iso-Guttiferone J and Structure Revision of Guttiferone J from Garcinia gummi-gutta: A Combined Experimental and Integrated QM/NMR Approach.

Many polyprenylated acylphloroglucinols with fascinating chemical structures and intriguing biological activities have been identified as key to phytochemicals isolated from Garcinia, Hypericum, and related genera. In the present work, two chiral, tautomeric, highly-oxygenated polyprenylated acylphloroglucinols tethered with acyl and prenyl moieties on a bicyclo[3.3.1]nonanetrione core were isolated from the 95% ethanolic extract of Garcinia gummi-gutta fruit. The structures of both compounds were elucidated based on the NMR and MS data with ambiguity in the exact position of the enol and keto functions at C-1 and C-3 of the core structure. The structures of both polyprenylated acylphloroglucinols were established as a structurally revised guttiferone J and the new iso-guttiferone J with the aid of gauge-independent atomic orbital NMR calculations, CP3 probability analyses, specific rotation calculations, and electronic circular dichroism calculations in combination with the experimental data. The structures of both compounds resemble hyperforin, a potent activator of the human pregnane X receptor. As expected, both compounds showed strong pregnane X receptor activation at 10 µM [7.1-fold (guttiferone J) and 5.0-fold (iso-guttiferone J)], explained by a molecular docking study, necessitating further in-depth investigation to substantiate the herb-drug interaction potential of G. gummi-gutta upon co-administration with pharmaceutical drugs.

Formulation and assessment of biological properties of garcinia indica fruit extract mouthrinse as an adjunct to oral hygiene regimen: an in vitro analysis.

The prevalence of gingivitis is substantial within the general population, necessitating rigorous oral hygiene maintenance. OBJECTIVE: This study assessed a Garcinia indica (GI) fruit extract-based mouthrinse, comparing it to a 0.1% turmeric mouthrinse and a 0.2% Chlorhexidine (CHX) mouthrinse. The evaluation encompassed substantivity, staining potential, antimicrobial efficacy and cytocompatibility. METHODOLOGY: The study employed 182 tooth sections. For antimicrobial analysis, 64 extracted human teeth coated with a polymicrobial biofilm were divided into four groups, each receiving an experimental mouthrinse or serving as a control group with distilled water. Microbial reduction was assessed through colony forming units (CFU). Substantivity was evaluated on 54 human tooth sections using a UV spectrophotometer, while staining potential was examined on 64 tooth sections. Cytocompatibility was tested using colorimetric assay to determine non-toxic levels of 0.2% GI fruit extract, 0.1% Turmeric, and 0.2% CHX. RESULTS: Data were analysed with one-way ANOVA (α=0.05). Cell viability was highly significant (p<0.001) in the 0.2% GI group (64.1±0.29) compared to 0.1% Turmeric (40.2±0.34) and 0.2% CHX (10.95±1.40). For antimicrobial activity, both 0.2% GI (20.18±4.81) and 0.2% CHX (28.22±5.41) exhibited no significant difference (P>0.05) at end of 12 hours. However, 0.1% Turmeric showed minimal CFU reduction (P<0.001). Substantivity results at 360 minutes indicated statistically significant higher mean release rate in 0.1%Turmeric (12.47±5.84 ) when compared to 0.2% GI (5.02±3.04) and 0.2% CHX (4.13±2.25) (p<0.001). The overall discoloration changes (∆E) were more prominent in the 0.2% CHX group (18.65±8.3) compared to 0.2% GI (7.61±2.4) and 0.1% Turmeric (7.32±4.9) (P<0.001). CONCLUSION: This study supports 0.2% GI and 0.1% Turmeric mouth rinses as potential natural alternatives to chemical mouth rinses. These findings highlight viability of these natural supplements in oral healthcare.

Isogarcinol inhibits nasopharyngeal carcinoma growth through mitochondria-mediated autophagic cell death.

