Neuroprotective Effects of Bexarotene and Icariin in a Diabetic Rat Model DOI Open Access
Dilek Ağırcan, Tuğba Melike Parlak, Öznur Tufan

et al.

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 30, 2024

Objective Type 2 diabetes mellitus (T2DM), a chronic metabolic disorder affecting over 400 million people globally, is increasingly recognized for its detrimental impact on the central nervous system. T2DM linked to neurodegenerative diseases like Alzheimer's and vascular dementia. This study investigates neuroprotective effects of bexarotene icariin in rat model, focusing brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), neurofilament-light chain (NfL) levels. Methods Before study, rats underwent fasting blood glucose tests, lipid profile assessments, general health evaluations, followed by high-fat diet two weeks single streptozotocin dose (35 mg/kg). Rats with levels ≥250 mg/dl were classified as (DM) continued throughout experiment. Forty-seven male Wistar Albino divided into six groups: healthy control group, DM group treated bexarotene, icariin, groups combinations low high doses icariin. After 45-day treatment, samples collected under thiopental sodium anesthesia, HbA1c (glycosylated hemoglobin) hematological parameters analyzed within eight hours, serum stored at -80°C further analysis. The animals then euthanized, brain tissues harvested, frozen, until examination. Brain BDNF, GFAP, NfL using ELISA (enzyme-linked immunosorbent assay). For comparing multiple groups, Kruskal-Wallis test was applied nonparametric data, one-way ANOVA used parametric Bonferroni's post hoc pairwise comparisons. Statistical significance determined two-tailed tests p < 0.05. Results Significant changes GFAP observed across (p 0.001). showed highest levels, while treatment exhibited reductions. also BDNF lowest increments. Conclusion highlights potential diabetic evidenced significant lack suggests that longer durations may be necessary observe these effects. Future research should include extended periods, larger sample sizes, varied dosages, comprehensive behavioral assessments better understand therapeutic agents.

Language: Английский

Establishing network pharmacology between natural polyphenols and Alzheimer’s disease using bioinformatic tools – An advancement in Alzheimer’s research DOI Creative Commons
Arunkumar Subramanian,

T. Tamilanban,

Vetriselvan Subramaniyan

et al.

Toxicology Reports, Journal Year: 2024, Volume and Issue: 13, P. 101715 - 101715

Published: Aug. 23, 2024

Alzheimer's disease (AD) is a major cause of disability and one the top causes mortality globally. AD remains public health challenge due to its prevalence, impact on patients caregivers, current lack cure. In recent years, polyphenols have garnered attention for their potential therapeutic effects AD. The objective study was establish network pharmacology between selected plant origin Insilico tools such as SwissADME, ProTox3.0, pkCSM, Swiss Target Prediction, DisGeNET, InterActiVenn, DAVID database, STRING Cytoscape/CytoHubba were employed multi-target polyphenolic compounds. present revealed that out 17 polyphenols, 10 ligands found possess drug-likeness nature along with desirable pharmacokinetic parameters lesser toxicity profile. Also, results highlighted possible interactions targets involved in Further, this has shed light mTOR pathway through autophagic mechanism. Overall, indicated could be better option treating Hence, consumption cocktails part diet produce more effective outcomes against disease. Additional studies are warranted future explore additional pathways genes provide comprehensive understanding regarding usage shortlisted derivatives prevention treatment

Language: Английский

Citations

4
Virtual Screening, Toxicity Evaluation and Pharmacokinetics of Erythrina Alkaloids as Acetylcholinesterase Inhibitor Candidates from Natural Products DOI Creative Commons

Afri Permana,

Abd Wahid Rizaldi Akili, Ari Hardianto

et al.

