Protective effect and mechanism of Ginkgo biloba extract-EGb 761 on STZ-induced diabetic cardiomyopathy in rats

Abstract

Diabetes mellitus (DM) is a complex metabolic disorder which leads to development of various long-term complications including cardiomyopathy. Oxidative stress due to hyperglycemia plays a key role in the development and progression of diabetic cardiomyopathy (DC). Oxidative stress causes the opening of mitochondrial permeability transition pore (mPTP) eventually leading to myocardium dysfunction. The Ginkgo biloba extract (EGb 761) has antioxidant and mitochondrial membrane potential stabilizing property. Therefore, this study was designed to evaluate the effect of EGb 761 and its possible mechanism of action in DC.Materials and Methods:DM was induced by single injection of Streptozotocin (STZ) (50 mg/kg, i.p.) and cardiac dysfunction was developed on 8th weeks after STZ injection. Cardiac dysfunction was assessed by measuring left ventricle weight/body weight (LVW/BW) ratio, left ventricle (LV) collagen content, LV protein content, serum lactate dehydrogenase (LDH) level.Results:EGb 761 treatment (started after 7th week of STZ injection and continued for 3 weeks) attenuated cardiac dysfunction in diabetic rats as evidenced by a decrease in LV collagen content, protein content, LVW/BW ratio, serum LDH level. Moreover, EGb 761 attenuated the oxido-nitrosative stress (thiobarbituric acid reactive substances, superoxide anion generation, myocardium nitrite) and concomitantly improved the antioxidant enzyme (reduced glutathione) level as compared to untreated diabetic rats. However, protective effect of EGb 761 was inhibited by atractyloside (mPTP opener) that was given for 3 weeks, 30 min before the EGb 761 treatment. These results indicate that EGb 761 corrects diabetic cardiac dysfunction probably by its direct radical scavenging activity and its ability to inhibit the opening of mPTP channel since the cardioprotective effect of EGb 761 was completely abolished by atractyloside.

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“…BB is one of the effective active components of EGb 761. To our knowledge, EGb 761 suppressed diabetic cardiac dysfunction in DM (Saini, Taliyan, & Sharma, ). Furthermore, EGb 761 had a vital effect in inducing insulin secretion and raising plasma insulin levels, which were responsive to oral glucose intake (Lim et al, ).…”

Cystathionine-γ lyase-derived hydrogen sulfide mediates the cardiovascular protective effects of moxonidine in diabetic rats

“…For example, the hyperglycemia (Fig. 2B) induction of osmotic diuresis (Abe et al, 2002), and oxidative stress (Saini et al, 2014), which suppresses myocardial function in STZ rats (Table 2), might ultimately, lower BP. By contrast, the sympathoexcitation caused by hyperglycemia-evoked neuronal oxidative stress (Patel et al, 2011), and the baroreflex dysfunction shown here (Table 2) and in some (Milan et al, 2007), but not in other (Patel and Zhang, 1995) studies, might tip the balance towards the slight elevation in BP in STZ rats (Table 2).…”

The Small Molecule Indirubin-3'-Oxime Inhibits Protein Kinase R: Antiapoptotic and Antioxidant Effect in Rat Cardiac Myocytes

“…PKR is activated through autophosphorylation and once activated it phosphorylates certain substrates including the α-subunit of eukaryotic initiation factor 2 [6,8]. PKR has also been reported to be activated by cellular stress, oxidative stress, metabolic stress, and inflammation [6,9,10,11] and these stress signals have also been observed under diabetic and vascular complications [12]. The PKR signaling pathway may therefore be an attractive target for the development of anti-diabetic and cardioprotective drugs.…”