- Journal Information
- Archive
- Submission
- For Reviewers
- Statement and Policies
- 个人中心
- 退出登录
浏览全部资源
扫码关注微信
- Journal Information
- Journal Introduction
- Editorial Board
- Youth Editorial Board
- Editorial Board Charter
- Subscriptions
- Archive
- Current Issue
- Past Issues
- Priority Publication
- Virtual Collection
- Recommended Articles
- Submission
- Submission Process
- Submission Guidelines
- Download
- Contact us
- For Reviewers
- Guidelines for Reviewers
- Peer Reviewed Policies
- Statement and Policies
- Ethics and Malpractice
- Research Ethics Policies
- Repetition Detection
- Corrections and Retractions
- Editorial Policies
- Open Access Statement
- Website Responsibility
Analgesic effect and mechanism of punicalagin on neuropathic pain in rats
- ZHONGGUO YAOFANG Vol. 36, Issue 10, Pages: 1191-1196(2025)
- 作者机构：
武汉市第四医院疼痛科，武汉 430035
- 作者简介：
- 基金信息：
DOI：10.6039/j.issn.1001-0408.2025.10.07
CLC： R965Received：04 November 2024，
Revised：2025-03-26，
Accepted：03 April 2025，
Published：30 May 2025
- 稿件说明：
移动端阅览
汪莉,周伶,吴成龙.安石榴苷对神经病理性疼痛大鼠的镇痛作用及机制 [J].中国药房,2025,36(10):1191-1196.
WANG Li,ZHOU Ling,WU Chenglong.Analgesic effect and mechanism of punicalagin on neuropathic pain in rats[J].ZHONGGUO YAOFANG,2025,36(10):1191-1196.
汪莉,周伶,吴成龙.安石榴苷对神经病理性疼痛大鼠的镇痛作用及机制 [J].中国药房,2025,36(10):1191-1196. DOI： 10.6039/j.issn.1001-0408.2025.10.07.
WANG Li,ZHOU Ling,WU Chenglong.Analgesic effect and mechanism of punicalagin on neuropathic pain in rats[J].ZHONGGUO YAOFANG,2025,36(10):1191-1196. DOI： 10.6039/j.issn.1001-0408.2025.10.07.
摘要
目的
2
基于缺氧诱导因子1α（HIF-1α）/核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3（NLRP3）信号通路，探讨安石榴苷对神经病理性疼痛（NP）大鼠的镇痛作用及潜在机制。
方法
2
将雄性SD大鼠随机分为假手术组（18只）和造模组（72只），造模组大鼠以坐骨神经慢性压迫损伤法诱导建立NP模型。将造模成功的大鼠分为NP组、2-甲氧基雌二醇组（HIF-1α拮抗剂10 mg/kg）、安石榴苷组（300 mg/kg）、安石榴苷+二甲基草酰甘氨酸组（安石榴苷300 mg/kg+HIF-1α激动剂175 mg/kg），每组18只。各组大鼠腹腔注射和（或）灌胃相应药液或1%二甲基亚砜/生理盐水，每天1次，连续14 d。末次给药后，检测各组大鼠的机械缩足反射阈值（MWT）、热缩足反射潜伏期（TWL）和脊髓组织中肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β）、IL-6水平，观察其脊髓背角的形态学变化，检测其脊髓背角的神经元凋亡率、NLRP3/离子钙结合衔接分子1（Iba-1）共定位情况（以NLRP3
+
/Iba-1
+
细胞数计）以及脊髓组织中HIF-1α、NLRP3、凋亡相关斑点样蛋白（ASC）、胱天蛋白酶1（caspase-1）的表达情况。
结果
2
与假手术组比较，NP组大鼠脊髓背角中神经原纤维明显增粗并缠绕成结，可见含嗜银颗粒的空泡变性；其MWT、TWL均降低或缩短，脊髓组织中TNF-α、IL-1β、IL-6水平，脊髓背角神经元凋亡率，NLRP3
+
/Iba-1
+
细胞数以及HIF-1α、NLRP3、ASC、caspase-1蛋白的表达均显著升高或上调（
P
＜0.05）。与NP组比较，2-甲氧基雌二醇组和安石榴苷组大鼠上述指标均显著改善（
P
＜0.05），而二甲基草酰甘氨酸则可显著逆转安石榴苷对上述指标的改善作用（
P
＜0.05）。
结论
2
安石榴苷可缓解NP大鼠的疼痛，其镇痛作用可能是通过抑制HIF-1α/NLRP3信号通路、阻碍脊髓背角小胶质细胞中NLRP3炎症小体的活化来实现的。
Abstract
OBJECTIVE
2
To investigate the analgesic effect and potential mechanism of punicalagin on neuropathic pain （NP） rats based on the hypoxia-inducible factor-1α （HIF-1α）/nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） signaling pathway.
