Catalpol Attenuates Oxidative Stress and Inflammation via Mechanisms Involving Sirtuin-1 Activation and NF-κB Inhibition in Experimentally-Induced Chronic Kidney Disease
Chronic kidney disease (CKD) is a stealthy disease, and its development is linked to mechanisms including inflammation and oxidative stress. Catalpol (CAT), an iridoid glucoside from the root of <i>Rehmannia glutinosa</i>, is reported to manifest anti-inflammatory, antioxidant, antiapopt...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/1/237 |
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| author | Nur Elena Zaaba Suhail Al-Salam Sumaya Beegam Ozaz Elzaki Javed Yasin Abderrahim Nemmar |
| author_facet | Nur Elena Zaaba Suhail Al-Salam Sumaya Beegam Ozaz Elzaki Javed Yasin Abderrahim Nemmar |
| author_sort | Nur Elena Zaaba |
| collection | DOAJ |
| description | Chronic kidney disease (CKD) is a stealthy disease, and its development is linked to mechanisms including inflammation and oxidative stress. Catalpol (CAT), an iridoid glucoside from the root of <i>Rehmannia glutinosa</i>, is reported to manifest anti-inflammatory, antioxidant, antiapoptotic and antifibrotic properties. Hence, we studied the possible nephroprotective effects of CAT and its mechanisms in an adenine-induced (0.2% <i>w</i>/<i>w</i> in feed for 4 weeks) murine model of CKD by administering 5 mg/kg CAT to BALB/c mice for the duration of 4 weeks except during weekends. Upon sacrifice, the kidney, plasma and urine were collected and various physiological, biochemical and histological endpoints were assessed. CAT significantly ameliorated the adenine-induced altered body and kidney weight, water intake, urine volume, and concentrations of urea and creatinine in plasma, as well as the creatinine clearance and the albumin and creatinine ratio. Moreover, CAT significantly ameliorated the effect of adenine-induced kidney injury by reducing the kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, cystatin C and adiponectin. Similarly, the augmented concentrations of markers of inflammation and oxidative stress in the adenine-treated group were markedly reduced with CAT pretreatment. Furthermore, CAT prevented adenine-induced deoxyribonucleic acid damage and apoptotic activity in the kidneys. Histologically, CAT significantly reduced the formation of tubular necrosis and dilation, as well as interstitial fibrosis in the kidney. In addition to that, CAT significantly decreased the adenine-induced increase in the phosphorylated NF-κB and reversed the reduced expression of sirtuin-1 in the kidney. In conclusion, CAT exhibits salutary effects against adenine-induced CKD in mice by mitigating inflammation, oxidative stress and fibrosis via mechanisms involving sirtuin-1 activation and NF-κB inhibition. Confirmatory studies are warranted in order to consider CAT as a potent nephroprotective agent against CKD. |
| first_indexed | 2024-03-09T12:02:54Z |
| format | Article |
| id | doaj.art-a02f2a19448b46808e37f2c026e14767 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T12:02:54Z |
| publishDate | 2023-01-01 |
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| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-a02f2a19448b46808e37f2c026e147672023-11-30T23:01:37ZengMDPI AGNutrients2072-66432023-01-0115123710.3390/nu15010237Catalpol Attenuates Oxidative Stress and Inflammation via Mechanisms Involving Sirtuin-1 Activation and NF-κB Inhibition in Experimentally-Induced Chronic Kidney DiseaseNur Elena Zaaba0Suhail Al-Salam1Sumaya Beegam2Ozaz Elzaki3Javed Yasin4Abderrahim Nemmar5Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain P.O. Box 15551, United Arab EmiratesDepartment of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain P.O. Box 15551, United Arab EmiratesDepartment of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain P.O. Box 15551, United Arab EmiratesDepartment of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain P.O. Box 15551, United Arab EmiratesDepartment