Rutaecarpine Protects against Acetaminophen-Induced Acute Liver Injury in Mice by Activating Antioxidant Enzymes
Rutaecarpine, an indolopyridoquinazolinone alkaloid isolated from the unripe fruit of <i>Evodia rutaecarpa</i>, is used to treat hypertension, postpartum hemorrhage, dysentery, and amenorrhea as a traditional medicine in Asia. We investigated the effect of rutaecarpine on acetaminophen-i...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-01-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/10/1/86 |
| _version_ | 1797413610427777024 |
|---|---|
| author | Jae Ho Choi Sun Woo Jin Gi Ho Lee Eun Hee Han Yong Pil Hwang Hye Gwang Jeong |
| author_facet | Jae Ho Choi Sun Woo Jin Gi Ho Lee Eun Hee Han Yong Pil Hwang Hye Gwang Jeong |
| author_sort | Jae Ho Choi |
| collection | DOAJ |
| description | Rutaecarpine, an indolopyridoquinazolinone alkaloid isolated from the unripe fruit of <i>Evodia rutaecarpa</i>, is used to treat hypertension, postpartum hemorrhage, dysentery, and amenorrhea as a traditional medicine in Asia. We investigated the effect of rutaecarpine on acetaminophen-induced hepatotoxicity in mice. Rutaecarpine was administered orally daily for seven consecutive days, followed by intraperitoneal injection of acetaminophen in mice on day seven to induce hepatotoxicity. Rutaecarpine pretreatment significantly decreased acetaminophen-induced serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) activities and hepatic malondialdehyde content and prevented acetaminophen-induced hepatic glutathione depletion. Furthermore, CYP2E1 expression was decreased by rutaecarpine pretreatment in a dose-dependent manner. Rutaecarpine pretreatment inhibited acetaminophen-induced expression of inflammatory cytokines by inhibiting NF-κB activation by JNK1/2. Also, rutaecarpine pretreatment promoted Nrf2-mediated activation of the antioxidant enzymes GCLC, HO-1, and NQO1. This indicates that the protective effect of rutaecarpine during acetaminophen-induced acute liver injury is mediated by the activation of antioxidant enzymes. Therefore, rutaecarpine has a protective effect of APAP-induced liver damage. |
| first_indexed | 2024-03-09T05:21:32Z |
| format | Article |
| id | doaj.art-bdf219a757064183b5196f4da56c6e3c |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T05:21:32Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-bdf219a757064183b5196f4da56c6e3c2023-12-03T12:40:48ZengMDPI AGAntioxidants2076-39212021-01-011018610.3390/antiox10010086Rutaecarpine Protects against Acetaminophen-Induced Acute Liver Injury in Mice by Activating Antioxidant EnzymesJae Ho Choi0Sun Woo Jin1Gi Ho Lee2Eun Hee Han3Yong Pil Hwang4Hye Gwang Jeong5Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 34134, KoreaDepartment of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 34134, KoreaDepartment of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 34134, KoreaDrug & Disease Target Research Team, Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI), Cheongju 28119, KoreaFisheries Promotion Division, Mokpo City 58613, KoreaDepartment of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 34134, KoreaRutaecarpine, an indolopyridoquinazolinone alkaloid isolated from the unripe fruit of <i>Evodia rutaecarpa</i>, is used to treat hypertension, postpartum hemorrhage, dysentery, and amenorrhea as a traditional medicine in Asia. We investigated the effect of rutaecarpine on acetaminophen-induced hepatotoxicity in mice. Rutaecarpine was administered orally daily for seven consecutive days, followed by intraperitoneal injection of acetaminophen in mice on day seven to induce hepatotoxicity. Rutaecarpine pretreatment significantly decreased acetaminophen-induced serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) activities and hepatic malondialdehyde content and prevented acetaminophen-induced hepatic glutathione depletion. Furthermore, CYP2E1 expression was decreased by rutaecarpine pretreatment in a dose-dependent manner. Rutaecarpine pretreatment inhibited acetaminophen-induced expression of inflammatory cytokines by inhibiting NF-κB activation by JNK1/2. Also, rutaecarpine pretreatment promoted Nrf2-mediated activation of the antioxidant enzymes GCLC, HO-1, and NQO1. This indicates that the protective effect of rutaecarpine during acetaminophen-induced acute liver injury is mediated by the activation of antioxidant enzymes. Therefore, rutaecarpine has a protective effect of APAP-induced liver damage.https://www.mdpi.com/2076-3921/10/1/86rutaecarpineNrf2antioxidanthepatotoxicityinflammatory cytokines |
| spellingShingle | Jae Ho Choi Sun Woo Jin Gi Ho Lee Eun Hee Han Yong Pil Hwang Hye Gwang Jeong Rutaecarpine Protects against Acetaminophen-Induced Acute Liver Injury in Mice by Activating Antioxidant Enzymes Antioxidants rutaecarpine Nrf2 antioxidant hepatotoxicity inflammatory cytokines |
| title | Rutaecarpine Protects against Acetaminophen-Induced Acute Liver Injury in Mice by Activating Antioxidant Enzymes |
| title_full | Rutaecarpine Protects against Acetaminophen-Induced Acute Liver Injury in Mice by Activating Antioxidant Enzymes |
| title_fullStr | Rutaecarpine Protects against Acetaminophen-Induced Acute Liver Injury in Mice by Activating Antioxidant Enzymes |
| title_full_unstemmed | Rutaecarpine Protects against Acetaminophen-Induced Acute Liver Injury in Mice by Activating Antioxidant Enzymes |
| title_short | Rutaecarpine Protects against Acetaminophen-Induced Acute Liver Injury in Mice by Activating Antioxidant Enzymes |
| title_sort | rutaecarpine protects against acetaminophen induced acute liver injury in mice by activating antioxidant enzymes |
| topic | rutaecarpine Nrf2 antioxidant hepatotoxicity inflammatory cytokines |
| url | https://www.mdpi.com/2076-3921/10/1/86 |
| work_keys_str_mv | AT jaehochoi rutaecarpineprotectsagainstacetaminopheninducedacuteliverinjuryinmicebyactivatingantioxidantenzymes AT sunwoojin rutaecarpineprotectsagainstacetaminopheninducedacuteliverinjuryinmicebyactivatingantioxidantenzymes AT giholee rutaecarpineprotectsagainstacetaminopheninducedacuteliverinjuryinmicebyactivatingantioxidantenzymes AT eunheehan rutaecarpineprotectsagainstacetaminopheninducedacuteliverinjuryinmicebyactivatingantioxidantenzymes AT yongpilhwang rutaecarpineprotectsagainstacetaminopheninducedacuteliverinjuryinmicebyactivatingantioxidantenzymes AT hyegwangjeong rutaecarpineprotectsagainstacetaminopheninducedacuteliverinjuryinmicebyactivatingantioxidantenzymes |