Evaluation of the Antioxidant, Antidiabetic, and Antiplasmodial Activities of Xanthones Isolated from Garcinia forbesii and Their In Silico Studies.

Johanis Wairata,Arif Fadlan,Edwin Risky Sukandar,Adi Setyo Purnomo,Taslim Ersam,Muhammad Taher

doi:10.3390/biomedicines9101380

Abstract

This study aimed to isolate xanthones from Garcinia forbesii and evaluated their activity in vitro and in silico. The isolated compounds were evaluated for their antioxidant activity by DPPH, ABTS and FRAP methods. The antidiabetic activity was performed against α-glucosidase and α-amylase enzymes. The antiplasmodial activity was evaluated using Plasmodium falciparum strain 3D7 sensitive to chloroquine. Molecular docking analysis on the human lysosomal acid-alpha-glucosidase enzyme (5NN8) and P. falciparum lactate dehydrogenase enzyme (1CET) and prediction of ADMET for the active compound, were also studied. For the first time, lichexanthone (1), subelliptenone H (2), 12b-hydroxy-des-D-garcigerrin A (3), garciniaxanthone B (4) and garcigerin A (5) were isolated from the CH2Cl2 extract of the stem bark of G. forbesii. Four xanthones (Compounds 2–5) showed strong antioxidant activity. In vitro α-glucosidase test showed that Compounds 2 and 5 were more active than the others, while Compound 4 was the strongest against α-amylase enzymes. In vitro antiplasmodial evaluation revealed that Compounds 2 and 3 showed inhibitory activity on P. falciparum. Molecular docking studies confirmed in vitro activity. ADMET predictions suggested that Compounds 1–5 were potential candidates for oral drugs. The isolated 2–5 can be used as promising phytotherapy in antidiabetic and antiplasmodial treatment.

Highlights

The genus Garcinia belongs to the family Clusiaceae of subfamily Clusioideae and tribe Garcinieae with more than 600 species are widely distributed in Africa, Asia, Australia, Polynesia, and Latin America [1]
6-O-methyl2-deprenylrheediaxanthone B, vieillardixanthone, forbexanthone, buchanaxanthone, isocudraniaxanthone A, and 5,7-dihydroxychromone have been isolated from the stem bark of Garcinia vieillardii and strongly active on DPPH assay [5]
To the best of our knowledge, this is the first report of the known compounds 1–5 from G. forbesii (Figure 1)

Summary

Introduction

The genus Garcinia belongs to the family Clusiaceae of subfamily Clusioideae and tribe Garcinieae with more than 600 species are widely distributed in Africa, Asia, Australia, Polynesia, and Latin America [1]. Garcinia is mainly found in tropical rain forest of Southeast Asia and West Africa [2] and rich of secondary metabolites i.e., biflavonoids, xanthones, biphenyls, polyprenylated benzophenone, depsidones, and triterpenoids with various bioactivities. 6-O-methyl2-deprenylrheediaxanthone B, vieillardixanthone, forbexanthone, buchanaxanthone, isocudraniaxanthone A, and 5,7-dihydroxychromone have been isolated from the stem bark of Garcinia vieillardii and strongly active on DPPH assay [5]. Polyisoprenylated xanthone guttiferone A from Garcinia aristata fruit displayed antiplasmodial activity against Plasmodium falciparum with IC50 values of 0.5 μM, comparable to chloroquine (IC50 values of 0.3 μM) [6]. Mckeanianones A–E and new biflavone mckeaniabiflavone isolated from Garcinia mckeaniana had been reported active to P. falciparum strain TM4 and K1 [7]

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