parameters to variable degrees. In conclusion, vitamin C could alleviate UVC-induced hepatotoxicity more than vitamin B12 by diminishing oxidative stress, inflammation, and DNA damage. This study could provide a reference for the clinical practice of vitamin C and B12 as radioprotective for workers in UVC disinfectant areas.

Subtle memory and cognitive changes may occur in uninephrectomized (Unix) patients long before the development of chronic kidney disease, such changes may be unnoticed. The dietary polyphenol, Resveratrol, displayed various neuroprotective effects, its role in chronic kidney disease is an area of intense studies. This work was designed to investigate the behavioural and molecular changes that may occur following 7 months of Unix in rats, and to determine whether Resveratrol intake can improve such pathology. Male Wistar rats were divided into three groups: sham operated, Unix and Unix group treated with Resveratrol (20 mg/kg/day). Rats were subjected to series of behavioural testing, different biochemical parameters along with RT-PCR and immunohistochemistry of the hippocampal tissue to track the development of functional or structural brain changes. Anxiety behaviour and reduced spatial memory performance were observed in rats 7 months post-nephrectomy; these deficits were remarkably reversed with Resveratrol. Among the species typical behaviour, burrowing was assessed; it showed significant impairment post-nephrectomy. Resveratrol intake was almost able to increase the burrowing behaviour. Decreased SIRT1 in immune-stained sections, oxidative stress, inflammatory changes, and increased AChE activity in hippocampal homogenates were found in Unix rats, and Resveratrol once more was capable to reverse such pathological changes. This work has investigated the occurrence of behavioural and structural brain changes 7 months following Unix and underlined the importance of Resveratrol to counterbalance the behavioural impairment, biochemical and brain pathological changes after uninephrectomy. These findings may raise the possible protective effects of Resveratrol intake in decreased kidney function., (© 2022. The Author(s).)

The peri- and post-menopausal periods have been described as the "window of vulnerability" for the development of depressive symptoms that impair women activities and quality of life. The etiopathogenesis of these symptoms is multifactorial and may confer resistance to traditional antidepressants. Attention is now directed toward phytochemicals for their pleiotropic functions and safer profiles. This study investigated the possible perturbation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways as an underlying mechanism of post-ovariectomy depression and highlighted the potential benefits of carnosic acid (CA) on the associated behavioral, biochemical, and histopathological alterations. Female Balb/c mice were randomly assigned to be sham-operated or ovariectomized (OVX). After 3 weeks, OVX mice received either a vehicle, CA (20 mg/kg/day), or tin protoporphyrin IX (SnPP-IX; a heme oxygenase-1 (HO-1) inhibitor; 50 μmol/kg/day) for 3 weeks. Our findings revealed that OVX mice had depressive but not anxiety-like behavior. Suppressed Nrf2 and its downstream signaling, and augmented proinflammatory markers were observed in both the hippocampus and prefrontal cortex. CA treatment alleviated depressive behavior, induced the expression of Nrf2, HO-1, thioredoxin-1, and brain-derived neurotrophic factor, and enhanced serotonin levels. CA also suppressed oxidative stress, reduced TNF-α, IL-1β, and iNOS mRNA expression, and ameliorated OVX-induced histopathological changes. SnPP-IX aggravated post-OVX behavioral, neurobiochemical, and histological deteriorations, and reduced CA-protective effects. In conclusion, Nrf2/HO-1 signaling suppression and the associated proinflammatory state are key mechanisms in post-OVX depression. CA exerts multifaceted neuroprotection in OVX mice and represents a promising candidate for clinical evaluation as an antidepressant., (© 2022. The Author(s).)

