Bavachin attenuates LPS-induced inflammatory response and inhibits the activation of NLRP3 inflammasome in macrophages

Yung Li Hung; Shu Chi Wang; Katsuhiko Suzuki; Shih Hua Fang; Chi Shuo Chen; Wei Chung Cheng; Chia Cheng Su; Hsin Chih Yeh; Hung Pin Tu; Po Len Liu; Ming Yii Huang; Chia Yang Li

doi:10.1016/j.phymed.2018.12.008

Bavachin attenuates LPS-induced inflammatory response and inhibits the activation of NLRP3 inflammasome in macrophages

Yung Li Hung, Shu Chi Wang, Katsuhiko Suzuki, Shih Hua Fang, Chi Shuo Chen, Wei Chung Cheng, Chia Cheng Su, Hsin Chih Yeh, Hung Pin Tu, Po Len Liu, Ming Yii Huang, Chia Yang Li

Research output: Contribution to journal › Article › peer-review

56 Scopus citations

Abstract

Background: Bavachin is a natural product isolated from Psoralea corylifolia L. that has been applied as a traditional medicine in Asian countries. However, the anti-inflammatory effects of bavachin on LPS-induced inflammation and NLRP3 inflammasome activation by macrophages remain unclear. Purpose: We investigated the anti-inflammatory effects of bavachin on LPS-activated murine macrophage cell line J774A.1 cells and murine peritoneal macrophages. Methods: J774A.1 cells and murine peritoneal macrophages were pre-treated with bavachin following LPS treatment. The concentrations of NO, PGE ₂ , IL-6 and IL-12p40 in cell culture supernatant were analyzed. The expressions of iNOS, COX-2, mPGES-1 and MAPKs were analyzed using Western blotting, while NF-κB activity was detected using promoter reporter assay. To examine the activation of NLRP3 inflammasome, J774A.1 cells were incubated with LPS, and then treated with bavachin following treatment with ATP. The concentration of IL-1β in the cell culture supernatant was measured. The expressions of NLRP3, ASC, caspase-1 and IL-1β were analyzed using Western blotting. The formation of inflammasome complex was observed by immunofluorescence microscopy. Results: Bavachin suppressed LPS-induced NO and PGE ₂ production, and decreased iNOS and mPGES-1 expression. Bavachin also reduced LPS-induced IL-6 and IL-12p40 production and decreased the activation of MAPKs and NF-κB. Additionally, bavachin suppressed NLRP3 inflammasome-derived IL-1β secretion, decreased caspase-1 activation, repressed mature IL-1β expression, and inhibited inflammasome complex formation. Furthermore, bavachin also suppressed the production of NO, IL-6 and IL-12p40 by LPS-stimulated murine peritoneal macrophages. Conclusion: Our experimental results indicated anti-inflammatory effects of bavachin exhibit attenuation of LPS-induced inflammation and inhibit activation of NLRP3 inflammasome in macrophages. These results suggest that bavachin might have potential in treating inflammatory and autoimmune diseases.

Original language	English (US)
Article number	152785
Journal	Phytomedicine
Volume	59
DOIs	https://doi.org/10.1016/j.phymed.2018.12.008
State	Published - Jun 2019
Externally published	Yes

Keywords

Bavachin
Inflammation
Macrophage
NLRP3 inflammasome
mPGES-1

ASJC Scopus subject areas

Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Complementary and alternative medicine

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10.1016/j.phymed.2018.12.008

Cite this

@article{88acdc992d6144beb0b1524a5217a562,

title = "Bavachin attenuates LPS-induced inflammatory response and inhibits the activation of NLRP3 inflammasome in macrophages",

