Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network
Mesaconitine (MA), one of the main diterpenoid alkaloids in Aconitum, has a variety of pharmacological effects, such as analgesia, anti-inflammation and relaxation of rat aorta. However, MA is a highly toxic ingredient. At present, studies on its toxicity are mainly focused on the heart and central...
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| Format: | Article |
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MDPI AG
2022-07-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/14/7/486 |
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| author | Qian Chen Kai Zhang Mingjie Jiao Jiakang Jiao Dongling Chen Yihui Yin Jia Zhang Fei Li |
| author_facet | Qian Chen Kai Zhang Mingjie Jiao Jiakang Jiao Dongling Chen Yihui Yin Jia Zhang Fei Li |
| author_sort | Qian Chen |
| collection | DOAJ |
| description | Mesaconitine (MA), one of the main diterpenoid alkaloids in Aconitum, has a variety of pharmacological effects, such as analgesia, anti-inflammation and relaxation of rat aorta. However, MA is a highly toxic ingredient. At present, studies on its toxicity are mainly focused on the heart and central nervous system, and there are few reports on the hepatotoxic mechanism of MA. Therefore, we evaluated the effects of MA administration on liver. SD rats were randomly divided into a normal saline (NS) group, a low-dose MA group (0.8 mg/kg/day) and a high-dose MA group (1.2 mg/kg/day). After 6 days of administration, the toxicity of MA on the liver was observed. Metabolomic and network toxicology methods were combined to explore the effect of MA on the liver of SD rats and the mechanism of hepatotoxicity in this study. Through metabonomics study, the differential metabolites of MA, such as L-phenylalanine, retinyl ester, L-proline and 5-hydroxyindole acetaldehyde, were obtained, which involved amino acid metabolism, vitamin metabolism, glucose metabolism and lipid metabolism. Based on network toxicological analysis, MA can affect HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway and FoxO signal pathway by regulating ALB, AKT1, CASP3, IL2 and other targets. Western blot results showed that protein expression of HMOX1, IL2 and caspase-3 in liver significantly increased after MA administration (<i>p</i> < 0.05). Combined with the results of metabonomics and network toxicology, it is suggested that MA may induce hepatotoxicity by activating oxidative stress, initiating inflammatory reaction and inducing apoptosis. |
| first_indexed | 2024-03-09T10:11:42Z |
| format | Article |
| id | doaj.art-91fd6b4897904646895a60557e010590 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-09T10:11:42Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-91fd6b4897904646895a60557e0105902023-12-01T22:45:34ZengMDPI AGToxins2072-66512022-07-0114748610.3390/toxins14070486Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology NetworkQian Chen0Kai Zhang1Mingjie Jiao2Jiakang Jiao3Dongling Chen4Yihui Yin5Jia Zhang6Fei Li7School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing 102488, ChinaSchool of Life Sciences, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing 102488, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing 102488, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing 102488, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing 102488, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing 102488, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing 102488, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing 102488, ChinaMesaconitine (MA), one of the main diterpenoid alkaloids in Aconitum, has a variety of pharmacological effects, such as analgesia, anti-inflammation and relaxation of rat aorta. However, MA is a highly toxic ingredient. At present, studies on its toxicity are mainly focused on the heart and central nervous system, and there are few reports on the hepatotoxic mechanism of MA. Therefore, we evaluated the effects of MA administration on liver. SD rats were randomly divided into a normal saline (NS) group, a low-dose MA group (0.8 mg/kg/day) and a high-dose MA group (1.2 mg/kg/day). After 6 days of administration, the toxicity of MA on the liver was observed. Metabolomic and network toxicology methods were combined to explore the effect of MA on the liver of SD rats and the mechanism of hepatotoxicity in this study. Through metabonomics study, the differential metabolites of MA, such as L-phenylalanine, retinyl ester, L-proline and 5-hydroxyindole acetaldehyde, were obtained, which involved amino acid metabolism, vitamin metabolism, glucose metabolism and lipid metabolism. Based on network toxicological analysis, MA can affect HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway and FoxO signal pathway by regulating ALB, AKT1, CASP3, IL2 and other targets. Western blot results showed that protein expression of HMOX1, IL2 and caspase-3 in liver significantly increased after MA administration (<i>p</i> < 0.05). Combined with the results of metabonomics and network toxicology, it is suggested that MA may induce hepatotoxicity by activating oxidative stress, initiating inflammatory reaction and inducing apoptosis.https://www.mdpi.com/2072-6651/14/7/486mesaconitinehepatotoxicitymetabonomicsnetwork toxicologyoxidative stressinflammatory response |
| spellingShingle | Qian Chen Kai Zhang Mingjie Jiao Jiakang Jiao Dongling Chen Yihui Yin Jia Zhang Fei Li Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network Toxins mesaconitine hepatotoxicity metabonomics network toxicology oxidative stress inflammatory response |
| title | Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network |
| title_full | Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network |
| title_fullStr | Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network |
| title_full_unstemmed | Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network |
| title_short | Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network |
| title_sort | study on the mechanism of mesaconitine induced hepatotoxicity in rats based on metabonomics and toxicology network |
| topic | mesaconitine hepatotoxicity metabonomics network toxicology oxidative stress inflammatory response |
| url | https://www.mdpi.com/2072-6651/14/7/486 |
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