Background: Increasing concerns are rising over women and adolescence in Arabic societies generally, and in Egyptian society specifically., Objectives: To identify the profile and reasons of the problem of sexual harassments among female college students., Methods: A cross-sectional study including randomly selected 976 female students from different faculties of Kafrelsheikh University using a predesigned questionnaire sheet., Results: The main perceived concept of sexual harassment was touching body (63.9%) followed by uncomfortable behaviors by the assault (51.8%). Among urban students, 47.1% reported frequent sexual harassment as compared to 26.5% among rural students. The main motives to harassment were absence of sanctions (42.8%) followed by masculine culture. Absence of punishment ranked first (54.1%) as one of reasons for the phenomenon of harassments in the community followed by wrong concepts about women (46%). The main reaction to harassment was feeling bad and wishing to act (32.9%) followed by feeling bad but helpless (26.0%). Only 25.5% reported taking proper action. Experience of harassment was significantly more reported by urban students compared to rural ones (12.6% and 4.1%, respectively (P = 0.001)., Conclusion: Sexual harassment is not uncommon from of violence especially in urban areas mainly due to absence of sanctions and majority did not have capacity to take proper actions., (© The Author(s) 2021. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Vitamin A is an essential nutrient with vital biological functions. The present study investigated the effect of different doses of vitamin A palmitate at different time intervals on thyroid hormones and glycemic markers., Methods: Male rats were administrated vitamin A palmitate at different doses (0, 0.7, 1.5, 3, 6, and 12 mg/kg, oral) and samples were collected at different time intervals of 2, 4, and 6 weeks. The levels of vitamin A, thyroid hormones (T3, T4, and TSH), deiodinases (Dio1 and Dio3), glycemic markers (blood insulin and fasting glucose levels, HOMA IR and HOMA β), retinol-binding protein 4 (RBP4) and the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) were measured., Results: The findings demonstrated that long-term supplementation with high doses of vitamin A palmitate resulted in hypothyroidism (lower T3 and T4 levels and elevated TSH levels) as well as upregulation of Dio1 and Dio3 expression levels. This effect was associated with elevated glucose and insulin levels, enhanced HOMA IR, and decreased HOMA B index. In addition, prolonged vitamin A supplementation significantly increased RBP4 levels that upregulated the expression of PEPCK., Conclusion: High doses of vitamin A supplementation increased the risk of hypothyroidism, modulated insulin sensitivity, and over a long period, increased the incidence of type 2 diabetes mellitus associated with oxidative stress and hepatitis., (© 2022. The Author(s).)

Berberine (BBR) is an isoquinoline alkaloid with several clinical therapeutic applications. Its low water solubility, absorption, and cellular bioavailability diminish BBR's therapeutic efficacy. In this study, BBR was encapsulated into bovine serum albumin nanoparticles (BSA NPs) core to reduce BBR limitations and enhance its clinical therapeutic properties. Several physicochemical characterization tools, such as Dynamic Light Scattering and Ultraviolet-Visible spectroscopic measurements, field emission transmission electron microscopy surface morphology, Fourier transforms infrared spectroscopy, thermal stability analysis, and releasing studies, were used to evaluate the BBR-BSA NPs. Compared to BBR, BBR-BSA nanoparticles demonstrated superior free radical scavenging and antioxidant capacities, anti-hemolytic and anticoagulant efficacies, and antimicrobial activities, as demonstrated by the findings of the in vitro studies. Furthermore, a stressed pancreatic rat model was induced using a high-fat, high-sucrose diet plus carbon tetrachloride injection. The in vivo results revealed that BBR-BSA NPs substantially restored peripheral glucose metabolism and insulin sensitivity. Oral administration of BBR-BSA NPs also improved pancreatic β-cells homeostasis, upregulated pancreatic antioxidant mechanisms, inhibited oxidants generation, and attenuated oxidative injury in the stressed pancreatic tissues. In conclusion, our in vitro and in vivo results confirmed that BBR-BSA NPs demonstrated more potent antioxidant properties and restored pancreatic homeostasis compared to BBR., (© 2022. The Author(s).)

Long-term glucocorticoids can alter sperm motility, vitality, or morphology, disrupting male reproductive function. This study scrutinized the synergistic benefits of two Egyptian plants against dexamethasone (Dexa)-induced testicular and autophagy dysfunction in male rats. Phytochemical ingredients and the combination index were estimated for Purslane ethanolic extract (PEE) and Chicory water extract (CWE). Four control groups received saline and 100 mg/kg of each PEE, CWE, and PEE/CWE, daily for 8 weeks. Dexa (1 mg/kg daily for 6 weeks) induced infertility where PEE, CWE, and PEE/CWE were given. Seminal analysis, male hormones, glycemic and oxidative stress markers, endoplasmic reticulum (ER) stress markers (Sigma 1R and GRP78), and autophagy regulators (Phospho-mTOR, LC3I/II, PI3KC3, and Beclin-1, P62, ATG5, and ATG7) were measured. The in vitro study illustrated the synergistic (CI < 1) antioxidant capacity of the PEE/CWE combination. Dexa exerts testicular damage by inducing oxidative reactions, a marked reduction in serum testosterone, TSH and LH levels, insulin resistance, ER stress, and autophagy. In contrast, the PEE and CWE extracts improve fertility hormones, sperm motility, and testicular histological alterations through attenuating oxidative stress and autophagy, with a synergistic effect upon combination. In conclusion, the administration of PEE/CWE has promised ameliorative impacts on male infertility and can delay disease progression.