BACKGROUND AND AIMS: Isogarcinol, a natural compound extracted from the fruits of Garcinia oblongifolia, has potential chemopreventive activity. This study aimed to elucidate the anti-tumor effects and mechanism of action of isogarcinol on nasopharyngeal carcinoma (NPC). METHODS: Isogarcinol was isolated from Garcinia oblongifolia by using chromatographic separation. The anti-tumor effects of isogarcinol in NPC cells were tested by MTT assay, flow cytometry, wound healing assay, western blotting, transwell assay, colony formation assay, immunofluorescence, and transmission electron microscopy (TEM). The anti-tumor efficacy in vivo was evaluated in NPC cells xenograft models. RESULTS: Functional studies revealed that isogarcinol inhibited the proliferation, colony formation, migration and invasion abilities of NPC cells in vitro. Isogarcinol caused mitochondrial damage to overproduce reactive oxygen species through reducing the mitochondrial membrane potential and ΔΨm. Isogarcinol also substantially inhibited NPC cells growth in a xenograft tumor model without any obvious toxicity when compared with paclitaxel (PTX). Mechanistic studies have illustrated that isogarcinol increased the Bax/Bcl-2 ratio, cleaved caspase-3, and cytoplasmic cytochrome C levels to induce mitochondrial apoptosis. The ROS overproduction by isogarcinol could suppress EMT pathway via decreasing the levels of p-Akt and Snail. Furthermore, isogarcinol promoted the conversion of LC3-Ⅰ to LC3-Ⅱ, but increased p62 level to block autophagic flux, resulting in the accumulation of damaged mitochondria to promote autophagic cell death in NPC cells. CONCLUSION: This study provides a new theoretical foundation for the anti-tumor application of Garcinia oblongifolia and confirms that isogarcinol could be developed as a candidate drug for NPC treatment with low toxicity.

Chromones and biflavonoids from Garcinia pedunculata and Garcinia nujiangensis and their anti-inflammatory activity.

Plants of the Garcinia genus were rich in structurally diverse and naturally bioactive components, while limited studies have been reported for Garcinia pedunculata Roxb. and G. nujiangensis C. Y. Wu & Y. H. Li. Four previously undescribed compounds including three chromones, garpedunchromones A-C (1-3), and one biflavonoid, nujiangbiflavone A (14), along with fifteen known analogs (4-13, 15-19) were isolated from G. pedunculata and G. nujiangensis. The structures of the isolated compounds were determined based on their HRESIMS data, extensive NMR spectroscopic analyses, and ECD calculations. The chromone derivatives were isolated from Garcinia for the first time. Compound 14 was a rare biflavonoid with C-3─C-6″ linkage. The biological evaluation of these isolates against NO production was conducted in the LPS-induced RAW 264.7 cells, resulting in the identification of a series of potent NO inhibitors, of which garpedunchromone B (2) was the most active with an IC50 value of 18.11 ± 0.96 µM. In the network pharmacology studies, the potential targets of compounds and inflammation were obtained from PharmMapper and GeneCards database. GO and KEGG enrichment analysis revealed that the overlapped targets were closely related to the major pathogenic processes linked to inflammation. Garpedunchromone B and proteins binding sites were being predicted.

Garciyunnanones A-R: Caged polycyclic polyprenylated acylphloroglucinols decorated with a lavandulyl substituent from Garcinia yunnanensis.

Garciyunnanones A-R (1-18), eighteen undescribed caged polycyclic polyprenylated acylphloroglucinols, two undescribed biogenetic congeners (19-20), and nineteen known analogues (21-39), were isolated from the stem barks of Garcinia yunnanensis Hu. All of these isolates are decorated with a C-5 lavandulyl substituent. Their structures and absolute configurations were confirmed by HRESIMS, 1D & 2D NMR spectroscopic analysis, quantum chemical calculations of electronic circular dichroism data, and single-crystal X-ray diffraction analysis. The X-ray crystallographic data of ten isolated caged compounds ascertained the absolute configuration of C-23 in the lavandulyl as S. The cytotoxicity on three cancer cell lines and the anti-nonalcoholic steatohepatitis activity of the isolates were tested. In a free fatty acid-induced L02 cell model, compounds 33 and 39 decreased intracellular lipid accumulation significantly.

