Jujuboside B alleviates acetaminophen-induced hepatotoxicity in mice by regulating Nrf2-STING signaling pathway
Background: Jujuboside B (JuB) is the main bioactive saponin component of Chinese anti-insomnia herbal medicine Ziziphi Spinosae Semen, which has been reported to possess varied pharmacological functions. Even though it has been traditionally used to treat inflammation- and toxicity-related diseases...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323013143 |
| _version_ | 1797390572901629952 |
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| author | Hong-Fei Wang Jia-Shuang Xu Ke Zong Zhi-Wei Liang Ren-Feng Li Jian-Feng Xue Jing Ding Long-Shuan Zhao |
| author_facet | Hong-Fei Wang Jia-Shuang Xu Ke Zong Zhi-Wei Liang Ren-Feng Li Jian-Feng Xue Jing Ding Long-Shuan Zhao |
| author_sort | Hong-Fei Wang |
| collection | DOAJ |
| description | Background: Jujuboside B (JuB) is the main bioactive saponin component of Chinese anti-insomnia herbal medicine Ziziphi Spinosae Semen, which has been reported to possess varied pharmacological functions. Even though it has been traditionally used to treat inflammation- and toxicity-related diseases, the effects of JuB on acetaminophen (APAP) overdose-induced hepatotoxicity have not been determined yet. Methods: C57BL/6 J mice were pre-treated with JuB (20 or 40 mg/kg) for seven days before APAP (400 mg/kg) injection. After 24 h of APAP treatment, serum, and liver tissues were collected to evaluate the therapeutic effects. To investigate whether the Nrf2-STING signaling pathway is involved in the protective effects of JuB against APAP-induced hepatotoxicity, the mice received the DMXAA (the specific STING agonist) or ML385 (the specific Nrf2 inhibitor) during the administration of JuB, and Hematoxylin-eosin staining, Real-time PCR, immunohistochemical, and western blot were performed. Results: JuB pretreatment reversed APAP-induced CYP2E1 accumulations and alleviated APAP-induced acute liver injury. Furthermore, JuB treatment significantly inhibited oxidative stress and the pro-inflammatory cytokines, as well as alleviated hepatocyte apoptosis induced by APAP. Besides, our result also demonstrated that JuB treatment upregulated the levels of total Nrf2, facilitated its nuclear translocation, upregulated the expression of HO-1 and NQO-1, and inhibited the APAP-induced STING pathway activation. Finally, we verified that the beneficial effects of JuB were weakened by DMXAA and ML385. Conclusion: Our study suggested that JuB could ameliorate APAP-induced hepatic damage and verified a previously unrecognized mechanism by which JuB prevented APAP-induced hepatotoxicity through adjusting the Nrf2-STING pathway. |
| first_indexed | 2024-03-08T23:13:47Z |
| format | Article |
| id | doaj.art-c0d641476c394aef8375ad941f817cb2 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-03-08T23:13:47Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-c0d641476c394aef8375ad941f817cb22023-12-15T07:22:28ZengElsevierEcotoxicology and Environmental Safety0147-65132024-01-01269115810Jujuboside B alleviates acetaminophen-induced hepatotoxicity in mice by regulating Nrf2-STING signaling pathwayHong-Fei Wang0Jia-Shuang Xu1Ke Zong2Zhi-Wei Liang3Ren-Feng Li4Jian-Feng Xue5Jing Ding6Long-Shuan Zhao7Department of Hepatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Pediatric Orthopaedics, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Corresponding authors.Department of Hepatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Corresponding authors.Background: Jujuboside B (JuB) is the main bioactive saponin component of Chinese anti-insomnia herbal medicine Ziziphi Spinosae Semen, which has been reported to possess varied pharmacological functions. Even though it has been traditionally used to treat inflammation- and toxicity-related diseases, the effects of JuB on acetaminophen (APAP) overdose-induced hepatotoxicity have not been determined yet. Methods: C57BL/6 J mice were pre-treated with JuB (20 or 40 mg/kg) for seven days before APAP (400 mg/kg) injection. After 24 h of APAP treatment, serum, and liver tissues were collected to evaluate the therapeutic effects. To investigate whether the Nrf2-STING signaling pathway is involved in the protective effects of JuB against APAP-induced hepatotoxicity, the mice received the DMXAA (the specific STING agonist) or ML385 (the specific Nrf2 inhibitor) during the administration of JuB, and Hematoxylin-eosin staining, Real-time PCR, immunohistochemical, and western blot were performed. Results: JuB pretreatment reversed APAP-induced CYP2E1 accumulations and alleviated APAP-induced acute liver injury. Furthermore, JuB treatment significantly inhibited oxidative stress and the pro-inflammatory cytokines, as well as alleviated hepatocyte apoptosis induced by APAP. Besides, our result also demonstrated that JuB treatment upregulated the levels of total Nrf2, facilitated its nuclear translocation, upregulated the expression of HO-1 and NQO-1, and inhibited the APAP-induced STING pathway activation. Finally, we verified that the beneficial effects of JuB were weakened by DMXAA and ML385. Conclusion: Our study suggested that JuB could ameliorate APAP-induced hepatic damage and verified a previously unrecognized mechanism by which JuB prevented APAP-induced hepatotoxicity through adjusting the Nrf2-STING pathway.http://www.sciencedirect.com/science/article/pii/S0147651323013143Jujuboside BAcetaminophenLiver injuryNrf2STING pathway |
| spellingShingle | Hong-Fei Wang Jia-Shuang Xu Ke Zong Zhi-Wei Liang Ren-Feng Li Jian-Feng Xue Jing Ding Long-Shuan Zhao Jujuboside B alleviates acetaminophen-induced hepatotoxicity in mice by regulating Nrf2-STING signaling pathway Ecotoxicology and Environmental Safety Jujuboside B Acetaminophen Liver injury Nrf2 STING pathway |
| title | Jujuboside B alleviates acetaminophen-induced hepatotoxicity in mice by regulating Nrf2-STING signaling pathway |
| title_full | Jujuboside B alleviates acetaminophen-induced hepatotoxicity in mice by regulating Nrf2-STING signaling pathway |
| title_fullStr | Jujuboside B alleviates acetaminophen-induced hepatotoxicity in mice by regulating Nrf2-STING signaling pathway |
| title_full_unstemmed | Jujuboside B alleviates acetaminophen-induced hepatotoxicity in mice by regulating Nrf2-STING signaling pathway |
| title_short | Jujuboside B alleviates acetaminophen-induced hepatotoxicity in mice by regulating Nrf2-STING signaling pathway |
| title_sort | jujuboside b alleviates acetaminophen induced hepatotoxicity in mice by regulating nrf2 sting signaling pathway |
| topic | Jujuboside B Acetaminophen Liver injury Nrf2 STING pathway |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323013143 |
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