Electroacupuncture improves gout arthritis pain via attenuating ROS-mediated NLRP3 inflammasome overactivation

Wei, Huina; Liu, Boyu; Yin, Chengyu; Zeng, Danyi; Nie, Huimin; Li, Yuanyuan; Tai, Yan; He, Xiaofen; Liu, Boyi

doi:10.1186/s13020-023-00800-1

Cited by 10 publications

(18 citation statements)

References 52 publications

(89 reference statements)

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“…We noticed in our recent studies that gouty arthritis model animals also developed obvious heat hyperalgesia 14 , 40 . AOS3 (200 mg/kg) treatment significantly alleviated heat hyperalgesia of model mice ( Figure S2 A&B).…”

Section: Resultsmentioning

confidence: 97%

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Well-defined alginate oligosaccharides ameliorate joint pain and inflammation in a mouse model of gouty arthritis

Yin,

Lyu,

Dong

et al. 2024

Theranostics

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Background: Gouty arthritis causes severe pain and inflammation. Alginate oligosaccharides (AOSs) are natural products derived from alginate and have anti-inflammatory properties. We explored the potential effects of AOSs with different degrees of polymerization (Dp) on gouty arthritis and associated mechanisms. Methods: We established a mouse model of gouty arthritis by injecting monosodium urate (MSU) into ankle joint. Nocifensive behavior, gait and ankle swelling were used to study AOS's effects. Biochemical assays, in vivo imaging, live cell Ca 2+ imaging, electrophysiology, RNA-sequencing, etc. were used for mechanism exploration. Results: AOS2 (Dp=2), AOS3 (Dp=3) and AOS4 (Dp=4) all inhibited ankle swelling, whereas AOS2&3 produced the most obvious analgesia on model mice. AOS3, which was picked for further evaluation, produced dose-dependent ameliorative effects on model mice. AOS3 reversed gait impairments but did not alter locomotor activity. AOS3 inhibited NLRP3 inflammasome activation and inflammatory cytokine up-regulation in ankle joint. AOS3 ameliorated MSU-induced oxidative stress and reactive oxygen species (ROS) production both in vivo and in vitro and reversed the impaired mitochondrial bioenergetics. AOS3 activated the Nrf2 pathway and promoted Nrf2 disassociation from Keap1-bound complex and Nrf2 nuclear translocation, thus facilitating antioxidant gene expression via Nrf2-dependent mechanism. Nrf2 gene deficiency abolished AOS3's ameliorative effects on pain, inflammation and oxidative stress in ankle joints of model mice. AOS3 reduced TRPV1 functional enhancement in DRG neurons and constrained neuroactive peptide release. Conclusions: AOS3 ameliorates gouty arthritis via activating Nrf2-dependent antioxidant signaling, resulting in suppression of ROS-mediated NLRP3 inflammasome activation and TRPV1 enhancement. AOS3 may be novel therapeutics for gouty arthritis.

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Section: Resultsmentioning

confidence: 97%

“…The mice were anesthetized with 2.5% isoflurane during the injection. Ankle swelling and mechanical hypersensitivity, which would occur 2 h after MSU injection, were regarded as criteria for successful establishment of the model as reported 14 .…”

Section: Methodsmentioning

confidence: 99%

Well-defined alginate oligosaccharides ameliorate joint pain and inflammation in a mouse model of gouty arthritis

Yin,

Lyu,

Dong

et al. 2024

Theranostics

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“…165 Inflammation during GA can expand without limitation, leading to joint necrosis and even death if there is no regulatory mechanism. 166,167 There is no doubt that multiple mechanisms are utilized to prevent endless inflammation from happening. Evidence has showed that several key mechanisms are involved in inflammatory regression during gouty arthritis.…”

Section: Inflammatory Resolutionmentioning

confidence: 99%

Targeting Neutrophil Extracellular Traps in Gouty Arthritis: Insights into Pathogenesis and Therapeutic Potential

