Hepatotoxic metabolites in Polygoni Multiflori Radix— Comparative toxicology in mice
Polygoni Multiflori Radix (PM) and Rhei radix et rhizoma (rhubarb) contain similar hepatocyte-toxic anthraquinones such as emodin (major free anthraquinone in PM), physcion and their glycosides. In clinical practice, PM hepatotoxicity has been widely reported, although rhubarb is not recognized as h...
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| Format: | Article |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1007284/full |
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| author | Shixiao Wang Shixiao Wang Xiang Kong Xiang Kong Ning Chen Ning Chen Pengwei Hu Pengwei Hu Hamza Boucetta Hamza Boucetta Zhaoliang Hu Zhaoliang Hu Xin Xu Xin Xu Pei Zhang Pei Zhang Xiang Zhan Xiang Zhan Ming Chang Ming Chang Rui Cheng Rui Cheng Wei Wu Wei Wu Min Song Min Song Yuting Lu Yuting Lu Taijun Hang Taijun Hang |
| author_facet | Shixiao Wang Shixiao Wang Xiang Kong Xiang Kong Ning Chen Ning Chen Pengwei Hu Pengwei Hu Hamza Boucetta Hamza Boucetta Zhaoliang Hu Zhaoliang Hu Xin Xu Xin Xu Pei Zhang Pei Zhang Xiang Zhan Xiang Zhan Ming Chang Ming Chang Rui Cheng Rui Cheng Wei Wu Wei Wu Min Song Min Song Yuting Lu Yuting Lu Taijun Hang Taijun Hang |
| author_sort | Shixiao Wang |
| collection | DOAJ |
| description | Polygoni Multiflori Radix (PM) and Rhei radix et rhizoma (rhubarb) contain similar hepatocyte-toxic anthraquinones such as emodin (major free anthraquinone in PM), physcion and their glycosides. In clinical practice, PM hepatotoxicity has been widely reported, although rhubarb is not recognized as hepatotoxic. To clarify the substances basis (key components) of PM hepatotoxicity, based on the characteristic components’ similarity within PM, rhubarb and their concocted forms, a comparative sub-acute toxicity study was designed in mice. Nine groups of mice with 28 days of oral administration of these herbal extracts or 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG, major and unique characteristic component in PM)-herb combinations were set as follows: Group-1, control; Group-2, PM ethanol-extract (PME); Group-3, PM praeparata ethanol-extract (PMPE); Group-4, Rhubarb ethanol-extract (RME); Group-5, Steamed rhubarb ethanol-extract (RMPE); Group-6, TSG; Group-7, PMPE-TSG combination; Group-8, RME-TSG combination; Group-9, RMPE-TSG combination. Each experimental group received an equivalent emodin dose of 29 mg/kg except for the TSG group, and an equivalent TSG dose of 1,345 mg/kg except for the PMPE, RME and RMPE groups. The results showed that PME, PMPE-TSG and RME-TSG induced liver lesions and biochemical abnormalities of liver function compared with the control. In contrast, PMPE, RME, RMPE, TSG and RMPE-TSG caused no liver lesions and fewer biochemical abnormalities. Considering the related components, only the co-administration of high doses of TSG and emodin-8-O-β-D-glucoside (EMG, major anthraquinone glycoside in PM) in these groups could cause liver lesions. According to tissue distribution and correlation analysis, EMG dose was positively correlated with the high hepatic emodin and TSG exposure, and the hepatic emodin and TSG exposure were positively correlated with the biochemical abnormalities of liver function. Cell viability test in vitro showed emodin was more hepatotoxic than TSG and EMG, and mainly emodin and TSG of the three had synergistic hepatotoxic effects. Therefore, creatively using rhubarb as a reference, this study revealed that PM hepatotoxicity in mice mainly came from the integrative contribution of TSG, EMG and emodin. |
| first_indexed | 2024-04-11T10:05:38Z |
| format | Article |
| id | doaj.art-e127adb4d04e49f987264f97850ff530 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T10:05:38Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-e127adb4d04e49f987264f97850ff5302022-12-22T04:30:16ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.10072841007284Hepatotoxic metabolites in Polygoni Multiflori Radix— Comparative toxicology in miceShixiao Wang0Shixiao Wang1Xiang Kong2Xiang Kong3Ning Chen4Ning Chen5Pengwei Hu6Pengwei Hu7Hamza Boucetta8Hamza Boucetta9Zhaoliang Hu10Zhaoliang Hu11Xin Xu12Xin Xu13Pei Zhang14Pei Zhang15Xiang Zhan16Xiang Zhan17Ming Chang18Ming Chang19Rui Cheng20Rui Cheng21Wei Wu22Wei Wu23Min Song24Min Song25Yuting Lu26Yuting Lu27Taijun Hang28Taijun Hang29Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, ChinaDepartment of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, ChinaDepartment of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, ChinaDepartment of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, ChinaDepartment of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, ChinaDepartment