Toxicological landscape of Fuzi: a comprehensive study on the spatial distribution of toxicants and regional neurotoxicity variability in zebrafish
Fuzi, a Chinese herb widely used in clinical settings, exhibits varying levels of toxicity depending on its geographical origin. Diester-type alkaloids are the primary contributors to the toxicity of Fuzi. This study aims to investigate regional differences and underlying mechanisms of Fuzi-induced...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1500527/full |
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| author | Xiaoqi Pan Xiaoqi Pan Tianyu Liang Han Feng Weiying Liu Qiaoxin Mou Xiaoyu Yan |
| author_facet | Xiaoqi Pan Xiaoqi Pan Tianyu Liang Han Feng Weiying Liu Qiaoxin Mou Xiaoyu Yan |
| author_sort | Xiaoqi Pan |
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| description | Fuzi, a Chinese herb widely used in clinical settings, exhibits varying levels of toxicity depending on its geographical origin. Diester-type alkaloids are the primary contributors to the toxicity of Fuzi. This study aims to investigate regional differences and underlying mechanisms of Fuzi-induced neurotoxicity across China. Matrix-assisted laser desorption/Ionization mass spectrometry imaging (MALDI-MSI) method was employed to map the spatial distribution of six key diester-type alkaloids from Fuzi samples originating from five major regions. The results showed that the diester-type alkaloids were primarily distributed in the cuticle of Anguo- and Ludian-Fuzi, in the cuticle, cork, and pith of Butuo-Fuzi, in the phloem and pith tissues of Chenggu-Fuzi, and in the cuticle, cork, inner phloem, and pith of Jiangyou-Fuzi. When zebrafish were exposed to a Fuzi decoction for 24 h, it was observed that Jiangyou-Fuzi induced the most significant neurobehavioral abnormalities, lipid peroxidation damage, and aberrant neurotransmitters release. RNA sequencing analysis further indicated that the amino acid metabolism, ErbB, cGMP-PKG, and p53 signaling pathways-regulated by changes in the expression of Glub, Mao, GAB1, PRKG1B, PSEN2, and BAXα genes were disrupted to varying extents by Fuzi from different origins. In summary, the regional variability in the neurotoxicity of Fuzi can be attributed to differences in the distribution of its active compounds and underlying mechanisms. Among the samples tested, Jiangyou-Fuzi exhibited the highest neurotoxicity, followed by Anguo-, Chenggu-, Ludian-, and Butuo-Fuzi. |
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| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-3f4a656c9150472f9e58f0a1c70fc7e82025-02-05T07:32:33ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-02-011510.3389/fphar.2024.15005271500527Toxicological landscape of Fuzi: a comprehensive study on the spatial distribution of toxicants and regional neurotoxicity variability in zebrafishXiaoqi Pan0Xiaoqi Pan1Tianyu Liang2Han Feng3Weiying Liu4Qiaoxin Mou5Xiaoyu Yan6State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaSchool of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaFuzi, a Chinese herb widely used in clinical settings, exhibits varying levels of toxicity depending on its geographical origin. Diester-type alkaloids are the primary contributors to the toxicity of Fuzi. This study aims to investigate regional differences and underlying mechanisms of Fuzi-induced neurotoxicity across China. Matrix-assisted laser desorption/Ionization mass spectrometry imaging (MALDI-MSI) method was employed to map the spatial distribution of six key diester-type alkaloids from Fuzi samples originating from five major regions. The results showed that the diester-type alkaloids were primarily distributed in the cuticle of Anguo- and Ludian-Fuzi, in the cuticle, cork, and pith of Butuo-Fuzi, in the phloem and pith tissues of Chenggu-Fuzi, and in the cuticle, cork, inner phloem, and pith of Jiangyou-Fuzi. When zebrafish were exposed to a Fuzi decoction for 24 h, it was observed that Jiangyou-Fuzi induced the most significant neurobehavioral abnormalities, lipid peroxidation damage, and aberrant neurotransmitters release. RNA sequencing analysis further indicated that the amino acid metabolism, ErbB, cGMP-PKG, and p53 signaling pathways-regulated by changes in the expression of Glub, Mao, GAB1, PRKG1B, PSEN2, and BAXα genes were disrupted to varying extents by Fuzi from different origins. In summary, the regional variability in the neurotoxicity of Fuzi can be attributed to differences in the distribution of its active compounds and underlying mechanisms. Among the samples tested, Jiangyou-Fuzi exhibited the highest neurotoxicity, followed by Anguo-, Chenggu-, Ludian-, and Butuo-Fuzi.https://www.frontiersin.org/articles/10.3389/fphar.2024.1500527/fullFuzidiester-type alkaloidsregional differences neurotoxicityMALDI-MSIRNA sequencing |
| spellingShingle | Xiaoqi Pan Xiaoqi Pan Tianyu Liang Han Feng Weiying Liu Qiaoxin Mou Xiaoyu Yan Toxicological landscape of Fuzi: a comprehensive study on the spatial distribution of toxicants and regional neurotoxicity variability in zebrafish Frontiers in Pharmacology Fuzi diester-type alkaloids regional differences neurotoxicity MALDI-MSI RNA sequencing |
| title | Toxicological landscape of Fuzi: a comprehensive study on the spatial distribution of toxicants and regional neurotoxicity variability in zebrafish |
| title_full | Toxicological landscape of Fuzi: a comprehensive study on the spatial distribution of toxicants and regional neurotoxicity variability in zebrafish |
| title_fullStr | Toxicological landscape of Fuzi: a comprehensive study on the spatial distribution of toxicants and regional neurotoxicity variability in zebrafish |
| title_full_unstemmed | Toxicological landscape of Fuzi: a comprehensive study on the spatial distribution of toxicants and regional neurotoxicity variability in zebrafish |
| title_short | Toxicological landscape of Fuzi: a comprehensive study on the spatial distribution of toxicants and regional neurotoxicity variability in zebrafish |
| title_sort | toxicological landscape of fuzi a comprehensive study on the spatial distribution of toxicants and regional neurotoxicity variability in zebrafish |
| topic | Fuzi diester-type alkaloids regional differences neurotoxicity MALDI-MSI RNA sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1500527/full |
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