Irpexols A-C, xanthone derivatives from the endophyte fungus Irpex laceratus A878.

Three new xanthone derivatives irpexols A-C (1-3) and five known xanthones including three dimeric ones were successfully isolated from Irpex laceratus A878, an endophytic fungus of the family Irpicaceae from the medicinal plant Pogostemon cablin (Blanco) Bentham (Lamiaceae). The structures of these compounds were elucidated by extensive spectroscopic analyses including ultraviolet-visible spectroscopy (UV), infrared spectroscopy (IR), mass spectrometry (MS), and nuclear magnetic resonance (NMR). All of the three new compounds (1-3) share a de-aromatic and highly­oxygenated xanthone skeleton. In addition, the cytotoxic activity of compounds 1-8 were evaluated against SF-268, MCF-7, HepG2, and A549 tumor cell lines. The results revealed that compound 6 showed moderate cytotoxic activity with the IC50 values ranging from 24.83 to 45.46 µM, while the IC50 values of the positive control adriamycin was ranging from 1.11 to 1.44 µM.

Xanthones and benzophenones isolated from the endophytic fungus Penicillium sp. ct-28 of Corydlis tomentella and their cytotoxic activity.

One new xanthone, griseophenexanthone A (1), one new benzophenone, digriseophene A (2), and 14 previously reported compounds were isolated from the culture of Penicillium sp. ct-28, an endophytic fungus of Corydlis tomentella. The structures of the isolated compounds were identified by an extensive analysis of HRESIMS, 1D and 2D NMR. MTT assay showed that six xanthones (1 and 3-7) significantly inhibited cell proliferation in four cancer cell lines, with IC50 values ranging from 18.12 ± 2.42 to 85.55 ± 7.66 µM. Our results showed that slight structural changes led to obvious activity differences among these compounds. We also investigated the effects of the six xanthones on cell cycle and apoptosis in human hepatoma HepG2 cells. Compound 7 caused cell cycle arrest at G1 phase, compounds 5 and 6 caused cell cycle arrest at S phase, whereas compounds 1, 3 and 4 had no effects on cell cycle distribution. All six xanthones induced apoptosis in dose-dependent manners in HepG2 cells accompanied by degradation of PARP and activation of caspase 3. The structure-activity relationship analysis revealed that the effects of these xanthones on cell cycle and apoptosis in HepG2 cells were closely related to the substituent groups on their skeleton. Our studies provide novel insights for the structural optimization of xanthones in the development of new anticancer drugs.

Cytotoxic new caged-polyprenylated xanthonoids from Garcinia oligantha.

Caged-polyprenylated xanthonoids represent a rare class of natural products. This type of compounds is mainly isolated from Genus Garcinia. Phytochemical studies on the leaves and twigs of Garcinia oligantha led to the isolation of four new caged-polyprenylated xanthonoids, oliganthone CF (1-4), and two new simple xanthones (5-6), oliganthaxanthone D and oliganthaxanthone E. Eight known other polyprenylated xanthones (7-14) including five caged-polyprenylated xanthonoids (7-11) were also isolated. Their structures were elucidated based on the analyses of extensive spectroscopic data. All the isolated compounds except for 5, 6 and 14 showed cell viability reducing effect against human lung cancer A549 cells. Compounds 1-3 were proved to be potential apoptosis inducing agents.

Mangiferin and Hesperidin Transdermal Distribution and Permeability through the Skin from Solutions and Honeybush Extracts (Cyclopia sp.)-A Comparison Ex Vivo Study.

