Protective Roles of N-trans-feruloyltyramine Against Scopolamine-Induced Cholinergic Dysfunction on Cortex and Hippocampus of Rat Brains

Objective: To study the protective effects of N-trans-feruloyltyramine (NTF) on scopolamine-induced cholinergic dysfunction, apoptosis, and inflammation in rat brains. Materials and Methods: Treatments were administered intraperitoneally (i.p.). Wistar rats (8-week-old) were allocated into 4 groups (n = 3) as follows: scopolamine-only, NTF-only, NTF + scopolamine and control. Spatial cognition was evaluated by Morris water maze. ROS assay and Western blot analyses were conducted in 3 brain regions: the frontal cortex, hippocampus, and temporal cortex. Results: NTF treatment inhibited scopolamine-induced memory impairment and significantly attenuated scopolamine-induced changes in the three brain regions. Investigated scopolamine-associated changes were as follows: increases in ROS production and BACE1 level, decrease in ChAT level, increases in inflammatory and apoptotic markers, and activation of signaling pathway kinases related to inflammation and apoptosis. Conclusion: With its in vivo antioxidant, cholinergic-promoting, anti-apoptosis, and anti-inflammatory biological activities, NTF is a promising candidate to be further investigated as a potential treatment for Alzheimer’s-associated neurodegeneration.

Download Full-text

Anthocyanins As Modulators of Cell Redox-Dependent Pathways in Non-Communicable Diseases

Current Medicinal Chemistry ◽

10.2174/0929867325666181112093336 ◽

2020 ◽

Vol 27 (12) ◽

pp. 1955-1996 ◽

Cited By ~ 4

Author(s):

Antonio Speciale ◽

Antonella Saija ◽

Romina Bashllari ◽

Maria Sofia Molonia ◽

Claudia Muscarà ◽

...

Keyword(s):

Human Health ◽

Biological Activities ◽

Wide Spectrum ◽

Antioxidant Defenses ◽

Noncommunicable Diseases ◽

Protective Effects ◽

Pathological Conditions ◽

Chronic Pulmonary Diseases ◽

Underlying Mechanisms

: Chronic Noncommunicable Diseases (NCDs), mostly represented by cardiovascular diseases, diabetes, chronic pulmonary diseases, cancers, and several chronic pathologies, are one of the main causes of morbidity and mortality, and are mainly related to the occurrence of metabolic risk factors. Anthocyanins (ACNs) possess a wide spectrum of biological activities, such as anti-inflammatory, antioxidant, cardioprotective and chemopreventive properties, which are able to promote human health. Although ACNs present an apparent low bioavailability, their metabolites may play an important role in the in vivo protective effects observed. : This article directly addresses the scientific evidences supporting that ACNs could be useful to protect human population against several NCDs not only acting as antioxidant but through their capability to modulate cell redox-dependent signaling. In particular, ACNs interact with the NF-κB and AP-1 signal transduction pathways, which respond to oxidative signals and mediate a proinflammatory effect, and the Nrf2/ARE pathway and its regulated cytoprotective proteins (GST, NQO, HO-1, etc.), involved in both cellular antioxidant defenses and elimination/inactivation of toxic compounds, so countering the alterations caused by conditions of chemical/oxidative stress. In addition, supposed crosstalks could contribute to explain the protective effects of ACNs in different pathological conditions characterized by an altered balance among these pathways. Thus, this review underlines the importance of specific nutritional molecules for human health and focuses on the molecular targets and the underlying mechanisms of ACNs against various diseases.

Download Full-text

Ginkgo biloba Extract Protects against Methotrexate-Induced Hepatotoxicity: A Computational and Pharmacological Approach

Molecules ◽

10.3390/molecules25112540 ◽

2020 ◽

Vol 25 (11) ◽

pp. 2540

Author(s):

Lina Tariq Al Kury ◽

Fazli Dayyan ◽

Fawad Ali Shah ◽

Zulkifal Malik ◽

Atif Ali Khan Khalil ◽

...

