4-Methoxycinnamic acid attenuates schizophrenia-like behaviors induced by MK-801 in mice. (1st March 2022)

• Record Type: Journal Article
• Authors: Jeong, Yongwoo; Bae, Ho Jung; Park, Keontae; Bae, Hyo Jeoung; Yang, Xingquan; Cho, Young-jin; Jung, Seo Yun; Jang, Dae Sik; Ryu, Jong Hoon
• Is Part Of: Journal of ethnopharmacology. Volume 285(2022)
• Publication Date: 2022-03-01
• Subjects: 4-Methoxycinnamic acid -- Schizophrenia -- Cognitive function -- Social interaction -- PI3K-Akt-GSK-3β signaling pathway; NMDA N-methyl-D-aspartate -- PPI prepulse inhibition -- Akt protein kinase B -- GSK-3β glycogen synthase kinase-3β -- PI3K phosphoinositide 3-kinase -- ASR acoustic startle response -- n.s. non-stimulus -- NOR novel object recognition task -- SIT social interaction task -- OFT open field task -- SDS-PAGE sodium dodecyl sulfate polyacrylamide gel electrophoresis -- PVDF polyvinylidene difluoride -- TTBS Tween 20/Tris-buffered saline -- ANOVA analysis of variance; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2021.114864
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Scrophularia buergeriana has been used for traditional medicine as an agent for reducing heat in the blood and for nourishing kidney ' Yin '. Therefore, S. buergeriana might be a potential treatment for mental illness, especially schizophrenia, which may be attenuated by supplying kidney Yin and reducing blood heat. In a pilot study, we found that S. buergeriana alleviated sensorimotor gating dysfunction induced by MK-801. Aim of the study: In the present study, we attempted to reveal the active component(s) of S. buergeriana as a candidate for treating sensorimotor gating dysfunction, and we identified 4-methoxycinnamic acid. We explored whether 4-methoxycinnamic acid could affect schizophrenia-like behaviors induced by hypofunction of the glutamatergic neurotransmitter system. Materials and methods: Mice were treated with 4-methoxycinnamic acid (3, 10, or 30 mg/kg, i.g.) under MK-801-induced schizophrenia-like conditions. The effect of 4-methoxycinnamic acid on schizophrenia-like behaviors were explored using several behavioral tasks. We also used Western blotting to investigate which signaling pathway(s) is involved in the pharmacological activities of 4-methoxycinnamic acid. Results: 4-Methoxycinnamic acid ameliorated MK-801-induced prepulse inhibition deficits, social interaction disorders and cognitive impairment by regulating the phosphorylation levels of PI3K, Akt and GSK-3β signaling in the prefrontal cortex. And there were no adverse effects in terms of catalepsy and motor coordination impairments. Conclusion: Collectively, 4-methoxycinnamic acid would be a potential candidate for treating schizophrenia with fewer adverse effects, especially the negative symptoms and cognitive dysfunctions. Graphical abstract: Image 1