Polyphenolic compounds-mangiferin and hesperidin-are, among others, the most important secondary metabolites of African shrub Cyclopia sp. (honeybush). The aim of this study was to compare the percutaneous absorption of mangiferin and hesperidin from solutions (water, ethanol 50%, (v/v)) and extracts obtained from green and fermented honeybush (water, ethanol 50%, (v/v)). Research was performed with the Bronaugh cells, on human dorsal skin. The mangiferin and hesperidin distributions in skin layers (stratum corneum, epidermis, and dermis) and in acceptor fluid (in every 2, 4, 6, and 24 h) were evaluated by HPLC-Photodiode Array Coulometric and Coulometric Electrochemical Array Detection. The transdermal distribution of hesperidin was also demonstrated by fluorescence microscopy. Results indicated that mangiferin and hesperidin were able to cross the stratum corneum and penetrate into the epidermis and dermis. An advantage of hesperidin penetration into the skin from the water over ethanol solution was observed (451.02 ± 14.50 vs. 357.39 ± 4.51 ng/cm2), as well as in the mangiferin study (127.56 ± 9.49 vs. 97.23 ± 2.92 ng/cm2). Furthermore, mangiferin penetration was more evident from nonfermented honeybush ethanol extract (189.85 ± 4.11 ng/cm2) than from solutions. The permeation of mangiferin and hesperidin through the skin to the acceptor fluid was observed regardless of whether the solution or the honeybush extract was applied. The highest ability to permeate the skin was demonstrated for the water solution of hesperidin (250.92 ± 16.01 ng/cm2), while the hesperidin occurring in the extracts permeated in a very low capacity. Mangiferin from nonfermented honeybush ethanol extract had the highest ability to permeate to the acceptor fluid within 24 h (152.36 ± 8.57 ng/cm2).

Cudraxanthone L inhibits gastric cancer by regulating the MAPK signalling and promoting FAS-mediated pathway.

Gastric cancer (GC) is one of the most common malignancies and has the second highest lethal rate in the world; thus, finding new medicines with high potency and low toxicity is urgent. Cudrania tricuspidata (Carr.) Bur. ex Lavallee (Moraceae) is a traditional medicinal herb that is considered to have antitumour efficacy. We extracted and isolated cudraxanthone L (CXL) from Cudrania tricuspidata and evaluated its anti-cancer efficacy. CXL treatment inhibited angiogenesis of chorioallantoic membrane (CAM) and repressed the cell viability of various human cancer cells, indicating it presented the antitumour potential. Among them, CXL presented the best inhibitory effects on MGC803 cells. In addition, the invasion, migration and clonogenicity were significantly repressed, S phase of the cell cycle was arrested, and apoptosis was induced when MGC803 cells were treated with CXL. The results of RNA sequencing, qRT-PCR and western blotting verified that CXL regulated the MAPK signalling pathway and induced apoptosis by FAS-mediated pathway. The in vivo data revealed that CXL arrested tumour growth without toxic effects and upregulated the protein levels in FAS-mediated pathway in MGC803 gastric cancer-bearing mice. In summary, we demonstrate CXL presents impactful anti-GC efficacy by regulating the MAPK signalling pathway and promoting the FAS-mediated pathway.

Screening out the anti-insomnia components from Prunella vulgaris L. based on plasma pharmacochemistry combined with pharmacodynamic experiments and UPLC-MS/MS analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Prunella vulgaris L. (P. vulgaris) is a medicinal plant belonging to the Labiatae family, and its dried spikes is called as Xiakucao in China, which is a common traditional Chinese medicine with the activities of clearing the liver and expelling fire, improving eyesight, dispersing nodules and detumescence. Modern pharmacological studies have proved that P. vulgaris has various pharmacological activities such as immunomodulatory, antiviral, antibacterial and anti-insomnia activities. AIMS OF THIS REVIEW: P. vulgaris have been reported to have anti-insomnia effects. Nevertheless, the pharmacodynamic substance basis of this anti-insomnia effect is still unclear. The aim of this study was to identify the active components responsible for evoking the anti-insomnia effect of P. vulgaris and to evaluate its anti-insomnia effect. MATERIALS AND METHODS: In this study, we proposed a method combined with pharmacodynamic experiments, extraction and enrichment of chemical components, and the plasma pharmacochemistry to screen out the anti-insomnia components of P. vulgaris. Firstly, the active eluted fraction of the ethanol extract was screened out based on pharmacodynamic tracing method, and then the chemical composition was analyzed systematically by UPLC-MS/MS. Thirdly, pharmacodynamic tracing method and silica gel column chromatography were employed to screen out the active fraction of 70% ethanol eluted fraction, and its bioactive components in vitro and in vivo were identified by UPLC-MS/MS. Finally, screening out the anti-insomnia components of P. vulgaris by comparing the difference between in vivo and in vitro components, and three potentially bioactive ingredients were validated experimentally. RESULTS: It was confirmed that the fraction eluted with 70% ethanol from macroporous adsorption resin column was responsible for the anti-insomnia efficacy, and 55 compounds were identified or preliminarily identified. Then totally 9 compounds in vitro and 12 compounds in vivo from the active fraction of 70% ethanol eluted fraction were tentatively identified. Among them, mangiferin, rosmarinic acid and salviaflaside were the prototype components of P. vulgaris, which indicated that the three compounds might play the key role in the anti-insomnia activities. In vivo, compared to blank control group, the three compounds significantly shortened the sleeping latency and prolonged the sleeping time produced by pentobarbital sodium. CONCLUSIONS: This study clarified that mangiferin, rosmarinic acid and salviaflaside were considered as the anti-insomnia components of P. vulgaris. This is the first study on screening out the active ingredients responsible for evoking the anti-insomnia effect of P. vulgaris. The three compounds of P. vulgaris may help develop one or more drugs to prevent or treat insomnia. Further investigations are recommended to define the mechanism of the anti-insomnia activity of P. vulgaris.