Oxidative stress associated with long-term glucocorticoids administration is a route through which secondary osteoporosis can be developed. The therapeutic potential of Phoenix dactilyfera L. pits is offered by their balanced, valuable and diverse phytochemical composition providing protective potential against oxidative reactions, making it a good candidate to treat glucocorticoid-induced osteoporosis (GIO). This study evaluates the possible anti-osteoporotic effect of date pit extract (DPE) against dexamethasone (DEXA)-induced osteoporosis. Male rats were allocated into three control groups, which received saline, low and high doses of DPE (150 and 300 mg/kg/day), respectively. Osteoporosis-induced groups that received DEXA (1 mg/kg/day) were divided into DEXA only, DPE (2 doses) + DEXA, and ipriflavone + DEXA. Femoral bone minerals density and bone mineral content, bone oxidative stress markers, Wnt signaling, osteoblast and osteoclast differentiation markers, and femur histopathology were evaluated. DPE defeated the oxidative stress, resulting in ameliorative changes in Wnt signaling. DPE significantly reduced the adipogenicity and abolished the osteoclastogenic markers (RANKL/OPG ratio, ACP, TRAP) while enhancing the osteogenic differentiation markers (Runx2, Osx, COL1A1, OCN). In Conclusion DPE restored the balanced proliferation and differentiation of osteoclasts and osteoblasts precursors. DPE can be considered a promising remedy for GIO, especially at a low dose that had more potency.

Long-term exposure to environmental neurotoxic metals is implicated in the induction of dementia and cognitive decline. The present study aims to illustrate the therapeutic role of ipriflavone as a synthetic isoflavone against environmental metal-induced cognitive impairment in rats. Dementia was induced by a mixture of aluminum, cadmium, and fluoride for 90 days followed by ipriflavone for a further 30 days.  Metal-treated animals exhibited abnormal behaviors in the Morris water maze task. Neuropathological biomarkers including oxidative stress (TBARS, NO, SOD, GPX, GST, and GSH), inflammation (TNF- α, IL-6, and IL-1β), neurotransmission (AChE and MAO), and insulin resistance (insulin, insulin receptor, and insulin-degrading enzyme) were altered, which consequently elevated the level of amyloid-β42 and tau protein in the hippocampus tissues inducing neuronal injury. Ipriflavone significantly (P < 0.05) ameliorated the neurobehavioral abnormalities and the cognitive dysfunction biomarkers via antioxidant/anti-inflammatory mechanism. Moreover, ipriflavone downregulated the mRNA expression level of amyloid precursor protein and tau protein, preventing amyloid plaques and neurofibrillary tangle aggregation at P < 0.05. A molecular docking study revealed that ipriflavone has a potent binding affinity towards AChE more than donepezil and acts as a strong AChE inhibitor. Our data concluded that the therapeutic potential of ipriflavone against dementia could provide a new strategy in AD treatment., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Titanium (IV)-dithiophenolate complex chitosan nanocomposites (DBT-CSNPs) are featured by their antibacterial activities, cytotoxicity, and capacity to bind with DNA helixes. In this study, their therapeutic effects against rat liver damage induced by carbon tetrachloride (CCl 4 ) and their anti-proliferative activity against human liver cancer (HepG2) cell lines were determined. Results of treatment were compared with cisplatin treatment. Markers of apoptosis, oxidative stress, liver functions, and liver histopathology were determined. The results showed that DBT-CSNPs and DBT treatments abolished liver damage induced by CCl 4 and improved liver architecture and functions. DNA fragmentation, Bax, and caspase-8 were reduced, but Bcl-2 and the Bcl-2/Bax ratios were increased. However, there was a non-significant change in the oxidative stress markers. DBT-CSNPs and DBT inhibited the proliferation of HepG2 cells by arresting cells in the G2/M phase and inducing cell death. DBT-CSNPs were more efficient than DBT. Low doses of DBT and DBT-CSNPs applied to healthy rats for 14 days had no adverse effect. DBT and DBT-CSNP treatment gave preferable results than the treatment with cisplatin. In conclusion, DBT-CSNPs and DBT have anti-apoptotic activities against liver injuries and have anti-neoplastic impacts. DBT-CSNPs are more efficient. Both compounds can be used in pharmacological fields.

