Cytotoxic and Anti-Inflammatory Activities of Dihydroisocoumarin and Xanthone Derivatives from Garcinia picrorhiza.

Garcinia picrorhiza, a woody plant native to Sulawesi and Maluku Islands, Indonesia, has been traditionally used as a wound healing ointment. In our continuous search for bioactive compounds from this plant, 15 phenolic compounds were isolated from its stem bark, including a previously undescribed dihydroisocoumarin, 2'-hydroxyannulatomarin, and two undescribed furanoxanthones, gerontoxanthone C hydrate and 3'-hydroxycalothorexanthone. The structures of the new metabolites were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR and HRESIMS. Gerontoxanthone C hydrate possessed cytotoxicity against four cancer cells (KB, HeLa S3, MCF-7, and Hep G2) with IC50 values ranging from 5.6 to 7.5 µM. Investigation on the anti-inflammatory activities showed that 3'-hydroxycalothorexanthone inhibited NO production in RAW 264.7 and BV-2 cell lines with IC50 values of 16.4 and 13.8 µM, respectively, whereas only (-)-annulatomarin possessed inhibition activity on COX-2 enzyme over 10% at 20 µM. This work describes the presence of 3,4-dihydroisocoumarin structures with a phenyl ring substituent at C-3, which are reported the first time in genus Garcinia. These findings also suggest the potential of furanxanthone derivatives as cytotoxic and anti-inflammatory agents for further pharmacological studies.

Picrorhizones A-H, Polyprenylated Benzoylphloroglucinols from the Stem Bark of Garcinia picrorhiza.

Eight new polyprenylated benzoylphloroglucinol derivatives (1-8) and four known analogues (9-12) were isolated from the stem bark of Garcinia picrorhiza. Their structures were determined by spectroscopic data analysis (1D and 2D NMR and HRESIMS), and the absolute configurations were established by single-crystal X-ray diffraction combined with experimental and calculated ECD data. The new metabolites represent rare examples of benzoylphloroglucinols bearing a cyclobutyl-containing side chain. The isolated compounds were evaluated for their cytotoxic properties against five types of human cancer cells (KB, HeLa S3, MCF-7, Hep G2, and HT-29 cells) and their inhibitory activities against COX-1 and COX-2 enzymes. The cytotoxicity results showed that compound 6 was active against KB, HeLa S3, MCF-7, and Hep G2 cancer cells, with IC50 values ranging from 5.9 to 9.4 µM. Among the compounds tested for cyclooxygenase inhibition, compound 8 possessed the highest inhibitory effect toward COX-1 (35.2 ± 9.6% inhibition at 20 µM).

Tetrandraxanthones A-I, Prenylated and Geranylated Xanthones from the Stem Bark of Garcinia tetrandra.

Nine new xanthones, tetrandraxanthones A-I (1-9), and 22 known xanthones (10-31) were isolated from Garcinia tetrandra stem bark. The structures of 1-9 were characterized through detailed spectroscopic analysis, including HRESIMS and 2D NMR data. Among the compounds tested for their cytotoxicity, 26 showed significant cytotoxic effects against five human cancer cell lines, including MCF-7, HT-29, KB, Hep G2, and HeLa S3, with IC50 values in the range of 1.6-3.4 µM, while 10 and 11 were cytotoxic against the MCF-7, HeLa S3, and KB cell lines, with IC50 values of 4.3-9.0 µM.

20(S)-Ginsenoside Rh2 as aldose reductase inhibitor from Panax ginseng.

The root of Panax ginseng C. A. Meyer (Araliaceae) is a well-known herbal medicine in East Asia. The major bioactive metabolites in this root are commonly identified as ginsenosides. A series of ginsenosides were determined for in vitro human recombinant aldose reductase. This Letter aims to clarify the structural requirement for aldose reductase inhibition. We discovered that only ginsenoside 20(S)-Rh2 showed potent against aldose reductase, with an IC50 of 147.3 µM. These results implied that the stereochemistry of the hydroxyl group at C-20 may play an important role in aldose reductase inhibition. An understanding of these requirements is considered necessary in order to develop a new type of aldose reductase inhibitor. Furthermore, P. ginseng might be an important herbal medicine in preventing diabetic complications.

