Vanillic Acid Reduces Pain-Related Behavior in Knee Osteoarthritis Rats Through the Inhibition of NLRP3 Inflammasome-Related Synovitis

Ma, Zhenyuan; Huang, Zhengquan; Zhang, Li; Li, Xiaochen; Xiao, Yancheng; Shi, Xianglin; Zhang, Haosheng; Liao, Taiyang

doi:10.3389/fphar.2020.599022

Cited by 21 publications

(17 citation statements)

References 34 publications

(28 reference statements)

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“…The top 40 pathways of KEGG results were visualized with a dot plot ( Figure 3(a) ). KEGG results indicated that the PI3K/AKT pathway [ 35 ], Toll-like receptor pathway [ 36 ], NOD-like receptor pathway [ 37 ], TNF pathway [ 38 ], and HIF-1 pathway [ 39 ] were closely related to OA. A network of 6 OA-related pathways and their corresponding targets is shown in Figure 3(b) .…”

Section: Resultsmentioning

confidence: 99%

Integrating Network Pharmacology and Experimental Validation to Explore the Key Mechanism of Gubitong Recipe in the Treatment of Osteoarthritis

Chen

Liu

Luo

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. Gubitong Recipe (GBT) is a prescription based on the Traditional Chinese Medicine (TCM) theory of tonifying the kidney yang and strengthening the bone. A previous multicentral randomized clinical trial has shown that GBT can effectively relieve joint pain and improve quality of life with a high safety in treating osteoarthritis (OA). This study is aimed at elucidating the active compounds, potential targets, and mechanisms of GBT for treating OA. Method. The network pharmacology method was used to predict the key active compounds, targets, and mechanisms of GBT in treating OA. An OA rat model was established with Hulth surgery, and the pathological changes of articular cartilage were observed to evaluate the effects of GBT. Chondrocytes were stimulated with LPS to establish in vitro models, and key targets and mechanisms predicted by network pharmacology were verified via qRT-PCR, ELISA, western blot, and immunofluorescence. The Contribution Index Model and molecular docking were used to determine the key active compounds of GBT and the major nodes affecting predicted pathways. Result. A total of 500 compounds were acquired from related databases, where 87 active compounds and their 254 corresponding targets were identified. 2979 OA-related genes were collected from three databases, 150 of which were GBT-regulating OA genes. The compound-target network weight analysis and PPI results showed that IL-6 and PGE2 are key targets of GBT in treating OA. KEGG results showed that PI3K/AKT, Toll-like receptor, NFκB, TNF, and HIF-1 are the key signaling pathways. An in vivo experiment showed that GBT could effectively suppress cartilage degradation of OA rats. In vitro experiments demonstrated that GBT can inhibit the key targets of KEGG-related pathways. Molecular-docking results suggested that luteolin, licochalcone A, and β-carotene were key targets of GBT, and the mechanisms may be associated with the NFκB signaling pathway. Blockage experiments showed that the NFκB pathway is the key pathway of GBT in treating OA. Conclusion. This study verified that GBT can effectively protect articular cartilage through multitarget and multipathway, and its inhibitory effect on the NFκB pathway is the most key mechanism in treating OA.

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Section: Resultsmentioning

confidence: 99%

Integrating Network Pharmacology and Experimental Validation to Explore the Key Mechanism of Gubitong Recipe in the Treatment of Osteoarthritis

Chen

Liu

Luo

et al. 2022

Computational and Mathematical Methods in Medicine

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“…Inhibition of inflammasomes, which are involved in the activation of GSDMD, prevents OA pathogenesis in various animal models [ 42 – 45 ]. Therefore, we determined the impact of GSDMD deficiency on the joints in the PTOA model induced by meniscal ligamentous injury (MLI).…”

Section: Resultsmentioning

confidence: 99%

Gasdermin D deficiency attenuates arthritis induced by traumatic injury but not autoantibody-assembled immune complexes

