Saikosaponin C ameliorates tau-related pathology by modulating oxidative stress and MAPK axis in Alzheimer's disease
Notice bibliographique
Résumé
Ethnopharmacological relevance Saikosaponin C (SSc), a traditional Chinese herbal medicine, is a triterpene saponin and an active compound extracted from Radix Bupleuri. It has been demonstrated to have neuroprotective effects in cellular models of neurodegenerative diseases; however, its precise mechanism of action in alleviating tau pathology in Alzheimer's disease (AD), as well as its potential to improve cognitive deficits in animal models, has not yet been elucidated. Aim of the study In this study, we investigated the in vivo therapeutic effects of SSc on a human tau (hTau) mouse model expressing normal hTau isoforms in terms of tau-related pathology (tauopathy) and the underlying mechanisms. Materials and methods For the animal study, C57BL/6 mice received stereotaxic brain injections of adeno-associated virus (AAV)-hTau in the absence or presence of SSc. The Morris water maze test was employed to evaluate the therapeutic effects of SSc on memory and learning. Tau phosphorylation in the brain was assessed by immunofluorescence and Western blotting. Dendritic spine maturation, an indicator of synaptic plasticity, was determined by assessing doublecortin expression and performing automatic dendritic spine analysis. GFAP and Iba1 immunoreactivity were observed as indicators of neuroinflammation. Dityrosine formation and superoxide dismutase 2 expression were measured to monitor oxidative stress. For the mechanistic study, RNA-Seq was used to identify tauopathy-related changes in gene expression. Furthermore, the effects of SSc on aluminum chloride (AlCl 3 )-induced cytotoxicity, oxidative stress, tau phosphorylation, and mitogen-activated protein kinase (MAPK) signaling were evaluated. Results We found that SSc significantly relieved spatial memory impairment and alleviated the pathological hallmarks of AD-like tau, such as excessive tau phosphorylation and oxidative stress, in AAV-hTau-injected mice. SSc also relieved the deficit in dendritic spine density in mice with tauopathy-associated dementia. Neuroinflammation, another hallmark of AD-like pathology, was reduced by SSc treatment. Furthermore, SSc attenuated AlCl 3 -induced tau pathology, such as neurotoxicity and abnormal tau phosphorylation, by targeting oxidative stress and the downstream MAPK pathway. Conclusions Our results suggest that SSc treatment ameliorates cognitive deficits and related tau pathological features in the hTau AD mouse model. The antioxidant effects of SSc might be responsible for the therapeutic potential of SSc in protecting against tau pathology and cognitive decline.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».