Hubei Engineering Technology Research Center of Chinese Materia Medica Processing, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China.
2 Hubei Provincial Traditional Chinese Medicine Formula Granule Engineering Technology Research Center, Jing Brand Chizhengtang Pharmaceutical Co., Ltd., Huangshi 435100, China.
J Tradit Chin Med. 2023 Oct;43(6):1110-1117. doi: 10.19852/j.cnki.jtcm.20230404.003.
To study the anti-inflammatory and anti-tussive effects of Qingfei Dayuan granules (, QFDY), and to evaluate the acute and sub-chronic toxicity of QFDY.
Anti-inflammatory effects were evaluated by murine model of xylene induced ear edema in mice. Ear swelling degree was calculated and tumor necrosis factor-α, interleukin-1β and interleukin-6 were determined. Anti-tussive evaluations were carried out in the mouse cough model induced by ammonia liquor. Latent period cough and number of cough within 3 min were counted. In acute toxicity study, the rats were randomly divided into test group and solvent control group. Body weighs, food intakes and general clinical signs were monitored. In the sub-chronic toxicity study, QFDY was administered to rats at 0, 4, 8 and 16 g/kg per day for 28 and 30 d of post treatment was conducted. Mortalities, clinical signs, body weight changes, food intakes, ophthalmological examinations, hematological parameters, biochemical indicators, electrolyte indicators, urinalyses and histopathological examinations were monitored.
QFDY significantly inhibited the development of ear edema in anti-inflammatory assay and decreased cough frequency caused by ammonia liquor. The results presented a dose-effect relationship. In acute toxicity study, no abnormality exhibited at dose of 24.0 g/kg per day during the 14-d observation period. In the sub-chronic toxicity study, higher reticulocyte count, lymphocyte and lower Cl-, blood urea nitrogen were analyzed compared with the solvent control group. But the differences were considered to be incidental and not clinically toxic. Obvious dose-effect relationship of urine color was observed, and the three test groups at the end of the experiments resulted in significant increase in urobilinogen, bilirubin, ketone body and urine leukocyte. However, all the positive indicators returned to normal in the recovery period. Therefore, no toxicological changes were found during the study period.
QFDY showed significant anti-inflammatory and anti-tussive effects in mice. The lethal dose (LD50) of per oral QFDY in rats was estimated to be more than 24.0 g/kg per day and the no observed adverse effect level was over 16 g/kg per day, which suggested that QFDY is relatively safe for oral medication at the present dose on rats. Our experimental results provide a reference for the further development and research of QFDY.
研究清肺大院颗粒（QFDY）的抗炎、镇咳作用，并评价 QFDY 的急性毒性和亚慢性毒性。
采用二甲苯致小鼠耳肿胀模型评价抗炎作用，计算耳肿胀度，检测肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6。采用氨溶液诱导小鼠咳嗽模型评价镇咳作用，记录潜伏期咳嗽次数和 3 min 内咳嗽次数。在急性毒性试验中，将大鼠随机分为试验组和溶剂对照组，观察大鼠体重、摄食量和一般临床体征。在亚慢性毒性试验中，大鼠分别灌胃给予 QFDY 0、4、8 和 16 g/kg，连续给药 28 d 和 30 d 后处死，观察死亡率、临床体征、体重变化、摄食量、眼科检查、血液学参数、血液生化指标、电解质指标、尿液分析和组织病理学检查。
QFDY 可显著抑制抗炎试验中小鼠耳肿胀的发展，减少氨溶液引起的咳嗽频率，且呈现一定的剂量效应关系。在急性毒性试验中，24.0 g/kg 剂量组在 14 d 观察期内无异常表现。在亚慢性毒性试验中，与溶剂对照组比较，试验组大鼠出现较高的网织红细胞计数、淋巴细胞计数和较低的 Cl-、血尿素氮，但认为这些差异是偶然的，无临床毒性。尿液颜色呈明显的剂量效应关系，试验结束时，三组试验大鼠尿液胆红素、尿胆原、酮体和白细胞均显著增加，但在恢复期所有阳性指标均恢复正常。因此，在研究期间未发现毒理学变化。
QFDY 对小鼠具有显著的抗炎、镇咳作用。QFDY 灌胃给药的 LD50 估计大于 24.0 g/kg，未观察到不良作用水平大于 16.0 g/kg，提示在目前剂量下 QFDY 对大鼠口服给药相对安全。本实验结果为 QFDY 的进一步开发和研究提供了参考。
