
Panax notoginseng saponin relieving the inflammatory pain caused by complete Freund’s adjuvant by inhibiting the activation of astrocytes in mice
YUAN Lei YANG Zhi-wei YANG Hui LIU Zheng-hai HE Jie WAN Wei
Acta Anatomica Sinica ›› 2024, Vol. 55 ›› Issue (1) : 25-31.
Panax notoginseng saponin relieving the inflammatory pain caused by complete Freund’s adjuvant by inhibiting the activation of astrocytes in mice
YUAN Lei1 YANG Zhi-wei1 YANG Hui2 LIU Zheng-hai3 HE Jie4 WAN Wei1*
Objective To analyse the analgesic effect and possible mechanism of panax notoginseng saponin (PNS) on mouse models of chronic inflammatory pain caused by complete Freund’s adjuvant (CFA). Methods A total of 48 male C57BL/6J mice were divided randomly into four groups: normal saline control group (Ctrl), CFA group (CFA), CFA + PNS group (CFA+PNS), CFA + dexamethasone (DEX) group (CFA+DEX). Von Frey filaments were used to detect mechanical pain in mice. Immunohistochemistry was used to detect the number and morphological changes of glial fibrillary acidic protein (GFAP) positive astrocytes. Western blotting was used to detect the expressions of GFAP, nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, interleukin (IL)-1β, and IL-18 in mice’s spinal cord segments in each group. Results Compared with the Ctrl group, mice in the CFA group showed a significant decrease in mechanical pain thresholds at day 1, day 3, day 5, day 7, and day 14. Additionally, there was a significant decrease in NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of the mice. PNS intervention could relieve mechanical pain and down-regulate the expressions of NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of mice, with no significant difference compared with the CFA+DEX group. CFA group mice had significantly more GFAP positive cells in their posterior horns than Ctrl group mice, as measured by immunohistochemistry; PNS intervention decreased the number of GFAP positive cells in the posterior horn of the spinal cord in model mice;DEX had no effect on the number of GFAP positive cells in the dorsal horn of spinal cord. According to Western blotting results, GFAP expression in the spinal cord of the CFA group was significantly more than that of the Ctrl group; PNS intervention significantly reduced GFAP expression in the spinal cord of CFA group mice;DEX had no effect on the expression of GFAP in the posterior horn of spinal cord. Conclusion PNS has a good alleviating effect on inflammatory pain, and its mechanism may be related to inhibition of astrocyte activation and NLRP3 inflammasome activation.
Panax notoginseng saponins
[1] Li J, Chen Y, Liu J, et al. Elevated expression and activity of sodium leak channel contributes to neuronal sensitization of inflammatory pain in rats [J]. Front Mol Neurosci,2021,14:723395.
[2]Gu Y, Chen S, Mo Y, et al. Electroacupuncture attenuates CFA-induced inflammatory pain by regulating CaMKⅡ[J]. Neural Plast,2020,2020:8861994.
[3]Li J, Su S, Xu Z, et al. Potential roles of gut microbiota and microbial metabolites in chronic inflammatory pain and the mechanisms of therapy drugs[J]. Ther Adv Chronic Dis,2022,13:20406223221091177.
[4]Tang J, Bair M, Descalzi G. Reactive astrocytes: critical players in the development of chronic pain[J]. Front Psychiatry, 2021,12:682056.
[5]Ji RR, Donnelly CR, Nedergaard M. Astrocytes in chronic pain and itch[J]. Nat Rev Neurosci, 2019,20(11):667-685.
[6]Gorina YV, Salmina AB, Erofeev AI, et al. Astrocyte activation markers[J]. Biochemistry (Mosc), 2022,87(9):851-870.
[7]De la Luz-Cuellar YE, Rodríguez-Palma EJ, Franco-Enzástiga ú, et al. Blockade of spinal α5-GABAA receptors differentially reduces reserpine-induced fibromyalgia-type pain in female rats[J]. Eur J Pharmacol,2019,858:172443.
[8]Zhang H, Li F, Li WW, et al. The inflammasome as a target for pain therapy[J]. Br J Anaesth, 2016,117(6):693-707.
[9]O’Brien WT, Pham L, Symons GF, et al. The NLRP3 inflammasome in traumatic brain injury: potential as a biomarker and therapeutic target[J]. J Neuroinflammation,2020,17(1):104.