Acmoxanthones A-E, New Lavandulated Xanthones from Hypericum acmosepalum N. Robson.

Acmoxanthones A-E (1-5), five new lavandulylated xanthones, were isolated from the aerial parts of Hypericum acmosepalum, together with four known xanthones. Their structures with absolute configurations were elucidated on the basis of analysis of MS, NMR and chiroptical properties. A bioassay against high glucose-induced damage on human umbilical vein endothelial cells (HUVECs) showed ananixanthone (6) and osajaxanthone (7) had potential antioxidative damage activity with EC50 values of 10.5 µg/mL and 7.6 µg/mL, respectively, while 3-hydroxy-2,4-dimethoxyxanthone (8) exhibited cytotoxic effect on the damaged cells with IC50 values of 7.1 µg/mL.

Garcinoxanthones SV, new xanthone derivatives from the pericarps of Garcinia mangostana together with their cytotoxic and antioxidant activities.

Xanthones (9H-xanthene-9-ones) are considered to be very promising compounds due to a variety of interesting biological and pharmacological activities. In this study, column chromatography of the methanol extract of the Garcinia mangostana L. pericarps resulted in the isolation of four new xanthones (garcinoxanthones SV, 1-4) and five known analogs including garcinone E (5), 11-hydroxy-1-isomangostin (6) mangostenone E (7), 1,3,6,7-tetrahydroxyxanthone (8), and α-mangostin (9). The structures of the new compounds were elucidated by NMR, HRESIMS, and ECD spectra. Compound 8 (1,3,6,7-tetrahydroxyxanthone) was found from the G. mangostana pericarps for the first time. All the isolated compounds (1-8) were evaluated for their 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity and cytotoxicity in vitro against three human cancer cell lines including SK-LU-1, MCF7, and HT-29 cell lines. Compounds 3, 5, and 8 exhibited significant DPPH scavenging capacity with IC50 values of 68.55, 63.05, and 28.45 µM, respectively, in comparison with ascorbic acid (IC50 = 48.03 µM). Compounds 5 and 8 showed moderate cytotoxic effects against the three human cancer cell lines with IC50 value ranges of 19.86-27.38 µM.

Isolation and characterization of bioactive xanthones from Hippocratea africana (Willd.)Loes.ex Engl. (Celastraceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Hippocratea africana root is used in African folk medicine for the treatment of several ailments, including pain and inflammation. AIM OF THE STUDY: To isolate anti-inflammatory and analgesic compounds from the roots of H. africana, with accompanying antioxidant potentials. MATERIALS AND METHODS: Dichloromethane, ethyl acetate, and aqueous fractions of H. africana roots, and isolated compounds from the bioactive ethyl acetate fraction were evaluated for anti-inflammatory and analgesic activities using the xylene induced oedema in mice and thermal induced pain models, respectively. The antioxidant potentials of isolated compounds were tested in 2,2-diphenyl-1-picryhydrazyl radical and ferric reducing antioxidant power assays. Structures were elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR experiments, ionization mass spectrometry, and comparison with literature data. RESULTS: Isoathyriol (1,3,7-trihydroxy-6-methoxyxanthone) and norathyriol (1,3,6,7-tetrahydroxyxanthone) were isolated from the potent anti-inflammatory and analgesic ethyl acetate fraction of H. africana roots. Isoathyriol and norathyriol demonstrated good anti-inflammatory, analgesic, and antioxidant properties compared with the standards used in each assay. CONCLUSIONS: This study substantiates the use of H. africana root extract in the alleviation of inflammation and pain, and reports the characterization of secondary metabolites in H. africana and for the first time the presence of xanthones in Hippocratea genus.