of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain P.O. Box 15551, United Arab EmiratesDepartment of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain P.O. Box 15551, United Arab EmiratesChronic kidney disease (CKD) is a stealthy disease, and its development is linked to mechanisms including inflammation and oxidative stress. Catalpol (CAT), an iridoid glucoside from the root of <i>Rehmannia glutinosa</i>, is reported to manifest anti-inflammatory, antioxidant, antiapoptotic and antifibrotic properties. Hence, we studied the possible nephroprotective effects of CAT and its mechanisms in an adenine-induced (0.2% <i>w</i>/<i>w</i> in feed for 4 weeks) murine model of CKD by administering 5 mg/kg CAT to BALB/c mice for the duration of 4 weeks except during weekends. Upon sacrifice, the kidney, plasma and urine were collected and various physiological, biochemical and histological endpoints were assessed. CAT significantly ameliorated the adenine-induced altered body and kidney weight, water intake, urine volume, and concentrations of urea and creatinine in plasma, as well as the creatinine clearance and the albumin and creatinine ratio. Moreover, CAT significantly ameliorated the effect of adenine-induced kidney injury by reducing the kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, cystatin C and adiponectin. Similarly, the augmented concentrations of markers of inflammation and oxidative stress in the adenine-treated group were markedly reduced with CAT pretreatment. Furthermore, CAT prevented adenine-induced deoxyribonucleic acid damage and apoptotic activity in the kidneys. Histologically, CAT significantly reduced the formation of tubular necrosis and dilation, as well as interstitial fibrosis in the kidney. In addition to that, CAT significantly decreased the adenine-induced increase in the phosphorylated NF-κB and reversed the reduced expression of sirtuin-1 in the kidney. In conclusion, CAT exhibits salutary effects against adenine-induced CKD in mice by mitigating inflammation, oxidative stress and fibrosis via mechanisms involving sirtuin-1 activation and NF-κB inhibition. Confirmatory studies are warranted in order to consider CAT as a potent nephroprotective agent against CKD.https://www.mdpi.com/2072-6643/15/1/237catalpolchronic kidney diseaseadenineinflammationoxidative stressapoptosis |
| spellingShingle | Nur Elena Zaaba Suhail Al-Salam Sumaya Beegam Ozaz Elzaki Javed Yasin Abderrahim Nemmar Catalpol Attenuates Oxidative Stress and Inflammation via Mechanisms Involving Sirtuin-1 Activation and NF-κB Inhibition in Experimentally-Induced Chronic Kidney Disease Nutrients catalpol chronic kidney disease adenine inflammation oxidative stress apoptosis |
| title | Catalpol Attenuates Oxidative Stress and Inflammation via Mechanisms Involving Sirtuin-1 Activation and NF-κB Inhibition in Experimentally-Induced Chronic Kidney Disease |
| title_full | Catalpol Attenuates Oxidative Stress and Inflammation via Mechanisms Involving Sirtuin-1 Activation and NF-κB Inhibition in Experimentally-Induced Chronic Kidney Disease |
| title_fullStr | Catalpol Attenuates Oxidative Stress and Inflammation via Mechanisms Involving Sirtuin-1 Activation and NF-κB Inhibition in Experimentally-Induced Chronic Kidney Disease |
| title_full_unstemmed | Catalpol Attenuates Oxidative Stress and Inflammation via Mechanisms Involving Sirtuin-1 Activation and NF-κB Inhibition in Experimentally-Induced Chronic Kidney Disease |
| title_short | Catalpol Attenuates Oxidative Stress and Inflammation via Mechanisms Involving Sirtuin-1 Activation and NF-κB Inhibition in Experimentally-Induced Chronic Kidney Disease |
| title_sort | catalpol attenuates oxidative stress and inflammation via mechanisms involving sirtuin 1 activation and nf κb inhibition in experimentally induced chronic kidney disease |
| topic | catalpol chronic kidney disease adenine inflammation oxidative stress apoptosis |
| url | https://www.mdpi.com/2072-6643/15/1/237 |
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