Cardioprotective effects of rutin via alteration in TNF-α, CRP, and BNP levels coupled with antioxidant effect in STZ-induced diabetic rats

Abstract

Diabetic cardiomyopathy (DCM) is a dreadful complication of diabetes responsible for 80 % mortality in diabetic patients, but unfortunately its pharmacotherapy is still incomplete. Rutin is a naturally occurring flavonoid having a long history of use in nutritional supplements for its action against oxidative stress, inflammation, and hyperglycemia, the key players involved in the progression of DCM, but remains unexplored for its role in DCM. This study was conducted to address this lacuna. It was performed in 4-week-old Streptozotocin-induced (45 mg/kg) diabetic rats for a period of 24 weeks to mimic the cardiotoxic effect of chronic hyperglycemia in diabetic patient's heart and to investigate the effect of rutin (50 mg/kg/day) in ameliorating these effects. Heart of the diabetic rats showed altered ECG parameters, reduced total antioxidant capacity, increased inflammatory assault, and degenerative changes. Interestingly, rutin treatment significantly ameliorated these changes with decrease in blood glucose level (p > 0.001), % HbA1c (p > 0.001) and reduced expression of TNF-α (p < 0.001), CRP (p < 0.001), and BNP (p < 0.01) compared to diabetic control rats. In addition, rutin provided significant protection against diabetes associated oxidative stress (p < 0.05), prevented degenerative changes in heart, and improved ECG parameters compared to diabetic control rats. The heart-to-body weight ratio was significantly reduced in rutin treatment group compared to diabetic control rats (p < 0.001). In conclusion, this study implicates that oxidative stress and inflammation are the central players involved in the progression of DCM and rutin ameliorates DCM through its antioxidant and anti-inflammatory actions on heart.

Ameliorative effect of Rutin on sodium fluoride‐induced hypertension through modulation of Kim‐1/NF‐κB/Nrf2 signaling pathway in rats

“…This may also corroborate the observed higher expressions of Kim‐1 which has been reported as risk factor for cardiomyopathy such as cardiomyopathies and cardiovascular mortality . The ability of Rutin to down regulate the expressions of CTnI also confirms the cardioprotective effect of Rutin in streptozotocin‐induced diabetic cardiomyopathy as previously described . In this study, NaF alone down regulated Nrf2 while it was upregulated by co‐administration with Rutin with 100 mg/kg of Rutin showing more expressions of Nrf2.…”

“…72 The ability of Rutin to down regulate the expressions of CTnI also confirms the cardioprotective effect of Rutin in streptozotocin-induced diabetic cardiomyopathy as previously described. 79 In this study, NaF alone down regulated Nrf2 while it was upregulated by co-administration with Rutin with 100 mg/kg of Rutin showing more expressions of Nrf2. We proposed that lower dosage of Rutin might be needed in the induction of transcription factor that controls antioxidant enzymes such as Nfr2 while higher dosage of Rutin might become pro-oxidant.…”

Glucose‐mediated protein glycation: Contribution of methanolic extract of Ceratonia siliqua L. in protection and in vitro potential inhibition of acetylcholinesterase

“…Rutin has shown anti‐inflammatory effect, anti‐arteriosclerosis (Oke‐Altuntas, Aslim, Duman, Gulpinar, & Kartal, ), anticarcinogenic, cytoprotective, and hepatoprotective activities (Niture, Ansari, & Naik, ). Rutin is also an antioxidant compound, (Al‐Rejaie et al, ), via its capacity to increase the glutathione, Vitamine C and E; and to act against lipid peroxidation in diabetic rats (Saklani et al, ).…”

Diabetes-Related Cardiac Dysfunction

“…This increase in production leads to increased ROS levels [22]. There have been several studies showcasing the benefits of using antioxidant drugs in patients with cardiovascular injuries [232425]. The carotenoid bixin possesses anti-inflammatory and antioxidant activities, and was shown to inhibit cardiac fibrosis and to decrease proinflammatory cytokines.…”

“…Mito-TEMPO ((2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride) was shown to reduce ROS, decrease apoptosis, and decrease hypertrophy in both type 1 and type 2 diabetes [24]. The flavonoid quercetin-3-O-rutinoside (Rutin), ameliorates the reduced antioxidant capacity, increased inflammation, and degenerative changes in mice with streptozotocin-induced diabetes [25]. Nrf2, Mito-TEMPO, and Rutin all show promise in reducing factors that contribute to the formation of DCM.…”