New dihydrochromene and xanthone derivatives from Lisotrigona furva propolis.

A new dihydrochromene derivative, named lisofurvin (1) and a xanthone, named dihydrobrasixanthone B (2) together with twenty one known compounds (3-23) were isolated from propolis of the stingless bee Lisotrigona furva. Their chemical structures were determined by means of spectroscopic methods including 1D and 2D NMR, and MS. The chemical constituents are predominantly geranyl(oxy) xanthones and Cratoxylum cochinchinense was suggested as a resin source, besides two other plants Mangifera indica and dammar trees (Dipterocarpaceae). Compound 1 showed significant cytotoxic activity against KB, HepG-2, and Lu-1 cancer cell lines with IC50 values range from 12.63 to 15.17 µg/mL. Several isolated compounds were active against one to four tested cancer cell lines. In addition, among the isolated compounds, α-mangostin (15) displayed the strongest antimicrobial activity against three Gram (+) strains, P. aeruginosa, and C. albicans with MIC values ranging between 1 and 2 µg/mL. Compound 22 showed good activity against three Gram (+) strains and C. albicans.

Ethanolic Garcinia mangostana extract and α-mangostin improve dextran sulfate sodium-induced ulcerative colitis via the suppression of inflammatory and oxidative responses in ICR mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is an inflammatory disorder of the colon. Garcinia mangostana Linn. (GM) has been traditionally used for its anti-inflammatory and antioxidant activities. AIM OF THE STUDY: The effects of GM and its bioactive constituent α-mangostin on dextran sulfate sodium (DSS)-induced UC in mice were investigated. MATERIALS AND METHODS: Adult ICR mice (n = 63) were pretreated with ethanolic GM extract at 40, 200, and 1000 mg/kg/day (GM40, GM200, and GM1000), α-mangostin at 30 mg/kg/day, or sulfasalazine at 100 mg/kg/day (SA) for 7 consecutive days. On days 4-7, UC was induced in the mice by the oral administration of DSS (40 kDa, 6 g/kg/day), while control mice received distilled water. The UC disease activity index (DAI) and histological changes were recorded. The activities of myeloperoxidase, catalase, and superoxide dismutase, and the levels of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) were determined. The mRNA expression of inflammatory related genes including proinflammatory cytokine Tnf-α, Toll-like receptor (Tlr-2), adhesion molecules (Icam-1 and Vcam-1), and monocyte chemoattractant protein (Mcp-1) were evaluated. RESULTS: Treatment with GM or α-mangostin decreased the UC DAI and protected against colon shortening and spleen and kidney enlargement. GM and α-mangostin prevented histological damage, reduced mast cell infiltration in the colon, and decreased myeloperoxidase activity. GM and α-mangostin increased catalase and superoxide dismutase activity and decreased ROS, NO, and MDA production. GM downregulated mRNA expression of Tnf-α, Tlr-2, Icam-1, Vcam-1, and Mcp-1. CONCLUSIONS: GM and α-mangostin attenuated the severity of DSS-induced UC via anti-inflammatory and antioxidant effects. Therefore, GM is a promising candidate for development into a novel therapeutic agent for UC.

Xanthones from Securidaca inappendiculata antagonized the antirheumatic effects of methotrexate in vivo by promoting its secretion into urine.

