Pharmacodynamics and acute toxicity studies of Shangke Jiegu tablet with or without cinnabar

Purpose: 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. Materials and methods: 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. Results: 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 tailflick test), and soft tissue contusion repair compared with the control (p < 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. Conclusion: 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.