Sim Yeomoon, Oh Hyein, Oh Dal-Seok, Kim Namkwon, Gu Pil Sung, Choi Jin Gyu, Kim Hyo Geun, Kang Tong Ho, Oh Myung Sook
Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.
Division for Medical Research, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.
BMC Complement Altern Med. 2015 Oct 27;15:388. doi: 10.1186/s12906-015-0922-y.
Rhei Rhizoma (RR) has been widely used as laxative and processed to alter its therapeutic actions or reduce its side effects. In this study, we evaluated experimentally the clinical application guideline that RR should be alcohol-steamed seven times before being used in elderly patients, as described in Dongeuibogam, the most famous book on Korean traditional medicine.
Unprocessed RR (RR-U) was soaked in rice wine, steamed and then fully dried (RR-P1). The process was repeated four (RR-P4) or seven times (RR-P7). Reversed-phase high-performance liquid chromatography was used to determine the RR-U, RR-P1, RR-P4 and RR-P7 (RRs) constituents. To evaluate the effect of RRs on liver toxicity, human hepatoma cells (HepG2) were treated with RRs at 100 μg/mL for 4 h and then cell viabilities were measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. To confirm the effects in vivo, 5-week-old male Sprague-Dawley rats were treated with RRs at 3 g/kg/day for 21 days. Body weight and serum biochemical parameters were measured and liver histology was assessed.
The levels of sennosides decreased in processed RRs in an iteration-dependent manner, while the emodin level was unaffected. In HepG2 cells, cell viability was reduced with RR-U, while the toxicity decreased according to the number of processing cycles. The changes in body weight, relative liver weight and liver enzymes of RR-U-treated rats were reduced in processed RRs-treated rats. Histopathological analysis indicated swelling and cholestasis improved following seven times alcohol-steaming cycles.
These results provide experimental evidence that RR-P7 almost completely reduces RR hepatotoxicity.
大黄已被广泛用作泻药,并经过炮制以改变其治疗作用或减少其副作用。在本研究中,我们通过实验评估了《东医宝鉴》(韩国最著名的传统医学书籍)中所述的大黄在用于老年患者之前应酒蒸七次的临床应用指南。
将生大黄(RR-U)用米酒浸泡、蒸煮,然后充分干燥(RR-P1)。该过程重复四次(RR-P4)或七次(RR-P7)。采用反相高效液相色谱法测定RR-U、RR-P1、RR-P4和RR-P7(RRs)的成分。为评估RRs对肝毒性的影响,将人肝癌细胞(HepG2)用100μg/mL的RRs处理4小时,然后使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法测量细胞活力。为在体内证实其效果,对5周龄雄性Sprague-Dawley大鼠以3g/kg/天的剂量给予RRs,持续21天。测量体重和血清生化参数,并评估肝脏组织学。
经炮制的RRs中番泻苷的含量以迭代依赖的方式降低,而大黄素水平未受影响。在HepG2细胞中,RR-U降低了细胞活力,而毒性根据炮制周期数降低。RR-U处理的大鼠的体重、相对肝脏重量和肝酶的变化在RRs处理的大鼠中有所减轻。组织病理学分析表明,经过七次酒蒸周期后,肿胀和胆汁淤积有所改善。
这些结果提供了实验证据,表明RR-P7几乎完全降低了大黄的肝毒性。