Wogonin effects on the efflux transporters BCRP and MRP2, explain its effectiveness in ulcerative colitis: Implications for metabolic and transport interactions
Wogonin is a flavonoid with efficacy in ulcerative colitis (UC), while the mechanism of its action remains to be fully elucidated. Previous research has indicated that the triple recycling significantly enhances the bioavailability of flavonoids. The efflux transporters, breast cancer resistance pro...
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Elsevier
2025-02-01
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| author | Yuanyuan Liu Zerong Zhang Xiaoyan Li Qinghong Hu Zhangyu Jiang Jia Lv Jiayi Xue Dongyu Wang Jianxiong Cao Lingyu Li Xiaowen Ou Lijun Zhu Zhongqiu Liu Tao Su |
| author_facet | Yuanyuan Liu Zerong Zhang Xiaoyan Li Qinghong Hu Zhangyu Jiang Jia Lv Jiayi Xue Dongyu Wang Jianxiong Cao Lingyu Li Xiaowen Ou Lijun Zhu Zhongqiu Liu Tao Su |
| author_sort | Yuanyuan Liu |
| collection | DOAJ |
| description | Wogonin is a flavonoid with efficacy in ulcerative colitis (UC), while the mechanism of its action remains to be fully elucidated. Previous research has indicated that the triple recycling significantly enhances the bioavailability of flavonoids. The efflux transporters, breast cancer resistance protein (BCRP) and multidrug resistance-associated protein 2 (MRP2) are critical regulatory molecules within the enterohepatic triple recycling pathways. Therefore, we investigated the regulatory impact of wogonin on BCRP and MRP2, as well as the roles of these transporters in wogonin's therapeutic efficacy in UC. Using dextran sulfate sodium (DSS)-induced UC model, we found that the anti-UC efficacy of wogonin was diminished in Bcrp-/--Mrp2-/- mice compared to wild-type (WT) mice. In these knockout mice, the content of wogonin was increased in the plasma but decreased in the colon tissues, suggesting that deficiencies in BCRP and MRP2 hinder the efflux of wogonin, resulting in elevated content in the plasma. Moreover, in vitro results showed that after knockout of BCRP and MRP2, the concentration of wogonin increased, and its UGT metabolite wogonoside decreased in both cells and mitochondria. These indicate that inhibiting efflux transporters suppresses cellular and mitochondrial glucuronidation metabolism. Interestingly, proteomic sequencing of mitochondrial subcellular organelles revealed that wogonin exhibited anti-UC effects by inhibiting afamin (AFM), with these effects modulated by BCRP and MRP2. These findings not only suggest a new mechanism for the anti-UC effects of wogonin, but also provide a pharmacological foundation for the clinical use of wogonin in treating UC. |
| format | Article |
| id | doaj-art-2b0fcdf778e642bba540fad365d58e75 |
| institution | Kabale University |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-2b0fcdf778e642bba540fad365d58e752025-02-08T04:59:36ZengElsevierPharmacological Research1096-11862025-02-01212107570Wogonin effects on the efflux transporters BCRP and MRP2, explain its effectiveness in ulcerative colitis: Implications for metabolic and transport interactionsYuanyuan Liu0Zerong Zhang1Xiaoyan Li2Qinghong Hu3Zhangyu Jiang4Jia Lv5Jiayi Xue6Dongyu Wang7Jianxiong Cao8Lingyu Li9Xiaowen Ou10Lijun Zhu11Zhongqiu Liu12Tao Su13State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China; Shenzhen Hospital, Beijing University of Chinese Medicine, Shenzhen, Guangdong 518000, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, ChinaShenzhen Hospital, Beijing University of Chinese Medicine, Shenzhen, Guangdong 518000, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, ChinaShenzhen Hospital, Beijing University of Chinese Medicine, Shenzhen, Guangdong 518000, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China; Chinese Medicine Guangdong Laboratory, Guangdong, Hengqin, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, China; Corresponding authors at: State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China; Chinese Medicine Guangdong Laboratory, Guangdong, Hengqin, China; Corresponding authors at: State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, ChinaWogonin is a flavonoid with efficacy in ulcerative colitis (UC), while the mechanism of its action remains to be fully elucidated. Previous research has indicated that the triple recycling significantly enhances the bioavailability of flavonoids. The efflux transporters, breast cancer resistance protein (BCRP) and multidrug resistance-associated protein 2 (MRP2) are critical regulatory molecules within the enterohepatic triple recycling pathways. Therefore, we investigated the regulatory impact of wogonin on BCRP and MRP2, as well as the roles of these transporters in wogonin's therapeutic efficacy in UC. Using dextran sulfate sodium (DSS)-induced UC model, we found that the anti-UC efficacy of wogonin was diminished in Bcrp-/--Mrp2-/- mice compared to wild-type (WT) mice. In these knockout mice, the content of wogonin was increased in the plasma but decreased in the colon tissues, suggesting that deficiencies in BCRP and MRP2 hinder the efflux of wogonin, resulting in elevated content in the plasma. Moreover, in vitro results showed that after knockout of BCRP and MRP2, the concentration of wogonin increased, and its UGT metabolite wogonoside decreased in both cells and mitochondria. These indicate that inhibiting efflux transporters suppresses cellular and mitochondrial glucuronidation metabolism. Interestingly, proteomic sequencing of mitochondrial subcellular organelles revealed that wogonin exhibited anti-UC effects by inhibiting afamin (AFM), with these effects modulated by BCRP and MRP2. These findings not only suggest a new mechanism for the anti-UC effects of wogonin, but also provide a pharmacological foundation for the clinical use of wogonin in treating UC.http://www.sciencedirect.com/science/article/pii/S1043661824005152WogoninUlcerative colitisBCRPMRP2Pharmacokinetics |
| spellingShingle | Yuanyuan Liu Zerong Zhang Xiaoyan Li Qinghong Hu Zhangyu Jiang Jia Lv Jiayi Xue Dongyu Wang Jianxiong Cao Lingyu Li Xiaowen Ou Lijun Zhu Zhongqiu Liu Tao Su Wogonin effects on the efflux transporters BCRP and MRP2, explain its effectiveness in ulcerative colitis: Implications for metabolic and transport interactions Pharmacological Research Wogonin Ulcerative colitis BCRP MRP2 Pharmacokinetics |
| title | Wogonin effects on the efflux transporters BCRP and MRP2, explain its effectiveness in ulcerative colitis: Implications for metabolic and transport interactions |
| title_full | Wogonin effects on the efflux transporters BCRP and MRP2, explain its effectiveness in ulcerative colitis: Implications for metabolic and transport interactions |
| title_fullStr | Wogonin effects on the efflux transporters BCRP and MRP2, explain its effectiveness in ulcerative colitis: Implications for metabolic and transport interactions |
| title_full_unstemmed | Wogonin effects on the efflux transporters BCRP and MRP2, explain its effectiveness in ulcerative colitis: Implications for metabolic and transport interactions |
| title_short | Wogonin effects on the efflux transporters BCRP and MRP2, explain its effectiveness in ulcerative colitis: Implications for metabolic and transport interactions |
| title_sort | wogonin effects on the efflux transporters bcrp and mrp2 explain its effectiveness in ulcerative colitis implications for metabolic and transport interactions |
| topic | Wogonin Ulcerative colitis BCRP MRP2 Pharmacokinetics |
| url | http://www.sciencedirect.com/science/article/pii/S1043661824005152 |
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