Anti-diabetic Effect of Punica granatum Flower Polyphenols Extract in Type 2 Diabetic Rats: Activation of Akt/GSK-3β and Inhibition of IRE1α-XBP1 Pathways

Abstract

Type 2 diabetes mellitus (T2DM) is the most common type of diabetes with more than hundreds of millions of patients worldwide. However, the medicines for treatment of T2DM are very limited. In China, Punica granatum L. flower (PGF) has been used as an anti-diabetic herb in the herbal medicine. The activity involves in improvement of insulin sensitivity. However, the underlying mechanism of action is elusive. The current study was designed to address this issue by investigating the effect of polyphenols extract of PGF in diabetic rats. A rat model was orally administrated with PGF polyphenols extract at doses of 50 and 100 mg/kg for 4 weeks. Insulin sensitivity was improved as indicated by oral glucose tolerance test (OGTT), insulin tolerance test (ITT) and homeostasis model assessment of insulin resistance (HOMA-IR). At the molecular level, insulin signaling activity was improved with an elevation in insulin-stimulated phosphorylation of insulin receptor substrate (IRS-1), Akt and GSK-3β. Endoplasmic reticulum (ER) stress signals including phosphorylation of inositol-requiring kinase1 (IRE1) and activation of X box binding protein (XBP-1) splicing were decreased by the PGF treatment. Expressions of IRE1α, XBPs, and CHOP were all decreased by PGF. Blood lipid profile, liver glycogen content and antioxidant status were improved by PGF in the rats. The observations suggest that PGF is able to lower glucose levels in T2DM rats by improving the insulin resistance. The mechanism is likely related to the activation of Akt-GSK3β signaling pathway and inhibition of ER stress.

Protective effect of pomegranate (Punica granatum) extract against diabetic changes in adult male rat liver: Histological study

“…Blood glucose control by PPE was reported by many authors,[25] which confirm the effect of PPE in this study where its administration prior to diabetes induction keep blood glucose near-normal levels, preventing hyperglycemia adverse effects on different organs including liver.…”

The Hypoglycaemic and Hypolipidemic Effects of Aqueous Extract of <i>Alkanna strigosa</i> in Alloxan Induced Diabetic Rats

“…After the treatment of the diabetic rats, their body weight increased again. Similar effects were also observed by other researchers [35][36][37]. The synthetic oral hypoglycemic agents can produce a series of side effects.…”

Evaluation of the in vitro ⍺‐amylase inhibitory, antiglycation, and antioxidant properties ofPunica granatumL. (pomegranate) fruit peel acetone extract and its effect on glucose uptake and oxidative stress in hepatocytes

“…Huang et al (2005) reported gallic acid as a major component of the methanolic extract of the flowers, which may be partly responsible for its anti‐hyperglycemic, as well as glucose transporter type 4 expression and insulin sensitivity modulatory effects of the extract in Zucker diabetic fatty rats. Other studies further confirmed that the ethanolic extract of the flower ameliorated diabetes‐induced hyperglycemia, insulin insensitivity, dyslipidemia and oxidative stress in STZ‐induced (Manoharan et al, 2009) and high‐fat‐diet‐induced (Tang et al, 2018) diabetic rats. In addition, polyphenol rich (HPLC: 8.3% of ellagic acid, 1.49% of gallic acid, 0.79% of pyrogallic acid, and 18.27% of tannic acid) (Yu et al, 2017) and hydroalcoholic extracts (Adnyana, Sukandar, Yuniarto, & Finna, 2014) of the leaves showed antiobesogenic activities by inhibiting pancreatic lipase activities and reducing fat intestinal absorption.…”