<i>Zanthoxylum piperitum</i> Benn. Attenuates Monosodium Urate-Induced Gouty Arthritis: A Network Pharmacology Investigation of Its Anti-Inflammatory Mechanisms

<b>Background:</b> Monosodium urate crystal accumulation in the joints is the cause of gout, an inflammatory arthritis that is initiated by elevated serum uric acid levels. It is the most prevalent form of inflammatory arthritis, affecting millions worldwide, and requires effective treat...

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Main Authors: Sung Wook Kim, Soo Hyun Jeong, Jong Uk Kim, Mi Hye Kim, Wonwoong Lee, Cheol-Jung Lee, Tae Han Yook, Gabsik Yang
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/1/29
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author Sung Wook Kim
Soo Hyun Jeong
Jong Uk Kim
Mi Hye Kim
Wonwoong Lee
Cheol-Jung Lee
Tae Han Yook
Gabsik Yang
author_facet Sung Wook Kim
Soo Hyun Jeong
Jong Uk Kim
Mi Hye Kim
Wonwoong Lee
Cheol-Jung Lee
Tae Han Yook
Gabsik Yang
author_sort Sung Wook Kim
collection DOAJ
description <b>Background:</b> Monosodium urate crystal accumulation in the joints is the cause of gout, an inflammatory arthritis that is initiated by elevated serum uric acid levels. It is the most prevalent form of inflammatory arthritis, affecting millions worldwide, and requires effective treatments. The necessity for alternatives with fewer side effects is underscored by the frequent adverse effects of conventional therapies, such as urate-lowering drugs. IL-1β is a potential therapeutic target due to its significant role in the inflammatory response induced by MSU. <i>Zanthoxylum piperitum</i> Benn. (ZP), a shrub that possesses antibacterial, antioxidant, and anti-inflammatory properties, has demonstrated potential in the treatment of inflammatory conditions. <b>Methods:</b> For anti-inflammatory properties of ZP, Raw264.7 cell stimulated LPS were treated ZP and using RNA-seq with Bone marrow derived macrophage, we observed to change inflammatory gene. Pharmacological networks were conducted to select target gene associated with ZP. For in vivo, mice were injected MSU in footpad for induce gouty arthritis model. The components of ZP were analyzed using GC-MS, and distilled extracts of ZP (deZP) were prepared. <b>Results:</b> In vitro, deZP decreased inflammatory cytokines. However, in vivo, it also decreased paw thickness and IL-1β levels. The anti-inflammatory effects of deZP are believed to be mediated through the NLRP3 inflammasome pathway, as indicated by RNA sequencing and network pharmacology analyses. <b>Conclusions:</b> ZP has an anti-inflammatory effect and regulation of the NLRP3 inflammasome in vitro and in vivo. Further research, including clinical trials, is required to confirm the safety of deZP, determine the optimal dosing, and evaluate its long-term effects.
