Cong-En Zhang1, Ming Niu2, Qi Li2, Yan-Ling Zhao2, Zhi-Jie Ma3, Yin Xiong4, Xiao-Ping Dong5, Rui-Yu Li1, Wu-Wen Feng1, Qing Dong1, Xiao Ma1, Yun Zhu6, Zheng-Sheng Zou7, Jun-Ling Cao8, Jia-Bo Wang9, Xiao-He Xiao10. 1. China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, PR China; College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China. 2. China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, PR China. 3. Beijing Friendship Hospital, Capital Medical University, Beijing, PR China. 4. Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, PR China. 5. College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China. 6. Integrative Medical Center, 302 Military Hospital, Beijing, PR China. 7. Diagnosis and Treatment Center for Non-infectious Diseases, 302 Military Hospital, Beijing, PR China. 8. Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, PR China. 9. China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, PR China. Electronic address: pharm_sci@126.com. 10. China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, PR China. Electronic address: pharmacy302xxh@126.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum L. is a famous traditional Chinese medicine that has always been perceived to be safe. Recently, the increasing case reports on hepatotoxicity induced by Raw P. multiflorum (RP) have attracted particular attention. However, the diagnosis and identification of RP-induced hepatotoxicity are still very difficult for its unknown mechanism and the lack of specific biomarkers. AIM OF THE STUDY: To further explore the toxicity and metabolic mechanisms involved in the hepatotoxicity induced by RP. MATERIALS AND METHODS: The hepatotoxicity induced by RP and its processed products (PP) (dosed at 20g/kg for 4 weeks) on rats were investigated using conventional approaches including the biochemical analysis and histopathological observations. Further, a urinary metabolomic approach was developed to study the metabolic disturbances caused by RP and PP, followed by the pattern recognition approach and pathways analysis. RESULTS: RP showed obvious hepatotoxity whereas PP did not. 16 potential biomarkers (pyridoxamine, 4-pyridoxic acid, citrate et al.) differentially expressed in RP group were identified compared with the control and PP-treated groups. The pathways analysis showed that vitamin B6 metabolism, tryptophan metabolism and citrate cycle might be the major enriched pathways involved in the hepatotoxicity of the herb. CONCLUSION: 16 differentially expressed metabolites were identified to be involved in the RP-induced hepatotoxicity. Vitamin B6 metabolism might be mostly related to the hepatotoxicity induced by RP. This finding may provide a potential therapeutic target or option to treat hepatotoxicity induced by RP.
ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum L. is a famous traditional Chinese medicine that has always been perceived to be safe. Recently, the increasing case reports on hepatotoxicity induced by Raw P. multiflorum (RP) have attracted particular attention. However, the diagnosis and identification of RP-induced hepatotoxicity are still very difficult for its unknown mechanism and the lack of specific biomarkers. AIM OF THE STUDY: To further explore the toxicity and metabolic mechanisms involved in the hepatotoxicity induced by RP. MATERIALS AND METHODS: The hepatotoxicity induced by RP and its processed products (PP) (dosed at 20g/kg for 4 weeks) on rats were investigated using conventional approaches including the biochemical analysis and histopathological observations. Further, a urinary metabolomic approach was developed to study the metabolic disturbances caused by RP and PP, followed by the pattern recognition approach and pathways analysis. RESULTS: RP showed obvious hepatotoxity whereas PP did not. 16 potential biomarkers (pyridoxamine, 4-pyridoxic acid, citrate et al.) differentially expressed in RP group were identified compared with the control and PP-treated groups. The pathways analysis showed that vitamin B6 metabolism, tryptophan metabolism and citrate cycle might be the major enriched pathways involved in the hepatotoxicity of the herb. CONCLUSION: 16 differentially expressed metabolites were identified to be involved in the RP-induced hepatotoxicity. Vitamin B6 metabolism might be mostly related to the hepatotoxicity induced by RP. This finding may provide a potential therapeutic target or option to treat hepatotoxicity induced by RP.
Authors: Dae Uk Kim; Jae Yoon Chung; Seong Chul Jin; Mi Hye Kim; Richard Komakech; Ki-Shuk Shim; Yong-Goo Kim; Woong Mo Yang; Youngmin Kang Journal: Evid Based Complement Alternat Med Date: 2020-04-24 Impact factor: 2.629