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Myocardial infarction (MI) is the leading cause of death among cardiovascular diseases. Reperfusion, the most harmful phase, is accompanied byinflammatory, oxidative, andapoptotic cascades in cardiomyocytes, impairing thehemodynamic and histologic status of the cardiac tissue. The Scrophularia genus is well known for the cardioprotective effects of its species, showing beneficial impacts on blood pressure and arrhythmias in previous studies.

Regarding the mechanisms involved in MI and the cardioprotective effects of the Scrophularia genus, in this study, we evaluated the cardioprotective effects of Scrophularia atropatana on MI.

Isoproterenol (ISO) injections (100 mg/kg, sc, 24-hour intervals) were used to induce MI in rats. In intervention groups, two hours after the first ISO injection, 5, 10, and 20 mg/kg S. atropatana extract was administered by gavage (24-hour intervals) for three days. Cardiac hemodynamic parameters were measured by placing a catheter into the right carotid artery and the left ventricle. Total antioxidant status (TAS), malondialdehyde (MDA) and lactate levels, and histopathologic changes were evaluated.

Induction of MI was accompanied by declined median arterial pressure (MAP), left ventricular systolic pressure (LVSP), and total antioxidant status (TAS) levels. In contrast, the heart rate, left ventricle end-diastolic pressure (LVEDP), malondialdehyde (MDA), and lactate levels were elevated in the MI group. Scrophularia atropatana treatment increased the MAP, LVSP, and TAS levels and significantly reduced the heart rate, LVEDP, MDA, and lactate levels. Also, S. atropatana treatment prevented histopathologic changes post-MI.

The improving effects of S. atropatana on MI injuries suggest its potential as a complementary cardioprotective medication.

Type 2 diabetes mellitus is a chronic metabolic disorder with prominent vascular injuries. In this condition, the levels of multiple pro- and anti-angiogenic factors have been shown to change. This study aimed to investigate the possible effect of metformin on proangiogenic factor, endocan levels, via the modulation of p-AMPK/AMPK axis in diabetic mice.

Mice were randomly assigned to one of 4 groups (n=6): Control (normal saline) and the diabetic group was injected streptozotocin and two groups were given 50 and 100 mg/kg metformin orally, once daily for two weeks after diabetes induction. Endocan protein levels were detected in the liver and kidneys by ELISA and immunofluorescence analysis. Phosphorylation of AMPK was assessed using western blotting. Histological examination was performed to follow the metformin effect on Von Willebrand factor expression and diabetes-related pathologies.

ELISA assay showed an elevated levels of endocan in the renal and hepatic tissues of diabetic mice following treatment with metformin (p<0.05). Immunofluorescence and immunohistochemistry examination of kidneys showed that the increase of endocan protein coincided with the promotion of vWF factors in mice treated with metformin (p<0.05). We did not find endocan factor in hepatic tissue of diabetic mice pre- and post-treatment with metformin. Western blotting confirmed the phosphorylation of AMPK by metformin in kidneys (p<0.05), but these changes did not reach statistically significant levels in hepatic tissues (p>0.05).

Metformin could change the endocan levels during diabetic condition possibly by the modulation of p-AMPK/AMPK axis.

Drug repositioning is one of the common strategies of new indications and therapeutic targets for already known drugs.  Drug repositioning is known by various names in textbooks such as drug re-proposing, re-profiling, re-tasking and therapeutic switching. Drugs may act through multiple molecular targets. Although perhaps designed for specificity, modulate several targets. This “Poly-pharmacology” may also be essential for efficacy. This “off-targets” may also lead to side-effect. Repositioning vs traditional drug discovery reduces time, reduces risk, and reduces cost.  Bleeding disorder observation of aspirin (a wonder drug) over the years (1891) was made repeatedly leading to the suggestion by Craven (1953) that aspirin might be used for the prevention of thrombosis. The historically unintentional, serendipitous, or constrained research effort is now being replaced by systematic, high-throughput and rational pursuit of new therapeutic uses for marketed drugs, drugs in development, or as a drug salvaging strategy.