title: Evaluation of the safety and adverse effects of goreisan/wulingsan, a traditional Japanese-chinese herbal formulation (kampo), in a rat model: a toxicological evaluation.
abstract: Diarrhea is the second leading cause of death among children less than 5 years of age. Most of these deaths occur in developing countries in the tropical areas of Africa and South Asia. Goreisan/Wulingsan, a formula of Japanese-Chinese medicinal herbs (Kampo), has been used for the treatment of diarrhea and vomiting from ancient times in East Asia. Therefore, we planned a randomized controlled clinical trial of Goreisan/Wulingsan in Bangladeshi children. Although it is believed to be safe in East Asia, information regarding its toxicity on animals is scarce. Since Goreisan/Wulingsan has never been used in Bangladesh, it was necessary to ensure the safety of the formula in an animal experiment. Rats were assigned to a control group (normal saline, n = 4) or various Goreisan/Wulingsan groups (n = 26) receiving doses of 1 to 8 mg/g/day (7.7 to 61.5 times the recommended pediatric dose) over a period of 25 days. Their activities and health conditions were observed until they were sacrificed, after which blood samples were collected for biochemical liver function tests. The kidneys, liver and heart tissue were collected for histopathological study. No lethality was observed during the experiment. All of the rats consumed the doses completely and no constipation was observed, suggesting the absence of any inhibitory effect on intestinal motion. Also, no abnormal neurological activity was detected, nor any significant elevation of AST, ALT or ALP levels, except for AST and ALT at the highest dose of 8 mg/g/day. Histopathological studies of the kidneys, liver and heart tissues revealed no abnormalities. In conclusion, our results showed that Goreisan/Wulingsan is safe for rats, thereby justifying the use of the drug in a human trial.
authors.affiliation: Department of Pediatrics, Institute of Child and Mother Health , Dhaka, Bangladesh ; Currently at the Department of Pediatrics, School of Medicine, University of Malaysia Sabah , Kota Kinabalu, Sabah, Malaysia.
authors.forename: Selim
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections (RCC-ERI), Research Institute for Microbial Diseases, Osaka University , Nonthaburi, Thailand (Currently at the Department of Infectious Diseases and Respiratory Medicine, Kusatsu General Hospital, Kusatsu City, Shiga Prefecture, Japan).
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Uchida
authors.affiliation: Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections (RCC-ERI), Research Institute for Microbial Diseases, Osaka University , Nonthaburi, Thailand (Currently at the Department of Infectious Diseases and Respiratory Medicine, Kusatsu General Hospital, Kusatsu City, Shiga Prefecture, Japan).
authors.forename: Maleeha
authors.initials: M
authors.lastname: Hussain
authors.affiliation: Department of Pediatrics, Institute of Child and Mother Health , Dhaka, Bangladesh ; Currently at Department of Pediatrics, Sir Salimullah Medical College , Dhaka, Bangladesh.
authors.forename: Arm Luthful
authors.initials: AL
authors.lastname: Kabir
authors.affiliation: Biomedical Research Centre, University of Dhaka , Dhaka, Bangladesh.
authors.forename: Mohammed Zakiur
authors.initials: MZ
authors.lastname: Rahman
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka , Dhaka, Bangladesh.
authors.forename: Mohammad Sharifur
authors.initials: MS
authors.lastname: Rahman
authors.affiliation: Section of Public Health and Nursing, Nagasaki University School of Health Science , Nagasaki City, Japan.
authors.forename: Sumihisa
authors.initials: S
authors.lastname: Honda
authors.affiliation: Currently at Department of Pediatrics, Sir Salimullah Medical College , Dhaka, Bangladesh.
authors.forename: Mohammad Abdur
authors.initials: MA
authors.lastname: Rashid
keywords: Kampo; histopathology; inhibition of intestinal motion; liver function; toxicology