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spelling doaj-art-50a4fbf2600043d38e89dc3b37435c982025-01-24T13:45:04ZengMDPI AGPharmaceuticals1424-82472024-12-011812910.3390/ph18010029<i>Zanthoxylum piperitum</i> Benn. Attenuates Monosodium Urate-Induced Gouty Arthritis: A Network Pharmacology Investigation of Its Anti-Inflammatory MechanismsSung Wook Kim0Soo Hyun Jeong1Jong Uk Kim2Mi Hye Kim3Wonwoong Lee4Cheol-Jung Lee5Tae Han Yook6Gabsik Yang7College of Korea Medicine, Woosuk University, Jeonju-si 54986, Republic of KoreaCollege of Korea Medicine, Woosuk University, Jeonju-si 54986, Republic of KoreaCollege of Korea Medicine, Woosuk University, Jeonju-si 54986, Republic of KoreaCollege of Korea Medicine, Woosuk University, Jeonju-si 54986, Republic of KoreaDepartment of Pharmacy, College of Pharmacy, Woosuk University, Wanju 55338, Republic of KoreaResearch Center for Materials Analysis, Korea Basic Science Institute, Daejeon 34133, Republic of KoreaCollege of Korea Medicine, Woosuk University, Jeonju-si 54986, Republic of KoreaCollege of Korea Medicine, Woosuk University, Jeonju-si 54986, Republic of Korea<b>Background:</b> Monosodium urate crystal accumulation in the joints is the cause of gout, an inflammatory arthritis that is initiated by elevated serum uric acid levels. It is the most prevalent form of inflammatory arthritis, affecting millions worldwide, and requires effective treatments. The necessity for alternatives with fewer side effects is underscored by the frequent adverse effects of conventional therapies, such as urate-lowering drugs. IL-1β is a potential therapeutic target due to its significant role in the inflammatory response induced by MSU. <i>Zanthoxylum piperitum</i> Benn. (ZP), a shrub that possesses antibacterial, antioxidant, and anti-inflammatory properties, has demonstrated potential in the treatment of inflammatory conditions. <b>Methods:</b> For anti-inflammatory properties of ZP, Raw264.7 cell stimulated LPS were treated ZP and using RNA-seq with Bone marrow derived macrophage, we observed to change inflammatory gene. Pharmacological networks were conducted to select target gene associated with ZP. For in vivo, mice were injected MSU in footpad for induce gouty arthritis model. The components of ZP were analyzed using GC-MS, and distilled extracts of ZP (deZP) were prepared. <b>Results:</b> In vitro, deZP decreased inflammatory cytokines. However, in vivo, it also decreased paw thickness and IL-1β levels. The anti-inflammatory effects of deZP are believed to be mediated through the NLRP3 inflammasome pathway, as indicated by RNA sequencing and network pharmacology analyses. <b>Conclusions:</b> ZP has an anti-inflammatory effect and regulation of the NLRP3 inflammasome in vitro and in vivo. Further research, including clinical trials, is required to confirm the safety of deZP, determine the optimal dosing, and evaluate its long-term effects.https://www.mdpi.com/1424-8247/18/1/29<i>Zanthoxylum piperitum</i>NLRP3 inflammasomemonosodium urate crystalsgouty arthritisnetwork pharmacology
spellingShingle Sung Wook Kim
Soo Hyun Jeong
Jong Uk Kim
Mi Hye Kim
Wonwoong Lee
Cheol-Jung Lee
Tae Han Yook
Gabsik Yang
<i>Zanthoxylum piperitum</i> Benn. Attenuates Monosodium Urate-Induced Gouty Arthritis: A Network Pharmacology Investigation of Its Anti-Inflammatory Mechanisms
Pharmaceuticals
<i>Zanthoxylum piperitum</i>
NLRP3 inflammasome
monosodium urate crystals
gouty arthritis
network pharmacology
title <i>Zanthoxylum piperitum</i> Benn. Attenuates Monosodium Urate-Induced Gouty Arthritis: A Network Pharmacology Investigation of Its Anti-Inflammatory Mechanisms
title_full <i>Zanthoxylum piperitum</i> Benn. Attenuates Monosodium Urate-Induced Gouty Arthritis: A Network Pharmacology Investigation of Its Anti-Inflammatory Mechanisms
title_fullStr <i>Zanthoxylum piperitum</i> Benn. Attenuates Monosodium Urate-Induced Gouty Arthritis: A Network Pharmacology Investigation of Its Anti-Inflammatory Mechanisms
title_full_unstemmed <i>Zanthoxylum piperitum</i> Benn. Attenuates Monosodium Urate-Induced Gouty Arthritis: A Network Pharmacology Investigation of Its Anti-Inflammatory Mechanisms
title_short <i>Zanthoxylum piperitum</i> Benn. Attenuates Monosodium Urate-Induced Gouty Arthritis: A Network Pharmacology Investigation of Its Anti-Inflammatory Mechanisms
title_sort i zanthoxylum piperitum i benn attenuates monosodium urate induced gouty arthritis a network pharmacology investigation of its anti inflammatory mechanisms
topic <i>Zanthoxylum piperitum</i>
NLRP3 inflammasome
monosodium urate crystals
gouty arthritis
network pharmacology
url https://www.mdpi.com/1424-8247/18/1/29
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