Antioxidant, Anti-Diabetic, and Anti-Inflammation Activity of Garcinia livingstonei Aqueous Leaf Extract: A Preliminary Study.

Diabetes mellitus (DM) is the second leading cause of mortality globally. The increased concern for DM is due to the underlying complications accompanying hyperglycaemia, associated with oxidative stress and consequent inflammation. The investigation of safe and effective treatments for DM is necessary. In the present study, the cytotoxicity, phytochemical analysis, antioxidant capacity, anti-inflammatory, and antidiabetic effects in an aqueous extract of Garcinia livingstonei leaves were assessed. All tested extract concentrations showed no toxicity against C3A hepatocytes. Several phenolic compounds were identified using ultra-high performance liquid chromatography mass spectrometry (UHPLC-MS). The total polyphenol content was 100.9741 mg GAE/g, 16.7712 mg CE/g flavanols, and 2.3548 mg QE/g flavonols. The antioxidant capacity values were 253.4268 mg AAE/g, 192.232 mg TE/g, and 167.8724 mg TE/g for ferric reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC), and 2,2-diphenyl-1-pycrylhydrazyl (DPPH), respectively. The plant extract significantly (p < 0.05) demonstrated anti-inflammatory and hypoglycaemic effects in a dose-dependent manner, with the α-glucosidase inhibition of the extract being higher (p < 0.05) than in the standard conventional drug (acarbose). The findings of this study revealed the potential of the constituents of G. livingstonei aqueous leaf extract in DM treatment. Further studies on the preparation and mechanisms of action of the plant in DM treatment are recommended.

α-Glucosidase Inhibitory Components from Garcinia pedunculata Fruits.

From Garcinia pedunculata Roxb. fruits, two undescribed aromatic compounds including a benzofuran and a depsidone derivative, and a new natural product, together with four known compounds were isolated. Through the analysis of spectroscopic data, high resolution mass spectrum and calculated nuclear magnetic resonance, their structures were determined. The α-glucosidase inhibitory activity of the isolates was evaluated. And compound 3 exhibited a moderate inhibitory effect on α-glucosidase. The molecular docking of compound 3 was performed to elucidate the interaction with α-glucosidase.

Discovery of Gambogic acid as an antibacterial adjuvant against vancomycin-resistant enterococci in vitro and in vivo.

BACKGROUND: The emergence and spread of vancomycin-resistant enterococci (VRE) have posed a significant challenge to clinical treatment, underscoring the need to develop novel strategies. As therapeutic options for VRE are limited, discovering vancomycin enhancer is a feasible way of combating VRE. Gambogic acid (GA) is a natural product derived from the resin of Garcinia hanburyi Hook.f. (Clusiaceae), which possesses antibacterial activity. PURPOSE: This study aimed to investigate the potential of GA as an adjuvant to restore the susceptibility of VRE to vancomycin. METHODS: In vitro antibacterial and synergistic activities were evaluated against vancomycin-susceptible and resistant strains by the broth microdilution method for the Minimal Inhibitory Concentrations (MICs) determination, and checkerboard assay and time-kill curve analysis for synergy evaluation. In vivo study was conducted on a mouse multi-organ infection model. The underlying antibacterial mechanism of GA was also explored. RESULTS: GA showed a potent in vitro activity against all tested strains, with MICs ranging from 2 to 4 µg/ml. The combination of GA and vancomycin exhibited a synergistic effect against 18 out of 23 tested VRE strains, with a median fractional inhibitory concentration index (FICI) of 0.254, and demonstrated a synergistic effect in the time-kill assay. The combination therapy exhibited a significant reduction in tissue bacterial load compared with either compound used alone. GA strongly binds to the ParE subunit of topoisomerase IV, a bacterial type II DNA topoisomerase, and suppresses its activity. CONCLUSIONS: The study suggests that GA has a significant antibacterial activity against enterococci, and sub-MIC concentrations of GA can restore the activity of vancomycin against VRE in vitro and in vivo. These findings indicate that GA has the potential to be a new antibacterial adjuvant to vancomycin in the treatment of infections caused by VRE.

