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