Keyword(s):

Ginkgo Biloba ◽

Liver Toxicity ◽

Serum Alkaline Phosphatase ◽

Biological Activities ◽

Research Work ◽

Ginkgo Biloba Extract ◽

Tnf Α ◽

Drug Receptor ◽

Apoptosis And Inflammation

Ginkgo biloba extract possess several promising biological activities; currently, it is clinically employed in the management of several diseases. This research work aimed to extrapolate the antioxidant and anti-inflammatory effects of Ginkgo biloba (Gb) in methotrexate (MTX)-induced liver toxicity model. These effects were analyzed using different in vivo experimental approaches and by bioinformatics analysis. Male SD rats were grouped as follows: saline; MTX; Gb (pretreated for seven days with 60, 120, and 180 mg/kg daily dose before MTX treatment); silymarin (followed by MTX treatment); Gb 180 mg/kg daily only; and silymarin only. Histopathological results revealed that MTX induced marked hepatic injury, associated with a substantial surge in various hepatic enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), and serum alkaline phosphatase (ALP). Furthermore, MTX caused the triggering of oxidative distress associated with a depressed antioxidant system. All these injury markers contributed to a significant release of apoptotic (caspase-3 and c-Jun N-terminal kinases (JNK)) and tumor necrosis factor (TNF-α)-like inflammatory mediators. Treatment with Gb counteracts MTX-mediated apoptosis and inflammation dose-dependently along with modulating the innate antioxidative mechanisms such as glutathione (GSH) and glutathione S-transferase (GST). These results were further supplemented by in silico study to analyze drug-receptor interactions (for several Gb constituents and target proteins) stabilized by a low energy value and with a good number of hydrogen bonds. These findings demonstrated that Gb could ameliorate MTX-induced elevated liver reactive oxygen species (ROS) and inflammation, possibly by JNK and TNF-α modulation.

Download Full-text

DNA PROTECTIVE ACTIVITY OF TWO SPECIES OF THE „SCROPHULARIA“ GENUS 2021ICCBIKG (2021)

10.46793/iccbi21.218m ◽

2021 ◽

Author(s):

Sanja Matić ◽

◽

Pavle Mašković ◽

Katarina Šipovac

Keyword(s):

Dna Damage ◽

Plant Species ◽

Biological Activities ◽

Wistar Rat ◽

Negative Control ◽

Control Treatment ◽

Protective Effects ◽

A Value ◽

Antigenotoxic Effects

Plants from the genus Scrophularia, family Scrophulariaceae have numerous biological activities such as antibacterial, antioxidant, antiprotozoal, antitumor, hepatoprotective, and antidiabetic. However, as far as we know, genotoxic and antigenotoxic effects of these two plant species remain unexplored. The present study aimed to evaluate possible in vivo protective effects of the methanol extracts of two plant species of the Scrophularia genus, Scrophularia canina L. and S. alata Gilib., against carbon tetrachloride (CCl4)-induced DNA damage in albino Wistar rat. A significant increase in total comet score has been shown in animals receiving CCl4 compared with the negative control. Treatment with either S. alata or S. canina extracts reduced CCl4 induced DNA damage as indicated by the percentage of reduction in total comet score with a value above 50%.

Download Full-text

Apparent thinning of human visual cortex during childhood is associated with myelination

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1904931116 ◽

2019 ◽

Vol 116 (41) ◽

pp. 20750-20759 ◽

Cited By ~ 59

Author(s):

Vaidehi S. Natu ◽

Jesse Gomez ◽

Michael Barnett ◽

Brianna Jeska ◽

Evgeniya Kirilina ◽

...

Keyword(s):