Caged Xanthones and Biphenyls Isolated from the Tropical Plant Garcinia lateriflora.

Four cytotoxic heptacyclic caged-xanthones [gambogefic acids B-E (1-4)], a cytotoxic hexacyclic caged-xanthone [garcilatelic acid (5)], and four biphenyl derivatives [garcilatelibiphenyls A-D (6-9)] were newly isolated in a phytochemical study of a 50% MeOH/CH2Cl2 extract of Garcinia lateriflora (Clusiaceae). The isolated compounds were evaluated for antiproliferative activity against five human tumor cell lines including a vincristine-resistant line. The new caged-xanthones displayed potent activity with IC50 values from 0.5 to 6.7 µM against all tested tumor cell lines.

Garcinia macrophylla: a Promising Underutilized Source of Bioactive Compounds in the Amazonia - A Review.

Native species from the Amazonia are still unknown or underutilized and few information about their chemical and biological properties are available in the literature. Among the underutilized plant species in the Amazonia, Garcinia macrophylla can be seen as a promising source of bioactive compounds with relevant biological properties. The stem bark and leaves were the main investigated plant parts, mainly concerning the antioxidant, antibacterial, cytotoxicity and antidiabetic properties. However, the bioactive compounds and biological properties of the edible fruits were not yet reported. Systematic investigations covering the Amazonia biome, concerning plants and vegetables as strategic resources are of paramount importance for the sustainable development of the forest. Therefore, this review gathered the available information in the literature concerning general aspects, chemical profile and biological properties of G. macrophylla, for the first time, which highlighted that systematic and robust in vitro and in vivo research, are still needed to elucidate the phytochemical profiles and associated relevant biological properties.

Antiproliferative polycyclic polyprenylated acylphloroglucinols from Garcinia paucinervis.

Bioassay-guided isolation of the stems of Garcinia paucinervis led to one new adamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), (-)-garpauvinin A (1), and four known analogues (2-5). The structure and absolute configuration of 1 was established via spectroscopic techniques and ECD method. All the isolates displayed moderate antiproliferative activity against HL-60, PC-3 and Caco-2 human cancer cell lines with IC50 values ranging from 0.81 to 19.92 µM, and exhibited low toxicity on WPMY-1 normal human cells, showing selectivity between normal and malignant prostate cells. The biosynthetic pathways of the isolated PPAPs were proposed.

Thermal performance study of a PV-driven innovative solar dryer with and without sensible heat storage for drying of Garcinia Pedunculata.

Uneven drying is the key drawback of a conventional multi-tray dryer. Therefore, an improved active solar dryer with and without integrated sensible heat storage (SHS) was proposed. A unique feature of this dryer is its movable walls from the sides of the dryer to transform it to an indirect or mixed-mode as and when necessary. Garcinia Pedunculata (GP) is a local seasonal medicinal fruit in Northeast India. Drying kinetics of GP, the dryer performance and economic analysis of dryer were evaluated in the indirect solar dryer without SHS (Exp. I), mixed-mode solar dryer without SHS (Exp. II), indirect solar dryer with SHS (Exp. III), mixed-mode solar dryer with SHS (Exp. IV), and open sun drying (OSD). The dryer's average efficiencies were 18.12%, 22.37%, 21.74%, and 24.46% for Exp. I, Exp. II, Exp. III, and Exp. IV, respectively. The moisture content of GP was reduced to 12.09% in wet basis (w.b.) from 87.99% (w.b.). The overall drying time for Exp. I, Exp. II, OSD, Exp. III and Exp. IV were 31, 26, 53, 28, and 10 h, respectively. From the eleven drying models, the Two-Term model was the best-fitted model for Exp. I, Exp. II, OSD and Exp. III, and Midilli and Kucuk model was for Exp. IV. The final product's fragrance and colour are better for Exp. IV. Developing this dryer for Exp. I, Exp. II, Exp. III and Exp. IV, the price required was around 25,000, 27,000, 26,000, and 28,000 INR (1 US$ = 74.57 INR), respectively, while the economic payback periods are 1.6 years, 0.9 year, 1.4 years, and 0.59 year, respectively.