Antiplasmodial and anticancer activities of xanthones isolated from Garcinia bancana Miq.

This report describes the isolation and characterization of xanthones from Garcinia bancana Miq. and evaluates their antiplasmodial and anticancer activities. Macluraxanthone (1), isojacareubin (2), and gerontoxanthone C (3) were isolated from the stem bark of G. bancana Miq. for the first time. In silico molecular docking studies revealed the hydrogen bonding and steric interactions between xanthones (1-3) and PfLDH/VEGFR2. The in vitro antiplasmodial activity was assayed against the chloroquine-sensitive Plasmodium falciparum strain 3D7 by the lactate dehydrogenase (LDH) method. The anticancer evaluation was evaluated against the A549, MCF-7, HeLa, and B-16 cancer cell lines. Compounds (1) (IC50 8.45-16.71 µM) and (3) (IC50 9.69-14.86 µM) showed more potent anticancer activity than compound (2) (IC50 25.46-31.31 µM), as well for their antiplasmodial activity (4.28 µM, 5.52 µM, 11.45 µM). Our findings indicated the potential of G. bancana Miq. as a natural resource of antiplasmodial and anticancer compounds.

Adsorption and decolorization study of reactive black 5 by immobilized metal-organic framework of UiO-66 and Gloeophyllum trabeum fungus.

This study aimed to investigate immobilized metal-organic framework (MOF) UiO-66 and brown-rot fungus Gloeophyllum trabeum (GT) in PVA-SA matrices for adsorption and decolorization of reactive black 5 (RB5). Furthermore, UiO-66/GT@PVA-SA composite was successfully fabricated and obtained by immobilizing UiO-66 and GT mycelia into a mixture of PVA-SA. This composite demonstrated a decolorization ability of 80.12% for RB5 after 7 days. The composite's reusability was assessed for three cycles; at last, it only achieved 21%. This study reported that adsorption of RB5 by the composite followed a pseudo-second-order kinetic model with a correlation coefficient (R2) of 0.9997. The Freundlich model was found to be suitable for the isotherm adsorption. The process was also spontaneous and feasible, as indicated by the negative ΔG value. Subsequently, four metabolite products resulting from decolorization of RB5 by UiO-66/GT@PVA-SA composite were proposed, namely: C24H19N5Na2O13S4 (m/z = 762), C10H13N2O8S2- (m/z = 353), C12H9N4O7S2- (m/z = 384), and C10H13O8S2- (m/z = 325).

A new biphenyl from the stem bark of Garcinia macrantha A.C.Sm.

In our continuation of exploring antidiabetic agents from Garcinia species, we found that the methanolic extract of G. macrantha A.C.Sm. exhibited considerable α-glucosidase inhibition of 58.20 ± 0.37% in sucrose substrate and 39.86 ± 2.07% in maltose substrate at 100 µg/mL. Phytochemical investigation on the extract revealed the presence of a new biphenyl, macrabiphenyl A, which was successfully elucidated by means of spectroscopic methods (HRESIMS and 1D and 2D NMR). The α-glucosidase inhibitory evaluation indicated that the new compound was weakly active against the enzyme.

Biological Activity Evaluation and In Silico Studies of Polyprenylated Benzophenones from Garcinia celebica.

This study aimed to isolate polyprenylated benzophenones from the rootbark of Garcinia celebica and assess their activities in vitro and in silico. The antioxidant activity was evaluated by the DPPH, ABTS, and FRAP methods. The cytotoxicity was evaluated against HeLa, MCF-7, A549, and B16 cancer cell lines. The antiplasmodial activity was performed against the chloroquine-sensitive Plasmodium falciparum strain 3D7. Molecular docking was analyzed on alpha-estrogen receptor (3ERT) and P. falciparum lactate dehydrogenase enzyme (1CET). The prediction of ADMET for the compounds was also studied. For the first time, (-)-cycloxanthochymol, isoxanthochymol, and xanthochymol were isolated from the root bark of Garcinia celebica. The antioxidant and cytotoxicity evaluation showed that all benzophenones exhibited antioxidant activity compared to gallic acid and quercetin as positive controls and also exhibited strong activity against HeLa, MCF-7, A549, and B16 cell lines compared to cisplatin as the positive control. The antiplasmodial evaluation showed that isoxanthochymol exhibited activity against the chloroquine-sensitive P. falciparum strain 3D7. In addition, the in silico molecular docking study supported in vitro activities. The ADMET analysis also indicated the isolated benzophenones are potential oral drug candidates.

