Paeoniflorin Alleviates Lipopolysaccharide-Induced Neuroinflammation and Depression Through the Keap1/Nrf2/HO-1 Signaling Pathway
Depression is associated with bidirectional interactions between inflammatory responses and behavioral dysfunction. Paeoniflorin (PF), a monoterpene glycoside derived from <i>Paeonia lactiflora</i>, exhibits potent anti-inflammatory properties. This study investigates the therapeutic eff...
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MDPI AG
2025-05-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/14/5/585 |
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| author | Zhuoyue Hu Xing Wang Tian Shi Lei Yang Boxi Zhang Bo Shang Ruizhi He Shichen Yi Jiao He Jing Hu Yanjun Cao |
| author_facet | Zhuoyue Hu Xing Wang Tian Shi Lei Yang Boxi Zhang Bo Shang Ruizhi He Shichen Yi Jiao He Jing Hu Yanjun Cao |
| author_sort | Zhuoyue Hu |
| collection | DOAJ |
| description | Depression is associated with bidirectional interactions between inflammatory responses and behavioral dysfunction. Paeoniflorin (PF), a monoterpene glycoside derived from <i>Paeonia lactiflora</i>, exhibits potent anti-inflammatory properties. This study investigates the therapeutic effects of PF on lipopolysaccharide (LPS)-induced depression-like behaviors in mice and neuroinflammation in BV2 microglial cells. Mice were co-administered PF (20, 40, or 80 mg/kg/day) and LPS (2 mg/kg) for 7 days. Behavioral tests; Nissl staining; and Golgi, Iba1, DLG4, and cytokine assays were conducted. Additionally, hippocampal NF-κB, Nrf2, and BDNF signaling pathways were analyzed using Western blots. In BV2 cells, oxidative stress and the Nrf2/HO-1 pathway were assessed using CCK-8, flow cytometry, and Western blotting after 24 h of LPS and PF treatment. PF significantly alleviated LPS-induced depression-like behaviors, increased hippocampal neuron and dendritic spine density, and upregulated synaptic proteins (PSD95, SNAP25, and BDNF). Mechanistically, PF suppressed NLRP3 inflammasome activation via the Akt/GSK3β pathway, reduced pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and enhanced the Nrf2/HO-1 antioxidant axis. In BV2 cells, PF restored mitochondrial membrane potential, inhibited apoptosis, and decreased cytokine levels (TNF-α, IL-1β, and IL-6) by inhibiting TLR4/NF-κB signaling. In conclusion, PF significantly improved LPS-induced depression-like behaviors and attenuated neuroinflammation in BV2 microglial cells, highlighting its potential as a therapeutic agent for inflammation-associated depression. |
| format | Article |
| id | doaj-art-7ba522b20fee41af9866f515ebbc0934 |
| institution | DOAJ |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-7ba522b20fee41af9866f515ebbc09342025-08-20T03:14:39ZengMDPI AGAntioxidants2076-39212025-05-0114558510.3390/antiox14050585Paeoniflorin Alleviates Lipopolysaccharide-Induced Neuroinflammation and Depression Through the Keap1/Nrf2/HO-1 Signaling PathwayZhuoyue Hu0Xing Wang1Tian Shi2Lei Yang3Boxi Zhang4Bo Shang5Ruizhi He6Shichen Yi7Jiao He8Jing Hu9Yanjun Cao10School of Medicine, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Xi’an 710069, ChinaSchool of Medicine, Northwest University, Xi’an 710069, ChinaKey Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Xi’an 710069, ChinaDepression is associated with bidirectional interactions between inflammatory responses and behavioral dysfunction. Paeoniflorin (PF), a monoterpene glycoside derived from <i>Paeonia lactiflora</i>, exhibits potent anti-inflammatory properties. This study investigates the therapeutic effects of PF on lipopolysaccharide (LPS)-induced depression-like behaviors in mice and neuroinflammation in BV2 microglial cells. Mice were co-administered PF (20, 40, or 80 mg/kg/day) and LPS (2 mg/kg) for 7 days. Behavioral tests; Nissl staining; and Golgi, Iba1, DLG4, and cytokine assays were conducted. Additionally, hippocampal NF-κB, Nrf2, and BDNF signaling pathways were analyzed using Western blots. In BV2 cells, oxidative stress and the Nrf2/HO-1 pathway were assessed using CCK-8, flow cytometry, and Western blotting after 24 h of LPS and PF treatment. PF significantly alleviated LPS-induced depression-like behaviors, increased hippocampal neuron and dendritic spine density, and upregulated synaptic proteins (PSD95, SNAP25, and BDNF). Mechanistically, PF suppressed NLRP3 inflammasome activation via the Akt/GSK3β pathway, reduced pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and enhanced the Nrf2/HO-1 antioxidant axis. In BV2 cells, PF restored mitochondrial membrane potential, inhibited apoptosis, and decreased cytokine levels (TNF-α, IL-1β, and IL-6) by inhibiting TLR4/NF-κB signaling. In conclusion, PF significantly improved LPS-induced depression-like behaviors and attenuated neuroinflammation in BV2 microglial cells, highlighting its potential as a therapeutic agent for inflammation-associated depression.https://www.mdpi.com/2076-3921/14/5/585paeoniflorindepressionlipopolysaccharideneuroinflammationNrf2/HO-1 |
| spellingShingle | Zhuoyue Hu Xing Wang Tian Shi Lei Yang Boxi Zhang Bo Shang Ruizhi He Shichen Yi Jiao He Jing Hu Yanjun Cao Paeoniflorin Alleviates Lipopolysaccharide-Induced Neuroinflammation and Depression Through the Keap1/Nrf2/HO-1 Signaling Pathway Antioxidants paeoniflorin depression lipopolysaccharide neuroinflammation Nrf2/HO-1 |
| title | Paeoniflorin Alleviates Lipopolysaccharide-Induced Neuroinflammation and Depression Through the Keap1/Nrf2/HO-1 Signaling Pathway |
| title_full | Paeoniflorin Alleviates Lipopolysaccharide-Induced Neuroinflammation and Depression Through the Keap1/Nrf2/HO-1 Signaling Pathway |
| title_fullStr | Paeoniflorin Alleviates Lipopolysaccharide-Induced Neuroinflammation and Depression Through the Keap1/Nrf2/HO-1 Signaling Pathway |
| title_full_unstemmed | Paeoniflorin Alleviates Lipopolysaccharide-Induced Neuroinflammation and Depression Through the Keap1/Nrf2/HO-1 Signaling Pathway |
| title_short | Paeoniflorin Alleviates Lipopolysaccharide-Induced Neuroinflammation and Depression Through the Keap1/Nrf2/HO-1 Signaling Pathway |
| title_sort | paeoniflorin alleviates lipopolysaccharide induced neuroinflammation and depression through the keap1 nrf2 ho 1 signaling pathway |
| topic | paeoniflorin depression lipopolysaccharide neuroinflammation Nrf2/HO-1 |
| url | https://www.mdpi.com/2076-3921/14/5/585 |
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