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Effects of pomegranate aril juice and its punicalagin on some key regulators of insulin resistance and oxidative liver injury in streptozotocin-nicotinamide type 2 diabetic rats

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Abstract

Nowadays, medicinal plants have been widely used everywhere to provide essential care for many disorders including diabetes. Recent reports assumed that the antidiabetic activities of pomegranate aril juice (PAJ) may be ascribed to its punicalagin (PCG). Therefore, the present study evaluated and compared the antidiabetic activities of PAJ and its PCG, and monitored some mechanisms of their actions in streptozotocin-nicotinamide (STZ-NA) type 2 diabetic rats. STZ-NA diabetic rats were given, orally/daily, PAJ (100 or 300 mg/kg body weight, containing 2.6 and 7.8 mg of PCG/kg body weight, respectively), pure PCG (2.6 or 7.8 mg/kg body weight), or distilled water (vehicle) for 6 weeks. PAJ (especially at the high dose) alleviated significantly (P < 0.05–0.001) most signs of type 2 diabetes including body-weight loss, insulin resistance (IR) and hyperglycemia through decreasing serum tumor necrosis factor-α concentration and the expression of hepatic c-Jun N-terminal kinase, and increasing the skeletal muscle weight and the expression of hepatic insulin receptor substrate-1 in STZ-NA diabetic rats. Also, it decreased significantly (P < 0.001) the oxidative liver injury in STZ-NA diabetic rats through decreasing the hepatic lipid peroxidation and nitric oxide production, and improving the hepatic antioxidant defense system. Although the low dose of PCG induced some modulation in STZ-NA diabetic rats, the high dose of PCG did not show any valuable antidiabetic activity, but induced many side effects. In conclusion, PAJ was safer and more effective than pure PCG in alleviating IR and oxidative liver injury in STZ-NA diabetic rats.

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Acknowledgements

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. NME-B, GR and EAE-H planned the study, designed all experiments, summarized, discussed and interpreted the results. AMH with assistance from EAE-H carried out all the experiments. AMH performed the statistical analysis with assistance from GR. GR and AMH drafted the manuscript.

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Correspondence to Gamal Ramadan.

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All animals were humanely treated in accordance with the principles of laboratory animal care of National Institutes of Health (NIH publication No. 86-23, revised 1985), and the study design including the animal experiments was approved by the Ain Shams University Research Ethics Committee (4/2013).

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El-Beih, N.M., Ramadan, G., El-Husseiny, E.A. et al. Effects of pomegranate aril juice and its punicalagin on some key regulators of insulin resistance and oxidative liver injury in streptozotocin-nicotinamide type 2 diabetic rats. Mol Biol Rep 46, 3701–3711 (2019). https://doi.org/10.1007/s11033-019-04813-8

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