Advances and Applications in Bioinformatics and Chemistry, Journal Year: 2025, Volume and Issue: Volume 17, P. 179 - 201

Published: Feb. 1, 2025

Purpose: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited treatment options, necessitating the development of safer and more effective therapies. The potential alkaloids derived from genus Erythrina as acetylcholinesterase (AChE) inhibitors being investigated to enhance acetylcholine levels in brain, which crucial for AD. objective this study identify strong inhibitory capacity against AChE favorable pharmacokinetic profiles. Materials Methods: A multi-step computational approach was employed, beginning virtual screening 143 alkaloid structures using molecular docking human crystal structure. binding affinities were compared known inhibitor, galantamine. top alkaloid, 8-oxoerymelanthine ( 128 ), subjected further analysis through dynamics simulations, evaluating its stability interactions. In silico ADMET predictions conducted assess properties. applicability Lipinski's Rule Five applied evaluate oral drug-likeness. Results: 8-Oxoerymelanthine ) exhibited highest affinity remarkable simulations. toxicity indicated low risk mutagenicity, hepatotoxicity, cardiotoxicity. Pharmacokinetic assessments good absorption, moderate blood-brain barrier penetration, metabolic excretion profiles, supporting an orally active drug candidate. Conclusion: 8-Oxoerythmelanthine exhibits inhibitor balance efficacy, safety, These results warrant investigation preclinical clinical studies validate therapeutic safety treatment. Keywords: pharmacokinetics, silico, inhibitors,

Language: Английский

Citations

0
Safety Assessment of Resveratrol Surrogate Molecule 5 (RSM5): Acute and Sub-acute Oral Toxicity Studies in BALB/c Mice DOI Creative Commons
Arunkumar Subramanian,

T. Tamilanban,

Amar Daud Iskandar Abdullah

et al.

Toxicology Reports, Journal Year: 2025, Volume and Issue: 14, P. 101956 - 101956

Published: Feb. 14, 2025

Language: Английский

Citations

0
Recent Advances in Resveratrol Derivatives: Structural Modifications and Biological Activities DOI Creative Commons
Xiaohan Liu, Yong Pei, Jiahui Li

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(4), P. 958 - 958

Published: Feb. 19, 2025

Resveratrol, a naturally occurring phenolic stilbene molecule, has been intensively researched for its anti-inflammatory, anticancer, antioxidant, antibacterial, and neuroprotective properties. However, due to limited absorption probable hepatotoxicity, it is difficult employ directly as medication, limiting therapeutic applicability. Over the last five years, numerous structural changes in resveratrol have widely studied, resulting considerable improvements pharmacological activity drug availability. This work reviews biological activities structure-activity relationships (SARs) of derivatives, with goal providing useful insights discovery new derivatives.

Language: Английский

Citations

0
Neuroprotective Effects of Bexarotene and Icariin in a Diabetic Rat Model DOI Open Access
Dilek Ağırcan, Tuğba Melike Parlak, Öznur Tufan

et al.

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 30, 2024

Objective Type 2 diabetes mellitus (T2DM), a chronic metabolic disorder affecting over 400 million people globally, is increasingly recognized for its detrimental impact on the central nervous system. T2DM linked to neurodegenerative diseases like Alzheimer's and vascular dementia. This study investigates neuroprotective effects of bexarotene icariin in rat model, focusing brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), neurofilament-light chain (NfL) levels. Methods Before study, rats underwent fasting blood glucose tests, lipid profile assessments, general health evaluations, followed by high-fat diet two weeks single streptozotocin dose (35 mg/kg). Rats with levels ≥250 mg/dl were classified as (DM) continued throughout experiment. Forty-seven male Wistar Albino divided into six groups: healthy control group, DM group treated bexarotene, icariin, groups combinations low high doses icariin. After 45-day treatment, samples collected under thiopental sodium anesthesia, HbA1c (glycosylated hemoglobin) hematological parameters analyzed within eight hours, serum stored at -80°C further analysis. The animals then euthanized, brain tissues harvested, frozen, until examination. Brain BDNF, GFAP, NfL using ELISA (enzyme-linked immunosorbent assay). For comparing multiple groups, Kruskal-Wallis test was applied nonparametric data, one-way ANOVA used parametric Bonferroni's post hoc pairwise comparisons. Statistical significance determined two-tailed tests p < 0.05. Results Significant changes GFAP observed across (p 0.001). showed highest levels, while treatment exhibited reductions. also BDNF lowest increments. Conclusion highlights potential diabetic evidenced significant lack suggests that longer durations may be necessary observe these effects. Future research should include extended periods, larger sample sizes, varied dosages, comprehensive behavioral assessments better understand therapeutic agents.

Language: Английский

Citations

0