Trichosanthis Semen and Zingiberis Rhizoma Mixture Ameliorates Lipopolysaccharide-Induced Memory Dysfunction by Inhibiting Neuroinflammation
Neuroinflammation, a key pathological contributor to various neurodegenerative diseases, is mediated by microglial activation and subsequent secretion of inflammatory cytokines via the mitogen-activated protein kinase (MAPK) signaling pathway. Moreover, neuroinflammation leads to synaptic loss and m...
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/22/14015 |
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| author | Hyeri Im In Gyoung Ju Jin Hee Kim Seungmin Lee Myung Sook Oh |
| author_facet | Hyeri Im In Gyoung Ju Jin Hee Kim Seungmin Lee Myung Sook Oh |
| author_sort | Hyeri Im |
| collection | DOAJ |
| description | Neuroinflammation, a key pathological contributor to various neurodegenerative diseases, is mediated by microglial activation and subsequent secretion of inflammatory cytokines via the mitogen-activated protein kinase (MAPK) signaling pathway. Moreover, neuroinflammation leads to synaptic loss and memory impairment. This study investigated the inhibitory effects of PNP001, a mixture of Trichosanthis Semen and Zingiberis Rhizoma in a ratio of 3:1, on neuroinflammation and neurological deficits induced by lipopolysaccharide (LPS). For the in vitro study, PNP001 was administered in LPS-stimulated BV2 microglial cells, and reduced the pro-inflammatory mediators, such as nitric oxide, inducible nitric oxide synthase, and cyclooxygenase-2 by downregulating MAPK signaling. For the in vivo study, ICR mice were orally administered PNP001 for 18 consecutive days, and concurrently treated with LPS (1 mg/kg, <i>i.p.</i>) for 10 days, beginning on the 4th day of PNP001 administration. The remarkably decreased number of activated microglial cells and increased expression of pre- and post-synaptic proteins were observed more in the hippocampus of the PNP001 administered groups than in the LPS-treated group. Furthermore, daily PNP001 administration significantly attenuated long-term memory decline compared with the LPS-treated group. Our study demonstrated that PNP001 inhibits LPS-induced neuroinflammation and its associated memory dysfunction by alleviating microglial activation and synaptic loss. |
| first_indexed | 2024-03-09T18:18:06Z |
| format | Article |
| id | doaj.art-d594e186f686467e84dc07456dc588d4 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:18:06Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d594e186f686467e84dc07456dc588d42023-11-24T08:37:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221401510.3390/ijms232214015Trichosanthis Semen and Zingiberis Rhizoma Mixture Ameliorates Lipopolysaccharide-Induced Memory Dysfunction by Inhibiting NeuroinflammationHyeri Im0In Gyoung Ju1Jin Hee Kim2Seungmin Lee3Myung Sook Oh4Department of Integrated Drug Development and Natural Products, Graduate School, Kyung Hee University, Seoul 02447, KoreaDepartment of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, Seoul 02447, KoreaDepartment of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, KoreaDepartment of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, KoreaDepartment of Integrated Drug Development and Natural Products, Graduate School, Kyung Hee University, Seoul 02447, KoreaNeuroinflammation, a key pathological contributor to various neurodegenerative diseases, is mediated by microglial activation and subsequent secretion of inflammatory cytokines via the mitogen-activated protein kinase (MAPK) signaling pathway. Moreover, neuroinflammation leads to synaptic loss and memory impairment. This study investigated the inhibitory effects of PNP001, a mixture of Trichosanthis Semen and Zingiberis Rhizoma in a ratio of 3:1, on neuroinflammation and neurological deficits induced by lipopolysaccharide (LPS). For the in vitro study, PNP001 was administered in LPS-stimulated BV2 microglial cells, and reduced the pro-inflammatory mediators, such as nitric oxide, inducible nitric oxide synthase, and cyclooxygenase-2 by downregulating MAPK signaling. For the in vivo study, ICR mice were orally administered PNP001 for 18 consecutive days, and concurrently treated with LPS (1 mg/kg, <i>i.p.</i>) for 10 days, beginning on the 4th day of PNP001 administration. The remarkably decreased number of activated microglial cells and increased expression of pre- and post-synaptic proteins were observed more in the hippocampus of the PNP001 administered groups than in the LPS-treated group. Furthermore, daily PNP001 administration significantly attenuated long-term memory decline compared with the LPS-treated group. Our study demonstrated that PNP001 inhibits LPS-induced neuroinflammation and its associated memory dysfunction by alleviating microglial activation and synaptic loss.https://www.mdpi.com/1422-0067/23/22/14015neuroinflammationlipopolysaccharidemicrogliaMAPKsynapse |
| spellingShingle | Hyeri Im In Gyoung Ju Jin Hee Kim Seungmin Lee Myung Sook Oh Trichosanthis Semen and Zingiberis Rhizoma Mixture Ameliorates Lipopolysaccharide-Induced Memory Dysfunction by Inhibiting Neuroinflammation International Journal of Molecular Sciences neuroinflammation lipopolysaccharide microglia MAPK synapse |
| title | Trichosanthis Semen and Zingiberis Rhizoma Mixture Ameliorates Lipopolysaccharide-Induced Memory Dysfunction by Inhibiting Neuroinflammation |
| title_full | Trichosanthis Semen and Zingiberis Rhizoma Mixture Ameliorates Lipopolysaccharide-Induced Memory Dysfunction by Inhibiting Neuroinflammation |
| title_fullStr | Trichosanthis Semen and Zingiberis Rhizoma Mixture Ameliorates Lipopolysaccharide-Induced Memory Dysfunction by Inhibiting Neuroinflammation |
| title_full_unstemmed | Trichosanthis Semen and Zingiberis Rhizoma Mixture Ameliorates Lipopolysaccharide-Induced Memory Dysfunction by Inhibiting Neuroinflammation |
| title_short | Trichosanthis Semen and Zingiberis Rhizoma Mixture Ameliorates Lipopolysaccharide-Induced Memory Dysfunction by Inhibiting Neuroinflammation |
| title_sort | trichosanthis semen and zingiberis rhizoma mixture ameliorates lipopolysaccharide induced memory dysfunction by inhibiting neuroinflammation |
| topic | neuroinflammation lipopolysaccharide microglia MAPK synapse |
| url | https://www.mdpi.com/1422-0067/23/22/14015 |
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