Triptolide Suppresses NF-κB-Mediated Inflammatory Responses and Activates Expression of Nrf2-Mediated Antioxidant Genes to Alleviate Caerulein-Induced Acute Pancreatitis
Triptolide (TP), the main active ingredient of <i>Tripterygium wilfordii Hook.f.</i>, displays potent anti-inflammatory, antioxidant, and antiproliferative activities. In the present study, the effect of TP on acute pancreatitis and the underlying mechanisms of the disease were investiga...
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MDPI AG
2022-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/3/1252 |
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| author | Jing Yang Xujiao Tang Xue Ke Yutong Dai Jinsong Shi |
| author_facet | Jing Yang Xujiao Tang Xue Ke Yutong Dai Jinsong Shi |
| author_sort | Jing Yang |
| collection | DOAJ |
| description | Triptolide (TP), the main active ingredient of <i>Tripterygium wilfordii Hook.f.</i>, displays potent anti-inflammatory, antioxidant, and antiproliferative activities. In the present study, the effect of TP on acute pancreatitis and the underlying mechanisms of the disease were investigated using a caerulein-induced animal model of acute pancreatitis (AP) and an in vitro cell model. In vivo, pretreatment with TP notably ameliorated pancreatic damage, shown as the improvement in serum amylase and lipase levels and pancreatic morphology. Meanwhile, TP modulated the infiltration of neutrophils and macrophages (Ly6G staining and CD68 staining) and decreased the levels of proinflammatory factors (TNF-α and IL-6) through inhibiting the transactivation of nuclear factor-κB (NF-κB) in caerulein-treated mice. Furthermore, TP reverted changes in oxidative stress markers, including pancreatic glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA), in acute pancreatitis mice. Additionally, TP pretreatment inhibited intracellular reactive oxygen species (ROS) levels via upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and Nrf2-regulated redox genes expression (HO-1, SOD1, GPx1 and NQO1) in vitro. Taken together, our data suggest that TP exert protection against pancreatic inflammation and tissue damage by inhibiting NF-κB transactivation, modulating immune cell responses and activating the Nrf2-mediated antioxidative system, thereby alleviating acute pancreatitis. |
| first_indexed | 2024-03-09T23:49:28Z |
| format | Article |
| id | doaj.art-27980fd2256648dfb85ed9cd0e37b723 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:49:28Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-27980fd2256648dfb85ed9cd0e37b7232023-11-23T16:37:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-01233125210.3390/ijms23031252Triptolide Suppresses NF-κB-Mediated Inflammatory Responses and Activates Expression of Nrf2-Mediated Antioxidant Genes to Alleviate Caerulein-Induced Acute PancreatitisJing Yang0Xujiao Tang1Xue Ke2Yutong Dai3Jinsong Shi4School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, ChinaSchool of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, ChinaSchool of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, ChinaSchool of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, ChinaSchool of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, ChinaTriptolide (TP), the main active ingredient of <i>Tripterygium wilfordii Hook.f.</i>, displays potent anti-inflammatory, antioxidant, and antiproliferative activities. In the present study, the effect of TP on acute pancreatitis and the underlying mechanisms of the disease were investigated using a caerulein-induced animal model of acute pancreatitis (AP) and an in vitro cell model. In vivo, pretreatment with TP notably ameliorated pancreatic damage, shown as the improvement in serum amylase and lipase levels and pancreatic morphology. Meanwhile, TP modulated the infiltration of neutrophils and macrophages (Ly6G staining and CD68 staining) and decreased the levels of proinflammatory factors (TNF-α and IL-6) through inhibiting the transactivation of nuclear factor-κB (NF-κB) in caerulein-treated mice. Furthermore, TP reverted changes in oxidative stress markers, including pancreatic glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA), in acute pancreatitis mice. Additionally, TP pretreatment inhibited intracellular reactive oxygen species (ROS) levels via upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and Nrf2-regulated redox genes expression (HO-1, SOD1, GPx1 and NQO1) in vitro. Taken together, our data suggest that TP exert protection against pancreatic inflammation and tissue damage by inhibiting NF-κB transactivation, modulating immune cell responses and activating the Nrf2-mediated antioxidative system, thereby alleviating acute pancreatitis.https://www.mdpi.com/1422-0067/23/3/1252acute pancreatitistriptolideinflammatory responsesoxidative stress |
| spellingShingle | Jing Yang Xujiao Tang Xue Ke Yutong Dai Jinsong Shi Triptolide Suppresses NF-κB-Mediated Inflammatory Responses and Activates Expression of Nrf2-Mediated Antioxidant Genes to Alleviate Caerulein-Induced Acute Pancreatitis International Journal of Molecular Sciences acute pancreatitis triptolide inflammatory responses oxidative stress |
| title | Triptolide Suppresses NF-κB-Mediated Inflammatory Responses and Activates Expression of Nrf2-Mediated Antioxidant Genes to Alleviate Caerulein-Induced Acute Pancreatitis |
| title_full | Triptolide Suppresses NF-κB-Mediated Inflammatory Responses and Activates Expression of Nrf2-Mediated Antioxidant Genes to Alleviate Caerulein-Induced Acute Pancreatitis |
| title_fullStr | Triptolide Suppresses NF-κB-Mediated Inflammatory Responses and Activates Expression of Nrf2-Mediated Antioxidant Genes to Alleviate Caerulein-Induced Acute Pancreatitis |
| title_full_unstemmed | Triptolide Suppresses NF-κB-Mediated Inflammatory Responses and Activates Expression of Nrf2-Mediated Antioxidant Genes to Alleviate Caerulein-Induced Acute Pancreatitis |
| title_short | Triptolide Suppresses NF-κB-Mediated Inflammatory Responses and Activates Expression of Nrf2-Mediated Antioxidant Genes to Alleviate Caerulein-Induced Acute Pancreatitis |
| title_sort | triptolide suppresses nf κb mediated inflammatory responses and activates expression of nrf2 mediated antioxidant genes to alleviate caerulein induced acute pancreatitis |
| topic | acute pancreatitis triptolide inflammatory responses oxidative stress |
| url | https://www.mdpi.com/1422-0067/23/3/1252 |
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