Catalpol Attenuates Oxidative Stress and Inflammation via Mechanisms Involving Sirtuin-1 Activation and NF-κB Inhibition in Experimentally-Induced Chronic Kidney Disease

Abstract

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 Rehmannia glutinosa, 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% w/w 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.

Effects of Waterpipe Smoke Exposure on Experimentally Induced Chronic Kidney Disease in Mice

“…The rest of the right and left kidneys were individually wrapped in aluminium foil and then dipped in liquid nitrogen and kept at −80 °C, pending analysis. The preparation of kidney homogenates for the quantification of markers of oxidative stress and inflammation were carried out as described earlier [ 28 , 52 ].…”

“…Masson trichrome stains fibrous tissue blue. The percentage of blue-stained fibrotic area in each kidney section, stained with Masson trichrome stain, was evaluated and the fibrosis index was calculated and expressed as percentage according to the protocol previously reported [ 36 , 44 , 52 ].…”

Anti‐inflammatory effect and mechanism of catalpol in various inflammatory diseases

“…The development of chronic kidney disease is associated with mechanisms such as inflammation and oxidative stress. It was shown that the 4‐week oral treatment of CKD mice with 5 mg/kg catalpol significantly improved the inflammatory response in the tissues of CKD mice without causing any harmful side effects (Zaaba et al, 2023). However, further research is needed if it is to be applied in the clinical setting.…”

“…In summary, catalpol attenuates the inflammatory response in kidney injury by inhibiting the NF-κB signaling pathway.3.4.2 | Chronic kidney diseaseThe development of chronic kidney disease is associated with mechanisms such as inflammation and oxidative stress. It was shown that the 4-week oral treatment of CKD mice with 5 mg/kg catalpol significantly improved the inflammatory response in the tissues of CKD mice without causing any harmful side effects(Zaaba et al, 2023). However, further research is needed if it is to be applied in the clinical setting.3.4.3 | Diabetic nephropathy (DN)DN is one of the most common complications of diabetes and a major cause of end-stage kidney disease, the pathogenesis is still unclear, and current studies have shown that it is closely related to foot cell injury, microcirculatory dysfunction, inflammatory response, and oxidative stress(Elmarakby & Sullivan, 2012;Umanath & Lewis, 2018;Wada & Makino, 2013).…”

Natural Products and Health

“…Histologically, CAT demonstrates notable effects in reducing tubular necrosis, interstitial fibrosis, and dilation in the kidney. The beneficial effects of CAT against adenine-induced CKD in mouse models involve mechanisms such as sirtuin-1 activation and NF-κB inhibition [74].…”