Realgar is a mineral traditional medicine with definite efficacy. The function of realgar is detoxicating, insecticiding, eliminating dampness and phlegm, etc. It is widely applied in clinical practice by compatibility medicines. However, the safety and scientificalness of clinical application are questioned because of the toxic effect caused by arsenic compounds. At present, there are still many problems in the research of realgar, which are mainly manifested in three areas: the expression of main components and effective substances are inconsistent; the anti-tumor mechanism is difficult to explain at the molecular level; the mechanism of compatibility is not clear. As a result, realgar and realgar-containing Chinese patent medicines are frequently prohibited from entering the international market, and the reputation of traditional Chinese medicine is also damaged. This paper would analyze the research status of realgar at home and abroad as well as its problems from its main components, effective substances, anti-tumor mechanism and compatibility mechanism. In view of these difficulties, quantum chemical calculation method is proposed to solve them, so as to make up for the shortcomings and limitations of experimental technology and experimental conditions, reduce the cost of realgar research and improve research efficiency. Moreover, it provides inspiration for research of other mineral medicine.
Arsenicals ; pharmacology ; Medicine, Chinese Traditional ; Minerals ; Sulfides ; pharmacology

The aim of this paper was to observe the effect of Realgar and arsenic trioxide on gut microbiota. The mice were divided into low-dose Realgar group(RL), medium-dose Realgar group(RM), high-dose Realgar group(RH), and arsenic trioxide group(ATO), in which ATO and RL groups had the same trivalent arsenic content. Realgar and arsenic trioxide toxicity models were established after intragastric administration for 1 week, and mice feces were collected 1 h after intragastric administration on day 8. The effects of Realgar on gut microbiota of mice were observed through bacterial 16 S rRNA gene sequences. The results showed that Lactobacillus was decreased in all groups, while Ruminococcus and Adlercreutzia were increased. The RL group and ATO group were consistent in the genera of Prevotella, Ruminococcus, and Adlercreutzia but different in the genera of Lactobacillus and Bacteroides. Therefore, the effects of Realgar and arsenic trioxide with the same amount of trivalent arsenic on gut microbiota were similar, but differences were still present. Protective bacteria such as Lactobacillus were reduced after Realgar administration, causing inflammation. At low doses, the number of anti-inflammatory bacteria, such as Ruminococcus, Adlercreutzia and Parabacteroides increased, which can offset the slight inflammation caused by the imbalance of bacterial flora. At high doses, the flora was disturbed and the number of Proteobacteria was increased, with aggravated intestinal inflammation, causing edema and other inflammatory reactions. Based on this, authors believe that the gastrointestinal reactions after clinical use of Realgar may be related to flora disorder. Realgar should be used at a small dose in combination with other drugs to reduce intestinal inflammation.
Animals ; Arsenic Trioxide/pharmacology* ; Arsenicals/pharmacology* ; Bacteria/drug effects* ; Gastrointestinal Microbiome/drug effects* ; Mice ; Sulfides/pharmacology*

Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Cell Line, Tumor ; Humans ; Oxides ; pharmacology

This study was aimed to investigate the change of expression and activity of protein phosphatases type 2A (PP2A) during the apoptosis of NB4 and MR2 cells induced by Arsenic trioxide (ATO). NB4 and MR2 cells were incubated with Okadaic acid (OKA) (0.5 nmol/L), ATO (0.5 - 2.0 micromol/L), and the combination of OKA and ATO at the same doses as in the single-agent treatment respectively. Then the proliferation of NB4 and MR2 cells was determined by MTT assay, the morphologic changes of cells were evaluated by Wright's staining, the apoptosis rates were detected by flow cytometry. At last, the activities of PP2A were evaluated by the serine/threonine phosphatase assay system, and the levels of PP2A subunits were detected by Western blot analysis. The results showed that ATO inhibited proliferation of NB4 and MR2 cells, and the inhibition rates of ATO on the two cells significantly increased after the addition of OKA. OKA could augment the apoptosis of NB4 and MR2 cells induced by ATO. During the apoptosis of NB4 and MR2 cells, the activity of PP2A decreased with increasing concentration of ATO, and OKA augmented the inhibitory effect of ATO on the activity. The level of PP2A structural subunit (PP2A-A) decreased during ATO-induced apoptosis of NB4 and MR2 cells, that expressions of B and C subunits of PP2A were relatively unaltered. It is concluded that the activity of PP2A decreases with increasing concentration of ATO during the apoptosis of NB4 and MR2 cells, and the decrease of the activity of PP2A maybe is related to the repression of expression of PP2A -A subunit; the inhibition of the activity of PP2A can promote the ATO induced apoptosis of NB4 and MRL cells.
Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Cell Line, Tumor ; Humans ; Oxides ; pharmacology ; Protein Phosphatase 2 ; metabolism

