Dao-Chi Powder Ameliorates Pancreatitis-Induced Intestinal and Cardiac Injuries via Regulating the Nrf2-HO-1-HMGB1 Signaling Pathway in Rats
Dao-Chi powder (DCP) has been widely used in the treatment of inflammatory diseases in the clinical practice of traditional Chinese medicine, but has not been used in acute pancreatitis (AP). This study aimed to evaluate the effect of DCP on severe AP (SAP) and SAP-associated intestinal and cardiac...
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.922130/full |
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| author | Jiaqi Yao Yifan Miao Yumei Zhang Lv Zhu Huan Chen Xiajia Wu Yue Yang Xiaoyu Dai Qian Hu Meihua Wan Wenfu Tang |
| author_facet | Jiaqi Yao Yifan Miao Yumei Zhang Lv Zhu Huan Chen Xiajia Wu Yue Yang Xiaoyu Dai Qian Hu Meihua Wan Wenfu Tang |
| author_sort | Jiaqi Yao |
| collection | DOAJ |
| description | Dao-Chi powder (DCP) has been widely used in the treatment of inflammatory diseases in the clinical practice of traditional Chinese medicine, but has not been used in acute pancreatitis (AP). This study aimed to evaluate the effect of DCP on severe AP (SAP) and SAP-associated intestinal and cardiac injuries. To this end, an SAP animal model was established by retrograde injection of 3.5% taurocholic acid sodium salt into the biliopancreatic ducts of rats. Intragastric DCP (9.6 g/kg.BW) was administered 12 h after modeling. The pancreas, duodenum, colon, heart and blood samples were collected 36 h after the operation for histological and biochemical detection. The tissue distributions of the DCP components were determined and compared between the sham and the SAP groups. Moreover, molecular docking analysis was employed to investigate the interactions between the potential active components of DCP and its targets (Nrf2, HO-1, and HMGB1). Consequently, DCP treatment decreased the serum levels of amylase and the markers of gastrointestinal and cardiac injury, further alleviating the pathological damage in the pancreas, duodenum, colon, and heart of rats with SAP. Mechanistically, DCP rebalanced the pro-/anti-inflammatory cytokines and inhibited MPO activity and MDA levels in these tissues. Furthermore, Western blot and RT-PCR results showed that DCP intervention enhanced the expression of Nrf2 and HO-1 in the duodenum and colon of rats with SAP, while inhibiting the expression of HMGB1 in the duodenum and heart. HPLC-MS/MS analysis revealed that SAP promoted the distribution of ajugol and oleanolic acid to the duodenum, whereas it inhibited the distribution of liquiritigenin to the heart and ajugol to the colon. Molecular docking analysis confirmed that the six screened components of DCP had relatively good binding affinity with Nrf2, HO-1, and HMGB1. Among these, oleanolic acid had the highest affinity for HO-1. Altogether, DCP could alleviated SAP-induced intestinal and cardiac injuries via inhibiting the inflammatory responses and oxidative stress partially through regulating the Nrf2/HO-1/HMGB1 signaling pathway, thereby providing additional supportive evidence for the clinical treatment of SAP. |
| first_indexed | 2024-04-12T07:16:50Z |
| format | Article |
| id | doaj.art-35cd92df218f4ee094dc2a3f95d19fa6 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T07:16:50Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-35cd92df218f4ee094dc2a3f95d19fa62022-12-22T03:42:26ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-07-011310.3389/fphar.2022.922130922130Dao-Chi Powder Ameliorates Pancreatitis-Induced Intestinal and Cardiac Injuries via Regulating the Nrf2-HO-1-HMGB1 Signaling Pathway in RatsJiaqi Yao0Yifan Miao1Yumei Zhang2Lv Zhu3Huan Chen4Xiajia Wu5Yue Yang6Xiaoyu Dai7Qian Hu8Meihua Wan9Wenfu Tang10Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Traditional Chinese Medicine, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, ChinaClinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDao-Chi powder (DCP) has been widely used in the treatment of inflammatory diseases in the clinical practice of traditional Chinese medicine, but has not been used in acute pancreatitis (AP). This study aimed to evaluate the effect of DCP on severe AP (SAP) and SAP-associated intestinal and cardiac injuries. To this end, an SAP animal model was established by retrograde injection of 3.5% taurocholic acid sodium salt into the biliopancreatic ducts of rats. Intragastric DCP (9.6 g/kg.BW) was administered 12 h after modeling. The pancreas, duodenum, colon, heart and blood samples were collected 36 h after the operation for histological and biochemical detection. The tissue distributions of the DCP components were determined and compared between the sham and the SAP groups. Moreover, molecular docking analysis was employed to investigate the interactions between the potential active components of DCP and its targets (Nrf2, HO-1, and HMGB1). Consequently, DCP treatment decreased the serum levels of amylase and the markers of gastrointestinal and cardiac injury, further alleviating the pathological damage in the pancreas, duodenum, colon, and heart of rats with SAP. Mechanistically, DCP rebalanced the pro-/anti-inflammatory cytokines and inhibited MPO activity and MDA levels in these tissues. Furthermore, Western blot and RT-PCR results showed that DCP intervention enhanced the expression of Nrf2 and HO-1 in the duodenum and colon of rats with SAP, while inhibiting the expression of HMGB1 in the duodenum and heart. HPLC-MS/MS analysis revealed that SAP promoted the distribution of ajugol and oleanolic acid to the duodenum, whereas it inhibited the distribution of liquiritigenin to the heart and ajugol to the colon. Molecular docking analysis confirmed that the six screened components of DCP had relatively good binding affinity with Nrf2, HO-1, and HMGB1. Among these, oleanolic acid had the highest affinity for HO-1. Altogether, DCP could alleviated SAP-induced intestinal and cardiac injuries via inhibiting the inflammatory responses and oxidative stress partially through regulating the Nrf2/HO-1/HMGB1 signaling pathway, thereby providing additional supportive evidence for the clinical treatment of SAP.https://www.frontiersin.org/articles/10.3389/fphar.2022.922130/fullsevere acute pancreatitisDao-Chi powderoxidative stressinflammatory responsesNrf2/HO-1/HMGB1 |
| spellingShingle | Jiaqi Yao Yifan Miao Yumei Zhang Lv Zhu Huan Chen Xiajia Wu Yue Yang Xiaoyu Dai Qian Hu Meihua Wan Wenfu Tang Dao-Chi Powder Ameliorates Pancreatitis-Induced Intestinal and Cardiac Injuries via Regulating the Nrf2-HO-1-HMGB1 Signaling Pathway in Rats Frontiers in Pharmacology severe acute pancreatitis Dao-Chi powder oxidative stress inflammatory responses Nrf2/HO-1/HMGB1 |
| title | Dao-Chi Powder Ameliorates Pancreatitis-Induced Intestinal and Cardiac Injuries via Regulating the Nrf2-HO-1-HMGB1 Signaling Pathway in Rats |
| title_full | Dao-Chi Powder Ameliorates Pancreatitis-Induced Intestinal and Cardiac Injuries via Regulating the Nrf2-HO-1-HMGB1 Signaling Pathway in Rats |
| title_fullStr | Dao-Chi Powder Ameliorates Pancreatitis-Induced Intestinal and Cardiac Injuries via Regulating the Nrf2-HO-1-HMGB1 Signaling Pathway in Rats |
| title_full_unstemmed | Dao-Chi Powder Ameliorates Pancreatitis-Induced Intestinal and Cardiac Injuries via Regulating the Nrf2-HO-1-HMGB1 Signaling Pathway in Rats |
| title_short | Dao-Chi Powder Ameliorates Pancreatitis-Induced Intestinal and Cardiac Injuries via Regulating the Nrf2-HO-1-HMGB1 Signaling Pathway in Rats |
| title_sort | dao chi powder ameliorates pancreatitis induced intestinal and cardiac injuries via regulating the nrf2 ho 1 hmgb1 signaling pathway in rats |
| topic | severe acute pancreatitis Dao-Chi powder oxidative stress inflammatory responses Nrf2/HO-1/HMGB1 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.922130/full |
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