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.