Jing Zhou1, Nan Yao2, Shuxia Wang2, Dongchen An3, Kangna Cao3, Jiali Wei3, Ning Li3, Di Zhao3, Lirui Wang4, Xijing Chen5, Yang Lu6. 1. School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Longmian Avenue No. 639, 211198 Nanjing, Jiangsu province, China; Nanjing University of Chinese Medicine, Department of Pharmaceutical Analysis and Metabolomics, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Hongshan Road Shizi Street No. 100, 210028 Nanjing, Jiangsu province, China. 2. Nanjing University of Chinese Medicine, Department of Pharmaceutical Analysis and Metabolomics, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Hongshan Road Shizi Street No. 100, 210028 Nanjing, Jiangsu province, China. 3. School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Longmian Avenue No. 639, 211198 Nanjing, Jiangsu province, China. 4. School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Longmian Avenue No. 639, 211198 Nanjing, Jiangsu province, China. Electronic address: wanglirui@cpu.edu.cn. 5. School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Longmian Avenue No. 639, 211198 Nanjing, Jiangsu province, China. Electronic address: chenxj_lab@hotmail.com. 6. School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Longmian Avenue No. 639, 211198 Nanjing, Jiangsu province, China. Electronic address: luyangcpu@hotmail.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Gardenia (FG) is a widely used bitter and cold herb for clearing heat and detoxicating. Currently, toxicity of FG and its relative formula has been reported in many clinical and animal studies. However, no systematic research has been carried out on FG-related gastrointestinal (GI) injury which has been emphasized in China since the Ming Dynasty. AIM OF THE STUDY: The purpose of this article is to investigate whether FG could damage GI and explore the mechanisms involved. MATERIAL AND METHODS: FG was given to male mice by 7-day intragastric administration at average doses of 0.90 g (L group), 1.50 g (M group), and 3.00 g (H group) crude drug/kg FG. Comprehensive understanding of changes in weight, diarrhea degree, stool routine, histomorphology and inflammatory factors of stomach, small intestine, and colon for evaluating the effect of different doses of FG on GI injury. Moreover, metabolomics-based mechanisms exploration of FG on GI injury was carried out via HPLC-Q-TOF/MS analysis on mice urine. RESULTS: High dose FG caused GI injury with serious diarrhea, decreased weight, abnormal stool routine, sever alteration in histomorphology of small intestine and colon (mild change in stomach), and significant change in inflammatory factors. The results of metabolomics suggested that 55 endogenous metabolites dispersed in 21 significantly altered metabolic pathways in 3.00 g/kg crude FG treated mice. The hub metabolites of GI injury were mainly related with vitamin B6 metabolism, phenylalanine metabolism, arachidonic acid metabolism, and taurine and hypotaurine metabolism via correlated network analysis. CONCLUSION: FG affected the normal functions of GI via the regulating a variety of metabolic pathways to an abnormal state, and our results provided a research paradigm for the GI-injury of the relative bitter and cold traditional Chinese medicines.
ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Gardenia (FG) is a widely used bitter and cold herb for clearing heat and detoxicating. Currently, toxicity of FG and its relative formula has been reported in many clinical and animal studies. However, no systematic research has been carried out on FG-related gastrointestinal (GI) injury which has been emphasized in China since the Ming Dynasty. AIM OF THE STUDY: The purpose of this article is to investigate whether FG could damage GI and explore the mechanisms involved. MATERIAL AND METHODS: FG was given to male mice by 7-day intragastric administration at average doses of 0.90 g (L group), 1.50 g (M group), and 3.00 g (H group) crude drug/kg FG. Comprehensive understanding of changes in weight, diarrhea degree, stool routine, histomorphology and inflammatory factors of stomach, small intestine, and colon for evaluating the effect of different doses of FG on GI injury. Moreover, metabolomics-based mechanisms exploration of FG on GI injury was carried out via HPLC-Q-TOF/MS analysis on mice urine. RESULTS: High dose FG caused GI injury with serious diarrhea, decreased weight, abnormal stool routine, sever alteration in histomorphology of small intestine and colon (mild change in stomach), and significant change in inflammatory factors. The results of metabolomics suggested that 55 endogenous metabolites dispersed in 21 significantly altered metabolic pathways in 3.00 g/kg crude FG treated mice. The hub metabolites of GI injury were mainly related with vitamin B6 metabolism, phenylalanine metabolism, arachidonic acid metabolism, and taurine and hypotaurine metabolism via correlated network analysis. CONCLUSION: FG affected the normal functions of GI via the regulating a variety of metabolic pathways to an abnormal state, and our results provided a research paradigm for the GI-injury of the relative bitter and cold traditional Chinese medicines.