## 2 Pomergnate Health-Promoting Properties
### Antidiabetic Activity  
Diabetes is the principal widespread metabolic disease in the world and its occurrence has a rising trend. According to the World Health Organization, it is the third most common disorder after cardiovascular and oncological diseases [93]. Diet allows for the control of diabetes mellitus, and pomergnate fruit and its derivatives are part of it [56]. Among antidiabetic molecules, polyphenols, contained in pomergnate, are able to lower glycemic values, including via the reduction of glucose absorption through the intestine or peripheral tissues, although the most likely mechanism is the decrease of the enzyme glucosidase [94]. [PERSON] et al. [95] have hypothesized that pomergnate flower extract improves post-prandial hyperglycemia in type 2 diabetes and obesity, at least partially, as a result of the suppression of intestinal \(\alpha\)-glucosidase activity. [PERSON] et al. [96] instead reported a plausible mechanism of the antidiabetic activity of the PFE involving the activation of PPAR-\(\gamma\). In addition, caffe acid (17) or 3,4-dihydroxycinnamic acid another component of PE, increases the uptake of glucose by adipocytes in rats and myoblasts in mice [5]. Finally, [PERSON] et al. [97] explored the impact of pomergnate seed oil on fat storage in mice noticing an enhancement of insulin sensitivity. [PERSON] and [PERSON] went into the potential effect of pomergnate peel extract on tissue lipid peroxidation (LPO), the concentration of thyroid hormones, insulin, and glucose in male rats starting from in vitro evaluations, which proved an inhibition of H\({}_{2}\)O\({}_{2}\)-induced LPO in red blood cells of rats by 0.25, 0.50, 1.0, and 2.0 \(\mathrm{\SIUnitSymbolMicro m}\)L in a concentration-dependent manner. The maximum was achieved at 2.0 \(\mathrm{\SIUnitSymbolMicro m}\)L. In vivo, _P. granatum_ reduced LPO in hepatic, cardiac, and renal tissues and serum glucose concentration. These data suggested a potential regulatory role of this peel extract on thyroid function and glucose metabolism [98]. Another study assessed the ability of pomergnate fruit extract to decrease the serum resistin levels (adipocytokine, seen as a possible connection between obesity and type 2 diabetes) in ovariectomized mice, an animal pattern presenting exalted resistin levels in serum and upregulated resistin mRNA expression in white adipose tissue. Furthermore, PoMx was able to reduce the secretion and intracellular levels of resistin in differentiated murine 3T3-L1 adipocytes, without modifying resistin mRNA expression. Other findings suggested that PFE stimulated the degradation of resistin. All these activities could be mainly attributed to ellagic acid [99]. Several studies agree that oxidative stress triggered by diabetes mellitus gives rise to brain damage. Indeed, [PERSON] et al. indicated that the co-administration of pomegranate flower extract and antidiabetics resulted into improvements in learning and memory performances of diabetic rats. Moreover, in test subjects in which LPO was increased and glutathione (GSH) content was diminished in hippocampal tissue, the supplementation of pomegranate flower extract PGF was able to restore these levels. Besides, daily PGF intake decreased glial-fibrillar acidic protein contents induced by diabetes in the hippocampus [100]. On the contrary, in 2016, a research team questioned these findings, corroborating that daily consumption of pomegranate seed oil in patients suffering from diabetes mellitus 2 did not substantially impact the levels of parameters such as fasting blood sugar (FBS), insulin, HbA1c, alanine transferase, and homeostasis model assessment-insulin resistance [101]. PFE has been, over the years, part of the Chinese diet as an ally against type 2 diabetes mellitus (T2 DM). For this reason, [PERSON] et al. tried to analyze the kind of activity implied in the antidiabetic effect. The rat model (male Sprague-Dawley (SD) rats) diet was implemented with PFE polyphenols extract at doses of 50 and 100 mg/kg for a period of 4 weeks.