New Pregnane Glycosides Isolated from Caralluma hexagona Lavranos as Inhibitors of α-Glucosidase, Pancreatic Lipase, and Advanced Glycation End Products Formation

Abstract

Caralluma hexagona Lavranos (Family Asclepiadaceae) is an endemic herb in Yemen and Saudi Arabia, traditionally used to treat diabetes, abdominal pain, and stomach ulcers. Different extracts, fractions, and main constituents of C. hexagona were evaluated for their inhibitory activity against key enzymes in diabetes and hyperlipidemia, i.e., α-glucosidase and pancreatic lipase. In addition, the antioxidative effect and inhibition of advanced glycation end products (AGEs) were also assayed. Using a bioguided approach, the crude aqueous, methanolic extracts, methylene chloride (CH2Cl2), Diaion HP20 50% MeOH (DCF-1), and 100% MeOH (DCF-2) fractions of C. hexagona were evaluated for their possible α-glucosidase and pancreatic lipase inhibition and antioxidant activity. In addition, inhibition of AGE generation using bovine serum albumin (BSA)-fructose, BSA-methylglyoxal, and arginine-methylglyoxal models was carried out. Moreover, the main constituents of the most active fraction were isolated and identified using different chromatographic and sprectroscopic methods. From the most active CH2Cl2 fraction, four new pregnane glycosides were isolated and identified as 12β-O-benzoyl 3β,8β,12β,14β,20-pentahydroxy-(20S)-pregn-5-ene-3-O-β-d-glucopyranosyl-(1 → 4)-O-β-d-digitaloside (1), 3β,8β,14β,20-tetrahydroxy-(20S)-pregn-5-ene-3-O-β-d-glucopyranosyl-(1 → 4)-O-β-d-digitaloside-20-O-3-isoval-β-d-glucopyranoside (2), 3β,8β,14β,20-tetrahydroxy-(20R)-pregn-5-ene-3-O-β-d-glucopyranosyl-(1 → 4)-O-β-d-digitaloside-20-O-3-isoval-4-benzoyl-β-d-glucopyranoside (3A), and 3β,8β,14β,20-tetrahydroxy-(20R)-pregn-5-ene-3-O-β-d-glucopyranosyl-(1 → 4)-O-β-d-digitaloside-20-O-3,4 di-benzoyl-β-d-glucopyranoside (3B). Among the tested samples, the highest trolox equivalent (TE) antioxidant capacity (TEAC) was observed for DCF-1 with values of 128.53 ± 5.07, 378.58 ± 5.19, and 106.71 ± 5.66 μM TE/mg using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2’-azino-bis­(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant potential (FRAP) assays, respectively. The isolated apigenin-8-C-neohesperoside showed the highest antioxidant capacity (168.80 ± 1.80 and 278.21 ± 13.26 μM TE/mM) in DPPH and FRAP, respectively, while luteolin 4′-O-β-d-neohesperidoside had the highest TEAC (599.19 ± 9.57 μM TE/mM) in ABTS assay. Compounds 1, 2, and the mixture 3A and 3B inhibited α-glucosidase with IC50 values of 0.92 ± 0.02, 0.67 ± 0.01, and 0.74 ± 0.02 mM, respectively. In the AGE assays, DCF-1 showed the highest inhibitory effect in BSA-fructose and arginine-methylglyoxal models with IC50 values of 0.39 ± 0.02 and 0.77 ± 0.10 mg/mL, respectively. Among the isolated compounds, flavonoid compounds showed the highest antiglycation effect, while pregnanes revealed higher α-glucosidase inhibition. In conclusion, the current study revealed that C. hexagona is a promising Yemeni natural remedy, of which the major content of pregnane glycosides and flavonoids could be considered as a new therapeutic candidate targeting the metabolic syndrome.

Purification and Identification of Flavonoid Molecules from Rosa setate x Rosa rugosa Waste Extracts and Evaluation of Antioxidant, Antiproliferative and Antimicrobial Activities

“…Consequently, HP20 resin was considered as the most suitable adsorbent for further enrichment of TFs in Kushui rose waste. It is widely reported that HP20 resin can be chosen to recover natural products from plant materials [ 24 , 25 ].…”

Phenolics from Chrozophora oblongifolia Aerial Parts as Inhibitors of α-Glucosidases and Advanced Glycation End Products: In-Vitro Assessment, Molecular Docking and Dynamics Studies

“…Legumes and cereals are able to reduce postprandial glucose levels by decreasing carbohydrate absorption due to their high complex carbohydrates and fiber contents [9]. Moreover, many medicinal plants are known for activity in diabetic complications, like green tea, Garcinia cambogia, Nigella sativa, Hibiscus sabdariffa, Caralluma fimbriata [10], C. tuberculata [11], and C. hexagona [12]. The spurge family, Euphorbiaceae, is a large flowering plant family with 300 genera and about 7500 species that has different traditional uses [13].…”

Delving the Role of Caralluma fimbriata: An Edible Wild Plant to Mitigate the Biomarkers of Metabolic Syndrome

“…Flavone glycosides, pregnane glycosides, saponins, triterpenoids, and other flavonoids are important phytochemical constituents of C. fimbriata that have been studied against various pathological conditions and metabolic disorders. Pregnane glycosides are the secondary metabolites of C. fimbriata that are the steroidal compounds conjugated with sugar moiety [ 26 ]. They are related to altered lipid metabolism and inhibit the synthesis of fatty acids [ 18 , 27 ].…”

“…Insulin resistance and related disorders such as obesity and type 2 diabetes mellitus are linked to a high dietary fat intake. Controlling postprandial hyperglycemia and fat absorption through inhibition of enzymes responsible for glycoside and lipid hydrolysis should help to reduce MS complications [ 26 ]. The hypoglycemic action of the pregnane glycoside is mainly attributed to the lowering of intestinal glucose absorption or stimulation of pancreatic insulin production [ 58 ].…”