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      Urine Metabolomics Study on Potential Hepatoxic Biomarkers Identification in Rats Induced by Aurantio-Obtusin

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          Abstract

          Previous studies revealed the hepatotoxic effect of aurantio-obtusin on rats. The aim of this study was to identify potential biomarkers of urine caused by aurantio-obtusin. Sprague–Dawley (SD) rats with body weight of 0, 4, 40, and 200 mg/kg were orally given aurantio-obtusin for 28 days, and urine was collected for 24 h after the last administration. The urine metabolites in the aurantio-obtusin group and the control group were analyzed by ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). Twenty-three metabolites were identified as potential biomarkers, and 10 of them were up-regulated, including xanthosine, hippuric acid, 5-L-glutamyl-taurine, etc. The other 13 biomarkers were down-regulated, including thymidine, 3-methyldioxyindole, cholic acid, etc. The significant changes of these biomarkers indicated that purine metabolism, taurine and hypotaurine metabolism, primary bile acid biosynthesis, pyrimidine metabolism, and tryptophan metabolism played an important role in the hepatotoxicity of aurantio-obtusin in rats. In this paper, the safety and potential risk of aurantio-obtusin were studied for the first time by combining the toxicity of aurantio-obtusin with the results of urine metabolomics, which provided information for the mechanism of liver injury induced by aurantio-obtusin.

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          Herbal hepatotoxicity in traditional and modern medicine: actual key issues and new encouraging steps

          Plants are natural producers of chemical substances, providing potential treatment of human ailments since ancient times. Some herbal chemicals in medicinal plants of traditional and modern medicine carry the risk of herb induced liver injury (HILI) with a severe or potentially lethal clinical course, and the requirement of a liver transplant. Discontinuation of herbal use is mandatory in time when HILI is first suspected as diagnosis. Although, herbal hepatotoxicity is of utmost clinical and regulatory importance, lack of a stringent causality assessment remains a major issue for patients with suspected HILI, while this problem is best overcome by the use of the hepatotoxicity specific CIOMS (Council for International Organizations of Medical Sciences) scale and the evaluation of unintentional reexposure test results. Sixty five different commonly used herbs, herbal drugs, and herbal supplements and 111 different herbs or herbal mixtures of the traditional Chinese medicine (TCM) are reported causative for liver disease, with levels of causality proof that appear rarely conclusive. Encouraging steps in the field of herbal hepatotoxicity focus on introducing analytical methods that identify cases of intrinsic hepatotoxicity caused by pyrrolizidine alkaloids, and on omics technologies, including genomics, proteomics, metabolomics, and assessing circulating micro-RNA in the serum of some patients with intrinsic hepatotoxicity. It remains to be established whether these new technologies can identify idiosyncratic HILI cases. To enhance its globalization, herbal medicine should universally be marketed as herbal drugs under strict regulatory surveillance in analogy to regulatory approved chemical drugs, proving a positive risk/benefit profile by enforcing evidence based clinical trials and excellent herbal drug quality.
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            Health functions and structure–activity relationships of natural anthraquinones from plants

            Anthraquinone compounds with the anthraquinone ring structure are widely found in traditional Chinese medicines and they are attracting a lot of attention due to their good pharmacological activity. Anthraquinone compounds with the anthraquinone ring structure are widely found in traditional Chinese medicines and they are attracting a lot of attention due to their good pharmacological activity. Diversities of anthraquinones depend on their chemical structures, such as the number of anthraquinone rings and the substituents; what's more, the difference in chemical structure determines the difference in physiological activity. Based on results of previous studies, this review summarizes several natural anthraquinones identified from Chinese herbal medicines and their physiological activities including anti-cancer, anti-pathogenic microorganisms, anti-inflammatory, anti-oxidation, anti-osteoporosis, anti-depression, and anti-constipation. The source, effect, model, and action mechanism of the active anthraquinones are described in detail, from which their structure–activity relationship is summarized. By analyzing the relationship between anthraquinone structure and function, we found that, on the whole structure, the anthraquinone ring and anthraquinone glycosides have significant anticancer activity and anti-constipation activity, while for their substituents, anthraquinones substituted by alizarin have significant antioxidant activity and the polarity of the substituents is closely related to their antibacterial activities.
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              Cassiae semen: A review of its phytochemistry and pharmacology

              Cassiae semen (Leguminosae), a well-known traditional Chinese medicine, has been used for a number of centuries in areas of Southeast Asia, including Korea, Japan and China. The present review aims to provide updated and comprehensive information, on the botany, phytochemistry and pharmacology of Cassiae semen. The available information on Cassiae semen was collected using several different resources, including classic books on Chinese herbal medicine and a number of scientific databases, including the China Academic Journals full-text database, PubMed, SciFinder, the Web of Science and Science Direct. To date >70 chemical compounds have been isolated from Cassiae semen, and the major components have been determined to be anthraquinones, naphthopyrones and volatile oil. The crude extracts and pure compounds of Cassiae semen have been used as effective agents in preclinical and clinical practice due to their beneficial activities, including antihyperlipidemic, antidiabetic, neuroprotective, hepatoprotective, antibacterial, antioxidant and hypotensive activities. With the body of reported data, it has been suggested that Cassiae semen has convincing medicinal potential. However, the pharmacological mechanisms of the main bioactive compounds and the association between structure and activity require further investigation.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                12 August 2020
                2020
                : 11
                : 1237
                Affiliations
                [1] 1 College of Life Science and Bioengineering, Beijing University of Technology , Beijing, China
                [2] 2 Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine , Beijing, China
                Author notes

                Edited by: Eleonore Fröhlich, Medical University of Graz, Austria

                Reviewed by: Yubo Li, Tianjin University of Traditional Chinese Medicine, China; Yunping Qiu, Albert Einstein College of Medicine, United States; Feng Qiu, Tianjin University of Traditional Chinese Medicine, China

                *Correspondence: Xianglin Tang, tangxianglin@ 123456139.com ; Yue Gao, gaoyue@ 123456bmi.ac.cn

                This article was submitted to Predictive Toxicology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2020.01237
                7435054
                32903457
                97deccd5-17fa-4eb3-a4a6-84d738ddaefe
                Copyright © 2020 Xu, Wang, Ma, Tang and Gao

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 27 April 2020
                : 28 July 2020
                Page count
                Figures: 8, Tables: 0, Equations: 0, References: 54, Pages: 12, Words: 5660
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                aurantio-obtusin,liver injury,urine,metabolomics,ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry

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