Syneilesis palmata (Thunb.) Maxim. extract attenuates inflammatory responses via the regulation of TRIF-dependent signaling and inflammasome activation.
BACKGROUND
Syneilesis palmata (Thunb.) Maxim. (S. palmata, Asteraceae) is a traditional Korean therapeutic herb widely used to treat pain, arthritis, and other symptoms. This study provides the scientific basis for the anti-inflammatory effects of S. palmata extract (SP) in both in vitro and in vivo experimental models.


METHODS
Lipopolysaccharide (LPS)-stimulated murine macrophages were used to study the regulatory effect of SP on the inflammatory mediators in vitro. Bone marrow-derived macrophages were used to study the effects of SP on inflammasome activation. Escherichia coli-induced sepsis mouse model and LPS-induced endotoxin shock model were employed to study the effect of SP on in vivo efficacy.


RESULTS
SP inhibited the LPS-stimulated release of proinflammatory mediators, such as nitric oxide and interleukin (IL)-6 in RAW 264.7 cells. SP treatment also attenuated IL-1β secretion via the inhibition of NLRP3 inflammasome activation induced by monosodium urate, ATP, and nigericin. Further, SP ameliorated the severity of NLRP3 inflammasome-mediated symptoms in LPS-induced endotoxin and E. coli-induced sepsis mouse models. Mechanistic studies revealed that inhibitory effects of SP were mediated through the regulation of TRIF-dependent signaling and inflammasome activation.


CONCLUSIONS
This study was the first to reveal mechanistic-based evidence substantiating the traditional claims of SP in the treatment of inflammation-related disorders, such as pain and arthritis.
Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, Konkuk University, Chungju, South Korea.
Ji-Won
JW
Han
Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, Konkuk University, Chungju, South Korea.
Do-Wan
DW
Shim
Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, Konkuk University, Chungju, South Korea.
Eun-Jeong
EJ
Shim
Department of Food Science and Engineering, Seowon University, Cheongju, South Korea.
Myong-Ki
MK
Kim
Department of Natural Medicine Resources, Semyung University, Jecheon, South Korea.
Yong-Kook
YK
Shin
Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, Konkuk University, Chungju, South Korea.
Su-Bin
SB
Kwak
Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, Konkuk University, Chungju, South Korea.
Sushruta
S
Koppula
Division of Biological Science and Technology, Institute of Biomaterials, Yonsei University, Wonju, South Korea.
Tack-Joong
TJ
Kim
Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, Konkuk University, Chungju, South Korea.
Tae-Bong
TB
Kang
Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, Konkuk University, Chungju, South Korea. Electronic address: kwangho@kku.ac.kr.
Kwang-Ho
KH
Lee
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D019659:Asteraceae / Q000737:chemistry*; D002460:Cell Line; D004926:Escherichia coli / Q000472:pathogenicity; D005260:Female; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D033942:Adaptor Proteins, Vesicular Transport; D000893:Anti-Inflammatory Agents; D058847:Inflammasomes; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D010936:Plant Extracts; C476286:Ticam1 protein, mouse
Asteraceae; Inflammasome; Inflammation; Sepsis; TRIF