Effects of Compatibility of Niuhuang Jiedu Tablets on Arsenic Bioavailability of Realgar

Introduction: Niuhuang Jiedu Tablet (NJT) is a historical and widely used Chinese patent medicine. It is composed of realgar (As2S2) and seven other traditional Chinese medicines (TCMs). Arsenic (As) has been confirmed as toxicant and carcinogen to humans. As arsenic-containing TCMs, the safety of realgar and NJT is of growing concern. The compatibility of NJT has been proven to have a toxicity alleviation effect on realgar. The bioavailable fraction of realgar serves as the reliable assessment of internal As exposure and the related health hazards indicator. However, few studies have been conducted to study the bioavailability of realgar in combination with the other TCMs in NJT, but it is meaningful for elucidating the mechanism of toxicity alleviation effect of NJT on realgar. This study aimed to evaluate the impact of the co-exposure of the other TCMs in NJT on the bioavailability of realgar to reveal the toxicity alleviation effect of NJT on realgar. Methods: To determine the bioavailability of As from realgar, a method based on inductively coupled plasma mass spectrometry (ICP-MS) for detecting As in mice urine was established and validated. As bioavailability comparison was conducted after mice were gavaged with realgar and NJT at dosages equal to 1, 10 and 20 times the single therapeutic dose for humans. The influence of co-exposure of the other TCMs in NJT on the bioavailability of realgar was also investigated. Effects of compatibility of NJT on the toxicity of realgar with the therapeutic dose were also studied based on metabolic profiles analysis of 1H NMR spectra of urine and serum samples. Results: At the therapeutic dose, the compatibility of NJT did not affect the bioavailability of realgar, and no toxic effects of realgar were exhibited during a 7-day administration period. However, the As bioavailability, which was considered as the potential health risk, was reduced by the whole prescription if realgar was overdosed. Unlike the results of the normal therapeutic dose groups, the As bioavailability of realgar with doses equivalent to 10 and 20 times the therapeutic dose was significantly reduced by 31% and 36% in the corresponding NJT groups, respectively. The combination of Rhubarb, Scutellaria baicalensis, Platycodon grandiflorum, and Liquorice was confirmed to have a similar effect on reducing the bioavailability of realgar as the whole prescription. Discussion: It is important to pay attention to the rational clinical use of realgar-containing TCMs, especially regarding the potential health risks associated with As from prolonged or excessive usage. Further researches are needed to reveal the toxicity alleviation mechanisms of the compatibility of NJT on realgar. Conclusion: This study developed and validated an ICP-MS method for detecting As in mice urine. The impact of the other TCMs in NJT on the bioavailability of As in realgar was investigated. At the therapeutic dose, the bioavailability of As in realgar was not affected by the other TCMs in NJT. The combination of Rhubarb, Scutellaria baicalensis, Platycodon grandiflorum, and Liquorice could reduce the bioavailability of overdosed realgar in NJT.