et al. 2021

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Background Gasdermin D (GSDMD) is cleaved by several proteases including by caspase-1, a component of intracellular protein complexes called inflammasomes. Caspase-1 also converts pro-interleukin-1β (pro-IL-1β) and pro-IL-18 into bioactive IL-1β and IL-18, respectively. GSDMD amino-terminal fragments form plasma membrane pores, which mediate the secretion of IL-1β and IL-18 and cause the inflammatory form of cell death pyroptosis. Here, we tested the hypothesis that GSDMD contributes to joint degeneration in the K/BxN serum transfer-induced arthritis (STIA) model in which autoantibodies against glucose-6-phosphate isomerase promote the formation of pathogenic immune complexes on the surface of myeloid cells, which highly express the inflammasomes. The unexpected outcomes with the STIA model prompted us to determine the role of GSDMD in the post-traumatic osteoarthritis (PTOA) model caused by meniscus ligamentous injury (MLI) based on the hypothesis that this pore-forming protein is activated by signals released from damaged joint tissues. Methods Gsdmd+/+ and Gsdmd−/− mice were injected with K/BxN mouse serum or subjected to MLI to cause STIA or PTOA, respectively. Paw and ankle swelling and DXA scanning were used to assess the outcomes in the STIA model whereas histopathology and micro-computed tomography (μCT) were utilized to monitor joints in the PTOA model. Murine and human joint tissues were also examined for GSDMD, IL-1β, and IL-18 expression by qPCR, immunohistochemistry, or immunoblotting. Results GSDMD levels were higher in serum-inoculated paws compared to PBS-injected paws. Unexpectedly, ablation of GSDMD failed to reduce joint swelling and osteolysis, suggesting that GSDMD was dispensable for the pathogenesis of STIA. GSDMD levels were also higher in MLI compared to sham-operated joints. Importantly, ablation of GSDMD attenuated MLI-associated cartilage degradation (p = 0.0097), synovitis (p = 0.014), subchondral bone sclerosis (p = 0.0006), and subchondral bone plate thickness (p = 0.0174) based on histopathological and μCT analyses. Conclusion GSDMD plays a key role in the pathogenesis of PTOA, but not STIA, suggesting that its actions in experimental arthropathy are tissue context-specific.

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“…The rats were divided into seven groups ( n = 5), labeled as groups A, B, C, D, E, F, and G. DEHP dosage was administered accordingly using the protocol by Zhang et al (2018) , while VA and VC dosage were administered accordingly using the procedure by Ma et al (2020) .…”

Section: Methodsmentioning

confidence: 99%

Vanillic acid and vitamin C attenuated di-2-ethylhexyl phthalate-induced testicular toxicity in adult male rats

Ogunlade

Gbotolorun

Adedotun

et al. 2022

Reproduction and Fertility

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Background: Di-2-Ethylhexyl phthalate (DEHP) is an extensively used plasticizer which has raised some concerns about its safety on human health. This study aimed at evaluating the effects of Vanillic Acid (VA) and Vitamin C (VC) supplementation on DEHP-induced testicular toxicity. Methods: Thirty-five (35) adult male Wistar rats were randomly divided into seven groups (A-G) (n=5) receiving distilled water; 250 mg/kg bw of DEHP only; 30 mg/kg bw of VA and 250 mg/kg bw of DEHP; 30 mg/kg bw of VC and 250 mg/kg bw of DEHP; 30 mg/kg bw of DEHP plus 30 mg/kg bw of VA and 30 mg/kg bw of VC; 30 mg/kg bw of VA only; 30 mg/kg bw of VC respectively. At the end of the experiment, blood was taken from the heart via cardiac puncture and stored, semen was collected from the caudal epididymis for immediate sperm analysis, while the testes were excised and preserved for histological examination and biochemical analysis. Results: The results showed a significant decrease (p<0.05) in body weights, sperm motility, sperm volume, sperm viability and count, antioxidants levels and reproductive hormonal levels, with a significant increase (p<0.05) in sperm morphological defect and lipid peroxidation level in DEHP only group compared with the control but was ameliorated after VA and VC administration compared to the DEHP-only treated animals. Conclusion: Vanillic acid and Vitamin C supplementation attenuated the toxic effects of DEHP on the testicular functions, morphology and semen characterization of the experimental adult male Wistar rats.

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Vanillic Acid Reduces Pain-Related Behavior in Knee Osteoarthritis Rats Through the Inhibition of NLRP3 Inflammasome-Related Synovitis

Cited by 21 publications

References 34 publications

Integrating Network Pharmacology and Experimental Validation to Explore the Key Mechanism of Gubitong Recipe in the Treatment of Osteoarthritis

Integrating Network Pharmacology and Experimental Validation to Explore the Key Mechanism of Gubitong Recipe in the Treatment of Osteoarthritis

Gasdermin D deficiency attenuates arthritis induced by traumatic injury but not autoantibody-assembled immune complexes

Vanillic acid and vitamin C attenuated di-2-ethylhexyl phthalate-induced testicular toxicity in adult male rats

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