Plumbagin protects the myocardial damage by modulating the cardiac biomarkers, antioxidants, and apoptosis signaling in the doxorubicin‐induced cardiotoxicity in rats

Abstract

Cardiovascular disease created enormous health and economic burdens worldwide, which is responsible for the highest mobility and mortality that results in nearly 6.2% of in‐hospital deaths every year. Plumbagin is a major bioactive compound that occurs in the Plumbago indica and P. zeylanica with numerous therapeutic benefits. The current research exploration was planned to investigate the therapeutic role of plumbagin against doxorubicin stimulated cardiotoxicity in rats. The cardiotoxicity was stimulated to the rats by administering the 2.5 mg/kg of doxorubicin for 14 days with concurrent supplementation with plumbagin. The hemodynamic parameters were studied by using the tail‐cuff plethysmography. The lipid peroxidation and antioxidant status was examined by the standard procedures. The myocardial function and damage markers were assessed with the help of commercial kits. The expression status of inflammatory markers and PI3K/Akt signaling markers were investigated by reverse transcription polymerase chain reaction (RT‐PCR) and western blotting analysis, respectively. The plumbagin supplementation appreciably regained the body weight and heart weight of the investigational animals. Hemodynamic parameters and antioxidants statuses were escalated by the plumbagin treatment. The severe elevation in the cardiac damage markers and inflammatory markers were noticeably ameliorated by the plumbagin treatment. The plumbagin treatment also assuaged the overexpression of inflammatory and apoptotic proteins in the heart tissues of doxorubicin‐challenged rats. The histopathological analysis revealed that the plumbagin appreciably protected the heart tissues from the doxorubicin‐induced damages. The findings of this exploration evidenced that plumbagin treatment attenuated the doxorubicin‐stimulated cardiotoxicity in rats.

Cinnamomum zeylanicum Blume (Ceylon cinnamon) bark extract attenuates doxorubicin induced cardiotoxicity in Wistar rats

“…Similar to these results ABEC which has high polyphenolic content and in vitro antioxidant effect also showed cardio protection against doxorubicin treatment by significantly reducing the release of cardiac biomarkers. Several other studies also reported results consistent with the present study ( Afsar et al, 2017 , Oyagbemi et al, 2018 , Li et al, 2020 ). In the present study, high concentrations of NT-proBNP was observed in doxorubicin treated rats indicating an increased ventricular dysfunction while the pre-treatment with ABEC lead to a significant reduction in NT-proBNP concentration.…”

“…Doxorubicin induced cardiotoxicity was biochemically confirmed by the increase in oxidative stress as shown by the reduced antioxidant markers such as GSH, GPx, GR, SOD and catalase and total antioxidant capacity ( Baniahmad et al, 2020 ). Several previous investigations showed that doxorubicin treatment increases oxidative stress in rats and plant extracts or some other compounds with significant antioxidant activity have the ability to attenuate free radical induced oxidative stress indicating an increased activity of antioxidant markers ( Singh et al, 2008 , Al-Harthi et al, 2014 , Hamza et al, 2016 , Afsar et al, 2017 , Alam et al, 2018 , Shaker et al, 2018 , Li et al, 2020 ). In the present study, pre-treatment with ABEC also exhibited a significant increase in GSH and other antioxidant enzymes and total antioxidant capacity suggesting that pre-treatment with the plant extract may replenish the cardiomyocytes with antioxidant enzymes which exert cardioprotective effect against doxorubicin induced cardiotoxicity.…”

Cardiorenal Protective Effect of Costunolide against Doxorubicin-Induced Toxicity in Rats by Modulating Oxidative Stress, Inflammation and Apoptosis

“…Another critical factor involved in DXB-induced toxicity is inflammation, which involves the degradation of NF-κB protein and subsequent enhancement of proinflammatory cytokine generation [ 30 ]. The involvement of several proinflammatory cytokines particularly IL-6, IL-1β and TNF-α in DXB-induced cardiorenal toxicity was extensively highlighted by previous studies [ 31 , 32 ]. Oxidative-induced translocation and modulation of NF-κB to the nucleus stimulates the transcription of proinflammatory cytokine genes [ 7 , 30 , 33 , 34 ].…”

Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT

“…PL (5-hydroxy-2-methyl-1,4-naphthoquinone, C 11 H 8 O 3 ) is a kind of hydroxyl-naphthoquinone which was extracted from the Plumbago genus plants. It is reported a variety of remarkable pharmacological properties that include antioxidant [ 10 ], anti-inflammatory [ 11 ], antifungal [ 12 ], antibacterial [ 13 ], antidiabetic [ 14 ] and neuroprotective properties [ 15 ]. Importantly, it exhibits its therapeutic potential in various types of malignant tumors in recent years [ 16 – 18 ].…”