An experimental study on providing a scientific evidence for seven-time alcohol-steaming of Rhei Rhizoma when clinically used.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These results provide experimental evidence that RR-P7 almost completely reduces RR hepatotoxicity.
Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. yeomeong@khu.ac.kr.
Yeomoon
Y
Sim
Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. hin812@khu.ac.kr.
Hyein
H
Oh
Division for Medical Research, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea. dalsoh@gmail.com.
Dal-Seok
DS
Oh
Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. kop03@khu.ac.kr.
Namkwon
N
Kim
Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. sbgps@khu.ac.kr.
Pil Sung
PS
Gu
Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. choijg2002@khu.ac.kr.
Jin Gyu
JG
Choi
Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-west Pharmaceutical Research Institute, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. kimhyogeun@khu.ac.kr.
Hyo Geun
HG
Kim
Department of Oriental Medicinal Materials & Processing, College of Life Sciences, Kyung Hee University, Gyeonggi-do, Republic of Korea. panjae@khu.ac.kr.
Tong Ho
TH
Kang
Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. msohok@khu.ac.kr.|Department of Oriental Pharmaceutical Science, College of Pharmacy and Kyung Hee East-west Pharmaceutical Research Institute, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. msohok@khu.ac.kr.
Myung Sook
MS
Oh
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004339:Drug Compounding / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000633:toxicity; D004642:Emodin / Q000032:analysis; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008297:Male; D051381:Rats; D012250:Rheum / Q000737:chemistry / Q000633:toxicity; D027343:Rhizome / Q000737:chemistry / Q000633:toxicity; D012676:Senna Extract / Q000032:analysis; D000081226:Sennosides
D004365:Drugs, Chinese Herbal; D000081226:Sennosides; D012676:Senna Extract; D004642:Emodin