abstract = " Background: Bavachin is a natural product isolated from Psoralea corylifolia L. that has been applied as a traditional medicine in Asian countries. However, the anti-inflammatory effects of bavachin on LPS-induced inflammation and NLRP3 inflammasome activation by macrophages remain unclear. Purpose: We investigated the anti-inflammatory effects of bavachin on LPS-activated murine macrophage cell line J774A.1 cells and murine peritoneal macrophages. Methods: J774A.1 cells and murine peritoneal macrophages were pre-treated with bavachin following LPS treatment. The concentrations of NO, PGE 2 , IL-6 and IL-12p40 in cell culture supernatant were analyzed. The expressions of iNOS, COX-2, mPGES-1 and MAPKs were analyzed using Western blotting, while NF-κB activity was detected using promoter reporter assay. To examine the activation of NLRP3 inflammasome, J774A.1 cells were incubated with LPS, and then treated with bavachin following treatment with ATP. The concentration of IL-1β in the cell culture supernatant was measured. The expressions of NLRP3, ASC, caspase-1 and IL-1β were analyzed using Western blotting. The formation of inflammasome complex was observed by immunofluorescence microscopy. Results: Bavachin suppressed LPS-induced NO and PGE 2 production, and decreased iNOS and mPGES-1 expression. Bavachin also reduced LPS-induced IL-6 and IL-12p40 production and decreased the activation of MAPKs and NF-κB. Additionally, bavachin suppressed NLRP3 inflammasome-derived IL-1β secretion, decreased caspase-1 activation, repressed mature IL-1β expression, and inhibited inflammasome complex formation. Furthermore, bavachin also suppressed the production of NO, IL-6 and IL-12p40 by LPS-stimulated murine peritoneal macrophages. Conclusion: Our experimental results indicated anti-inflammatory effects of bavachin exhibit attenuation of LPS-induced inflammation and inhibit activation of NLRP3 inflammasome in macrophages. These results suggest that bavachin might have potential in treating inflammatory and autoimmune diseases. ",

keywords = "Bavachin, Inflammation, Macrophage, NLRP3 inflammasome, mPGES-1",

author = "Hung, {Yung Li} and Wang, {Shu Chi} and Katsuhiko Suzuki and Fang, {Shih Hua} and Chen, {Chi Shuo} and Cheng, {Wei Chung} and Su, {Chia Cheng} and Yeh, {Hsin Chih} and Tu, {Hung Pin} and Liu, {Po Len} and Huang, {Ming Yii} and Li, {Chia Yang}",

note = "Funding Information: This study was supported by Kaohsiung Medical University “Aim for the Top Universities Grant” [grant no. KMU-TP105E17], and grants from the Ministry of Science and Technology, Taiwan, R.O.C. [grant no. MOST 106-2320-B-037-020], [grant no. MOST 105-2628-B-037-004-MY2] and [grant no. MOST 107-2320-B-037-019]. Publisher Copyright: {\textcopyright} 2018 The Author(s)",

year = "2019",

month = jun,

doi = "10.1016/j.phymed.2018.12.008",

language = "English (US)",

volume = "59",

journal = "Phytomedicine",

issn = "0944-7113",

publisher = "Urban und Fischer Verlag Jena",

}

TY - JOUR

T1 - Bavachin attenuates LPS-induced inflammatory response and inhibits the activation of NLRP3 inflammasome in macrophages

AU - Hung, Yung Li

AU - Wang, Shu Chi

AU - Suzuki, Katsuhiko

AU - Fang, Shih Hua

AU - Chen, Chi Shuo

AU - Cheng, Wei Chung

AU - Su, Chia Cheng

AU - Yeh, Hsin Chih

AU - Tu, Hung Pin

AU - Liu, Po Len

AU - Huang, Ming Yii

AU - Li, Chia Yang

N1 - Funding Information: This study was supported by Kaohsiung Medical University “Aim for the Top Universities Grant” [grant no. KMU-TP105E17], and grants from the Ministry of Science and Technology, Taiwan, R.O.C. [grant no. MOST 106-2320-B-037-020], [grant no. MOST 105-2628-B-037-004-MY2] and [grant no. MOST 107-2320-B-037-019]. Publisher Copyright: © 2018 The Author(s)

