Background <p>Magnolol isolated from Magnolia (<i>Magnolia</i> sp.) flowers are used to support the treatment of diabetes. The aim of this study was to investigate the effects of magnolol on the liver antioxidant status in rats with type 2 diabetes and assess oxidative stress parameters at both biochemical and molecular levels.</p> Methods <p>Mature male Wistar rats with high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetes were administered magnolol at doses of 5 or 25&#xa0;mg/kg body weight <i>po</i> for 4 weeks. Then, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), the concentrations of advanced protein oxidation products (AOPPs) and malondialdehyde (MDA), the total antioxidant response (TAR), and the total oxidative status (TOS) were assessed using commercially available colorimetric kits according to the manufacturers’ protocols. The mRNA levels of the cytochrome P450 family 1 subfamily A member 2 (<i>CYP1A2</i>), cytochrome P450 family 2 subfamily E member 1 (<i>CYP2E1</i>), nuclear factor erythroid 2-related factor 2 (<i>NFE2L2</i>), and Kelch like ECH-associated protein 1 (<i>KEAP1</i>) genes were determined using real-time quantitative reverse transcription–polymerase chain reaction (RT‒qPCR). All parameters were analyzed in liver samples.</p> Results <p>Compared with 5&#xa0;mg/kg magnolol, 25&#xa0;mg/kg magnolol had a more beneficial effect on several indicators of oxidative stress in the liver observed as significant decreases in the activity of SOD and CAT, as well as decreased MDA concentrations. Further, significant increases in the concentrations of AOPPs and native thiols were observed. The gene encoding <i>CYP2E1</i> was upregulated in diabetic rats compared with control rats. Moreover, compared with diabetic rats, diabetic rats treated with 25&#xa0;mg/kg magnolol presented increased expression of the <i>KEAP1</i> gene.</p> Conclusions <p>The induction of diabetes is known to disturb redox homeostasis. The administration of magnolol at the higher dose used in this study, might counteract the changes in the liver antioxidant status at both the molecular and biochemical levels. Owing to the positive alterations in some oxidative stress parameters, after further in-depth study, magnolol may be considered a promising compound that could be used to complement diabetes treatment.</p> Graphical Abstract <p></p>

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Effects of magnolol on the liver antioxidant status in rats with diabetes

  • Sławomir Dudek,
  • Weronika Borymska,
  • Maria Zych,
  • Dżesika Chełminiak,
  • Magdalena Kimsa-Dudek,
  • Ilona Kaczmarczyk-Żebrowska

摘要

Background

Magnolol isolated from Magnolia (Magnolia sp.) flowers are used to support the treatment of diabetes. The aim of this study was to investigate the effects of magnolol on the liver antioxidant status in rats with type 2 diabetes and assess oxidative stress parameters at both biochemical and molecular levels.

Methods

Mature male Wistar rats with high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetes were administered magnolol at doses of 5 or 25 mg/kg body weight po for 4 weeks. Then, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), the concentrations of advanced protein oxidation products (AOPPs) and malondialdehyde (MDA), the total antioxidant response (TAR), and the total oxidative status (TOS) were assessed using commercially available colorimetric kits according to the manufacturers’ protocols. The mRNA levels of the cytochrome P450 family 1 subfamily A member 2 (CYP1A2), cytochrome P450 family 2 subfamily E member 1 (CYP2E1), nuclear factor erythroid 2-related factor 2 (NFE2L2), and Kelch like ECH-associated protein 1 (KEAP1) genes were determined using real-time quantitative reverse transcription–polymerase chain reaction (RT‒qPCR). All parameters were analyzed in liver samples.

Results

Compared with 5 mg/kg magnolol, 25 mg/kg magnolol had a more beneficial effect on several indicators of oxidative stress in the liver observed as significant decreases in the activity of SOD and CAT, as well as decreased MDA concentrations. Further, significant increases in the concentrations of AOPPs and native thiols were observed. The gene encoding CYP2E1 was upregulated in diabetic rats compared with control rats. Moreover, compared with diabetic rats, diabetic rats treated with 25 mg/kg magnolol presented increased expression of the KEAP1 gene.

Conclusions

The induction of diabetes is known to disturb redox homeostasis. The administration of magnolol at the higher dose used in this study, might counteract the changes in the liver antioxidant status at both the molecular and biochemical levels. Owing to the positive alterations in some oxidative stress parameters, after further in-depth study, magnolol may be considered a promising compound that could be used to complement diabetes treatment.

Graphical Abstract