Nobiletin resolves left ventricular and renal changes in 2K-1C hypertensive rats
Abstract This study investigated the effects of nobiletin on cardiorenal changes and the underlying mechanisms involved in two-kidney, one-clip (2K-1C) hypertension. 2K-1C rats were treated with nobiletin (15 or 30 mg/kg/day) or losartan (10 mg/kg/day) for 4 weeks (n = 8/group). Nobiletin (30 mg/kg)...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-06-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-13513-6 |
| _version_ | 1811243123449266176 |
|---|---|
| author | Metee Iampanichakul Anuson Poasakate Prapassorn Potue Siwayu Rattanakanokchai Putcharawipa Maneesai Parichat Prachaney Wannapa Settheetham-Ishida Poungrat Pakdeechote |
| author_facet | Metee Iampanichakul Anuson Poasakate Prapassorn Potue Siwayu Rattanakanokchai Putcharawipa Maneesai Parichat Prachaney Wannapa Settheetham-Ishida Poungrat Pakdeechote |
| author_sort | Metee Iampanichakul |
| collection | DOAJ |
| description | Abstract This study investigated the effects of nobiletin on cardiorenal changes and the underlying mechanisms involved in two-kidney, one-clip (2K-1C) hypertension. 2K-1C rats were treated with nobiletin (15 or 30 mg/kg/day) or losartan (10 mg/kg/day) for 4 weeks (n = 8/group). Nobiletin (30 mg/kg) reduced high levels of blood pressure and circulating angiotensin II and angiotensin-converting enzyme activity in 2K-1C rats. Left ventricular (LV) dysfunction and remodelling in 2K-1C rats were alleviated in the nobiletin-treated group (P < 0.05). Nobiletin reduced the upregulation of Ang II type I receptor (AT1R)/JAK (Janus kinase)/STAT (signal transducer and activator of transcription) protein expression in cardiac tissue of 2K-1C rats (P < 0.05). The reduction in kidney function, and accumulation of renal fibrosis in 2K-1C rats were alleviated by nobiletin (P < 0.05). Overexpression of AT1R and NADPH oxidase 4 (Nox4) protein in nonclipped kidney tissue was suppressed in the nobiletin-treated group (P < 0.05). The elevations in oxidative stress parameters and the reductions in antioxidant enzymes were attenuated in 2K-1C rats treated with nobiletin (P < 0.05). In summary, nobiletin had renin-angiotensin system inhibitory and antioxidant effects and attenuated LV dysfunction and remodelling via restoration of the AT1R/JAK/STAT pathway. Nobiletin also resolved renal damage that was related to modulation of the AT1R/Nox4 cascade in 2K-1C hypertension. |
| first_indexed | 2024-04-12T14:02:05Z |
| format | Article |
| id | doaj.art-5433e1c8c8cd450c8d1eb0e8ad124612 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T14:02:05Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5433e1c8c8cd450c8d1eb0e8ad1246122022-12-22T03:30:10ZengNature PortfolioScientific Reports2045-23222022-06-0112111410.1038/s41598-022-13513-6Nobiletin resolves left ventricular and renal changes in 2K-1C hypertensive ratsMetee Iampanichakul0Anuson Poasakate1Prapassorn Potue2Siwayu Rattanakanokchai3Putcharawipa Maneesai4Parichat Prachaney5Wannapa Settheetham-Ishida6Poungrat Pakdeechote7Department of Physiology, Faculty of Medicine, Khon Kaen UniversityDepartment of Physiology, Faculty of Medicine, Khon Kaen UniversityDepartment of Physiology, Faculty of Medicine, Khon Kaen UniversityFaculty of Veterinary Medicine, Khon Kaen UniversityDepartment of Physiology, Faculty of Medicine, Khon Kaen UniversityDepartment of Anatomy, Faculty of Medicine, Khon Kaen UniversityDepartment of Physiology, Faculty of Medicine, Khon Kaen UniversityDepartment of Physiology, Faculty of Medicine, Khon Kaen UniversityAbstract This study investigated the effects of nobiletin on cardiorenal changes and the underlying mechanisms involved in two-kidney, one-clip (2K-1C) hypertension. 2K-1C rats were treated with nobiletin (15 or 30 mg/kg/day) or losartan (10 mg/kg/day) for 4 weeks (n = 8/group). Nobiletin (30 mg/kg) reduced high levels of blood pressure and circulating angiotensin II and angiotensin-converting enzyme activity in 2K-1C rats. Left ventricular (LV) dysfunction and remodelling in 2K-1C rats were alleviated in the nobiletin-treated group (P < 0.05). Nobiletin reduced the upregulation of Ang II type I receptor (AT1R)/JAK (Janus kinase)/STAT (signal transducer and activator of transcription) protein expression in cardiac tissue of 2K-1C rats (P < 0.05). The reduction in kidney function, and accumulation of renal fibrosis in 2K-1C rats were alleviated by nobiletin (P < 0.05). Overexpression of AT1R and NADPH oxidase 4 (Nox4) protein in nonclipped kidney tissue was suppressed in the nobiletin-treated group (P < 0.05). The elevations in oxidative stress parameters and the reductions in antioxidant enzymes were attenuated in 2K-1C rats treated with nobiletin (P < 0.05). In summary, nobiletin had renin-angiotensin system inhibitory and antioxidant effects and attenuated LV dysfunction and remodelling via restoration of the AT1R/JAK/STAT pathway. Nobiletin also resolved renal damage that was related to modulation of the AT1R/Nox4 cascade in 2K-1C hypertension.https://doi.org/10.1038/s41598-022-13513-6 |
| spellingShingle | Metee Iampanichakul Anuson Poasakate Prapassorn Potue Siwayu Rattanakanokchai Putcharawipa Maneesai Parichat Prachaney Wannapa Settheetham-Ishida Poungrat Pakdeechote Nobiletin resolves left ventricular and renal changes in 2K-1C hypertensive rats Scientific Reports |
| title | Nobiletin resolves left ventricular and renal changes in 2K-1C hypertensive rats |
| title_full | Nobiletin resolves left ventricular and renal changes in 2K-1C hypertensive rats |
| title_fullStr | Nobiletin resolves left ventricular and renal changes in 2K-1C hypertensive rats |
| title_full_unstemmed | Nobiletin resolves left ventricular and renal changes in 2K-1C hypertensive rats |
| title_short | Nobiletin resolves left ventricular and renal changes in 2K-1C hypertensive rats |
| title_sort | nobiletin resolves left ventricular and renal changes in 2k 1c hypertensive rats |
| url | https://doi.org/10.1038/s41598-022-13513-6 |
| work_keys_str_mv | AT meteeiampanichakul nobiletinresolvesleftventricularandrenalchangesin2k1chypertensiverats AT anusonpoasakate nobiletinresolvesleftventricularandrenalchangesin2k1chypertensiverats AT prapassornpotue nobiletinresolvesleftventricularandrenalchangesin2k1chypertensiverats AT siwayurattanakanokchai nobiletinresolvesleftventricularandrenalchangesin2k1chypertensiverats AT putcharawipamaneesai nobiletinresolvesleftventricularandrenalchangesin2k1chypertensiverats AT parichatprachaney nobiletinresolvesleftventricularandrenalchangesin2k1chypertensiverats AT wannapasettheethamishida nobiletinresolvesleftventricularandrenalchangesin2k1chypertensiverats AT poungratpakdeechote nobiletinresolvesleftventricularandrenalchangesin2k1chypertensiverats |