Assessing the multitargeted antidiabetic potential of three pomegranate peel‐specific metabolites: An in silico and pharmacokinetics study

Abstract

Diabetes is a chronic metabolic disorder that occurs due to impaired secretion of insulin, insulin resistance, or both. Recent studies show that the antidiabetic drugs used to control hyperglycemic levels are associated with undesirable adverse effects. Therefore, developing a safe and effective medicine with antidiabetic potential is needed. In this context, in silico studies are considered a rapid, effectual, and cost‐effective method in drug discovery procedures. It is evident from the literature that plant‐based natural components have shown promising outcomes in drug development to alleviate various diseases and hence have diversified the screening of potential antidiabetic agents. Purposely, in the present study, an in silico approach was performed on three Punica granatum peel metabolites (punicalin, punicalagin, and ellagic acid). All these three compounds were docked against nine protein targets involved in glucose metabolism (GFAT, PTP1β, PPAR‐ᵞ, TKIR, RBP4, α‐amylase, α‐glucosidase, GCK, and AQP‐2). These three pomegranate‐specific compounds demonstrated significant interactions with GFAT, PTP1β, PPAR‐ᵞ, TKIR, RBP4, α‐amylase, α‐glucosidase, GCK, and AQP‐2 protein targets. Specifically, punicalin, punicalagin, and ellagic acid revealed significant binding scores (−9.2, −9.3, −8.1, −9.1, −8.5, −11.3, −9.2, −9.5, −10.1 kcal/mol; −10, −9.9, −8.5, −8.9, −10.4, −9.0, −10.2, −9.4, −9.0 kcal/mol; and −8.1, −8.0, −8.0, −6.8, −8.7, −7.8, −8.3, −8.1, −8.1 kcal/mol, respectively), with nine protein targets mentioned above. Hence, punicalin, punicalagin, and ellagic acid can be promising candidates in drug discovery to manage diabetes. Furthermore, in vivo and clinical trials must be conducted to validate the outcomes of the current study.

Photoperiod-Dependent Effects on Blood Biochemical Markers of Phenolic-Enriched Fruit Extracts

“…Phenolic compounds have been shown to control glycemia, which is attributed to the inhibition of salivary and pancreatic enzymes during sugar digestion. 66 Specifically, some phenolic molecules that are mainly present in the obtained extracts have been reported as potential antidiabetic agents, such as didymin and punicalgin, 67,68 69 Photoperiod effects on blood glucose levels were also observed in F344 rats exposed to different photoperiods and consuming the enriched-phenolic grape seed extract GSPE for 9 weeks, although and unlike in the current study, GSPE increased its concentration in the L6 and L18 photoperiods compared to their respective control animals and treated and untreated L12-exposed animals. 21 In healthy animals, insulin is released by the pancreatic islets after carbohydrate meals to remove glucose from the bloodstream.…”

“…Phenolic compounds have been shown to control glycemia, which is attributed to the inhibition of salivary and pancreatic enzymes during sugar digestion . Specifically, some phenolic molecules that are mainly present in the obtained extracts have been reported as potential antidiabetic agents, such as didymin and punicalgin, , which are mainly present in orange and pomegranate extracts, respectively. In addition, another study showed that pomegranate and grape extracts could modulate carbohydrate digestive enzyme activity, including in vitro inhibition of α-amylase and α-glucosidase .…”

Chia (Salvia hispanica L.), a Pre-Hispanic Food in the Treatment of Diabetes Mellitus: Hypoglycemic, Antioxidant, Anti-Inflammatory, and Inhibitory Properties of α-Glucosidase and α-Amylase, and in the Prevention of Cardiovascular Disease

“…Despite the existence of several therapeutic agents for the treatment of DM, adverse effects have been observed, such as gastrointestinal disturbances, nausea, vomiting, hypoglycemia, and weight gain, and also the lack of effectiveness in some cases [97,98]. Nonetheless, the natural progression of DM calls for multiple drugs in addition to insulin.…”

Phytochemical profile, nutritional composition of pomegranate peel and peel extract as a potential source of nutraceutical: A comprehensive review

“…The peel of the pomegranate contains a variety of bioactive substances, including quercetin, catechin, antioxidants, minerals, and vitamins, as well as several potential health benefits (Pirzadeh et al., 2020 ). These substances are essential for preserving health and provide defense against a number of crippling conditions like cardiovascular diseases (CVD, diabetes, and specific types of cancer (Gull et al., 2023 ). The numerous uses of pomegranate peel in the fields of food biopreservation, the development of nutraceutical products, and the production of value‐added items are also explored through current research.…”