Investigation of Antidiabetic Effect of Pistacia atlantica Leaves by Activity-Guided Fractionation and Phytochemical Content Analysis by LC-QTOF-MS

Abstract

In this study, the antidiabetic, antiobesity, antioxidant, and antihyperlipidemic effects potential of Pistacia atlantica Desf. leaves were evaluated by in vitro methods. The effects of the leaves of the plant on pancreatic lipase, pancreatic cholesterol esterase, and PTP1B enzymes were investigated for the first time and it was observed that leaf methanol extract (IC50: 123.67 ± 0.40 μg/ml) and n-hexane sub-extract (IC50: 61.03 ± 0.11 μg/ml) had much stronger effects on pancreatic cholesterol esterase enzyme than simvastatin (IC50: 142.30 ± 5.67 μg/ml). The methanolic extract of P. atlantica leaves exerted strong inhibitory effect on the enzymes (α-amylase and α-glucosidase) effective on carbohydrate digestion. It was thought that the methanol extract could provide significant benefits against oxidative stress in diabetes mellitus since it showed antioxidant activities (DPPH radical scavenging activity and reducing power) as strong as reference compounds (ascorbic acid and quercetin). Qualitative and quantitative analyzes of rutin (0.328 ± 0.000 g/100 g dry extract), methyl gallate (5.245 ± 0.014 g/100 g dry extract), quercetin-3-O-glucoside (0.231 ± 0.000 g/100 g dry extract), and gallic acid (0.528 ± 0.127 g/100 g dry extract) in methanol extract were performed by RP-HPLC. The phytochemical content of the active sub-fraction obtained from the leaf methanol extract by activity-guided fractionation and column chromatography studies was characterized by LC-QTOF-MS. The presence of trigalloylglucose, digalloylglucose, and methyl gallate in the G6 coded sub-fraction obtained by chromatographic techniques from the ethyl acetate sub-extract, which has the highest inhibitory effect on α-amylase and α-glucosidase enzymes, was determined by LC-QTOF-MS. In addition to the G5 coded subfraction, a strong α-glucosidase enzyme inhibitory activity was also observed in the G6 coded sub-fraction, and methyl gallate, methyl digallate, 2″-O-galloyl-quercetin-3-O-hexoside, and myricetin-3-O-hexoside were identified in this sub-fraction. This study displayed that the methanol extract of P. atlantica leaves could be a potential source for bioactive compounds with antidiabetic effects by showing inhibitory effects on enzymes involved in carbohydrate digestion.

Antidiabetic, hypolipidemic, and antioxidant activities of Pistacia atlantica: A systematic review and meta‐analysis of preclinical studies

“…Phytochemical studies have evidenced that terpenes as the main components of various plants are capable of exerting BG-lowering effects. It has been also reported that monoterpenes content of PA such as α-pinene and β-pinene, could act as potent inhibitors of α-amylase and α-glucosidase (Kasabri et al, 2011;Pekacar, 2022). It seems that oleic and linoleic acid in PA oil has a suitable effect on glycemic indices F I G U R E 9 Forest plot of standardized mean difference (SMD) and 95% confidence interval (CI) in malondialdehyde (MDA) between intervention and comparison group following the consumption of PA (Pistacia atlantica).…”

“…Phytochemical studies have evidenced that terpenes as the main components of various plants are capable of exerting BG‐lowering effects. It has been also reported that monoterpenes content of PA such as α‐pinene and β‐pinene, could act as potent inhibitors of α‐amylase and α‐glucosidase (Kasabri et al, 2011; Pekacar, 2022). It seems that oleic and linoleic acid in PA oil has a suitable effect on glycemic indices based on the observations about the consumption of a diet high with these fatty acids (Garg, 1994; Jamshidi et al, 2018).…”

Nutraceutical Content and Biological Properties of Lipophilic and Hydrophilic Fractions of the Phytocomplex from Pistacia atlantica Desf. Buds, Roots, and Fruits

“…Numerous studies have been conducted to demonstrate the wide range of pharmacological activities at the expense of P. atlantica , including antibacterial [ 10 , 11 , 12 ], antioxidant [ 11 , 12 , 13 , 14 ], antidiabetic [ 14 , 15 , 16 ], anti-inflammatory [ 12 , 17 ], hepatoprotective [ 18 ], antitumor [ 19 , 20 ], anti-acetylcholinesterase [ 21 , 22 ], and antihyperlipidemic effects [ 23 ]. In fact, there are various chemical compounds in this plant species that may justify its potential therapeutic role, including triterpenoids, flavonoids, other phenolic compounds, tannins, fatty acids, and phytosterols [ 4 , 24 ].…”

Effect of Ecotype and Environment on Oil Content, Fatty Acid, and Sterol Composition of Seed, Kernel, and Epicarp of the Atlas Pistachio

“…The various parts of the Atlas pistachio, including the resin, leaves, fruits and galls, have been used for a long time in diverse regions as efficient remedies for a wide range of diseases. For instance, leaves, gull, and gum resin have a wound-healing effect and have been used to treat digestive and gastrointestinal disorders, diabetes, Alzheimer, hepatic, kidney, and brain diseases [1][2][3][4]. The Atlas pistachio's fruits are also a very abundant source of bioactive compounds [5,6].…”