Oxidative and Excitatory Neurotoxic Stresses in CRISPR/Cas9-Induced Kynurenine Aminotransferase Knockout Mice: A Novel Model for Despair-Based Depression and Post-Traumatic Stress Disorder

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 20, 2025

Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) metabolized via Trp-kynurenine (KYN) metabolic pathway, generates a variety bioactive molecules. Dysregulation KYN metabolism, particularly low levels kynurenic acid (KYNA), appears be neuropsychiatric disorders. The majority KYNA produced by aadat (kat2) gene-encoded mitochondrial kynurenine aminotransferase (KAT) isotype 2. Little known about consequences deleting enzyme gene. Methods: In CRISPR/Cas9-induced knockout (kat2-/-) mice, we examined effects on emotion, memory, motor function, Trp its metabolite levels, activities plasma urine 8-week-old males compared wild-type mice. Results: Transgenic mice showed more depressive-like behaviors forced swim test, but not tail suspension, anxiety, or memory tests. They also had fewer center field corner entries, shorter walking distances, jumping counts open test. Plasma generally consistent with those urine: antioxidant KYNs, 5-hydroxyindoleacetic acid, indole-3-acetic were lower; KATs, kynureninase, monoamine oxidase/aldehyde dehydrogenase lower, 3-monooxygenase was higher; oxidative excitotoxicity indices higher. displayed depression-like behavior learned helplessness model, emotional indifference, deficits, coupled decrease KYNA, shift metabolism toward KYN-3-hydroxykynurenine partial gut microbial Trp-indole pathway metabolite. Conclusions: This first evidence that gene induces uniquely experiences despair, appear associated excitatory neurotoxic stresses. may lead development double-hit preclinical model despair-based depression, better understanding these complex conditions, effective therapeutic strategies elucidating relationship between PTSD pathogenesis.

Language: Английский

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The Pharmacology and Toxicology of Ginkgolic Acids: Secondary Metabolites from Ginkgo biloba

The American Journal of Chinese Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 31

Published: Jan. 29, 2025

Ginkgolic acids (GAs) are distinctive secondary metabolites of Ginkgo biloba (G. biloba) primarily found in its leaves and seeds, with the highest concentration located exotesta. GAs classified as long-chain phenolic compounds, exhibit structural similarities to lignoceric acid. Their diversity arises from variations length side chains their number double bonds, resulting six distinct forms within G. extracts (GBE). Of these, GA (C15:1) is most prevalent. As inhibitors SUMOylation, demonstrate significant antitumor activity, can exert antineoplastic effects through multiple pathways, which positions them potentially promising therapeutic agents for cancer treatment. Additionally, notable anti-inflammatory, antibacterial, antiviral properties, highlighting multifaceted medicinal potential. Although pharmacological properties have been extensively investigated, associated risks liver kidney damage must not be overlooked. induce hepatic by promoting cellular apoptosis, oxidative stress, disruption various metabolic processes. Furthermore, a limited studies indicated that may nephrotoxicity, well adverse on skin nervous system. Due recognized toxicity, typically regulated 5[Formula: see text]ppm standardized leaf extract EGb 761. Currently, there no definitive evidence supporting mutagenic toxicity GAs. This review synthesizes recent advancements understanding toxicological GAs, along underlying mechanisms. It anticipated this will stimulate scholarly discourse elicit valuable insights.

Language: Английский

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Ginkgo Biloba and Long COVID: In Vivo and In Vitro Models for the Evaluation of Nanotherapeutic Efficacy

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(5), P. 1562 - 1562

Published: May 22, 2023

Coronavirus infections are neuroinvasive and can provoke injury to the central nervous system (CNS) long-term illness consequences. They may be associated with inflammatory processes due cellular oxidative stress an imbalanced antioxidant system. The ability of phytochemicals anti-inflammatory activities, such as Ginkgo biloba, alleviate neurological complications brain tissue damage has attracted strong ongoing interest in neurotherapeutic management long COVID. biloba leaf extract (EGb) contains several bioactive ingredients, e.g., bilobalide, quercetin, ginkgolides A–C, kaempferol, isorhamnetin, luteolin. have various pharmacological medicinal effects, including memory cognitive improvement. through its anti-apoptotic, antioxidant, impacts function other conditions like those While preclinical research on therapies for neuroprotection shown promising results, clinical translation remains slow challenges (e.g., low drug bioavailability, limited half-life, instability, restricted delivery target tissues, poor capacity). This review emphasizes advantages nanotherapies using nanoparticle approaches overcome these challenges. Various experimental techniques shed light molecular mechanisms underlying response help comprehend pathophysiology sequelae SARS-CoV-2 infection. To develop novel therapeutic agents systems, methods mimicking been used lipid peroxidation products, mitochondrial respiratory chain inhibitors, models ischemic damage). We hypothesize beneficial effects EGb COVID-19 symptoms, evaluated either vitro or vivo animal stress.

Language: Английский

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The Therapeutic Potential of Bee Venom-Derived Apamin and Mellitin Conjugates in Cancer Treatment: A Systematic Review

Pharmacological Research, Journal Year: 2024, Volume and Issue: unknown, P. 107430 - 107430

Published: Sept. 1, 2024

Language: Английский

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Antioxidants in Age-Related Diseases and Anti-Aging Strategies

Antioxidants, Journal Year: 2022, Volume and Issue: 11(10), P. 1868 - 1868

Published: Sept. 21, 2022

Aging is an intricate process and important risk factor in the development advancement of many disorders [...].

Language: Английский

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