Date pits are nutritious by-products, containing high levels of indigestible carbohydrates and polyphenols. To maximize the biological effects of the active ingredients, the hard shell of the polysaccharide must be degraded. Therefore, the current study aimed to assess the protective potentials of date pits extract (DP) and fungal degraded date pits extract (FDDP) against scopolamine (SCO)-induced neurodegeneration in male rats. Date pits were subjected to fungal degradation and extraction, followed by the measurement of phytochemicals and free radical scavenging activities. Forty-two adult Sprague-Dawley male rats were divided into seven groups: three control groups administered with either saline, DP or FDDP; four groups with neurodegeneration receiving SCO (ip 2 mg/kg/day, SCO group) with no treatment, SCO with DP (oral 100 mg/kg/day, DP + SCO group), SCO with FDDP (oral, 100 mg/kg/day, FDDP + SCO group), and SCO with donepezil (DON, oral, 2.25 mg/kg/day, DON + SCO group). The treatment duration was 28 days, and in the last 14 days, SCO was administered daily. Morris water maze test, acetylcholine esterase activity, oxidative stress, markers of inflammation and amyloidogenesis, and brain histopathology were assessed., (© 2021. The Author(s).)

Purpose: A novel coronavirus (COVID-19) that has not been previously identified in humans and has no specific treatment has recently spread. Treatment trials using antiviral and immune-modulating drugs such as hydroxychloroquine (HCQ) were used to control this viral outbreak however several side effects have emerged. Berberine (BER) is an alkaloid that has been reported to reveal some pharmacological properties including antioxidant and antimicrobial activities. Additionally, Zinc oxide nanoparticles (ZnO-NPs) possess potent antioxidant and anti-inflammatory properties. Therefore, this study was undertaken to estimate the efficiency of both BER and synthetic ZnO/BER complex as an anti-COVID-19 therapy., Methods: First, the ZnO/BER complex was prepared by the facile mixing method. Then in vitro studies on the two compounds were conducted including VeroE6 toxicity, anti-COVID-19 activity, determination of inhibitory activity towards papain-like proteinase (PL pro) and spike protein- and receptor- binding domain (RBD) as well as assessment of drug toxicity on RBCs., Results: The results showed that ZnO/BER complex acts as an anti-COVID-19 by inhibiting spike protein binding with angiotensin-converting enzyme II (ACE II), PL pro activity, spike protein and E protein levels, and expression of both E-gene and RNA dependent RNA polymerase (RdRp) at a concentration lower than that of BER or ZnO-NPs alone. Furthermore, ZnO/BER complex had antioxidant and antimicrobial properties where it prevents the auto oxidation of 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and the culture of lower respiratory system bacteria that affected Covid 19 patients. The ZnO/BER complex prevented as well the HCQ cytotoxic effect on both RBC and WBC (in vitro) and hepatotoxicity, nephrotoxicity and anemia that occurred after HCQ long administration in vivo., Conclusion: The ZnO/BER complex can be accounted as promising anti-COVID 19 candidate because it inhibited the virus entry, replication, and assembly. Furthermore, it could be used to treat a second bacterial infection that took place in hospitalized COVID 19 patients. Moreover, ZnO/BER complex was found to eliminate the toxicity of long-term administration of HCQ in vivo ., Competing Interests: Conflict of interestAll authors (D.A. Ghareeb, S.R. Saleh, M.G. Seadawy, M.S. Nofal, S.A. Abdulmalek, S.F. Hassan, S.M. Khedr, M.G. AbdElwahab, A.A. Sobhy, A.A. Abdel-Hamid, A.M. Yassin, A.A.A. Elmoneam, A.A. Masoud, M.M.Y. Kaddah, S.A. El-Zahaby, A.M. Al-mahallawi, A.M. El-Gharbawy, A. Zaki, I.K. Seif, M.Y. Kenawy, M. Amin, K. Amer, M.A. El Demellawy) declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper., (© The Korean Society of Pharmaceutical Sciences and Technology 2021.)