PY - 2019/6

Y1 - 2019/6

N2 - Background: Bavachin is a natural product isolated from Psoralea corylifolia L. that has been applied as a traditional medicine in Asian countries. However, the anti-inflammatory effects of bavachin on LPS-induced inflammation and NLRP3 inflammasome activation by macrophages remain unclear. Purpose: We investigated the anti-inflammatory effects of bavachin on LPS-activated murine macrophage cell line J774A.1 cells and murine peritoneal macrophages. Methods: J774A.1 cells and murine peritoneal macrophages were pre-treated with bavachin following LPS treatment. The concentrations of NO, PGE 2 , IL-6 and IL-12p40 in cell culture supernatant were analyzed. The expressions of iNOS, COX-2, mPGES-1 and MAPKs were analyzed using Western blotting, while NF-κB activity was detected using promoter reporter assay. To examine the activation of NLRP3 inflammasome, J774A.1 cells were incubated with LPS, and then treated with bavachin following treatment with ATP. The concentration of IL-1β in the cell culture supernatant was measured. The expressions of NLRP3, ASC, caspase-1 and IL-1β were analyzed using Western blotting. The formation of inflammasome complex was observed by immunofluorescence microscopy. Results: Bavachin suppressed LPS-induced NO and PGE 2 production, and decreased iNOS and mPGES-1 expression. Bavachin also reduced LPS-induced IL-6 and IL-12p40 production and decreased the activation of MAPKs and NF-κB. Additionally, bavachin suppressed NLRP3 inflammasome-derived IL-1β secretion, decreased caspase-1 activation, repressed mature IL-1β expression, and inhibited inflammasome complex formation. Furthermore, bavachin also suppressed the production of NO, IL-6 and IL-12p40 by LPS-stimulated murine peritoneal macrophages. Conclusion: Our experimental results indicated anti-inflammatory effects of bavachin exhibit attenuation of LPS-induced inflammation and inhibit activation of NLRP3 inflammasome in macrophages. These results suggest that bavachin might have potential in treating inflammatory and autoimmune diseases.

AB - Background: Bavachin is a natural product isolated from Psoralea corylifolia L. that has been applied as a traditional medicine in Asian countries. However, the anti-inflammatory effects of bavachin on LPS-induced inflammation and NLRP3 inflammasome activation by macrophages remain unclear. Purpose: We investigated the anti-inflammatory effects of bavachin on LPS-activated murine macrophage cell line J774A.1 cells and murine peritoneal macrophages. Methods: J774A.1 cells and murine peritoneal macrophages were pre-treated with bavachin following LPS treatment. The concentrations of NO, PGE 2 , IL-6 and IL-12p40 in cell culture supernatant were analyzed. The expressions of iNOS, COX-2, mPGES-1 and MAPKs were analyzed using Western blotting, while NF-κB activity was detected using promoter reporter assay. To examine the activation of NLRP3 inflammasome, J774A.1 cells were incubated with LPS, and then treated with bavachin following treatment with ATP. The concentration of IL-1β in the cell culture supernatant was measured. The expressions of NLRP3, ASC, caspase-1 and IL-1β were analyzed using Western blotting. The formation of inflammasome complex was observed by immunofluorescence microscopy. Results: Bavachin suppressed LPS-induced NO and PGE 2 production, and decreased iNOS and mPGES-1 expression. Bavachin also reduced LPS-induced IL-6 and IL-12p40 production and decreased the activation of MAPKs and NF-κB. Additionally, bavachin suppressed NLRP3 inflammasome-derived IL-1β secretion, decreased caspase-1 activation, repressed mature IL-1β expression, and inhibited inflammasome complex formation. Furthermore, bavachin also suppressed the production of NO, IL-6 and IL-12p40 by LPS-stimulated murine peritoneal macrophages. Conclusion: Our experimental results indicated anti-inflammatory effects of bavachin exhibit attenuation of LPS-induced inflammation and inhibit activation of NLRP3 inflammasome in macrophages. These results suggest that bavachin might have potential in treating inflammatory and autoimmune diseases.

KW - Bavachin

KW - Inflammation

KW - Macrophage

KW - NLRP3 inflammasome

KW - mPGES-1

UR - http://www.scopus.com/inward/record.url?scp=85064400462&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064400462&partnerID=8YFLogxK

U2 - 10.1016/j.phymed.2018.12.008

DO - 10.1016/j.phymed.2018.12.008

M3 - Article

C2 - 31009850

AN - SCOPUS:85064400462

SN - 0944-7113

VL - 59

JO - Phytomedicine

JF - Phytomedicine

M1 - 152785

ER -

Bavachin attenuates LPS-induced inflammatory response and inhibits the activation of NLRP3 inflammasome in macrophages

Abstract

Keywords

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