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Trichosanthis Semen and Zingiberis Rhizoma Mixture Ameliorates Lipopolysaccharide-Induced Memory Dysfunction by
Hyeri Im1, In Gyoung Ju2, Jin Hee Kim3
1Department of Integrated Drug Development and Natural Products, Graduate School, Kyung Hee University, Seoul 02447, Korea.
Abstract:
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.p.) 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.
Insights
PNP001, a herbal mixture, reduces neuroinflammation and memory loss by calming microglial activation and preventing synaptic damage. This natural compound effectively combats lipopolysaccharide-induced neurological deficits.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Neuroinflammation, driven by microglial activation and MAPK signaling, contributes to neurodegeneration, synaptic loss, and memory impairment.
- Lipopolysaccharide (LPS) is a common inducer of experimental neuroinflammation.
Purpose of the Study:
- To investigate the inhibitory effects of PNP001, a herbal mixture (Trichosanthis Semen and Zingiberis Rhizoma, 3:1 ratio), on LPS-induced neuroinflammation and memory deficits.
- To elucidate the underlying mechanisms of PNP001's action, including its impact on microglial activation and synaptic integrity.
Main Methods:
- In vitro: LPS-stimulated BV2 microglial cells were treated with PNP001 to assess its effects on pro-inflammatory mediators and MAPK signaling.
- In vivo: ICR mice received oral PNP001 treatment and intraperitoneal LPS injection. Microglial activation, synaptic protein expression, and long-term memory were evaluated.
Main Results:
- PNP001 downregulated pro-inflammatory mediators (nitric oxide, iNOS, COX-2) in vitro by inhibiting MAPK signaling.
- In vivo, PNP001 significantly reduced microglial activation and increased pre- and post-synaptic protein expression in the hippocampus.
- PNP001 administration attenuated LPS-induced long-term memory decline.
Conclusions:
- PNP001 effectively inhibits LPS-induced neuroinflammation and associated memory dysfunction.
- The therapeutic effects of PNP001 are mediated by the alleviation of microglial activation and synaptic loss.
- PNP001 represents a potential therapeutic agent for neurodegenerative diseases characterized by neuroinflammation.
