Mechanism of DaiTongXiao in the treatment of gouty arthritis through the NLRP3 signaling pathway
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved..
ETHNOPHARMACOLOGICAL RELEVANCE: DaiTongXiao (DTX) is a traditional Chinese Dai folk formulation utilized for gouty arthritis treatment, with substantial evidence supporting its anti-inflammatory properties. The NLRP3 inflammasome disorder is tightly linked to the development of many inflammatory diseases.
AIM OF THE STUDY: To elucidate the therapeutic efficacy of DTX in gouty arthritis and reveal its potential underlying mechanism.
MATERIALS AND METHODS: The primary active constituents in DTX were determined through ultraviolet spectrophotometry and gas chromatography. Rats underwent induction with monosodium urate (MSU), followed by treatment of J774A.1 cells with adenosine triphosphate (ATP) activation and lipopolysaccharide (LPS) induction and the subsequent culture in Dulbecco's modified Eagle's medium. The degree of foot joint swelling in rats was assessed, and ankle joints were evaluated through H&E staining. Enzyme-linked immunosorbent assay was performed to measure the levels of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in both serum and cells. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to determine the relative mRNA expression levels of NLRP3, ASC, Caspase-1, and NF-κB in J774A.1 macrophages. The expression of NLRP3, ASC, Caspase-1, and NF-κB was examined by western blotting.
RESULTS: DTX could alleviate MSU-induced joint swelling in rats, as evidenced by a reduction in joint inflammation. Moreover, DTX effectively enhanced the survival rate of J774A.1 cells following LPS induction and ATP activation. Furthermore, DTX significantly reduced IL-1β, IL-6, IL-8, and TNF-α levels in both cell culture medium and rat serum. RT-PCR results revealed that DTX notably downregulated the mRNA expression levels of NLRP3, ASC, Caspase-1, and NF-κB in J774A.1 cells. Additionally, DTX downregulated NLRP3, ASC, NF-κB, and Caspase-1 expression in the joint tissue.
CONCLUSIONS: DTX exerts a significant anti-gouty arthritis effect, with its mechanism being tightly linked to the NLRP3 inflammatory signaling pathway. This pathway may be modulated by inhibiting IL-1β differentiation and maturation by downregulating NLRP3, ASC, Caspase-1, and NF-κB protein expression. This, in turn, leads to a reduction in the release of IL-6, IL-8, and TNF-α, ultimately impeding gouty arthritis progression.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:319 |
|---|---|
| Enthalten in: |
Journal of ethnopharmacology - 319(2024), Pt 3 vom: 30. Jan., Seite 117313 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liu, Feifan [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 27.11.2023 Date Revised 21.02.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.jep.2023.117313 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM364168501 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM364168501 | ||
| 003 | DE-627 | ||
| 005 | 20240222091439.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jep.2023.117313 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1301.xml |
| 035 | |a (DE-627)NLM364168501 | ||
| 035 | |a (NLM)37924998 | ||
| 035 | |a (PII)S0378-8741(23)01183-2 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Liu, Feifan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mechanism of DaiTongXiao in the treatment of gouty arthritis through the NLRP3 signaling pathway |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 27.11.2023 | ||
| 500 | |a Date Revised 21.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a ETHNOPHARMACOLOGICAL RELEVANCE: DaiTongXiao (DTX) is a traditional Chinese Dai folk formulation utilized for gouty arthritis treatment, with substantial evidence supporting its anti-inflammatory properties. The NLRP3 inflammasome disorder is tightly linked to the development of many inflammatory diseases | ||
| 520 | |a AIM OF THE STUDY: To elucidate the therapeutic efficacy of DTX in gouty arthritis and reveal its potential underlying mechanism | ||
| 520 | |a MATERIALS AND METHODS: The primary active constituents in DTX were determined through ultraviolet spectrophotometry and gas chromatography. Rats underwent induction with monosodium urate (MSU), followed by treatment of J774A.1 cells with adenosine triphosphate (ATP) activation and lipopolysaccharide (LPS) induction and the subsequent culture in Dulbecco's modified Eagle's medium. The degree of foot joint swelling in rats was assessed, and ankle joints were evaluated through H&E staining. Enzyme-linked immunosorbent assay was performed to measure the levels of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in both serum and cells. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to determine the relative mRNA expression levels of NLRP3, ASC, Caspase-1, and NF-κB in J774A.1 macrophages. The expression of NLRP3, ASC, Caspase-1, and NF-κB was examined by western blotting | ||
| 520 | |a RESULTS: DTX could alleviate MSU-induced joint swelling in rats, as evidenced by a reduction in joint inflammation. Moreover, DTX effectively enhanced the survival rate of J774A.1 cells following LPS induction and ATP activation. Furthermore, DTX significantly reduced IL-1β, IL-6, IL-8, and TNF-α levels in both cell culture medium and rat serum. RT-PCR results revealed that DTX notably downregulated the mRNA expression levels of NLRP3, ASC, Caspase-1, and NF-κB in J774A.1 cells. Additionally, DTX downregulated NLRP3, ASC, NF-κB, and Caspase-1 expression in the joint tissue | ||
| 520 | |a CONCLUSIONS: DTX exerts a significant anti-gouty arthritis effect, with its mechanism being tightly linked to the NLRP3 inflammatory signaling pathway. This pathway may be modulated by inhibiting IL-1β differentiation and maturation by downregulating NLRP3, ASC, Caspase-1, and NF-κB protein expression. This, in turn, leads to a reduction in the release of IL-6, IL-8, and TNF-α, ultimately impeding gouty arthritis progression | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a DaiTongXiao (DTX) | |
| 650 | 4 | |a Gouty arthritis | |
| 650 | 4 | |a Mechanism | |
| 650 | 4 | |a NLRP3 inflammasome | |
| 650 | 4 | |a Pharmacodynamics | |
| 650 | 7 | |a NLR Family, Pyrin Domain-Containing 3 Protein |2 NLM | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 650 | 7 | |a Interleukin-6 |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a Interleukin-8 |2 NLM | |
| 650 | 7 | |a Inflammasomes |2 NLM | |
| 650 | 7 | |a Uric Acid |2 NLM | |
| 650 | 7 | |a 268B43MJ25 |2 NLM | |
| 650 | 7 | |a Caspase 1 |2 NLM | |
| 650 | 7 | |a EC 3.4.22.36 |2 NLM | |
| 650 | 7 | |a Adenosine Triphosphate |2 NLM | |
| 650 | 7 | |a 8L70Q75FXE |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 700 | 1 | |a Shen, Fanyi |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Yuanmei |e verfasserin |4 aut | |
| 700 | 1 | |a Wan, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Lijie |e verfasserin |4 aut | |
| 700 | 1 | |a He, Jinglin |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Yuhuan |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Peixin |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of ethnopharmacology |d 1980 |g 319(2024), Pt 3 vom: 30. Jan., Seite 117313 |w (DE-627)NLM00095196X |x 1872-7573 |7 nnns |
| 773 | 1 | 8 | |g volume:319 |g year:2024 |g number:Pt 3 |g day:30 |g month:01 |g pages:117313 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jep.2023.117313 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 319 |j 2024 |e Pt 3 |b 30 |c 01 |h 117313 | ||