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. 2023 Oct;31(10):101762.
doi: 10.1016/j.jsps.2023.101762. Epub 2023 Aug 25.

Multi-target action of Garcinia livingstonei extract and secondary metabolites against fatty acid synthase, α-glucosidase, and xanthine oxidase

Azza M Abdul-Rahman  1 , Ahlam Elwekeel  1 , Reem S Alruhaimi  2 , Emadeldin M Kamel  3 , Albandari Bin-Ammar  4 , Ayman M Mahmoud  5   6 , Abeer S Moawad  1 , Mohamed A Zaki  1
Affiliations

Multi-target action of Garcinia livingstonei extract and secondary metabolites against fatty acid synthase, α-glucosidase, and xanthine oxidase

Azza M Abdul-Rahman et al. Saudi Pharm J. 2023 Oct.

Abstract

Garcinia livingstonei is a traditional herbal medicine that showed beneficial health effects and bioactivities. Four compounds have been isolated from the plant leaves and were elucidated as lupeol, betulin, podocarpusflavone A, and amentoflavone. The inhibitory activities of G. livingstonei extract and isolated metabolites against fatty acid synthase (FAS), α-glucosidase, and xanthine oxidase (XO) were investigated in vitro. The affinity of the compounds toward the studied enzymes was investigated in silico. The plant extract inhibited FAS, α-glucosidase, and XO with IC50 values of 26.34, 67.88, and 33.05 µg/mL, respectively. Among the isolated metabolites, betulin exhibited the most inhibitory activity against α-glucosidase and XO with IC50 values of 38.96 and 30.94 µg/mL, respectively. Podocarpusflavone A and betulin were the most potent inhibitors of FAS with IC50 values of 24.08 and 27.96 µg/mL, respectively. Computational studies corroborated these results highlighting the interactions between metabolites and the enzymes. In conclusion, G. livingstonei and its constituents possess the potential to modulate enzymes involved in metabolism and oxidative stress.

Keywords: Alpha-glucosidase; Fatty acid synthase; Garcinia livingstonei; Xanthine oxidase.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Chemical structures of compounds 1-4 isolated from G. livingstonei leaves.
Fig. 2
Fig. 2
FAS inhibitory activity of compounds 1–4 and G. livingstonei extract. Data are mean ± SD, (N = 3).
Fig. 3
Fig. 3
Binding interactions of compounds 1–4 with TE domain of FAS.
Fig. 4
Fig. 4
Binding interactions of compounds 1–4 with KS domain of FAS.
Fig. 5
Fig. 5
α-glucosidase inhibitory activity of compounds 1–4, G. livingstonei extract and acarbose. Data are mean ± SD, (N = 3).
Fig. 6
Fig. 6
Binding interactions of compounds 1 and 2 with α-glucosidase.
Fig. 7
Fig. 7
Binding interactions of compounds 3 and 4 with α-glucosidase.
Fig. 8
Fig. 8
XO inhibitory activity of compounds 1–4, G. livingstonei extract and allopurinol. Data are mean ± SD, (N = 3).
Fig. 9
Fig. 9
Binding interactions of compounds 1 and 2 with XO.
Fig. 10
Fig. 10
Binding interactions of compounds 3 and 4 with XO.
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