Yin/Yang associated differential responses to Psoralea corylifolia Linn. In rat models: an integrated metabolomics and transcriptomics study
Abstract Ethnopharmacological relevance Psoralea corylifolia Linn. (BGZ) is a commonly used traditional Chinese medicine (TCM) for the treatment of kidney-yang deficiency syndrome (Yangsyn) with good curative effect and security. However, BGZ was also reported to induce liver injury in recent years....
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | Chinese Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13020-023-00793-x |
| _version_ | 1797451485201563648 |
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| author | Ming-Liang Zhang Xu Zhao Wei-Xia Li Xiao-Yan Wang Ming Niu Hui Zhang Yu-Long Chen De-Xin Kong Yuan Gao Yu-Ming Guo Zhao-Fang Bai Yan-Ling Zhao Jin-Fa Tang Xiao-He Xiao |
| author_facet | Ming-Liang Zhang Xu Zhao Wei-Xia Li Xiao-Yan Wang Ming Niu Hui Zhang Yu-Long Chen De-Xin Kong Yuan Gao Yu-Ming Guo Zhao-Fang Bai Yan-Ling Zhao Jin-Fa Tang Xiao-He Xiao |
| author_sort | Ming-Liang Zhang |
| collection | DOAJ |
| description | Abstract Ethnopharmacological relevance Psoralea corylifolia Linn. (BGZ) is a commonly used traditional Chinese medicine (TCM) for the treatment of kidney-yang deficiency syndrome (Yangsyn) with good curative effect and security. However, BGZ was also reported to induce liver injury in recent years. According to TCM theory, taking BGZ may induce a series of adverse reactions in patients with kidney-yin deficiency syndrome (Yinsyn), which suggests that BGZ-induced liver damage may be related to its unreasonable clinical use. Aim of the study Liver injury caused by TCM is a rare but potentially serious adverse drug reaction, and the identification of predisposed individuals for drug-induced liver injury (DILI) remains challenging. The study aimed to investigate the differential responses to BGZ in Yangsyn and Yinsyn rat models and identify the corresponding characteristic biomarkers. Materials and methods The corresponding animal models of Yangsyn and Yinsyn were induced by hydrocortisone and thyroxine + reserpine respectively. Body weight, organ index, serum biochemistry, and Hematoxylin and Eosin (HE) staining were used to evaluate the liver toxicity effect of BGZ on rats with Yangsyn and Yinsyn. Transcriptomics and metabonomics were used to screen the representative biomarkers (including metabolites and differentially expressed genes (DEGs)) changed by BGZ in Yangsyn and Yinsyn rats, respectively. Results The level changes of liver organ index, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), suggested that BGZ has liver-protective and liver-damaging effects on Yangsyn and Yinsyn rats, respectively, and the results also were confirmed by the pathological changes of liver tissue. The results showed that 102 DEGs and 27 metabolites were significantly regulated related to BGZ’s protective effect on Yangsyn, which is mainly associated with the glycerophospholipid metabolism, arachidonic acid metabolism, pantothenate, and coenzyme A (CoA) biosynthesis pathways. While 28 DEGs and 31 metabolites, related to the pathway of pantothenate and CoA biosynthesis, were significantly regulated for the BGZ-induced liver injury in Yinsyn. Furthermore, 4 DEGs (aldehyde dehydrogenase 1 family member B1 (Aldh1b1), solute carrier family 25 member 25 (Slc25a25), Pim-3 proto-oncogene, serine/threonine kinase (Pim3), out at first homolog (Oaf)) and 4 metabolites (phosphatidate, phosphatidylcholine, N-Acetylleucine, biliverdin) in the Yangsyn group and 1 DEG [galectin 5 (Lgals5)] and 1 metabolite (5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate) in Yinsyn group were significantly correlated to the ALT and AST levels of BGZ treated and untreated groups (receiver operating characteristic (ROC) ≥ 0.9). Conclusions Yinsyn and Yangsyn are the predisposed syndromes for BGZ to exert liver damage and liver protection respectively, which are mainly related to the regulation of amino acid metabolism, lipid metabolism, energy metabolism, and metabolism of cofactors and vitamins. The results further suggest that attention should be paid to the selection of predisposed populations when using drugs related to the regulation of energy metabolism, and the Yinsyn/Yangsyn animal models based on the theory of TCM syndromes may be a feasible method for identifying the susceptible population to receive TCM. |
| first_indexed | 2024-03-09T14:55:20Z |
| format | Article |
| id | doaj.art-8440d916dbb34a6c8749486e64139236 |
| institution | Directory Open Access Journal |
| issn | 1749-8546 |
| language | English |
| last_indexed | 2024-03-09T14:55:20Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Medicine |
| spelling | doaj.art-8440d916dbb34a6c8749486e641392362023-11-26T14:13:51ZengBMCChinese Medicine1749-85462023-08-0118112310.1186/s13020-023-00793-xYin/Yang associated differential responses to Psoralea corylifolia Linn. In rat models: an integrated metabolomics and transcriptomics studyMing-Liang Zhang0Xu Zhao1Wei-Xia Li2Xiao-Yan Wang3Ming Niu4Hui Zhang5Yu-Long Chen6De-Xin Kong7Yuan Gao8Yu-Ming Guo9Zhao-Fang Bai10Yan-Ling Zhao11Jin-Fa Tang12Xiao-He Xiao13Henan Province Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese MedicineSenior Department of Hepatology, The Fifth Medical Center of PLA General HospitalHenan Province Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese MedicineHenan Province Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese MedicineSenior Department of Hepatology, The Fifth Medical Center of PLA General HospitalHenan Province Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese MedicineHenan