Effect of Berberine on Activation of TLR4-NFκB Signaling Pathway and NLRP3 Inflammasome in Patients with Gout

DANG Wan-tai; XU Dan; ZHOU Jing-guo

doi:10.1007/s11655-022-3720-7

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Effect of Berberine on Activation of TLR4-NFκB Signaling Pathway and NLRP3 Inflammasome in Patients with Gout

Original Article | Updated：2023-01-05

- Effect of Berberine on Activation of TLR4-NFκB Signaling Pathway and NLRP3 Inflammasome in Patients with Gout
- Chinese Journal of Integrative Medicine Vol. 29, Issue 1, Pages: 10-18(2023)
- Affiliations：
  
  Chengdu Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu (610500), China
- Author bio：
  
  Prof. XU Dan, E-mail: 447926416@qq.com
- Funds：
- DOI：10.1007/s11655-022-3720-7
  CLC：
- Published：01 January 2023，
  
  Published Online：20 September 2022，
  
  Accepted：15 September 2021
Scan for full text
DANG Wan-tai, XU Dan, ZHOU Jing-guo. Effect of Berberine on Activation of TLR4-NFκB Signaling Pathway and NLRP3 Inflammasome in Patients with Gout. [J]. Chinese Journal of Integrative Medicine 29(1):10-18(2023)
DOI：

DANG Wan-tai, XU Dan, ZHOU Jing-guo. Effect of Berberine on Activation of TLR4-NFκB Signaling Pathway and NLRP3 Inflammasome in Patients with Gout. [J]. Chinese Journal of Integrative Medicine 29(1):10-18(2023) DOI： 10.1007/s11655-022-3720-7.

摘要

Abstract

Objective:

To determine the effects of berberine (BBR) on the activation of toll-like receptor 4 (TLR4)

nuclear factor (NF) κB (NF-κB) signaling and NLRP3 inflammasome in patients with gout.

Methods:

Peripheral blood mononuclear cells (PBMCs) were obtained from 24 acute (AP) and 41 non-acute (NAP) phases of primary gout patients

respectively

as well as 30 healthy controls (HC). TLR4

NF-κB (p65)

NLRP3

apoptosis-associated specklike protein containing a CARD (PYCARD)

cysteinyl aspartate specific proteinase-1 (CASP1)

and interleukin-1β (IL-1β) mRNA expression levels in PBMCs were measured by quantitative reverse transcriptase polymerase chain reaction. The protein levels of TLR4

myeloid differentiation factor 88 (MyD88)

NF-κB (p50/65)

inhibitor of kappa B kinase α/β (IKKα/β)

NF-κB inhibitor α (IKBα)

phospho-IKKα/β (p-IKKα/β)

NLRP3

PYCARD

and CASP1 were monitored by Western blotting. Serum IL-1β protein level was measured using enzyme-linked immunosorbent assay (ELISA). In addition

PBMCs from HC and macrophages derived from a spontaneously immortalized monocyte-like cell line (THP-1) were stimulated using monosodium urate (MSU

100 μg/mL)

0.1% dimethyl sulfoxide

25 μmol/L BBR

and 10

and 50 μmol/L BBR+100 μg/mL MSU for different time periods. The protein levels of IL-1β and IL-18 in cell culture supernatants was measured by ELISA

and the protein expressions of TLR4

MyD88

NF-κB (p50/p65)

IKKα/β

IκBα

p-IKKα/β

NLRP3

PYCARD

and CASP1 in macrophages were analyzed by Western blotting.

Results:

(1) TLR4

NF-κB (p65)

PYCARD

CASP1

and IL-1β mRNA levels in PBMCs were significantly higher in the AP group than in the HC group (

0.05). The NLRP3 mRNA expression levels in PBMCs were found to be significantly lower in the AP and NAP groups than in the HC group (

0.05

0.01). (2) The protein levels of TLR4

IKKβ

MyD88

NF-κB

p-IKKα/β

PYCARD

and CASP1 in PBMCs were significantly higher

and those of IκBα

IKKα

and NLRP3 were found to be significantly lower in the AP group than in the HC group (

0.05 or

0.01). (3) The serum IL-1β protein levels were significantly higher in the AP and NAP groups than in the HC group (

0.01). (4) The IL-1β protein level was significantly lower in the culture supernatants of the PBMCs stimulated with MSU for 3 and 6 h in the 25 and 50 μmoL/L BBR groups compared with that in the MSU group (

0.01). (5) The protein levels of IL-1β and IL-18 were also significantly lower in the culture supernatants of macrophages stimulated with MSU for 3 and 6 h in BBR groups compared with those in the MSU group (

0.01). (6) The protein levels of TLR4

MyD88

NF-κB (p50

p65

p105)

IKKα/β

p-IκBα

p-IKKα/β

PYCARD

and CASP1 were significantly differed between the macrophages stimulated with MSU for 0.5 and 6 h in BBR groups compared with those in the MSU group (

0.05 or

0.01).

Conclusions:

Activation of TLR4-NFκB signaling and NLRP3 inflammasome by MSU crystals drives the progression of gout inflammation. BBR ameliorates gouty inflammation

which is mechanistically associated with its regulation of TLR4-NF-κB signaling and NLRP3 inflammasome expression.

关键词

Keywords

berberinegoutTLR4-NF-κBNLRP3 inflammasomemonosodium urate

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Department of Gastroenterology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine

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