Background: At the end of 2019, the new Coronavirus disease 2019 (COVID-19) strain causing severe acute respiratory syndrome swept the world. From November 2019 till February 2021, this virus infected nearly 104 million, with more than two million deaths and about 25 million active cases. This has prompted scientists to discover effective drugs to combat this pandemic., Area Covered: Drug repurposing is the magic bullet for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Therefore, several drugs have been investigated in silico, in vitro, as well as through human trials such as anti-SARS-CoV2 agents, or to prevent the complications resulting from the virus. In this review, the mechanisms of action of different therapeutic strategies are summarized. According to the WHO, different classes of drugs can be used, including anti-malarial, antiviral, anti-inflammatory, and anti-coagulant drugs, as well as angiotensin-converting enzyme inhibitors, antibiotics, vitamins, zinc, neutralizing antibodies, and convalescent plasma therapy. Recently, there are some vaccines which are approved against SARS-CoV2., Expert Opinion: A complete understanding of the structure and function of all viral proteins that play a fundamental role in viral infection, which contribute to the therapeutic intervention and the development of vaccine in order to reduce the mortality rate., Supplementary Information: The online version contains supplementary material available at 10.1007/s40005-021-00520-4., Competing Interests: Conflict of interestAll authors (D.A. Ghareeb, S.R. Saleh, M.S. Nofal, M.M.Y. Kaddah, S.F. Hassan, I.K. Seif, S.A. El-Zahaby, S.M. Khedr, M.Y. Kenawy, A.A. Masoud, S.A. Soudi, A.A. Sobhy, J.G. Sery, M.G. Abd El-Wahab, A.A. Abd Elmoneam, A.M. Al-mahallawi, and M.A. El-Demellawy) declare that they have no conflict of interest., (© The Korean Society of Pharmaceutical Sciences and Technology 2021.)

Background: Berberine (BBR), an isoquinoline alkaloid, acts as a multipotent active pharmaceutical ingredient to counteract several types of dementia based on its numerous pharmacological actions including antioxidant, anti-inflammatory, cholesterol-lowering effect, and inhibition of Aβ production and AChE. However, BBR suffers from poor absorption, bioavailability and brain drug uptake. The present study is directed for the formulation and characterization of Chitosan BBR-Nanoparticles (BBR-NPs) as well as the estimation of its neuroprotective effects against scopolamine induced cognitive impairments., Methods: BBR-NPs were formulated using the ionic gelation method, and tripolyphosphate was chosen as a crosslinker. Nanoparticles size, zeta potential, encapsulation efficiency and releasing profile were estimated. To investigate the neuroprotective effects, adult fifty-six Wistar male rats were randomly distributed into three control groups, received saline, polyethylene glycol or Chitosan- NPs, respectively; induced group, received scopolamine (2 mg/ kg, i.p.) and three treated groups were orally administrated BBR (50 mg/ kg), BBR- NP (7 mg/ kg) and donepezil (2.25 mg/ kg, as positive control) followed by scopolamine injection after 40 min, daily for 4 weeks. Morris water maze test, oxidative stress parameters, cholinergic and amyloid-β processing intermediates, as well as neuroplasticity markers and histopathological examination were assessed., Results: Our results showed that BBR- NPs were better than BBR and donepezil as BBR- NPs were powerful inhibitory ligands towards AChE and Aβ42 formation and significantly down-regulated Tau, iNOS and BACE gene expression in rats' hippocampus. BBR-NPs administration, at 1/6 of BBR therapeutic recommended dose, significantly improved learning and memory function. This could be accredited to the diminution of oxidative stress and amyloid-β toxicity in addition to the improvement of the neuroplasticity markers., Conclusion: The enhancing effect of BBR- NPs could be related to the enhancing of its bioavailability, absorption and brain drug uptake, which need more investigation in future work., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a multifactorial etiology and significantly increasing incidence during the last decade. Hence, developing an effective therapy is crucial for public health. The current study aimed to examine the dual prophylactic/therapeutic potential of a nutraceutical formula based on aqueous extract of roasted date seeds, and nigella and virgin-olive oils against experimentally-induced Alzheimer's disease in rats. Alzheimer's disease-like pathology was induced in male Wistar rats using oral CuSO 4 (200 mg/Kg/day for two months). The nutraceutical formula was given orally to experimental animals (10 mL/kg/d) for 14 days before (as prophylaxis) and after Alzheimer's disease induction and its therapeutic effect in both cases is tested in comparison to donepezil (0.5 mg/kg/d). The nutraceutical formula was found to ameliorate the CuSO 4 -induced neuronal damage and regenerate the affected hippocampus tissue and significantly improvemed in learning ability. The formula was also effective in decreasing brain amyloid-β, tau protein, TNF-α level, iNOS level in hippocampus, oxidative stress level, and inhibiting acetylcholinesterase activity and expression in brain and hippocampus, respectively. Further, an increase in GSH levels, activities of SOD, and GST and levels of hippocampus ADAM 17 and brain phospholipids was observed. In conclusion, the studied nutraceutical formula is proved to be effective in ameliorating Alzheimer's neurodegenerative progression with added-prophylactic potential., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Liver damage involves oxidative stress and a progression from chronic hepatitis to hepatocellular carcinoma (HCC). The increased incidence of liver disease in Egypt and other countries in the last decade, coupled with poor prognosis, justify the critical need to introduce alternative chemopreventive agents that may protect against liver damage. The aim of this study was to evaluate the efficacy of exopolysaccharide-peptide (PSP) complex extracted from Pleurotus ostreatus as a hepatoprotective agent against diethylnitrosamine (DEN)/carbon tetrachloride (CCL 4 )-induced hepatocellular damage in rats. The levels of liver injury markers (ALT, AST and ALP) were substantially increased following DEN/CCl 4 treatment. DEN/CCl 4 - induced oxidative stress was confirmed by elevated levels of lipid peroxidation and decreased levels of superoxide dismutase, glutathione-S-transferase, and reduced glutathione. PSP reversed these alterations in the liver and serum, and provided protection evidenced by reversal of histopathological changes in the liver. The present study demonstrated that PSP extract from P. ostreatus exhibited hepatoprotective and antioxidant effects against DEN/CCl 4 -induced hepatocellular damage in rats. Given the high prevalence of HCV-related liver damage in Egypt, our results suggest further clinical evaluation of P. ostreatus extracts and their potential hepatoprotective effects in patients with liver disease., (© 2020 Published by Elsevier B.V.)