University of Traditional Chinese MedicineHenan Province Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese MedicineSchool of Traditional Chinese Medicine, Capital Medical UniversitySenior Department of Hepatology, The Fifth Medical Center of PLA General HospitalSenior Department of Hepatology, The Fifth Medical Center of PLA General HospitalCollege of Pharmacy, Chengdu University of Traditional Chinese MedicineHenan Province Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine, The First Affiliated Hospital of Henan University of Traditional Chinese MedicineSenior Department of Hepatology, The Fifth Medical Center of PLA General HospitalAbstract Ethnopharmacological relevance Psoralea corylifolia Linn. (BGZ) is a commonly used traditional Chinese medicine (TCM) for the treatment of kidney-yang deficiency syndrome (Yangsyn) with good curative effect and security. However, BGZ was also reported to induce liver injury in recent years. According to TCM theory, taking BGZ may induce a series of adverse reactions in patients with kidney-yin deficiency syndrome (Yinsyn), which suggests that BGZ-induced liver damage may be related to its unreasonable clinical use. Aim of the study Liver injury caused by TCM is a rare but potentially serious adverse drug reaction, and the identification of predisposed individuals for drug-induced liver injury (DILI) remains challenging. The study aimed to investigate the differential responses to BGZ in Yangsyn and Yinsyn rat models and identify the corresponding characteristic biomarkers. Materials and methods The corresponding animal models of Yangsyn and Yinsyn were induced by hydrocortisone and thyroxine + reserpine respectively. Body weight, organ index, serum biochemistry, and Hematoxylin and Eosin (HE) staining were used to evaluate the liver toxicity effect of BGZ on rats with Yangsyn and Yinsyn. Transcriptomics and metabonomics were used to screen the representative biomarkers (including metabolites and differentially expressed genes (DEGs)) changed by BGZ in Yangsyn and Yinsyn rats, respectively. Results The level changes of liver organ index, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), suggested that BGZ has liver-protective and liver-damaging effects on Yangsyn and Yinsyn rats, respectively, and the results also were confirmed by the pathological changes of liver tissue. The results showed that 102 DEGs and 27 metabolites were significantly regulated related to BGZ’s protective effect on Yangsyn, which is mainly associated with the glycerophospholipid metabolism, arachidonic acid metabolism, pantothenate, and coenzyme A (CoA) biosynthesis pathways. While 28 DEGs and 31 metabolites, related to the pathway of pantothenate and CoA biosynthesis, were significantly regulated for the BGZ-induced liver injury in Yinsyn. Furthermore, 4 DEGs (aldehyde dehydrogenase 1 family member B1 (Aldh1b1), solute carrier family 25 member 25 (Slc25a25), Pim-3 proto-oncogene, serine/threonine kinase (Pim3), out at first homolog (Oaf)) and 4 metabolites (phosphatidate, phosphatidylcholine, N-Acetylleucine, biliverdin) in the Yangsyn group and 1 DEG [galectin 5 (Lgals5)] and 1 metabolite (5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate) in Yinsyn group were significantly correlated to the ALT and AST levels of BGZ treated and untreated groups (receiver operating characteristic (ROC) ≥ 0.9). Conclusions Yinsyn and Yangsyn are the predisposed syndromes for BGZ to exert liver damage and liver protection respectively, which are mainly related to the regulation of amino acid metabolism, lipid metabolism, energy metabolism, and metabolism of cofactors and vitamins. The results further suggest that attention should be paid to the selection of predisposed populations when using drugs related to the regulation of energy metabolism, and the Yinsyn/Yangsyn animal models based on the theory of TCM syndromes may be a feasible method for identifying the susceptible population to receive TCM.https://doi.org/10.1186/s13020-023-00793-xPsoraleae FructusLiver injuryPredisposed individualMetabolomicsTranscriptomics |
| spellingShingle | Ming-Liang Zhang Xu Zhao Wei-Xia Li Xiao-Yan Wang Ming Niu Hui Zhang Yu-Long Chen De-Xin Kong Yuan Gao Yu-Ming Guo Zhao-Fang Bai Yan-Ling Zhao Jin-Fa Tang Xiao-He Xiao Yin/Yang associated differential responses to Psoralea corylifolia Linn. In rat models: an integrated metabolomics and transcriptomics study Chinese Medicine Psoraleae Fructus Liver injury Predisposed individual Metabolomics Transcriptomics |
| title | Yin/Yang associated differential responses to Psoralea corylifolia Linn. In rat models: an integrated metabolomics and transcriptomics study |
| title_full | Yin/Yang associated differential responses to Psoralea corylifolia Linn. In rat models: an integrated metabolomics and transcriptomics study |
| title_fullStr | Yin/Yang associated differential responses to Psoralea corylifolia Linn. In rat models: an integrated metabolomics and transcriptomics study |
| title_full_unstemmed | Yin/Yang associated differential responses to Psoralea corylifolia Linn. In rat models: an integrated metabolomics and transcriptomics study |
| title_short | Yin/Yang associated differential responses to Psoralea corylifolia Linn. In rat models: an integrated metabolomics and transcriptomics study |
| title_sort | yin yang associated differential responses to psoralea corylifolia linn in rat models an integrated metabolomics and transcriptomics study |
| topic | Psoraleae Fructus Liver injury Predisposed individual Metabolomics Transcriptomics |
| url | https://doi.org/10.1186/s13020-023-00793-x |
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