Phillygenin reduced neuropathic pain by inhibiting the rats’ TLR4/MyD88/NF-κB pathway.
Filigenina reduce el dolor neuropático en ratas inhibiendo la vía del TLR4/MyD88/NF-κB.
Palabras clave:
dolor neuropático, filigenia, citocinas proinflamatorias, TLR4, MyD88
Resumen
Para dilucidar los efectos de la filigenina (PHI) y el mecanismo potencial en la señalización de TLR4 y MyD88/NF-κB en el dolor neuropático en estudios con animales, se construyeron modelos de lesión por constricción crónica (CCI) para la inducción del dolor neuropático utilizando ratas SpragueDawley macho. La PHI (20 mg/kg) se administró por vía intragástrica. Se implementaron las pruebas de von Frey y Hargreaves para determinar el 50% del umbral de retracción de la pata (PWT) y la latencia de retracción de la pata (PWL). Se utilizó un ensayo de óxido nítrico (NO) para la detección del nivel de NO, y se empleó un ensayo ELISA para medir la expresión de citocinas proinflamatorias. Se realizaron transferencia Western y RT-qPCR para la detección del nivel de proteína y ARNm. El tratamiento con PHI mejoró significativamente el 50% del PWT y la PWL. La PHI disminuyó significativamente los niveles de NO y redujo los niveles de TNF-α, IL-1β e IL-6. PHI también disminuyó la expresión de TLR4 y MyD88 e inhibió la fosforilación de NF-κB. PHI mejoró el estado inflamatorio y alivió el dolor neuropático en ratas con CCI, actuando sobre TLR4 y suprimiendo la señalización MyD88/NF-κB.
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Guo J, Yan WR, Tang JK, Jin X, Xue HH, Wang T, Zhang LW, Sun QY, Liang ZX. Dietary phillygenin supplementation ameliorates aflatoxin B(1)-induced oxidative stress, inflammation, and apoptosis in chicken liver. Ecotoxicol Environ Saf 2022;236:113481.
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Ju M, Liu B, He H, Gu Z, Liu Y, Su Y, Zhu D, Cang J, Luo Z. MicroRNA-27a alleviates LPS-induced acute lung injury in mice via inhibiting inflammation and apoptosis through modulating TLR4/ MyD88/NF-κB pathway. Cell Cycle 2018;17(16):2001-2018.
Liu P, Yuan HB, Zhao S, Liu FF, Jiang YQ, Guo YX, Wang XL. Activation of GABA(B) receptor suppresses diabetic neuropathic pain through Toll-Like Receptor 4 signaling pathway in the spinal dorsal horn. Mediators Inflamm 2018;2018:6016272.
Rosenberger DC, Blechschmidt V, Timmerman H, Wolff A, Treede RD. Challenges of neuropathic pain: focus on diabetic neuropathy. J Neural Transm (Vienna) 2020;127(4):589-624.
St John Smith E. Advances in understanding nociception and neuropathic pain. J Neurol 2018;265(2):231-238.
Park J, Park HJ. Botulinum toxin for the treatment of neuropathic pain. Toxins (Basel) 2017;9: 9.
Liu J, Li JX, Wu R. Toll-Like Receptor 4: a novel target to tackle drug addiction? Handb Exp Pharmacol 2022;276:275-290.
Bolourani S, Brenner M, Wang P. The interplay of DAMPs, TLR4, and proinflammatory cytokines in pulmonary fibrosis. J Mol Med (Berl) 2021;99(10):1373-1384.
Zhou L, Liu Z, Wang Z, Yu S, Long T, Zhou X, Bao Y. Astragalus polysaccharides exerts immunomodulatory effects via TLR4-mediated MyD88-dependent signaling pathway in vitro and in vivo. Sci Rep 2017;7:44822.
Xu S, Wang J, Jiang J, Song J, Zhu W, Zhang F, Shao M, Xu H, Ma X, Lyu F. TLR4 promotes microglial pyroptosis via lncRNA-F630028O10Rik by activating PI3K/AKT pathway after spinal cord injury. Cell Death Dis 2020;11(8):693.
Cao L, Tanga FY, Deleo JA. The contributing role of CD14 in toll-like receptor 4 dependent neuropathic pain. Neuroscience 2009;158(2):896-903.
Liu L, Sun Y, Wen C, Jiang T, Tian W, Xie X, Cui X, Lu R, Feng J, Jin A, Wen S, Wei W. Metabolome analysis of genus Forsythia related constituents in Forsythia suspensa leaves and fruits using UPLC-ESI-QQQ-MS/MS technique. PLoS One 2022;17(6):e0269915.
Wang C, Ma C, Fu K, Gong LH, Zhang YF, Zhou HL, Li YX. Phillygenin attenuates carbon tetrachloride-induced liver fibrosis via modulating inflammation and gut microbiota. Front Pharmacol 2021;12:756924.
