Andrographolide improves PCP-induced schizophrenia-like behaviors through blocking interaction between NRF2 and KEAP1
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-inflamm...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-09-01
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| Series: | Journal of Pharmacological Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861321000499 |
| _version_ | 1819146169329123328 |
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| author | Xiying Wang Jia Liu Zhiping Dai Yuxiu Sui |
| author_facet | Xiying Wang Jia Liu Zhiping Dai Yuxiu Sui |
| author_sort | Xiying Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T13:09:39Z |
| format | Article |
| id | doaj.art-427b0aa485044bd18e2fe64a806a204f |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-22T13:09:39Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-427b0aa485044bd18e2fe64a806a204f2022-12-21T18:24:47ZengElsevierJournal of Pharmacological Sciences1347-86132021-09-011471917Andrographolide improves PCP-induced schizophrenia-like behaviors through blocking interaction between NRF2 and KEAP1Xiying Wang0Jia Liu1Zhiping Dai2Yuxiu Sui3Department of Psychiatry, The Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, China; Corresponding author.Department of Clinical Pharmacy, The Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Psychiatry, The Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Psychiatry, The Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing, ChinaSchizophrenia 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.http://www.sciencedirect.com/science/article/pii/S1347861321000499AndrographolideSchizophreniaNRF2Oxidative stressInflammation |
| spellingShingle | Xiying Wang Jia Liu Zhiping Dai Yuxiu Sui Andrographolide improves PCP-induced schizophrenia-like behaviors through blocking interaction between NRF2 and KEAP1 Journal of Pharmacological Sciences Andrographolide Schizophrenia NRF2 Oxidative stress Inflammation |
| title | Andrographolide improves PCP-induced schizophrenia-like behaviors through blocking interaction between NRF2 and KEAP1 |
| title_full | Andrographolide improves PCP-induced schizophrenia-like behaviors through blocking interaction between NRF2 and KEAP1 |
| title_fullStr | Andrographolide improves PCP-induced schizophrenia-like behaviors through blocking interaction between NRF2 and KEAP1 |
| title_full_unstemmed | Andrographolide improves PCP-induced schizophrenia-like behaviors through blocking interaction between NRF2 and KEAP1 |
| title_short | Andrographolide improves PCP-induced schizophrenia-like behaviors through blocking interaction between NRF2 and KEAP1 |
| title_sort | andrographolide improves pcp induced schizophrenia like behaviors through blocking interaction between nrf2 and keap1 |
| topic | Andrographolide Schizophrenia NRF2 Oxidative stress Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S1347861321000499 |
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