METHODS
2
Male SD rats were randomly divided into sham operation group （18 rats） and modeling group （72 rats）. NP rat model was established by chronic constriction injury （CCI） of sciatic nerve. The successfully modeled rats were divided into NP group， 2-methoxyestradiol group （HIF-1α antagonist 10 mg/kg）， punicalagi
n group （300 mg/kg）， and punicalagin+dimethyloxaloglycine group （punicalagin 300 mg/kg+HIF-1α agonist 175 mg/kg）， with 18 rats in each group. Rats in each group were injected intraperitoneally and/or intragastrically with the corresponding solution or 1% dimethyl sulfoxide/normal saline， once a day， for 14 consecutive days. After the last administration， the mechanical withdrawal threshold （MWT）， thermal withdrawal latency （TWL）， the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β） and IL-6 in spinal cord tissue were detected； the morphological changes in the spinal dorsal horn were observed. Apoptosis rate of spinal dorsal horn neurons， the co-localization of NLRP3/ionized calcium binding adapter molecule 1 （Iba-1） （calculated by the number of NLRP3
+
/Iba-1
+
cells） and the protein expressions of HIF-1α， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC） and caspase-1 in spinal cord tissue were detected.
RESULTS
2
Compared with the sham operation group， neurofibril in spinal dorsal horn of rats in NP group was thickened and wound into knots， and vacuolar degeneration containing silver granules was observed； the MWT and TWL were reduced or shortened； the levels of TNF-α， IL-1β and IL-6 in spinal cord tissue， the apoptosis rate of spinal dorsal horn neurons， the number of NLRP3
+
/Iba-1
+
cells， and protein expressions of HIF-1α， NLRP3， ASC and caspase-1 were significantly increased or up-regulated （
P
＜0.05）. Compared with the NP group， the above indexes were significantly improved in the 2-methoxyestradiol group and punicalagin group （
P
＜0.05）， while dimethyloxaloglycine could significantly reverse the improvement effect of punicalagin on the above indexes （
P
＜0.05）.
CONCLUSIONS
2
Punicalagin can relieve pain in NP rats， and its analgesic effect may be achieved by inhibiting HIF-1α/NLRP3 signaling pathway and blocking the activation of NLRP3 inflammasome in spinal dorsal horn microglia.
关键词
Keywords
references
RAYMOND T J . Chronic pain syndromes：chronic neuropathic pain [J ] . FP Essent ， 2023 ， 533 ： 27 - 40 .
PETHŐ G ， KÁNTÁS B ， HORVÁTH Á ， et al . The epigenetics of neuropathic pain：a systematic update [J ] . Int J Mol Sci ， 2023 ， 24 （ 24 ）： 17143 .
MICHELI L ， LUCARINI E ， NOBILI S ， et al . Ultramicronized N-palmitoylethanolamine contributes to morphine efficacy against neuropathic pain：implication of mast cells and glia [J ] . Curr Neuropharmacol ， 2024 ， 22 （ 1 ）： 88 - 106 .
JING B ， CHEN Z N ， SI W M ， et al . （+）-Catechin atte-nuates CCI-induced neuropathic pain in male rats by promo-ting the Nrf2 antioxidant pathway to inhibit ROS/TLR4/NF-κB-mediated activation of the NLRP3 inflammasome [J ] . J Neurosci Res ， 2024 ， 102 （ 8 ）： e25372 .
CHEN C ， SMITH M T . The NLRP3 inflammasome：role in the pathobiology of chronic pain [J ] . Inflammopharmacology ， 2023 ， 31 （ 4 ）： 1589 - 1603 .
HSIEH Y L ， CHOU L W ， CHANG P L ， et al . Low-level laser therapy alleviates neuropathic pain and promotes function recovery in rats with chronic constriction injury：possible involvements in hypoxia-inducible factor-1α（HIF-1α） [J ] . J Comp Neurol ， 2012 ， 520 （ 13 ）： 2903 - 2916 .
MO C ， XU M Y ， WEN C ， et al . Normalizing JMJD6 expression in rat spinal dorsal horn alleviates hyperal-gesia following chronic constriction injury [J ] . Front Neurosci ， 2018 ， 12 ： 542 .
SHI Z M ， JING J J ， XUE Z J ， et al . Stellate ganglion block ameliorated central post-stroke pain with comorbid anxiety and depression through inhibiting HIF-1α/NLRP3 signaling following thalamic hemorrhagic stroke [J ] . J Neuroinflammation ， 2023 ， 20 （ 1 ）： 82 .
