Paeonol Suppresses Neuroinflammatory Responses in LPS-Activated Microglia Cells.
In this work, we assessed the anti-inflammatory effects of paeonol (PAE) in LPS-activated N9 microglia cells, as well as its underlying molecular mechanisms. PAE had no adverse effect on the viability of murine microglia N9 cell line within a broad range (0.12∼75 μM). When N9 cell line was activated by LPS, PAE (0.6, 3, 15 μM) significantly suppressed the release of proinflammatory products, such as nitric oxide (NO), interleukin-1β (IL-1β), and prostaglandin E2 (PGE2), demonstrated by the ELISA assay. Moreover, the levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were significantly reduced in PAE-treated N9 microglia cells. We also examined some proteins involved in immune signaling pathways and found that PAE treatment significantly decreased the expression of TLR4, MyD88, IRAK4, TNFR-associated factor 6 (TRAF6), p-IkB-α, and NF-kB p65, as well as the mitogen-activated protein kinase (MAPK) pathway molecules p-P38, p-JNK, and p-ERK, indicating that PAE might act on these signaling pathways to inhibit inflammatory responses. Overall, we found that PAE had anti-inflammatory effect on LPS-activated N9 microglia cells, possibly via inhibiting the TLR4 signaling pathway, and it could be a potential drug therapy for inflammation-associated neurodegenerative diseases.
Department of Traditional Chinese Medicine, College of Pharmacy, Jinan University, No. 601 West Huangpu Avenue, Guangzhou, 510632, China.
Li Xia
LX
He
The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, 650021, China.
Xiaoyun
X
Tong
Department of Traditional Chinese Medicine, College of Pharmacy, Jinan University, No. 601 West Huangpu Avenue, Guangzhou, 510632, China.
Jing
J
Zeng
Department of Traditional Chinese Medicine, College of Pharmacy, Jinan University, No. 601 West Huangpu Avenue, Guangzhou, 510632, China.
Yuanqing
Y
Tu
Department of Traditional Chinese Medicine, College of Pharmacy, Jinan University, No. 601 West Huangpu Avenue, Guangzhou, 510632, China.
Saicun
S
Wu
Department of Traditional Chinese Medicine, College of Pharmacy, Jinan University, No. 601 West Huangpu Avenue, Guangzhou, 510632, China.
Manping
M
Li
Department of Traditional Chinese Medicine, College of Pharmacy, Jinan University, No. 601 West Huangpu Avenue, Guangzhou, 510632, China.
Huaming
H
Deng
Department of Traditional Chinese Medicine, College of Pharmacy, Jinan University, No. 601 West Huangpu Avenue, Guangzhou, 510632, China.
Miaomiao
M
Zhu
Department of Traditional Chinese Medicine, College of Pharmacy, Jinan University, No. 601 West Huangpu Avenue, Guangzhou, 510632, China.
Xiucun
X
Li
Department of Traditional Chinese Medicine, College of Pharmacy, Jinan University, No. 601 West Huangpu Avenue, Guangzhou, 510632, China.
Hong
H
Nie
Department of Traditional Chinese Medicine, College of Pharmacy, Jinan University, No. 601 West Huangpu Avenue, Guangzhou, 510632, China. doctormonkey@126.com.
Li
L
Yang
Department of Molecular Pharmacology, School of Traditional Chinese Materia Medica, Yunnan University of Traditional Chinese Medicine, 1076 Yuhua St., Kunming, 650500, China. hftxyy@hotmail.com.
Feng
http://orcid.org/0000-0003-4193-8057
F
Huang
D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000188:drug therapy*; D008070:Lipopolysaccharides; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D015213:Neuroimmunomodulation / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D000098:Acetophenones; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C013638:paeonol
anti-inflammatory; microglia cells; neurodegenerative disease; paeonol