Background: Neuroinflammation causes neurodegenerative conditions like Alzheimer's disease (AD). Ipriflavone (IP), therapeutic compound to postmenopausal osteoporosis, has limited estrogenic activity and is accounted as AChE inhibitor. The developing of drug delivery systems to enable drug targeting to specific sites increases the drug therapeutic effect., Objective: The aim of the present study was to formulate and evaluate ipriflavone loaded albumin nanoparticles (IP-Np) along with free ipriflavone against lipopolysaccharide (LPS) induced neuroinflammation in rats., Methods: Neuroinflammation was induced by intra-peritoneal (i.p) injection of LPS (250 μg/kg rat body weight) then treatments were conducted with (1) ipriflavone at two doses 50 mg/kg and 5 mg/kg, (2) IP-Np (5 mg ipriflavone/kg) or (3) IP-Np coated with polysorbate 80 (IP-Np-T80) (5 mg ipriflavone/kg). The alteration of the inflammatory response in male adult Wistar rats' brain hippocampus was investigated by examining associated indices using biochemical and molecular analyses., Results: A significant upsurge in inflammatory mediators and decline in antioxidant status were observed in LPS-induced rats. In one hand, ipriflavone (50 mg/kg), IP-Np and IP-Np-T80 ameliorated LPS induced brain hippocampal inflammation where they depreciated the level of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and enhanced antioxidant status. In another hand, ipriflavone at dose (5 mg/kg) didn't show the same therapeutic effect., Conclusion: The current study provides evidence for the potential neuroprotective effect of ipriflavone (50 mg/kg) against LPS-induced neuroinflammation in rats through its anti-inflammatory and antioxidant activities. Moreover, nanoparticles significantly attenuated neuroinflammation in concentration lower than the effective therapeutic dose of free drug ten times., Competing Interests: The authors have declared that no competing interests exist.

