Wang Taotao, Han Na, Li Qiao, Yang Ming, Xi Haoying, Liu Zhihui, Feng Ruimao, Yin Jun
Development and Utilization Key Laboratory of Northeast Plant Materials, Key Laboratory of Northeast Authentic Materials Research and Development in Liaoning Province, School of Traditional Chinese Meteria Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China.
Liaoning Institute for Drug Control, Chongshan West Road 7, Shenyang 110036, China.
Heliyon. 2022 Dec 9;8(12):e12144. doi: 10.1016/j.heliyon.2022.e12144. eCollection 2022 Dec.
To evaluate the function of cinnabar in Shangke Jiegu tablet (SKJGT) via pharmacodynamics and toxicity investigations to determine whether cinnabar should be removed from SKJGT.
The pharmacodynamic differences between SKJGT and cinnabar-free Shangke Jiegu tablet (CFSKJGT) were systematically compared in five animal models. Anti-inflammatory effects were assessed on ear swelling and paw edema by measuring the degree of swelling in each. Then, the acetic acid-induced writhing reaction and hot-water tail-flick were also evaluated by counting pain reactions. The pharmacodynamic effects on soft tissue contusions were identified through histopathological observation. Chemical markers of fracture healing, including osteocytes and the blood calcium and phosphorus level, were determined via radiographic examination and biochemical assay, respectively. In addition, the maximum dosages of SKJGT and CFSKJGT were tested in mice to compare their toxicities.
SKJGT and CFSKJGT showed anti-inflammation effects (swelling inhibition ratios of 40.8% and 44.0%, respectively), analgesia (pain threshold ratios of 48.2% and 44.1%, respectively, at 60 min in the hot-water tail-flick test), and soft tissue contusion repair compared with the control ( < 0.05), and the degree of swelling inhibition and the number of pain reactions were dose-dependent. SKJGT and CFSKJGT both significantly improved the bone healing in the rat fracture model, as indicated by the increased osteocyte size during weeks 1-6 and elevated blood calcium and blood phosphorus levels (reaching maximum concentrations of 7.5 mmol/L and 6.8 mmol/L, respectively) during weeks 1-2. The maximum doses for the SKJGT and CFSKJGT groups were 9.0 g/kg in the acute toxicity experiment. The seizure rate of the SKJGT group (25.0%) was lower than that of the CFSKJGT group (50.0%) when the toxicity was observed after administration.
This is the first report to investigate the pharmacodynamics and acute toxicity of cinnabar in SKJGT. Broadly, this study offers novel, valuable insights into the efficacy of cinnabar in prescribed SKJGT.
通过药效学和毒性研究评估上科接骨片中朱砂的作用，以确定是否应从上科接骨片中去除朱砂。
在五种动物模型中系统比较了上科接骨片与无朱砂上科接骨片（CFSKJGT）之间的药效学差异。通过测量耳部肿胀和爪部水肿的程度评估抗炎作用。然后，通过计数疼痛反应评估醋酸诱导的扭体反应和热水甩尾反应。通过组织病理学观察确定对软组织挫伤的药效学作用。分别通过X线检查和生化测定确定骨折愈合的化学标志物，包括骨细胞以及血钙和血磷水平。此外，在小鼠中测试了上科接骨片和无朱砂上科接骨片的最大剂量以比较它们的毒性。
与对照组相比，上科接骨片和无朱砂上科接骨片均显示出抗炎作用（肿胀抑制率分别为40.8%和44.0%）、镇痛作用（在热水甩尾试验中60分钟时疼痛阈值比率分别为48.2%和44.1%）以及软组织挫伤修复作用（P<0.05），且肿胀抑制程度和疼痛反应次数呈剂量依赖性。上科接骨片和无朱砂上科接骨片均显著改善了大鼠骨折模型中的骨愈合，表现为第1 - 6周骨细胞大小增加以及第1 - 2周血钙和血磷水平升高（分别达到最大浓度7.5 mmol/L和6.8 mmol/L）。在急性毒性实验中，上科接骨片组和无朱砂上科接骨片组的最大剂量均为9.0 g/kg。给药后观察毒性时，上科接骨片组的惊厥率（25.0%）低于无朱砂上科接骨片组（50.0%）。
这是首次对上科接骨片中朱砂的药效学和急性毒性进行研究的报告。总体而言，本研究为朱砂在上科接骨片中的疗效提供了新颖且有价值的见解。
