Wanthanee Hanchang1, Aree Khamchan2, Navinee Wongmanee2, Chananchida Seedadee2. 1. Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand. Electronic address: wanthaneeh@nu.ac.th. 2. Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand.
Abstract
AIMS: The current study was conducted to investigate the potential protective effects of hesperidin and its possible mechanisms of action on pancreatic β-cells in diabetes. MAIN METHODS: Male Sprague Dawley rats were made diabetic using 65 mg/kg intraperitoneal injection of streptozotocin, and then administered daily with 100 mg/kg of hesperidin over 4 weeks. On conclusion of the experiment, blood and pancreatic tissue were collected to determine the function of β-cells, apoptosis, oxidative stress, ER stress, and inflammation. KEY FINDINGS: Treatment of diabetic rats with hesperidin, significantly decreased fasting blood glucose and food intake, along with increased body weight, serum and pancreatic insulin levels, and pancreatic-duodenal homeobox-1 (PDX-1) protein expression. The beneficial roles of hesperidin on diabetic pancreatic β-cells exhibited an increment in antioxidant SOD and GPx activities, and a decrement in nitrotyrosine as well as malondialdehyde (MDA) levels. Additionally, the elevated concentration of TNF-α and expressions of ER stress maker GRP78 and CHOP proteins in the pancreas of diabetic rats were significantly diminished by hesperidin treatment. Furthermore, hesperidin effectively modulated expressions of apoptosis-regulatory proteins in diabetic rat pancreas, as revealed by upregulating anti-apoptotic Bcl-xL; with a concomitant downregulating pro-apoptotic Bax, cleaved caspase-3, and inhibiting the activation of DNA repair protein poly (ADP-ribose) polymerase (PARP). SIGNIFICANCE: Collectively, these findings suggest that hesperidin may have the potential to protect pancreatic β-cells and improve their function by suppressing oxidative and ER stress, along with activating its antioxidant, anti-inflammatory, and anti-apoptotic effects.
AIMS: The current study was conducted to investigate the potential protective effects of hesperidin and its possible mechanisms of action on pancreatic β-cells in diabetes. MAIN METHODS: Male Sprague Dawley rats were made diabetic using 65 mg/kg intraperitoneal injection of streptozotocin, and then administered daily with 100 mg/kg of hesperidin over 4 weeks. On conclusion of the experiment, blood and pancreatic tissue were collected to determine the function of β-cells, apoptosis, oxidative stress, ER stress, and inflammation. KEY FINDINGS: Treatment of diabeticrats with hesperidin, significantly decreased fasting blood glucose and food intake, along with increased body weight, serum and pancreatic insulin levels, and pancreatic-duodenal homeobox-1 (PDX-1) protein expression. The beneficial roles of hesperidin on diabetic pancreatic β-cells exhibited an increment in antioxidant SOD and GPx activities, and a decrement in nitrotyrosine as well as malondialdehyde (MDA) levels. Additionally, the elevated concentration of TNF-α and expressions of ER stress maker GRP78 and CHOP proteins in the pancreas of diabeticrats were significantly diminished by hesperidin treatment. Furthermore, hesperidin effectively modulated expressions of apoptosis-regulatory proteins in diabeticrat pancreas, as revealed by upregulating anti-apoptotic Bcl-xL; with a concomitant downregulating pro-apoptotic Bax, cleaved caspase-3, and inhibiting the activation of DNA repair protein poly (ADP-ribose) polymerase (PARP). SIGNIFICANCE: Collectively, these findings suggest that hesperidin may have the potential to protect pancreatic β-cells and improve their function by suppressing oxidative and ER stress, along with activating its antioxidant, anti-inflammatory, and anti-apoptotic effects.
Authors: Anna Mas-Capdevila; Joan Teichenne; Cristina Domenech-Coca; Antoni Caimari; Josep M Del Bas; Xavier Escoté; Anna Crescenti Journal: Nutrients Date: 2020-05-20 Impact factor: 5.717