Aim of the Work: Neuroinflammation can arise from metabolic disturbances accompanying type 2 diabetes mellitus (T2DM) with an implication of indoleamine 2,3-dioxygenase 1 (IDO1). The antioxidant and anti-inflammatory potentials of melatonin (Mel) can amend diabetic complications. Here, we examined the effect of exogenous melatonin on neuroinflammation in high fat diet (HFD)-induced T2DM rats., Main Methods: Twenty-one adult male Sprague-dawley rats were divided in to three groups: control group: fed commercial standard rat chow, T2DM group: fed with HFD for 16 weeks, and T2DM-Mel group: received HFD for 8 weeks, followed by weekly melatonin treatment (i.p injection 10 mg/kg in saline) for 8 weeks with continuous supply of HFD. After which, animals were submitted to euthanasia for brain and blood samples collection., Key Findings: In T2DM-Mel group the diabetic profile was ameliorated, and the state of low-grade systemic inflammation was alleviated through lowering serum pro-inflammatory cytokines (TNF-α and IL-6) and leptin while increasing adiponectin. Melatonin improved brain oxidative stress by increasing total antioxidant capacity and reduced glutathione (GSH), whereas malondialdehyde was declined. Melatonin reduced acetylcholinesterase (AChE) activity in blood and brain and its hippocampal expression, also hippocampal inducible nitric oxide synthase (iNOS) expression was reduced, moreover IDO1 hippocampal expression was declined, furthermore recovered neuronal morphology following melatonin treatment was also clearly viewed in the hippocampus under the light microscope in T2DM-Mel rats., Significance: Melatonin can be considered as a promising solution in preventing neuroinflammation development in T2DM owing to its ability to render the oxidative stress and accompanied low-grade systemic inflammation., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Several stressors like different types of heavy metals are found in the soil and can affect the growth and genomic integrity of wheat grains (Triticum aestivum L.). The aim of this study was to compare the effect of exogenous Cd (30, 60, 120 mg kg -1 ), Ni (50, 100 and 150 mg kg -1 ) or Pb (100, 200 and 300 mg kg -1 ) on wheat agronomic characteristics through the assessment of oxidative stress indices at protein and gene expression levels, photosynthetic pigments and genetic aberrations using RAPD analysis that were studied during two winter seasons (2015/2016 and 2016/2017). The results showed that all stressors significantly decreased the vegetative growth parameters, altered the activities of antioxidants enzymes in seedlings (after 30 days) and grains (after 5 months) and differently affected their expression levels in seedlings leaves and roots. Pb treated plants showed the poorest agronomic characteristics as it exhibited the worst affected wheat height, number of tillers, fresh and dry weight, flag leaf area as well as yield. Pb treatment caused poorest plant performance, it showed the highest proline content, least protein and chlorophyll contents, thus affects the overall plants growth followed by Cd and Ni, respectively. Furthermore, high Pb and Cd doses revealed highest degree of polymorphism and lowest degree of genome stability. Altogether, heavy metals accumulated mainly in wheat straw and induced genotoxic effect which consequently altered normal plant metabolism and pigment content which resulted in a significant reduction in wheat yield and quality. Moreover, Pb induced more genotoxic and phytotoxic effects than Cd and Ni., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The use of tyrosinase has confirmed to be the best means of recognizing safe, effective, and potent tyrosinase inhibitors for whitening skin. Twenty-four 2-phenoxy(thiomethyl)pyridotriazolopyrimidines were synthesized and characterized in our previous studies., Objective: The present work aimed to evaluate their cytotoxicity against HepG2 (hepatocellular carcinoma), A549 (pulmonary adenocarcinoma), MCF-7 (breast adenocarcinoma) and WRL 68 (embryonic liver) cell lines., Methods: MTT assay was employed to investigate the cytotoxicity, and a tyrosinase inhibitor screening kit was used to evaluate the Tyrosinase (TYR) inhibitory activity of the targets., Results: The tested compounds exhibited no considerable cytotoxicity, and nine of them were selected for a tyrosinase inhibitory test. Compounds 2b, 2m, and 5a showed good inhibitory percentages against TYR compared to that of kojic acid (reference substance). Molecular docking was performed to rationalize the Structure-Activity Relationship (SAR) of the target pyridotriazolopyrimidines and analyze the binding between the docked-selected compounds and the amino acid residues in the active site of tyrosinase., Conclusion: The target pyridotriazolopyrimidines were identified as a new class of tyrosinase inhibitors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Objective: Egypt produced 236,314 t of artichoke in 2016, which produce a huge amount of useless by-product, which can be used as cheaper source for many active compounds can be applied for some medical application. The objective of this study was to assess the toxicity of the artichoke by-product extract through its effect on rats' kidney, brain and liver biomarkers., Materials and Methods: Chemical composition of artichoke by-product (crude protein, crude fiber, crude fat and minerals) was determined. Conventional extraction (CE), microwave-assisted extraction (MAE) and ultrasonic-assisted extraction (UAE) extraction methods were used for artichoke by-product and comparison between them were performed according to antioxidant activity using DPPH and the phenolic profile identity using HPLC technique. Chronic oral gavage of thirty adult male albino rats for 4 weeks in the concentrations of (0.1, 0.5, 1 and 5 g kg-1) artichoke by-product extract was used for evaluation of its toxicity., Results: MAE with ethanol more suitable for extraction of the polyphenols (193.63±4.9 μg gallic acid equivalents (GAE) mg-1) and showed IC50 = 159.7 mg mL-1. Three major active phenolic compounds were identified benzoic acid, ellagic acid and caffeine. Rats administrated 5 g kg-1 artichoke extract have no changes in brain, liver and kidney parameters (p<0.05). Histology of brain and liver exhibited normal architecture., Conclusion: The results showed that the artichoke by-product extract had no any toxic effect on rats and considered be safe for human use even at a high level of doses (up to 5 g kg-1).

