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Niuhuang Jiedu Tablets (NJT) is a popular over-the-counter traditional Chinese medicine (TCM) preparation. It is composed of realgar (As2S2) and seven other TCMs. The safety of NJT is of growing concern because arsenic (As) is carcinogenic to humans. The toxicity of realgar in vivo can mainly be attributed to the absorbed and accumulated As. This study investigated the correlation between the detoxification effects of the other TCMs in NJT on realgar and their influences on arsenic accumulation of realgar in mice. Histopathological examination, clinical biochemical test, and metabolic profiling analysis were used to evaluate the toxicity of realgar. The concentration of arsenic in mice whole blood as the hazard indicator was determined by inductively coupled plasma mass spectrometry (ICP-MS). The compatibility of NJT could decrease arsenic bioaccumulation of realgar in mice whole blood and consequently reduce the toxicity of realgar, which could be considered as one detoxification mechanism to realgar in NJT. The combination of Rhei Radix et Rhizoma, Scutellariae Radix, Platycodonis Radix, and Glycyrrhizae Radix et Rhizoma exhibited almost the same effects as NJT in regulating the serum biochemical parameters and metabolic profiles disturbed by realgar and in reducing arsenic accumulation of realgar in mice whole blood. [ABSTRACT FROM AUTHOR]

Niuhuang Jiedu Tablets (NJT) is a popular over-the-counter traditional Chinese medicine (TCM) preparation. It is composed of realgar (As2S2) and seven other TCMs. The safety of NJT is of growing concern because arsenic (As) is carcinogenic to humans. The toxicity of realgar in vivo can mainly be attributed to the absorbed and accumulated As. This study investigated the correlation between the detoxification effects of the other TCMs in NJT on realgar and their influences on arsenic accumulation of realgar in mice. Histopathological examination, clinical biochemical test, and metabolic profiling analysis were used to evaluate the toxicity of realgar. The concentration of arsenic in mice whole blood as the hazard indicator was determined by inductively coupled plasma mass spectrometry (ICP-MS). The compatibility of NJT could decrease arsenic bioaccumulation of realgar in mice whole blood and consequently reduce the toxicity of realgar, which could be considered as one detoxification mechanism to realgar in NJT. The combination of Rhei Radix et Rhizoma, Scutellariae Radix, Platycodonis Radix, and Glycyrrhizae Radix et Rhizoma exhibited almost the same effects as NJT in regulating the serum biochemical parameters and metabolic profiles disturbed by realgar and in reducing arsenic accumulation of realgar in mice whole blood. [ABSTRACT FROM AUTHOR]

Objective. To investigate the influence of gut microbiota on arsenic accumulation of realgar in mice. Methods. Mice were treated with antibiotics to form a mouse model of gut microbial disruption. Antibiotic-treated and normally raised mice were given 15 mg/kg, 150 mg/kg, and 750 mg/kg realgar by gavage and 0.2 mg/kg and 1 mg/kg arsenic solution by subcutaneous injection for 7 days. The concentration of arsenic in mice whole blood was determined by inductively coupled plasma mass spectrometry (ICP-MS). Arsenic accumulation in antibiotic-treated mice and normally raised mice was compared. Results. After exposure to low dose (15 mg/kg) and middle dose (150 mg/kg) of realgar, significantly, more arsenic was accumulated in the whole blood of antibiotic-treated mice compared to normally raised counterparts, which indicated that the disruption of gut microbiota could lead to higher arsenic load of realgar in mice. The homeostasis of gut microbiota was supposed to be disrupted by high dose (750 mg/kg) of realgar because after exposure to high dose of realgar, there was no significant difference in arsenic accumulation between antibiotic-treated and normally raised mice. Furthermore, arsenic solution was administered by subcutaneous injection to mice to investigate the influence of gut microbial differences on arsenic accumulation in addition to the absorption process, and there was no significant difference in arsenic accumulation between mice with these two different statuses of gut microbiota. Conclusions. Gut microbiota disruption could increase arsenic accumulation of realgar in mice. [ABSTRACT FROM AUTHOR]

Niuhuang Jiedu tablet (NJT), a realgar (As2S2) containing Traditional Chinese Medicine (TCM), is a well-known formula. The safety of NJT is of growing concern since arsenic (As) is considered as one of the most toxic elements. NJT was demonstrated to be safer than realgar by our previous experiments and some other studies. The toxicity of realgar has been shown to be related to the amount of soluble or bioaccessible arsenic. In this study, the influences of the other TCMs in NJT on the bioaccessibility of arsenic from realgar, and the roles of gut microbiota during this process were investigated in vitro. Results showed that Dahuang (Rhei Radix et Rhizoma), Huangqin (Scutellariae Radix), Jiegeng (Platycodonis Radix), and Gancao (Glycyrrhizae Radix et Rhizoma) could significantly reduce the bioaccessibility of arsenic from realgar in artificial gastrointestinal fluids. Gut microbiota played an important role in decreasing the bioaccessibility of realgar because it was demonstrated to be able to absorb the soluble arsenic from realgar in the incubation medium. Dahuang, Huangqin, and Jiegeng could modulate the gut microbiota to enhance its arsenic absorption activity. [ABSTRACT FROM AUTHOR]

Niuhuang Jiedu Tablet (NJT) is a classical formula in treating acute tonsillitis, pharyngitis, and so on. In the formula, significant level of Realgar as a potentially toxic element is contained. Our previous experiments revealed that it was less toxic for combined Realgar in NJT. However, the active fraction of this prescription with toxicity alleviation effect on Realgar was still obscure. NJT was divided into five different polar fractions (NJT-PET, NJT-25, NJT-50, NJT-75, and NJT-95), and we explored the toxicity alleviation effect on Realgar. Based on 1H NMR spectra of urine and serum from rats, PCA and PLS-DA were performed to identify different metabolic profiles. Liver and kidney histopathology examinations and serum clinical chemistry analysis were also performed. With pattern recognition analysis of metabolites in urine and serum, Realgar group showed a clear separation from control group, while the metabolic profiles of NJT-PET, NJT-25, NJT-50, and NJT-95 groups were similar to Realgar group, and the metabolic profiles of NJT and NJT-75 groups were very close to control group. Statistics results were confirmed by the histopathological examination and biochemical assay. The present work indicated that 75% EtOH fraction of NJT was the most valid fraction with the toxicity alleviation effect on Realgar. [ABSTRACT FROM AUTHOR]