White Matter ◽

Temporal Cortex ◽

Mean Diffusivity ◽

Brain Regions ◽

Tissue Growth ◽

Quantitative Mri ◽

Childhood Development ◽

Cortical Thinning ◽

Ventral Temporal Cortex

Human cortex appears to thin during childhood development. However, the underlying microstructural mechanisms are unknown. Using functional magnetic resonance imaging (fMRI), quantitative MRI (qMRI), and diffusion MRI (dMRI) in children and adults, we tested what quantitative changes occur to gray and white matter in ventral temporal cortex (VTC) from childhood to adulthood, and how these changes relate to cortical thinning. T1 relaxation time from qMRI and mean diffusivity (MD) from dMRI provide independent and complementary measurements of microstructural properties of gray and white matter tissue. In face- and character-selective regions in lateral VTC, T1 and MD decreased from age 5 to adulthood in mid and deep cortex, as well as in their adjacent white matter. T1 reduction also occurred longitudinally in children’s brain regions. T1 and MD decreases 1) were consistent with tissue growth related to myelination, which we verified with adult histological myelin stains, and 2) were correlated with apparent cortical thinning. In contrast, in place-selective cortex in medial VTC, we found no development of T1 or MD after age 5, and thickness was related to cortical morphology. These findings suggest that lateral VTC likely becomes more myelinated from childhood to adulthood, affecting the contrast of MR images and, in turn, the apparent gray–white boundary. These findings are important because they suggest that VTC does not thin during childhood but instead gets more myelinated. Our data have broad ramifications for understanding both typical and atypical brain development using advanced in vivo quantitative measurements and clinical conditions implicating myelin.

Download Full-text

DL-3-n-Butylphthalide Attenuates Myocardial Hypertrophy by Targeting Gasdermin D and Inhibiting Gasdermin D Mediated Inflammation

Frontiers in Pharmacology ◽

10.3389/fphar.2021.688140 ◽

2021 ◽

Vol 12 ◽

Author(s):

Bingjiang Han ◽

Jiajun Xu ◽

Xiaowen Shi ◽

Zhanxiong Zheng ◽

Fengjie Shi ◽

...

Keyword(s):

Myocardial Hypertrophy ◽

Pressure Overload ◽

Pathophysiological Mechanism ◽

Protective Effects ◽

Ang Ii ◽

N Protein ◽

Cardioprotective Effects ◽

Induced Changes

Pressure overload leads to a hypertrophic milieu that produces deleterious cardiac dysfunction. Inflammation is a key pathophysiological mechanism underpinning myocardial hypertrophy. DL-3-n-butylphthalide (NBP), a neuroprotective agent, also has potent cardioprotective effects. In this study, the potential of NBP to antagonize myocardial hypertrophy was evaluated in C57BL/6 mice in vivo and in rat primary cardiomyocytes in vitro. In mice, NBP treatment reduced cardiac hypertrophy and dysfunction in a transverse aortic constriction (TAC)-induced pressure overload model. In angiotensin (Ang) II-challenged cardiomyocytes, NBP prevents cell size increases and inhibits gasdermin D (GSDMD)-mediated inflammation. Furthermore, overexpression of GSDMD-N reduced the protective effects of NBP against Ang II-induced changes. Using molecular docking and MD simulation, we found that the GSDMD-N protein may be a target of NBP. Our study shows that NBP attenuates myocardial hypertrophy by targeting GSDMD and inhibiting GSDMD-mediated inflammation.

Download Full-text

The variations of Endophilin A2-FoxO3a-autophagy signal in AngⅡ-induced dopaminergic neuron injury mouse model and By Biochanin A

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2021-0013 ◽

2021 ◽

Author(s):

Yi-Gui Yu ◽

Jun-Hui Han ◽

Hai-Xia Xue ◽

Weizu Li ◽

Wen-Ning Wu ◽

...

Keyword(s):

Mouse Model ◽

Molecular Mechanisms ◽

Biological Activities ◽

Beclin 1 ◽

Biochanin A ◽

Protective Effects ◽

Behavioral Dysfunction ◽

Related Proteins ◽

Neuron Injury

Biochanin A is a natural plant estrogen, with various biological activities such as anti-apoptosis, anti-oxidation and suppression of inflammatory. In this study, we investigated the protective effects of biochanin A on AngⅡ-induced dopaminergic neurons damage in vivo and molecular mechanisms. Spontaneous activity and motor ability of mice among groups was detected by open-field test and swim-test. The expression of TH, LC3BⅡ/LC3BⅠ, Beclin-1, P62, p-FoxO3a / FoxO3a, FoxO3 and Endophilin A2 were determined by western blot and immunohistochemistry or immunofluorescence staining. Our results showed that AngⅡ treatment significantly increased the behavioral dysfunction of mice and DA neurons damage. Meanwhile, AngⅡ treatment increased the expression of LC3BⅡ/LC3BⅠ, Beclin-1, P62 and FoxO3a and decreased the expression of Endophilin A2 and p-FoxO3a / FoxO3a, however, biochanin A treatment alleviate these changes. In summary, these results suggest that biochanin A exerts protective effects on AngⅡ-induced mouse model may be related to regulating Endophilin A2, FoxO3a and autophagy-related proteins. However, the specific mechanism is not yet clear and needs further study.