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

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.

α-VINIFERIN as a potential antidiabetic and antiplasmodial extracted from Dipterocarpus littoralis.

Over the past few decades, complementary medicine therapy using medicinal plants have been developed in healthcare. Phytochemical studies about medicinal plants have been conducted to verify their potency as medicinal remedies in modern therapeutics. Dipterocarpus littoralis commonly known as Meranti Jawa in Indonesia is traditionally used to treat diseases such as diarrhea, diabetic and malaria. This study aimed to isolate bioactive compounds from D. littoralis using bioguided fractionation method. The bioactivity measured were antioxidant, antidiabetic, and antiplasmodial activity. Alpha-glucosidase and alpha-amylase assays were applied to estimate the in vitro antidiabetic activity of D. littoralis. The antioxidant activities were determined by using the free radical scavenging assays 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2-2″-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Analysis of total flavonoid and phenolic contents were expressed as Quercetin Equivalent (QE) and Gallic Acid Equivalent (GAE), respectively. The in vitro antiplasmodial activity test of methanol extract of D. littoralis was also conducted against Plasmodium falciparum strain 3D7. Purification of the ethyl acetate fraction of the methanol extract of D. littoralis resulted in an oligostilbenes namely α-viniferin (1). The structure of the α-viniferin was characterized by comprehensive spectral analysis including IR, 1D and 2D NMR, and in comparison with the literature data. Compound 1 showed an alpha-glucosidase and alpha-amylase inhibitory activity with IC50 values of 256.17 and 212.79 µg/mL, respectively. The in vitro antiplasmodial activity test against Plasmodium falciparum strain 3D7 at a concentration of 100 µg/mL revealed a strong antiplasmodial inhibitory activity with IC50 value of 2.76 µg/mL. Our findings indicated that α-viniferin (1) which is isolated from D. littoralis extract could be regarded as potential antidiabetic and antiplasmodial resources in the future.

Xanthones and biphenyls from the stems of Garcinia cylindrocarpa and their cytotoxicity.

Six new compounds including four new xanthones, cylindroxanthones D-G (1-4), and two new biphenyls, cylindrobiphenyls A and B (5 and 6), were isolated from the stems of Garcinia cylindrocarpa together with 28 known compounds (7-34). The structures of the new compounds were established on the basis of extensive 1D and 2D NMR and HRESIMS spectroscopic analysis. Their cytotoxicity was evaluated against five human cancer cell lines including KB, HeLa S-3, MCF-7, Hep G2, and HT-29. Compound 23 showed strong cytotoxicity against KB, HeLa S-3, MCF-7, and Hep G2 cells with IC50 values in the range of 2.20-6.00 µM. Furthermore, compound 25 selectively exhibited good cytotoxicity against MCF-7 cells with IC50 value of 8.77 µM, while 31 showed good cytotoxicity against HT-29 cells with IC50 value of 9.18 µM.

Cylindroxanthones A-C, three new xanthones and their cytotoxicity from the stem bark of Garcinia cylindrocarpa.

Three new xanthones, cylindroxanthones A-C (1-3), were isolated from the stem bark of Garcinia cylindrocarpa. The structures were established on the basis of spectroscopic analysis. The molecular structure of 1 was unequivocally confirmed by single-crystal X-ray diffraction analysis. These three xanthones were evaluated regarding their cytotoxicity against KB, HeLa S-3, HT-29, MCF-7, and Hep G2 cancer cell lines. Compound 1 exhibited good cytotoxicity against KB cell with IC50 value of 2.36 µM.

The inhibitory activity of aldose reductase in vitro by constituents of Garcinia mangostana Linn.

We investigated aldose reductase inhibition of Garcinia mangostana Linn. from Indonesia. Dichloromethane extract of the root bark of this tree was found to demonstrate an IC50 value of 11.98 µg/ml for human aldose reductase in vitro. From the dichloromethane fraction, prenylated xanthones were isolated as potent human aldose reductase inhibitors. We discovered 3-isomangostin to be most potent against aldose reductase, with an IC50 of 3.48 µM.