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.

Synergistic combination of isogarcinol isolated from edible fruits of Garcinia multiflora and dexamethasone to overcome leukemia glucocorticoid resistance.

Isogarcinol (ISO), a cytotoxic polycyclic polyprenylated acylphloroglucinol isolated from the edible fruits of Garcinia multiflora. However, synergistic combination of ISO and dexamethasone (DEX) to overcome leukemia glucocorticoid resistance has never been investigated. Therefore, in this study, the effects of ISO in combination with DEX was conducted on leukemia in vivo and glucocorticoid resistance in vitro. As a result, the combination of the two compounds could efficiently inhibit leukemia progression in mice and reverse DEX resistance in acute lymphoblastic leukemia (ALL) Jurkat cells. Significantly, our findings indicated that c-Myc may be a potential target of ISO, as it is involved in cell cycle arrest and apoptosis by the combination of ISO and DEX in Jurkat cells. Furthermore, western blot analysis revealed that ISO and DEX inhibits the PI3K/Akt/mTOR signaling pathway and promotes the nuclear translocation of glucocorticoid receptor (GR), which activates target genes NR3C1 and TSC22D3, leading to apoptosis in Jurkat cells. Hence, our results suggest that ISO, as a safe and effective food-derived agent, can enhance the anti-leukemia effects of DEX.

Cytotoxic xanthones from Garcinia pedunculata fruits.

Eight previously undescribed and seven known xanthones were isolated from the fruits of Garcinia pedunculata Roxb. The structures were identified by a variety of spectroscopic methods as well as by comparison with the literature. The isolates showed appreciable cytotoxicity against three human tumor cell lines (HepG2, A549, and MCF-7). Pedunculaxanthone G exhibited inhibitory activities with IC50 values of 12.41, 16.51, and 15.45 µM against the cancer cell lines and induced cell apoptosis in HepG2 cells.

Cytotoxic depsidones and xanthones from Garcinia esculenta Y. H. Li.

Six new compounds, including two depsidones garciculendepsidones A and B (1 and 2), one prenylated xanthone garciculenxanthone (3) and three dimeric xanthones bigarciculenxanthones A-C (4-6), were isolated from the twigs and leaves of Garcinia esculenta Y. H. Li. Their structures were elucidated based on comprehensive analyses of spectral data, including HRESIMS, 1D and 2D NMR, and ECD calculation. All the isolates were tested for their cytotoxicity against five human cancer cell lines (myeloid leukemia HL-60, lung cancer A-549 cells, hepatocellular carcinoma SMMC-7721, breast cancer MDA-MB-231 and colon cancer SW480), among them, compounds 3-5 displayed cytotoxic potential, especially garciculenxanthone (3) had the lowest IC50 value of 8.2 µm for lung cancer A-549 cells.

Caged Polyprenylated Xanthones in Garcinia hanburyi and the Biological Activities of Them.

The previous phytochemical analyses of Garcinia hanburyi revealed that the main structural characteristic associated with its biological activity is the caged polyprenylated xanthones with a unique 4-oxatricyclo [4.3.1.03,7] dec-2-one scaffold, which contains a highly substituted tetrahydrofuran ring with three quaternary carbons. Based on the progress in research of the chemical constituents, pharmacological effects and modification methods of the caged polyprenylated xanthones, this paper presents a preliminary predictive analysis of their drug-like properties based on the absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties. It was found out that these compounds have very similar pharmacokinetic properties because they possess the same caged xanthone structure, the 9,10-double bond in a,b-unsaturated ketones are critical for the antitumor activity. The author believes that there is an urgent need to seek new breakthroughs in the study of these caged polyprenylated xanthones. Thus, the research on the route of administration, therapeutic effect, structural modification and development of such active ingredients is of great interest. It is hoped that this paper will provide ideas for researchers to develop and utilize the active ingredients derived from natural products.