Download Full-text

β- sitosterol in Various Pathological Conditions: An Update

Current Bioactive Compounds ◽

10.2174/1573407218666211230144036 ◽

2021 ◽

Vol 18 ◽

Author(s):

Poonam Yadav ◽

Chandan Chauhan ◽

Sanjiv Singh ◽

Sugato Banerjee ◽

Krishna Murti

Keyword(s):

Plasma Membranes ◽

Biological Activities ◽

Pharmacological Action ◽

Nutritional Supplement ◽

Biologically Active ◽

Lipid Lowering ◽

Protective Effects ◽

Nonalcoholic Fatty Liver

Abstract: Phytosteroids are biologically active compounds found naturally in herb plasma membranes, with a chemical composition similar to animal plasma membrane cholesterol. It can be found in almost all fats abundant plant’s diets. One of the vital phytosterols is β-sitosterol which has several biological activities. It has been proved in various in-vivo and in-vitro research in which β-sitosterol stabilized several physiological activities like as antioxidant, CNS activity (like anti-alzheimer, anxiolytic and sedative effects, CNS depressant activity), lipid-lowering effects (like nonalcoholic fatty liver disease), antidiabetic, anti-inflammatory and analgesic effects, anticancer and immunomodulatory, protective effects in pulmonary fibrosis, wound healing effects and anti-viral and COVID-19 activity. The experimental research on β-sitosterol shows that it can be used as a nutritional supplement to combat various existing diseases. In this review, we are highlighting the most significant pharmacological action of β-sitosterol on the basis of available literature.

Download Full-text

Attenuation of genotoxicity, oxidative stress, apoptosis and inflammation by rutin in benzo(a)pyrene exposed lungs of mice: plausible role of NF-κB, TNF-α and Bcl-2

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2015-0078 ◽

2016 ◽

Vol 13 (1) ◽

Cited By ~ 15

Author(s):

Ayaz Shahid ◽

Rashid Ali ◽

Nemat Ali ◽

Syed Kazim Hasan ◽

Summya Rashid ◽

...

Keyword(s):

Oxidative Stress ◽

Biological Activities ◽

Protective Effects ◽

Oral Gavage ◽

Carcinogenic Agent ◽

Tnf Α ◽

Lung Injuries ◽

Ameliorative Effect ◽

Apoptosis And Inflammation

Abstract: Benzo(a)pyrene [B(a)P] is an environmental contaminant and potential carcinogenic agent that causes lung injuries which leads to lung cancer. Rutin, a well-known flavonoid present in various natural sources, possesses biological activities such as anti-oxidative and anti-inflammatory properties. The aim of this study was to evaluate the protective effects of rutin against B(a)P-induced genotoxicity, oxidative stress, apoptosis and inflammation in Swiss albino mice.: Pretreatment of rutin was given by oral gavage at doses of 40 and 80 mg/kg body weight (b.wt.) for 7 days before the administration of a single oral dose of B(a)P (125 mg/kg b.wt.). The ameliorative effect of rutin on oxidative stress, apoptotic and inflammatory markers in lung tissues and genotoxicity was studied using an alkaline unwinding assay and DNA fragmentation.: B(a)P enhanced lipid peroxidation, xanthine oxidase, H: The findings of the present study supported the protective effect of rutin against B(a)P-induced lung toxicity and genotoxicity.

Download Full-text

Anxiety Therapeutic Interventions of β-Caryophyllene: A Laboratory-Based Study

Natural Product Communications ◽

10.1177/1934578x20962229 ◽

2020 ◽

Vol 15 (10) ◽

pp. 1934578X2096222

Author(s):

Keylla da Conceição Machado ◽

Márcia Fernanda Correia Jardim Paz ◽

José Victor de Oliveira Santos ◽

Felipe Cavalcanti Carneiro da Silva ◽

Jana Dimitrova Tchekalarova ◽

...