[10]Huang YD, Cheng JX, Shi Y, et al. Panax notoginseng: a review on chemical components, chromatographic analysis, P. notoginseng extracts, and pharmacology in recent five years[J]. China Journal of Chinese Materia Medica,2022,47(10):2584-2596.(in Chinese)
黄依丹,成嘉欣,石颖,等.近五年三七化学成分、色谱分析、三七提取物和药理活性的研究进展[J].中国中药杂志,2022,47(10):2584-2596.
[11]Fan YH, Xu Ch, Fei YR, et al. Determination of contents and encapsulation efficiencies of five saponins in Panax notoginseng saponins transfersomes[J]. Chinese Traditional and Herbal Drugs,2022,53(10):3006-3013. (in Chinese)
范煜航,徐畅,费雅蓉,等.三七总皂苷传递体中5种皂苷类成分含量与包封率的测定研究[J].中草药,2022,53(10):3006-3013.
[12]Uzayisenga R, Ayeka PA, Wang Y. Anti-diabetic potential of Panax notoginseng saponins (PNS): a review[J]. Phytother Res,2014,28(4):510-516.
[13]Ma CH, Chou WC, Wu CH, et al. Ginsenoside Rg3 attenuates TNF-α-induced damage in chondrocytes through regulating SIRT1-mediated anti-apoptotic and anti-inflammatory mechanisms[J]. Antioxidants (Basel), 2021,10(12):1972.
[14]Shoaib RM, Ahsan MZ, Akhtar U, et al. Ginsenoside Rb1, a principal effective ingredient of Panax notoginseng, produces pain antihypersensitivity by spinal microglial dynorphin A expression[J]. Neurosci Res, 2023, 188:75-87.
[15]Chaplan SR, Bach FW, Pogrel JW, et al. Quantitative assessment of tactile allodynia in the rat paw[J]. J Neurosci Methods, 1994,53(1):55-63.
[16]Li DY, Gao SJ, Sun J, et al. Targeting the nitric oxide/cGMP signaling pathway to treat chronic pain[J]. Neural Regen Res, 2023,18(5):996-1003.
[17]Deng D, Xu F, Ma L, et al. Electroacupuncture alleviates CFA-induced inflammatory pain via PD-L1/PD-1-SHP-1 pathway[J]. Mol Neurobiol, 2023,60(5):2922-2936.
[18]Ning N, Dang X, Bai C, et al. Panax notoginsenoside produces neuroprotective effects in rat model of acute spinal cord ischemia-reperfusion injury[J]. J Ethnopharmacol, 2012,139(2):504-512.
[19]Zhang RL,Wan W,Liu H,et al. Panax notoginseng saponins pretreatment affects the inflammatory visceral pain via upregulation of the glutamine synthetase in the rat spinal dorsal horn[J]. Acta Anatomica Sinica, 2015,24(1):20-24.(in Chinese)
张仁丽,万炜,刘红,等.三七总皂苷预处理对炎性内脏痛大鼠脊髓背角谷氨酰胺合成酶表达的影响[J].解剖学报,2015,46(1):20-24.
[20]Khafagy HF, Refaat AI, El-Sabae HH, et al. Efficacy of epidural dexamethasone versus fentanyl on postoperative analgesia[J]. J Anesth, 2010,24(4):531-536.
[21]Liu Y, Latremoliere A, Li X, et al. Touch and tactile neuropathic pain sensitivity are set by corticospinal projections[J]. Nature, 2018,561(7724):547-550.
[22]Ducza L, Szücs P, Hegedüs K, et al. NLRP2 is overexpressed in spinal astrocytes at the peak of mechanical pain sensitivity during complete freund adjuvant-induced persistent pain[J]. Int J Mol Sci, 2021, 22(21):11408.
[23]Xu H, Chen J, Chen P, et al. Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases[J]. Acta Pharm Sin B, 2023, 13(2):678-693.
[24]Lin J, Ren J, Zhu B, et al. Dimethyl itaconate attenuates CFA-induced inflammatory pain via the NLRP3/ IL-1β signaling pathway[J]. Front Pharmacol, 2022, 13:938979.
[25]de Graaf L, Aarts F. Dexamethason[J]. Nursing (Maarssen),2020, 26(12):52-55./
〈 |
|
〉 |