Andrographolide improves PCP-induced schizophrenia-like behaviors through blocking interaction between NRF2 and KEAP1
| Autor: | Yuxiu Sui, Jia Liu, Zhiping Dai, Xiying Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine food.ingredient NF-E2-Related Factor 2 Andrographolide Anti-Inflammatory Agents Phencyclidine Inflammation RM1-950 Pharmacology medicine.disease_cause Antioxidants NRF2 Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine food medicine Animals Mice Inbred ICR Kelch-Like ECH-Associated Protein 1 Epistasis Genetic Glutathione KEAP1 Andrographis Disease Models Animal 030104 developmental biology chemistry Oxidative stress Schizophrenia Molecular Medicine Therapeutics. Pharmacology Diterpenes medicine.symptom 030217 neurology & neurosurgery Andrographis paniculata Phytotherapy Signal Transduction medicine.drug |
| Zdroj: | Journal of Pharmacological Sciences, Vol 147, Iss 1, Pp 9-17 (2021) |
| ISSN: | 1347-8613 |
| Popis: | Schizophrenia is one of the foremost psychological illness around the world, and recent evidence shows that inflammation and oxidative stress may play a critical role in the etiology of schizophrenia. Andrographolide is a diterpenoid lactone from Andrographis paniculate, which has shown anti-inflammation and anti-oxidative effects. In this study, we explored whether andrographolide can improve schizophrenia-like behaviors through its inhibition of inflammation and oxidative stress in Phencyclidine (PCP)-induced mouse model of schizophrenia. We found that abnormal behavioral including locomotor activity, forced swimming and novel object recognition were ameliorated following andrographolide administration (5 mg/kg and 10 mg/kg). Andrographolide inhibited PCP-induced production of inflammatory cytokines, decreased p-p65, p-IκBα, p-p38 and p-ERK1/2 in the prefrontal cortex. Andrographolide significantly declined the level of MDA and GSH, as well as elevated the activity of SOD, CAT and GCH-px. In addition, andrographolide increased expression of NRF-2, HO-1 and NQO-1, promoted nuclear translocation of NRF-2 through blocking the interaction between NRF-2 and KEAP1, which may be associated with directly binding to NRF-2. Furthermore, antioxidative effects and anti-schizophrenia-like behaviors of andrographolide were compromised by the application of NRF-2 inhibitor ML385. In conclusion, these results suggested that andrographolide improved oxidative stress and schizophrenia-like behaviors induced by PCP through increasing NRF-2 pathway. |
| Databáze: | OpenAIRE |
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