This study was aimed at evaluating the efficacy of berberine-rich fraction (BF) as a protective and/or a therapeutic agent against inflammation and oxidative stress during male infertility. Sexually mature Sprague-Dawley male rats were divided into five groups treated with either corn oil, BF (100 mg/kg BW, orally, daily for 30 days), gossypol acetate (5 mg/kg BW, i.p.) eight times for 16 days, BF alone for 14 days then coadministered with gossypol acetate for the next 16 days (protected group), or gossypol acetate for 16 days then treated with BF for 30 days (treated group). All animals completed the experimental period (46 days) without obtaining any treatments in the gap period. Sperm parameters, oxidative index, and inflammatory markers were measured. Gossypol injection significantly decreased the semen quality and testosterone level that resulted from the elevation of testicular reactive oxygen and nitrogen species (TBARS and NO), TNF- α , TNF- α -converting enzyme, and interleukins (IL-1 β , IL-6, and IL-18) by 230, 180, 12.5, 97.9, and 300%, respectively, while interleukin-12 and tissue inhibitors of metalloproteinases-3 were significantly decreased by 59 and 66%, respectively. BF (protected and treated groups) significantly improved the semen quality, oxidative stress, and inflammation associated with male infertility. It is suitable to use more advanced studies to validate these findings.

Background: Alzheimer's disease is an age-related neurodegenerative disorder characterized clinically by a progressive loss of memory and cognitive functions resulting in severe dementia. Ipriflavone (IPRI) is a non-hormonal, semi-synthetic isoflavone, clinically used in some countries for the treatment and prevention of postmenopausal osteoporosis. Moreover, ipriflavone is a non-peptidomimetic small molecule AChE inhibitor with an improved bioavailability after systemic administration, due to its efficient blood-brain barrier permeability in comparison with peptidomimetic inhibitors., Objective: The present study aimed to evaluate the possible enhancing effects of IPRI on memory impairments caused by scopolamine administration., Methods: Male rats were administered IPRI (50 mg/kg, oral) 2 h before scopolamine injection (2 mg/kg, intraperitoneally injected) daily for 4 weeks. Effects of IPRI on acetylcholinesterase activity, amyloid-β precursor processing, and neuroplasticity in the rats' hippocampus were investigated., Results: Daily administration of IPRI reverted memory impairment caused by scopolamine as measured by the reduction of the escape latency. IPRI significantly alleviated the oxidative stress and restored the mRNA expression of both cAMP-response element-binding protein and brain-derived neurotrophic factor in the hippocampus. Furthermore, it significantly increased the expression of ADAM10 and ADAM17 (two putative α-secretase enzymes) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) that associated with decreased expression of β-secretase (BACE) in the hippocampus. Finally, both the amyloid-β (Aβ) and Tau pathologies were reduced., Conclusions: IPRI showed promising neuroprotective effects against scopolamine-induced memory dysfunction in rats. These findings contributed to the stimulation of α-secretase enzymes, the activation of MAPK/ERK1/2, and the alleviation of oxidative stress.

Two regioisomeric citrate-functionalized ciprofloxacin conjugates have been synthesized and their antimicrobial activities against a panel of clinically-relevant bacteria have been determined. Cellular uptake mechanisms were investigated using wild-type and ompF deletion strains of Escherichia coli K-12.