Preclinical safety evaluation of WangShiBaoChiWan

doi:10.5246/jcps.2022.01.004

Abstract

Abstract:

WangShiBaoChiWan (WSBCW) is a traditional Chinese medicine with a recorded administration history of more than 180 years. In the present study, the preclinical safety of WSBCW was evaluated the preclinical safety of WSBCW using a toxicity test, which consisted of an administration period of 28 d and a recovery period of 15 d. During the test, male and female SD rats were administered the medicine once a day by oral gavage, at a dose of 60 mg/kg/day, 600 mg/kg/day, or 1500 mg/kg/day. As a reference medicine, mosapride citrate was administered at a dose of 37.5 mg/kg/day, which was clinically equivalent to the high-dosage treatment of WSBCW. With all the dosage groups, statistically, no adverse effect was observed in terms of clinical observation, food intake, body weights, organ coefficient, blood biochemistry, and histopathology examination. No intestinal melanosis was observed in the rats. When the data were examined animal by animal, test substance-related adverse effects were found with the high-dosage rats in hematology assay. The deranged, however, reversible changes suggested a compromised intestinal barrier, which was also observed with in mosapride citrate-treated rats. In addition to the histopathology assay, molecular toxicology was explored using high-throughput gene sequencing. No evident toxicity was revealed. In summary, administration of WSBCW was well tolerated within a treatment of 28 d.

Key words: Toxicology, Traditional Chinese medicine, Deep sequencing

Supporting:

Tao Gao, Lei Liu, Yan Wu, Quan Du. Preclinical safety evaluation of WangShiBaoChiWan[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(1): 31-46.

Figures/Tables 14

Table 1. Summary of serum biochemistry data of WSBCW-treated rats at the end of the administration period. ALB, albumin (reference ranges: 38-ic); ALP, alkaline phosphatase (40–442); ALT, alanine aminotransferase (22–137); AMY, amylase (502–1113); T-BIL, total bilirubin (4–7); BUN, blood urea nitrogen (2.5–6.6); CA, calcium (2.4–2.7); PHOS, phosphorus (0.74–2.26); CRE, creatinine (ic-53); GLU, glucose (6.6–13.7); NA+, sodium (133–144); K+, potassium (3.6–5.3); TP, total protein (66–88); GLOB, globulin (12–35); HEM, hemolysin. Data are presented as mean ± SD.

Table 2. Summary of serum biochemistry data of WSBCW-treated rats at the end of the recovery period.

Table 3. Summary of hematology data of WSBCW-treated rats at the end of the administration period. WBC, white blood cell count (reference ranges: 2.10–19.50); LYM, lymphocyte (2.00–14.10); MON, monocyte (0.00–0.98); NEU, neutrophil (0.10–5.40); RBC, red blood cell count (5.30–10.00); HGB, hemoglobin (14.0–18.0); HCT, hematocrit value (35.00–52.00); MCV, mean corpuscular volume (50–62); MCH, mean corpuscular hemoglobin (16.0–23.0); MCHC, mean corpuscular hemoglobin concentration (31.0–40.0); RDW, red blood cell distribution width; RDWs, red blood cell distribution width SD; PTL, platelet count; MPV, mean platelet volume; PCT, procalcitonin (500–1000); PDW, platelet distribution width; PDWs, platelet distribution width SD. Data are presented as mean ± SD.

Table 4. Summary of hematology data of WSBCW-treated rats at the end of the recovery period.

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