Chaihu Guizhi Decoction Prevents Cognitive, Memory Impairments and Sensorimotor Gating Deficit Induced by N-methyl-d-aspartate Receptor Antibody in Mice.
J Ethnopharmacol
; : 118806, 2024 Sep 13.
Article
en En
| MEDLINE
| ID: mdl-39278296
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE Anti-NMDAR encephalitis is one of the most common types of autoimmune encephalitis, primarily presenting with prodromal symptoms, such as fever and headache, followed by a range of neurological and psychiatric symptoms. Chaihu Guizhi Decoction (CGD), a traditional Chinese medicine formulated by Zhang Zhongjing in the Eastern Han Dynasty, has been effectively used in clinical practice to treat the symptoms of Taiyang and Shaoyang disorders, including fever, headache, and psychiatric disorders. AIM OF THE STUDY To demonstrate the protective effects of CGD in an animal model of anti-NMDAR encephalitis and explore the potential mechanisms involved. MATERIALS AND METHODS:
UHPLC-HRMS was used to identify CGD's chemical components and serum metabolomic profiles. Network pharmacology and molecular docking were performed to predict potential targets of CGD for the treatment of anti-NMDAR encephalitis. The effect of CGD on anti-NMDAR encephalitis was evaluated using a mouse model induced by patients' antibodies. Behavioral tests were performed to assess cognitive impairment and schizophrenia-like behaviors. The effect of CGD on the cell-surface NMDAR GluN1 subunit in cultured neurons treated with patient antibodies was detected by immunofluorescence. Golgi staining was used to observe morphological changes in hippocampal dendrites. The expression of NMDAR-interacting proteins and various neuroreceptors in the hippocampus were examined to validate the targets predicted using network pharmacology and molecular docking.RESULTS:
CGD alleviated cognitive, memory, and sensorimotor gating deficits in mice treated with anti-NMDAR encephalitis patients' antibodies. Further experiments demonstrated the effect of CGD in preventing NMDAR reduction both in vitro and in vivo. Meanwhile, CGD regulated NMDAR-interacting proteins and dopamine receptors but did not affect hippocampal dendritic morphology and synaptic density. Additionally, CGD modifies metabolic pathways associated with anti-NMDAR encephalitis and other neurological and psychiatric disorders.CONCLUSIONS:
CGD exhibited protective effects against anti-NMDAR encephalitis by mitigating the antibody-induced reduction in NMDAR and NMDAR-interacting proteins.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
J Ethnopharmacol
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Irlanda