Wang X, Wang P, Du H, Li N, Jing T, Zhang R, Qi W, Hu Y, Liu T, Zhang L, Xu N, Wang Y, Zhang H, Ding X. Prediction of the active components and mechanism of Forsythia suspensa leaf against respiratory syncytial virus based on network pharmacology. Evid Based Complement Alternat Med 2022;2022:5643345.
Xue HH, Li JJ, Li SF, Guo J, Yan RP, Chen TG, Shi XH, Wang JD, Zhang LW. Phillygenin attenuated colon inflammation and improved intestinal mucosal barrier in DSS-induced colitis mice via TLR4/Src mediated MAPK and NF- κB signaling pathways. Int J Mol Sci 2023;24(3): 2238.
Bennett GJ, Xie YK. A peripheral mono-neuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988;33(1):87-107.
Guo D, Hu X, Zhang H, Lu C, Cui G, Luo X. Orientin and neuropathic pain in rats with spinal nerve ligation. Int Immuno-pharmacol 2018;58:72-79.
Cheng Z, Feng S, Yang L, Huang J, Chen X, Guo Y, Xiang Y, Peng B. Rat model of neuropathic pain induced by spinal nerve ligation: a new approach via an oblique lateral incision. J Pain Res 2024;17:2443- 2454.
Zhou S, Wen H, Han X, Li H. Phillygenin protects against osteoarthritis by repressing inflammation via PI3K/ Akt/NF-κB signaling: In vitro and vivo studies. Journal of Functional Foods 2021;80:104456.
Li Y, Yin C, Li X, Liu B, Wang J, Zheng X, Shao X, Liang Y, Du J, Fang J, Liu B. Electroacupuncture alleviates paclitaxel-induced peripheral neuropathic pain in eats via suppressing TLR4 signaling and TRPV1 upregulation in sensory neurons. Int J Mol Sci 2019;20: 23.
Navia-Pelaez JM, Choi SH, Dos Santos Aggum Capettini L, Xia Y, Gonen A, Agatisa-Boyle C, Delay L, Gonçalves Dos Santos G, Catroli GF, Kim J, Lu JW, Saylor B, Winkels H, Durant CP, Ghosheh Y, Beaton G, Ley K, Kufareva I, Corr M, Yaksh TL, Miller YI. Normalization of cholesterol metabolism in spinal microglia alleviates neuropathic pain. J Exp Med 2021; 18(7):e20202059.
Jin Y, Xu L, Xu Y. Effect of intrathecal injection of miRNA-138 on neuropathic pain in rats undergoing partial sciatic nerve ligation and its underlying mechanism. Ann Palliat Med 2021;10(6):68736882.
Zhang P, Yang M, Chen C, Liu L, Wei X, Zeng S. Toll-Like Receptor 4 (TLR4)/Opioid Receptor pathway crosstalk and impact on opioid analgesia, immune function, and gastrointestinal motility. Front Immunol 2020;11:1455.
Lin Y, Yang P. Phillygenin inhibits the inflammation and apoptosis of pulmonary epithelial cells by activating PPARγ signaling via downregulation of MMP8. Mol Med Rep 2021;24(5).
Guo J, Yan WR, Tang JK, Jin X, Xue HH, Wang T, Zhang LW, Sun QY, Liang ZX. Dietary phillygenin supplementation ameliorates aflatoxin B(1)-induced oxidative stress, inflammation, and apoptosis in chicken liver. Ecotoxicol Environ Saf 2022;236:113481.
Wang L, Yang JW, Lin LT, Huang J, Wang XR, Su XT, Cao Y, Fisher M, Liu CZ. Acupuncture attenuates inflammation in microglia of vascular dementia rats by inhibiting miR-93-mediated TLR4/ MyD88/NF-κB signaling pathway. Oxid Med Cell Longev 2020;2020:8253904.
Ju M, Liu B, He H, Gu Z, Liu Y, Su Y, Zhu D, Cang J, Luo Z. MicroRNA-27a alleviates LPS-induced acute lung injury in mice via inhibiting inflammation and apoptosis through modulating TLR4/ MyD88/NF-κB pathway. Cell Cycle 2018;17(16):2001-2018.
Liu P, Yuan HB, Zhao S, Liu FF, Jiang YQ, Guo YX, Wang XL. Activation of GABA(B) receptor suppresses diabetic neuropathic pain through Toll-Like Receptor 4 signaling pathway in the spinal dorsal horn. Mediators Inflamm 2018;2018:6016272.
Publicado
2025-03-06
Cómo citar
Hua, L., Zhou, W., Li, M., & Li, R. (2025). Phillygenin reduced neuropathic pain by inhibiting the rats’ TLR4/MyD88/NF-κB pathway.: Filigenina reduce el dolor neuropático en ratas inhibiendo la vía del TLR4/MyD88/NF-κB. Investigación Clínica, 66(1), 4-15. https://doi.org/10.54817/IC.v66n1a01
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