Keyword(s):

Biological Activities ◽

Neurological Diseases ◽

Radical Scavenging ◽

Artemia Salina ◽

Therapeutic Interventions ◽

Test Model ◽

Protective Effects ◽

In Vivo Test

The bicyclic sesquiterpene β-caryophyllene (BCP) has diverse biological activities, including antioxidant, anti-inflammatory, antidiabetic, and analgesic effects. This study evaluates anxiolytic, toxicity, and antioxidant effects of BCP using in vitro and in vivo test models. The anxiolytic effects were tested in Swiss albino mice ( Mus musculus) by applying the elevated plus-maze, rota-rod, light and dark, and hiding sphere models, while the toxicity was evaluated by brine shrimp ( Artemia salina) lethality bioassay. Additionally, the antioxidant capacity was tested by using 2,2-diphenyl-1-picrylhydrazyl radical, 2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid hydroxyl radical scavenging, and the Saccharomyces cerevisiae test model. The results suggest that BCP exerted a dose-dependent anxiolytic-like effect on the experimental animals. It did not show toxicity in A. salina at 24 hours. BCP showed a concentration-dependent free-radical-scavenging capacity, similar to the standard antioxidant Trolox. It also showed protective and repair capacities against hydrogen peroxide-induced damaging effects in isogenic and wild-type S. cerevisiae strains. Taken together, BCP exerted antioxidant and protective effects, which can be targeted to treat neurological diseases and disorders such as anxiety.

Download Full-text

In vivo mitochondrial and glycolytic impairments in patients with Alzheimer disease

Neurology ◽

10.1212/wnl.0000000000009249 ◽

2020 ◽

Vol 94 (15) ◽

pp. e1592-e1604 ◽

Cited By ~ 11

Author(s):

Tatsuhiro Terada ◽

Tomokazu Obi ◽

Tomoyasu Bunai ◽

Takashi Matsudaira ◽

Etsuji Yoshikawa ◽

...

Keyword(s):

Glucose Metabolism ◽

Alzheimer Disease ◽

Early Stage ◽

Temporal Cortex ◽

Standard Uptake Value ◽

Brain Regions ◽

Mitochondrial Activity ◽

Arterial Blood ◽

Positive Correlations

ObjectiveIn vivo glycolysis-related glucose metabolism and electron transport chain-related mitochondrial activity may be different regionally in the brains of patients with Alzheimer disease (AD). To test this hypothesis regarding AD pathophysiology, we measured the availability of mitochondrial complex-I (MC-I) with the novel PET probe [18F]2-tert- butyl-4-chloro-5–2H- pyridazin-3-one ([18F]BCPP-EF), which binds to MC-I, and compared [18F]BCPP-EF uptake with 18F-fluorodeoxyglucose ([18F]FDG) uptake in the living AD brain.MethodsFirst, the total distribution volume (VT) of [18F]BCPP-EF from 10 normal controls (NCs) was quantified using arterial blood samples and then tested to observe whether VT could substitute for the standard uptake value relative to the global count (SUVRg). Eighteen NCs and 14 different NCs underwent PET with [18F]BCPP-EF or [18F]FDG, respectively. Second, 32 patients with AD were scanned semiquantitatively with double PET tracers. Interparticipant and intraparticipant comparisons of the levels of MC-I activity ([18F]BCPP-EF) and glucose metabolism ([18F]FDG) were performed.ResultsThe [18F]BCPP-EF VT was positively correlated with the [18F]BCPP-EF SUVRg, indicating that the use of the SUVRg was sufficient for semiquantitative evaluation. The [18F]BCPP-EF SUVRg, but not the [18F]FDG SUVRg, was significantly lower in the parahippocampus in patients with AD, highlighting the prominence of oxidative metabolic failure in the medial temporal cortex. Robust positive correlations between the [18F]BCPP-EF SUVRg and [18F]FDG SUVRg were observed in several brain regions, except the parahippocampus, in early-stage AD.ConclusionsMitochondrial dysfunction in the parahippocampus was shown in early-stage AD. Mitochondria-related energy failure may precede glycolysis-related hypometabolism in regions with pathologically confirmed early neurodegeneration in AD.

Download Full-text