Wang Genbei, Liu Yuanxue, Wang Yu, Gao Wenyuan
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University Weijin Road Tianjin 300072 China
Tasly Academy, Tasly Holding Group Co., Ltd. No. 2 Pujihe East Road, Tasly TCM Garden, Beichen District Tianjin 300410 China.
RSC Adv. 2018 May 9;8(31):17060-17072. doi: 10.1039/c8ra00797g.
Rhizoma Paridis saponins (RPS) as active parts of Smith var. has been used as an anti-cancer drug in traditional Chinese medicine. In this study, RPS was first found to demonstrate a potent effect on markedly reducing the pain induced by cancer. Therefore, the aim of this study was to further explore the analgesic effect of RPS and its possible reaction pathway on H22 hepatocarcinoma cells inoculated in the hind right paw of mice. Cancer-induced pain model mice were randomly divided into 5 groups ( = 10) and orally administered with RPS (50-200 mg kg) for 2 weeks. On the last day of treatment, the pain behavior of mice was measured using hot-plate test and open field test, and brain tissues were sampled for detection of biochemical indices, malondialdehyde (MDA), superoxide dismutase (SOD), prostaglandin E2 (PGE2), serotonin (5-HT) and β-endorphin (β-EP). Moreover, the concentrations of NF-κB and IL-1β in the blood serum were measured by ELISA reagent kits. In addition, naloxone, the non-selective antagonist of opioid receptors, was used to identify the opioid receptors involved in RPS's action. It has been found that RPS alleviates cancer pain mainly the suppression of inflammatory pain induced by oxidative damage, such as decreasing MDA and PGE2 levels, renewing activity of SOD, as well as increasing 5-HT and β-EP in the brain and suppressing the expression of NF-κB and IL-1β in the serum in a concentration-dependent manner. Overall, the current study highlights that RPS has widespread potential antinociceptive effects on a mouse model of chronic cancer pain, which may be associated with the peripheral nervous system and the central nervous system.
重楼皂苷(RPS)作为七叶一枝花的活性成分,在传统中药中被用作抗癌药物。在本研究中,首次发现RPS对显著减轻癌症引起的疼痛具有显著效果。因此,本研究的目的是进一步探讨RPS对接种于小鼠右后爪的H22肝癌细胞的镇痛作用及其可能的反应途径。将癌症诱导的疼痛模型小鼠随机分为5组(每组n = 10),口服给予RPS(50 - 200 mg/kg),持续2周。在治疗的最后一天,使用热板试验和旷场试验测量小鼠的疼痛行为,并采集脑组织检测生化指标,包括丙二醛(MDA)、超氧化物歧化酶(SOD)、前列腺素E2(PGE2)、5-羟色胺(5-HT)和β-内啡肽(β-EP)。此外,用ELISA试剂盒检测血清中NF-κB和IL-1β的浓度。另外,使用阿片受体的非选择性拮抗剂纳洛酮来鉴定参与RPS作用的阿片受体。研究发现,RPS主要通过抑制氧化损伤诱导的炎性疼痛来减轻癌症疼痛,如降低MDA和PGE2水平、恢复SOD活性,以及浓度依赖性地增加脑中5-HT和β-EP的含量,并抑制血清中NF-κB和IL-1β的表达。总体而言,本研究强调RPS对慢性癌症疼痛小鼠模型具有广泛的潜在镇痛作用,这可能与外周神经系统和中枢神经系统有关。