Li Jiachuan, Hu Hu, Xu Xin, Zhu Dan, Chen Yisheng, Li Laiming
School of Pharmacy, Southwest Minzu University, Chengdu, China.
Department of Endocrinology and Nephrology, 363 Hospital, Chengdu, China.
Inflammopharmacology. 2025 Mar;33(3):1455-1471. doi: 10.1007/s10787-024-01620-x. Epub 2024 Dec 17.
Opioids/non-steroidal anti-inflammatory drugs are used to alleviate pain; however, they are expensive and can have adverse effects, especially when used over extended periods. Therefore, there is immense demand for innovative, non-addictive analgesics. Here, we report a novel plant-derived central anti-nociceptive agent, Liparis nervosa (Thunb.) Lindl. (LN), validated in animal pain models. Ethyl acetate fractions of L. nervosa (EALN) exhibited central anti-nociceptive activity in hot plate, tail immersion, formalin-induced paw oedema, and acetic acid-induced abdominal writhing tests. The chemical composition of the EALN was determined using ultra-high-performance liquid chromatography-mass spectrometry. Reserpine (monoamine transmitter-depleting agent) and naltrexone (opioid antagonist) partially suppressed the anti-nociceptive effect of EALN in both phases of the formalin test. Oral administration of EALN activated the endogenous opioid and central descending inhibitory systems by increasing β-endorphin, 5-hydroxytryptamine, and norepinephrine expression. EALN treatment increased the expression of γ-aminobutyric acid B; inhibited the expression of prostaglandin E2, substance P, calcitonin gene-related peptide, and c-Fos; and blocked the transmission of pain signals in the spinal cord. EALN treatment reduced the activity of nitric oxide and nitric oxide synthase in the central region and inhibited the nitric oxide-cyclic guanosine monophosphate signal transduction pathway, thereby attenuating the transmission of nociceptive information in the descending inhibitory pathways. The central anti-nociceptive effect of EALN was achieved by integrating these pathways. This study provides new insights into the pharmacologic action of LN and provide a therapeutic approach as a promising candidate for central anti-nociceptive agents.
阿片类药物/非甾体抗炎药用于缓解疼痛；然而，它们价格昂贵且可能有不良反应，尤其是长期使用时。因此，对创新的、无成瘾性的镇痛药有巨大需求。在此，我们报告一种新型植物源中枢性抗伤害感受剂，金线莲（Liparis nervosa (Thunb.) Lindl.，简称LN），已在动物疼痛模型中得到验证。金线莲的乙酸乙酯提取物（EALN）在热板法、尾部浸没法、福尔马林诱导的爪肿胀试验以及醋酸诱导的扭体试验中表现出中枢性抗伤害感受活性。使用超高效液相色谱 - 质谱法测定了EALN的化学成分。利血平（单胺递质耗竭剂）和纳曲酮（阿片类拮抗剂）在福尔马林试验的两个阶段均部分抑制了EALN的抗伤害感受作用。口服EALN通过增加β - 内啡肽、5 - 羟色胺和去甲肾上腺素的表达激活内源性阿片类和中枢下行抑制系统。EALN处理增加了γ - 氨基丁酸B的表达；抑制了前列腺素E2、P物质、降钙素基因相关肽和c - Fos的表达；并阻断了脊髓中疼痛信号的传递。EALN处理降低了中枢区域一氧化氮和一氧化氮合酶的活性，并抑制了一氧化氮 - 环磷酸鸟苷信号转导途径，从而减弱了下行抑制途径中伤害性信息的传递。EALN的中枢性抗伤害感受作用是通过整合这些途径实现的。本研究为LN的药理作用提供了新见解，并为中枢性抗伤害感受剂提供了一种有前景的候选治疗方法。