Indole Diterpene Derivatives from the Aspergillus flavus GZWMJZ-288, an Endophytic Fungus from Garcinia multiflora.

A new indole diterpene, 26-dihydroxyaflavininyl acetate (1), along with five known analogs (2-6) were isolated from the liquid fermentation of Aspergillus flavus GZWMJZ-288, an endophyte from Garcinia multiflora. The structures of these compounds were identified through NMR, MS, chemical reaction, and X-ray diffraction experiments. Enzyme inhibition activity screening found that compounds 1, 4, and 6 have a good binding affinity with NPC1L1, among which compound 6 exhibited a stronger binding ability than ezetimibe at a concentration of 10 µM. Moreover, compound 5 showed inhibitory activity against α-glucosidase with an IC50 value of 29.22 ± 0.83 µM, which is 13 times stronger than that of acarbose. The results suggest that these aflavinine analogs may serve as lead compounds for the development of drugs targeting NPC1L1 and α-glucosidase. The binding modes of the bioactive compounds with NPC1L1 and α-glucosidase were also performed through in silico docking studies.

A taxonomic revision of Garcinia section Xanthochymus (Clusiaceae) in Thailand.

Garcinia section Xanthochymus (Clusiaceae) is revised for Thailand with four native species, i.e., G. dulcis, G. nervosa, G. prainiana, and G. xanthochymus. All species are described with updated morphological descriptions, illustrations, and an identification key, together with notes on distributions, distribution maps, habitats and ecology, phenology, conservation assessments, etymology, vernacular names, uses, and specimens examined. Four taxa, G. andamanica, G. andamanica var. pubescens, G. cambodgiensis and G. vilersiana, are synonymized under G. dulcis, and two taxa, G. nervosa var. pubescens and G. spectabilis, are newly synonymized under G. nervosa. Nine names are lectotypified: G. dulcis and its associated synonyms (G. cambodgiensis and G. vilersiana), G. nervosa and its associated synonyms (G. andersonii, G. nervosa var. pubescens, and G. spectabilis), G. prainiana, and G. xanthochymus. All species have a conservation assessment of Least Concern (LC). The fruits of all species are edible and have a sour or sweet-sour taste.

[A new xanthone from hulls of Garcinia mangostana and its cytotoxic activity].

Eight compounds were isolated from ethyl acetate fraction of 80% ethanol extract of the hulls of Garcinia mangostana by silica gel, Sephadex LH-20 column chromatography, as well as prep-HPLC methods. By HR-ESI-MS, MS, 1D and 2D NMR spectral analyses, the structures of the eight compounds were identified as 16-en mangostenone E(1), α-mangostin(2), 1,7-dihydroxy-2-(3-methy-lbut-2-enyl)-3-methoxyxanthone(3), cratoxyxanthone(4), 2,6-dimethoxy-para-benzoquinone(5), methyl orselinate(6), ficusol(7), and 4-(4-carboxy-2-methoxyphenoxy)-3,5-dimethoxybenzoic acid(8). Compound 1 was a new xanthone, and compound 4 was a xanthone dimer, compound 5 was a naphthoquinone. All compounds were isolated from this plant for the first time except compounds 2 and 3. Cytotoxic bioassay suggested that compounds 1, 2 and 4 possessed moderate cytotoxicity, suppressing HeLa cell line with IC_(50) va-lues of 24.3, 35.5 and 17.1 µmol·L~(-1), respectively. Compound 4 also could suppress K562 cells with an IC_(50) value of 39.8 µmol·L~(-1).