Nauclea orientalis (L.) Bark Extract Protects Rat Cardiomyocytes from Doxorubicin-Induced Oxidative Stress, Inflammation, Apoptosis, and DNA Fragmentation.

The therapeutic efficacy of anthracycline antibiotic, doxorubicin (Dox), is hampered due to the dose-dependent cardiotoxicity. The objective of the study was to explore the counteraction of aqueous bark extract of Nauclea orientalis in Dox-induced cardiotoxicity in Wistar rats. The acute and subchronic toxicity study performed with 2.0 g/kg of the plant extract revealed biochemical and haematological parameters to be within the physiological range, and no histological alterations were observed in any organs isolated. Screening of plant extract for the protection of the myocardium from Dox-induced oxidative stress, inflammation, and apoptosis was performed on five groups of rats: control, plant extract control, Dox control (distilled water (D.H2O) 2 weeks + on the 11th day single injection of Dox, 18 mg/kg), plant + Dox (2.0 g/kg plant extract 2 weeks + on the 11th day Dox, 18 mg/kg), and positive control, dexrazoxane. A significant increase in cardiac biomarkers and lipid peroxidation (p < 0.001) and a significant decrease in antioxidant parameters (p < 0.001) were observed in the Dox control group. All these parameters were reversed significantly (p < 0.05) in the plant-pretreated group. The histopathological assessment of myocardial damage provided supportive evidence for the biochemical results obtained. Inflammatory markers, myeloperoxidase, expression of TNFα and caspase-3, and DNA fragmentation (TUNEL positive nuclei) were significantly elevated (p < 0.05), and expression of Bcl-2 was significantly decreased (p < 0.05) in the Dox control; however, all these parameters were significantly reversed in the plant extract-treated group. In conclusion, the aqueous bark extract of Nauclea orientalis (2.0 g/kg) has the ability to attenuate the Dox-induced oxidative stress, inflammation, apoptosis, and DNA fragmentation in Wistar rats.

Cardioprotective Potential of Murraya koenigii (L.) Spreng. Leaf Extract against Doxorubicin-Induced Cardiotoxicity in Rats.

Dose-dependent cardiotoxicity of doxorubicin may lead to irreversible congestive heart failure. Although multiple mechanisms are involved, generation of free radicals is the most commonly postulated mechanism. Therefore, free radical scavengers are considered as potential therapeutic agents. As Murraya koenigii leaves are a rich source of flavonoids and phenols, they have the ability to scavenge free radicals effectively. Therefore, the objective of this study was to investigate the cardioprotective potential of Murraya leaf extract against doxorubicin-induced cardiotoxicity in rats. Rats were randomly divided into five groups with 10 animals in each group. Doxorubicin was administered intraperitonially at 18 mg/kg while lyophilized plant extract was administered orally at 2 g/kg. Dexrazoxane, at 180 mg/kg, was used as the positive control. Cardiac damage of doxorubicin control was evident with a significant increase (p < 0.05) in cardiac troponin I, NT-pro BNP, AST, and LDH compared to the normal control. Plant-treated group showed cardioprotective effect by significantly reducing (p < 0.05) all of the above parameters compared to doxorubicin control (p < 0.05). Increased oxidative stress in doxorubicin control was evident with a significant reduction in reduced glutathione, glutathione reductase, glutathione peroxidase, total antioxidant capacity, superoxide dismutase, and catalase activity and a significant increase in lipid peroxidation compared to the control. Interestingly, treatment with Murraya leaf extract showed a significant increase in all of the above antioxidant parameters and a significant reduction in lipid peroxidation by showing an antioxidant effect. A significant increase in myeloperoxidase activity confirmed the increased inflammatory activity in doxorubicin control group whereas plant-treated group showed a significant reduction (p < 0.05) which expressed the anti-inflammatory effect of Murraya leaf extract. Doxorubicin-treated group showed histological evidence of extensive damage to the myocardium while plant-treated group showed a preserved myocardium with lesser degree of damage. Pretreatment with Murraya leaf extract may replenish cardiomyocytes with antioxidants and promote the defense against doxorubicin-induced cardiotoxicity.