Effect of Garcinia mangostana pericarp extract on glial NF-κB levels and expression of serum inflammation markers in an obese-type 2 diabetes mellitus animal model

Muflihatul Muniroh; Yora Nindita; Vega Karlowee; Yosef Purwoko; Nadya Diena Rahmah; Retno Widyowati; Suryono Suryono

doi:10.3892/br.2021.1439

Effect of Garcinia mangostana pericarp extract on glial NF-κB levels and expression of serum inflammation markers in an obese-type 2 diabetes mellitus animal model

Biomed Rep. 2021 Jul;15(1):63. doi: 10.3892/br.2021.1439. Epub 2021 Jun 3.

Authors

Muflihatul Muniroh¹, Yora Nindita², Vega Karlowee³, Yosef Purwoko^{1

4}, Nadya Diena Rahmah⁵, Retno Widyowati⁶, Suryono Suryono⁷

Affiliations

¹ Department of Physiology, Faculty of Medicine Diponegoro University, Semarang, Java 50275, Indonesia.
² Department of Pharmacology and Therapeutics, Faculty of Medicine Diponegoro University, Semarang, Java 50275, Indonesia.
³ Department of Anatomical Pathology, Faculty of Medicine Diponegoro University, Semarang, Java 50275, Indonesia.
⁴ Department of Internal Medicine, Faculty of Medicine Diponegoro University, Semarang, Java 50275, Indonesia.
⁵ Department of Nutrition Science, Faculty of Medicine Diponegoro University, Semarang, Java 50275, Indonesia.
⁶ Department of Pharmaceutical Science, Faculty of Pharmacy Airlangga University, Surabaya, East Java 60115, Indonesia.
⁷ Department of Physics, Faculty of Science and Mathematics Diponegoro University, Semarang, Java 50275, Indonesia.

Abstract

Type 2 diabetes mellitus (T2DM) is an age-related disease associated with cerebral inflammation and Alzheimer's disease. Garcinia mangostana pericarp (GMP) possesses antihyperglycemic, antidiabetic and anti-inflammatory effects. The aim of the present study was to evaluate the effect of GMP extract on cerebral inflammation in Wistar rats with T2DM by examining the expression levels of glial nuclear factor-κB (NF-κB), interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and superoxide dismutase (SOD). A total of 36 8-10-week-old male Wistar rats were randomly divided into six groups and provided a standard diet (normal control; C1), high-fat diet (HFD) with 200 g/kg GMP extract BW/day (GMP control; C2), HFD with streptozotocin-nicotinamide (diabetic control; C3), and HFD with 100 (M1), 200 (M2) or 400 g/kg body weight (BW)/day (M3) GMP extract for Wistar rats with diabetes. GMP extract was administered for 8 weeks after induction of T2DM was confirmed. Glial NF-κB activity was assessed by immunohistochemical staining, and by measuring IL-6 levels, TNF-α levels and SOD activity in the serum using ELISA. BW significantly increased following HFD treatment. After 7 weeks, the BW remained significantly higher compared with the normal control and GMP extract-treated groups, but decreased continuously in the T2DM groups. Glial NF-κB immunoreaction in the hippocampal region was significantly higher in the diabetic Wistar rats compared with the normal control Wistar rats, and 200 g/kg BW/day GMP significantly reduced its activity. The T2DM Wistar rats showed significantly higher expression levels of serum IL-6 and TNF-α and lower activity of SOD compared with the normal control Wistar rats. Meanwhile, rats in GMP groups M1, M2 and M3 exhibited significant reductions in the levels of IL-6 and TNF-α expression, and increases in SOD activity. GMP extract treatment effectively reduced hippocampal NF-κB, IL-6 and TNF-α levels and increased antioxidant SOD activity. These results suggest that GMP extract prevents cerebral inflammation in T2DM Wistar rats.

Keywords: Garcinia mangostana pericarp; cerebral inflammation; glial nuclear factor-κB; interleukin-6; mangosteen pericarp extract; superoxide dismutase; tumor necrosis factor-α; type 2 diabetes mellitus.

Grants and funding

Funding: The present study was supported by the Ministry of Research and Technology/National Research and Innovation Regency Republic of Indonesia (grant no. 201-04/UN7.6.1/PP/2020).