HERING N A ， LUETTIG J ， JEBAUTZKE B ， et al . The punicalagin metabolites ellagic acid and urolithin a exert different strengthening and anti-inflammatory effects on tight junction-mediated intestinal barrier function in vitro [J ] . Front Pharmacol ， 2021 ， 12 ： 610164 .
HARANISHI Y ， HARA K ， TERADA T . Analgesic potency of intrathecally administered punicalagin in rat neuropathic and inflammatory pain models [J ] . J Nat Med ， 2022 ， 76 （ 1 ）： 314 - 320 .
JAIN V ， PAREEK A ， BHARDWAJ Y R ， et al . Punicalagin and ellagic acid containing Punica granatum L. fruit rind extract prevents vincristine-induced neuropathic pain in rats：an in silico and in vivo evidence of GABAergic action and cytokine inhibiti on [J ] . Nutr Neurosci ， 2022 ， 25 （ 10 ）： 2149 - 2166 .
PENG J F ， ZHAO X N ， ZHANG M ， et al . Punicalagin attenuates ventricular remodeling after acute myocardial infarction via regulating the NLRP3/caspase-1 pathway [J ] . Pharm Biol ， 2023 ， 61 （ 1 ）： 963 - 972 .
姜政男 ， 张溢珈 ， 刘臻 ， 等 . 大鼠神经病理性疼痛模型的建立及其引起抑郁样状态伴失眠的机制 [J ] . 吉林大学学报（医学版） ， 2023 ， 49 （ 4 ）： 905 - 912 .
HE J ， QIN Z S ， CHEN X ， et al . HIF-1α ameliorates diabetic neuropathic pain via parkin-mediated mitophagy in a mouse model [J ] . Biomed Res Int ， 2022 ， 2022 ： 5274375 .
VIEIRA W F ， COELHO D R A ， LITWILER S T ， et al . Neuropathic pain，mood，and stress-related disorders：a lite-rature review of comorbidity and co-pathogenesis [J ] . Neurosci Biobehav Rev ， 2024 ， 161 ： 105673 .
VENUSOVA E ， KOLESAROVA A ， HORKY P ， et al . Physiological and immune functions of punicalagin [J ] . Nutrients ， 2021 ， 13 （ 7 ）： 2150 .
INOUE K . Microglia in neuropathic pain [J ] . Adv Neurobiol ， 2024 ， 37 ： 399 - 403 .
LIANG J H ， YU H ， XIA C P ， et al . Ginkgolide B effectively mitigates neuropathic pain by suppressing the activation of the NLRP3 inflammasome through the induction of mitophagy in rats [J ] . Biomed Pharmacother ， 2024 ， 177 ： 117006 .
SILVA SANTOS RIBEIRO P ， WILLEMEN H L D M ， VERSTEEG S ， et al . NLRP3 inflammasome activation in sensory neurons promotes chronic inflammatory and osteoarthritis pain [J ] . Immunother Adv ， 2023 ， 3 （ 1 ）： ltad022 .
WU D ， WANG P ， ZHAO C H ， et al . Levo-tetrahydropalmatine ameliorates neuropathic pain by inhibiting the activation of the Clec7a-MAPK/NF-κB-NLRP3 inflammasome axis [J ] . Phytomedicine ， 2023 ， 121 ： 155075 .
ZHU J S ， YANG J M ， XU J G . Erratum to “miR-223 inhibits the polarization and recruitment of macrophages via NLRP3/IL-1β pathway to meliorate neuropathic pain” [J ] . Pain Res Manag ， 2023 ， 2023 ： 9756947 .
HUA T ， KONG E L ， ZHANG H L ， et al . PRMT6 deficiency or inhibition alleviates neuropathic pain by decrea-sing glycolysis and inflammation in microglia [J ] . Brain Behav Immun ， 2024 ， 118 ： 101 - 114 .
XU S ， WANG J ， ZHONG J J ， et al . CD73 alleviates GSDMD-mediated microglia pyroptosis in spinal cord injury through PI3K/AKT/Foxo1 signaling [J ] . Clin Transl Med ， 2021 ， 11 （ 1 ）： e269 .
0
Views
104
下载量
0
CSCD
- L-PDFDownload
- WORDDownload
- Meta-XMLDownload
- BibTeXDownload
- EndnoteDownload
- RefMan Download
- NoteExpressDownload
- NoteFirstDownload
Publicity Resources
Related Articles
Related Author
Related Institution
- Address：8th Floor, Sihuan Building, No. 129 Daping Main Street, Yuzhong District, Chongqing, China Postal code：400042
- Technical support is provided by Beijing Founder Electronics co., LTD 渝ICP备15012710号
公网安备50010302001817 - It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
- Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.