of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, ChinaDepartment of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, ChinaDepartment of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, ChinaDepartment of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, ChinaDepartment of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, ChinaDepartment of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, ChinaDepartment of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, ChinaDepartment of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, ChinaDepartment of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, ChinaDepartment of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, ChinaDepartment of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, ChinaPolygoni Multiflori Radix (PM) and Rhei radix et rhizoma (rhubarb) contain similar hepatocyte-toxic anthraquinones such as emodin (major free anthraquinone in PM), physcion and their glycosides. In clinical practice, PM hepatotoxicity has been widely reported, although rhubarb is not recognized as hepatotoxic. To clarify the substances basis (key components) of PM hepatotoxicity, based on the characteristic components’ similarity within PM, rhubarb and their concocted forms, a comparative sub-acute toxicity study was designed in mice. Nine groups of mice with 28 days of oral administration of these herbal extracts or 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG, major and unique characteristic component in PM)-herb combinations were set as follows: Group-1, control; Group-2, PM ethanol-extract (PME); Group-3, PM praeparata ethanol-extract (PMPE); Group-4, Rhubarb ethanol-extract (RME); Group-5, Steamed rhubarb ethanol-extract (RMPE); Group-6, TSG; Group-7, PMPE-TSG combination; Group-8, RME-TSG combination; Group-9, RMPE-TSG combination. Each experimental group received an equivalent emodin dose of 29 mg/kg except for the TSG group, and an equivalent TSG dose of 1,345 mg/kg except for the PMPE, RME and RMPE groups. The results showed that PME, PMPE-TSG and RME-TSG induced liver lesions and biochemical abnormalities of liver function compared with the control. In contrast, PMPE, RME, RMPE, TSG and RMPE-TSG caused no liver lesions and fewer biochemical abnormalities. Considering the related components, only the co-administration of high doses of TSG and emodin-8-O-β-D-glucoside (EMG, major anthraquinone glycoside in PM) in these groups could cause liver lesions. According to tissue distribution and correlation analysis, EMG dose was positively correlated with the high hepatic emodin and TSG exposure, and the hepatic emodin and TSG exposure were positively correlated with the biochemical abnormalities of liver function. Cell viability test in vitro showed emodin was more hepatotoxic than TSG and EMG, and mainly emodin and TSG of the three had synergistic hepatotoxic effects. Therefore, creatively using rhubarb as a reference, this study revealed that PM hepatotoxicity in mice mainly came from the integrative contribution of TSG, EMG and emodin.https://www.frontiersin.org/articles/10.3389/fphar.2022.1007284/fullPolygoni multiflori radixrhei radix et rhizomatoxicologyhepatotoxicitytissue distributioncorrelation analysis |
| spellingShingle | Shixiao Wang Shixiao Wang Xiang Kong Xiang Kong Ning Chen Ning Chen Pengwei Hu Pengwei Hu Hamza Boucetta Hamza Boucetta Zhaoliang Hu Zhaoliang Hu Xin Xu Xin Xu Pei Zhang Pei Zhang Xiang Zhan Xiang Zhan Ming Chang Ming Chang Rui Cheng Rui Cheng Wei Wu Wei Wu Min Song Min Song Yuting Lu Yuting Lu Taijun Hang Taijun Hang Hepatotoxic metabolites in Polygoni Multiflori Radix— Comparative toxicology in mice Frontiers in Pharmacology Polygoni multiflori radix rhei radix et rhizoma toxicology hepatotoxicity tissue distribution correlation analysis |
| title | Hepatotoxic metabolites in Polygoni Multiflori Radix— Comparative toxicology in mice |
| title_full | Hepatotoxic metabolites in Polygoni Multiflori Radix— Comparative toxicology in mice |
| title_fullStr | Hepatotoxic metabolites in Polygoni Multiflori Radix— Comparative toxicology in mice |
| title_full_unstemmed | Hepatotoxic metabolites in Polygoni Multiflori Radix— Comparative toxicology in mice |
| title_short | Hepatotoxic metabolites in Polygoni Multiflori Radix— Comparative toxicology in mice |
| title_sort | hepatotoxic metabolites in polygoni multiflori radix comparative toxicology in mice |
| topic | Polygoni multiflori radix rhei radix et rhizoma toxicology hepatotoxicity tissue distribution correlation analysis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1007284/full |
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