Li,

Wu,

et al. 2024

JIR

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Gouty arthritis (GA) is an immune-mediated disorder characterized by severe inflammation due to the deposition of monosodium urate (MSU) crystals in the joints. The pathophysiological mechanisms of GA are not yet fully understood, and therefore, the identification of effective therapeutic targets is of paramount importance. Neutrophil extracellular traps (NETs), an intricate structure of DNA scaffold, encompassing myeloperoxidase, histones, and elastases -have gained significant attention as a prospective therapeutic target for gouty arthritis, due to their innate antimicrobial and immunomodulatory properties. Hence, exploring the therapeutic potential of NETs in gouty arthritis remains an enticing avenue for further investigation. During the process of gouty arthritis, the formation of NETs triggers the release of inflammatory cytokines, thereby contributing to the inflammatory response, while MSU crystals and cytokines are sequestered and degraded by the aggregation of NETs. Here, we provide a concise summary of the inflammatory processes underlying the initiation and resolution of gouty arthritis mediated by NETs. Furthermore, this review presents an overview of the current pharmacological approaches for treating gouty arthritis and summarizes the potential of natural and synthetic product-based inhibitors that target NET formation as novel therapeutic options, alongside elucidating the intrinsic challenges of these inhibitors in NETs research. Lastly, the limitations of HL-60 cell as a suitable substitute of neutrophils in NETs research are summarized and discussed. Series of recommendations are provided, strategically oriented towards guiding future investigations to effectively address these concerns. These findings will contribute to an enhanced comprehension of the interplay between NETs and GA, facilitating the proposition of innovative therapeutic strategies and novel approaches for the management of GA.

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“…The methods were adopted from our previous study [35] . Brie y, the mice were sacri ced on day 7 or 14.…”

Section: Immuno Uorescence Stainingmentioning

confidence: 99%

Electroacupuncture Alleviates Paclitaxel-induced Peripheral Neuropathy by Reducing CCL2-mediated Macrophage Infiltration in Sensory Ganglia and Sciatic Nerve

Li,

Xu,

Chen

et al. 2024

Preprint

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Background: Paclitaxel-induced peripheral neuropathy (PIPN) is a common side effect accompanying paclitaxel chemotherapy, resulting in sensory abnormality and neuropathic pain. Conventional medications lack effectiveness on PIPN. Clinical trials identified beneficial effects of acupuncture on PIPN among patients receiving chemotherapy. Here we explored the mechanisms underlying how acupuncture might alleviate PIPN. Methods: A mouse model of PIPN was established by repeated paclitaxel application. Electroacupuncture (EA) was applied at ST36 and BL60 acupoints of model mice. Immunostaining, flow cytometry, behavioral assay, in vivoimaging were utilized. Results: EA ameliorated mechanical and cold pain hypersensitivities, reduced sensory neuron damage and improved loss in intra-epidermal nerve fibers (IENFs) in model mice. Macrophage infiltration was observed in DRG and sciatic nerve of model mice, which was reduced by EA. EA affected M1-like pro-inflammatory macrophage infiltration in DRG, whereas it did not affect M2-like macrophages. DRG neurons released chemoattractant CCL2 that recruited macrophages via CCR2 to DRG. EA reduced CCL2 overproduction by DRG neurons and reduced macrophage infiltration. Blocking CCR2 mimicked EA’s anti-allodynic effect, whereas exogenously applying CCL2 reversed ameliorating effect of EA on macrophage infiltration and abolished EA’s anti-allodynia on model mice. EA ameliorated other signs of PIPN, including sensory neuron damage, sciatic nerve morphology impairment and IENFs loss. In mice inoculated with breast cancer cells, EA didn’t affect paclitaxel-induced antitumor effect. Conclusions: These findings suggest EA alleviates PIPN by reducing pro-inflammatory macrophage infiltration in sensory ganglia and sciatic nerve. Our study supports acupuncture to be used as a non-pharmacological therapy for PIPN.

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Electroacupuncture improves gout arthritis pain via attenuating ROS-mediated NLRP3 inflammasome overactivation

Cited by 10 publications

References 52 publications

Well-defined alginate oligosaccharides ameliorate joint pain and inflammation in a mouse model of gouty arthritis

Well-defined alginate oligosaccharides ameliorate joint pain and inflammation in a mouse model of gouty arthritis

Targeting Neutrophil Extracellular Traps in Gouty Arthritis: Insights into Pathogenesis and Therapeutic Potential

Electroacupuncture Alleviates Paclitaxel-induced Peripheral Neuropathy by Reducing CCL2-mediated Macrophage Infiltration in Sensory Ganglia and Sciatic Nerve

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