This study was to establish a model to explore anti- RSV effect of different administration method of Chinese medicine realgar on respiratory syncytial virus type A (RSV-A) replication in Hep-2 cells. Using high-energy ball milling with distilled water to prepare realgar nanoparticles,the concentration of nanometer realgar was tested by molybdenum blue staining method and the size of realgar nanoparticles was tested on Nano Series. Cell culture with ribavirin as a positive control was applied to observe the effect of anti-respiratory syncytial virus type A replication through prevention, treatment or direct inactivation of three different drug administration methods. Realgar nano-particles was found to be a potential inhibitor of RSV-A in a concentration-dependent manner with the median toxic concentration(TC50) of 0.649 microg/mL in Hep-2 cell culture. The median inhibition concentration (IC50) was 0.20 microg/mL when drug was added before virus infection. The IC50 was 0.13 microg/mL when drug was added after virus infection,and it was 0.16 microg/mL when the drug was mixed with virus and added. The therapeutic index (TI) was 3.18, 4.99 and 4.11, respectively. The results showed realgar nanoparticles could inhibit the replication of the RSV and inactivate the RSV in vitro.
Arsenicals ; pharmacology ; Nanoparticles ; Respiratory Syncytial Viruses ; drug effects ; physiology ; Sulfides ; pharmacology ; Virus Replication ; drug effects

Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Cell Line, Tumor ; drug effects ; Humans ; Leukemia ; pathology ; Oxides ; pharmacology

OBJECTIVETo investigate whether ascorbic acid could enhance the efficacy of arsenic trioxide (As(2)O(3)) combined with 2, 3-dimethoxy-1, 4-naphthoquinone (DMNQ) in inducing the apoptosis of leukemia cell line U937 and its possible mechanism.

METHODSFlow cytometry and electron microscopy were applied to detect apoptosis of U937 cells after treatment with various combinations of As(2)O(3), DMNQ and ascorbic acid for 24 hours.

RESULTSAs(2)O(3) and DMNQ induced-apoptosis of U937 cells was enhanced (35.24%-->61.20%) upon cotreatment with ascorbic acid. Catalase could reverse this effect of DMNQ. Ascorbic acid had no effect on DMNQ-induced apoptosis of U937 cells.

CONCLUSIONAscorbic acid enhanced the apoptosis of U937 cells via reactive oxygen species-dependent pathway in the presence of As(2)O(3).

Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Ascorbic Acid ; pharmacology ; Drug Synergism ; Flow Cytometry ; Humans ; Naphthoquinones ; pharmacology ; Oxides ; pharmacology ; U937 Cells

Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; HeLa Cells ; pathology ; Humans ; Leukemia, Promyelocytic, Acute ; pathology ; Oxides ; pharmacology

This study was aimed to investigate the effects of arsenic trioxide (As2O3) combined with TPA on cell cycle, cell differentiation and apoptosis of K562 cell line, and their possible mechanisms. K562 cells were treated with 200 nmol/L TPA, 2 µmol/L As2O3 alone and 200 nmol/L TPA combined with 2 µmol/L As2O3. The proliferative inhibition rates were determined with CCK-8. Annexin V and agarose gel electrophoresis were adopted to detect apoptosis. Colony formation test was used to determine the colony-formation efficiency. Flow cytometry was used to detect the cell differentiation and cell cycle changes. Western blot was employed to detect the expression of P38 and p-P38 proteins. The results showed that combination treatment had synergistic effects on the proliferative inhibition and apoptosis, which were much higher than those treated alone. As2O3 could decrease the colony formation ability of K562 cells. The cells treated with both TPA and As2O3 expressed far more CD11b antigens compared with cells exposed to As2O3 alone. K562 cells treated with TPA were arrested in G1 phase compared with the control group, As2O3 increased the percentage of K562 cells in the G2 phase. The combination treatment increased the expression of p-P38 of K562 cells compared with the cells exposed As2O3 alone. It is concluded that TPA can enhance the effect of As2O3 on inducing apoptosis and adjusting cell cycle , which will expect to provide a new therapeutic program.
Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Cell Cycle ; drug effects ; Drug Synergism ; Humans ; K562 Cells ; Oxides ; pharmacology ; Tetradecanoylphorbol Acetate ; pharmacology

OBJECTIVE: To study synergistic effect of Vitamin C (VitC) combined with arsenic trioxide (As2 O3)-on human laryngocarcinoma Hep-2 cell line apoptosis. METHOD: Human laryngocarcinoma cell line Hep-2 was cultured in vitro, and incubated with As2 O3 or jointly with VitC. The inhibition ability of Hep-2 cells was determined by methyl thiazolyl tetrazolium (MTT) assay, while the apoptosis was mensurated by the flow cytometry with Annexin-V/PI. RESULT: Compared with the use of As2 O3 separately, the combination of As2 O3 and VitC could increase the inhibition ability and the apoptosis rate of Hep-2 cells markedly (P < 0.05). CONCLUSION Combination of As2 O3 with VitC could markedly increase arsenic trioxide (As2 O3)-induced apoptosis of Hep-2 cells.
Apoptosis ; drug effects ; Arsenic Trioxide ; Arsenicals ; pharmacology ; Ascorbic Acid ; pharmacology ; Cell Line, Tumor ; Drug Synergism ; Humans ; Oxides ; pharmacology