BACKGROUND: This study was designed to characterize the interaction between Securidaca inappendiculata Hassk. derived xanthones and methotrexate (MTX). METHODS: Collagen-induced arthritis (CIA) was induced in rats, which were treated with MTX, a xanthone-rich fraction (XRF), or MTX+XRF by gavage for 30 days. Clinical efficacy was assessed based on arthritis scores, serological analysis, and histological examination. Protein expression was investigated by either immunohistochemical or immunoblotting methods. MTX concentrations were determined by HPLC or LC-MS methods. Obtained results were further validated by in vitro assays using 1,7-dihydroxy-3,4-dimethoxyxanthone and HEK 293 T cells. RESULTS: XRF antagonized the antirheumatic effects of MTX in vivo, suggested by higher levels of proinflammatory cytokines, and severer swelling and deformation of joints in CIA rats in the MTX+XRF group compared with MTX monotherapy. XRF reduced MTX concentration in plasma and promoted its excretion into urine. As a result, XRF attenuated MTX-induced edema of the proximal tubule. Furthermore, XRF restored the decreased expression of organic anion transporter three (OAT3), which accounts for MTX secretion in the kidney. Consistently, 1,7-dihydroxy-3,4-dimethoxyxanthone promoted the cellular intake of MTX by increasing OTA3 expression. CONCLUSION: It is suggested that the combined use of S. inappendulata with MTX should be optimized to avoid the antagonistic effects and improve the safety of the MTX regimen.

Cytotoxic and Antiproliferative Effects of ß-Mangostin on Rat C6 Glioma Cells Depend on Oxidative Stress Induction via PI3K/AKT/mTOR Pathway Inhibition.

BACKGROUND: Glioma is the most common malignant tumor of the nervous system, which accounts for more than 45% of central nervous system tumors and seriously threatens our health. Because of high mortality rate, limitations, and many complications of traditional treatment methods, new treatment methods are urgently needed. ß-Mangostin is a natural compound derived from the fruit of Garcinia mangostana L. and it has anticancer activity in several types of cancer cells. However, the antitumor effect of ß-mangostin in glioma has not been clarified. Hence, this study aimed to investigate its therapeutic effects on gliomas. MATERIALS AND METHODS: To study the effect of ß-mangostin on glioma cells, cell viability assay, reactive oxygen species production, cell cycle, apoptosis, and mitochondrial membrane potential were evaluated in the C6 cell line in vitro. Immunofluorescence and Western blotting were used to analyze protein expression and phosphorylation to study its mechanism of action. A subcutaneous xenograft model was used to investigate the effect of ß-mangostin on tumorigenesis in vivo. RESULTS: We found that ß-mangostin can inhibit glioma cell growth and induce oxidative damage in vitro. In addition, it reduces the phosphorylated form levels of PI3K, AKT and mTOR. Furthermore, the phosphorylated form levels of PI3K, AKT and mTOR were increased after the PI3K inhibitor was added. In vivo experiments showed that ß-mangostin can inhibit tumor growth as shown by its reduced size and weight. CONCLUSION: This study suggests that ß-mangostin can inhibit cell proliferation and induce oxidative damage in cells. It is the first study to demonstrate that ß-mangostin induces oxidative damage in glioma cells by inhibiting the PI3K/AKT/mTOR signaling pathway.

Tetrahydroxanthone-chromanone heterodimers from lichen Usnea aciculifera and their cytotoxic activity against human cancer cell lines.

Four new tetrahydroxanthone-chromanone heterodimers, usneaxanthones E-H (1-4) together with eleven known compounds (5-15) were isolated from lichen Usnea aciculifera Vain (Parmeliaceae). Their structures and absolute configurations, particularly the central and axial chiralities, were unambiguously demonstrated by a combination of spectroscopic data (1D, 2D NMR, HRESIMS), electronic circular dichroism (ECD) experiments, and single-crystal X-ray crystallographic analyses. The cytotoxicity of new compounds was evaluated on four human cancer cell lines including HCT116 colorectal cancer, MCF-7 breast cancer, A549 lung cancer, and OVCAR-3 ovarian cancer. Compounds 1-4 exhibited good cytotoxicity against all tested cancer cell lines, except ovarian cancer, with the best IC50 value of 3.37 µM. All compounds showed potent cytotoxicity against HCT116 colon cancer with IC50 value from 3.37 to 4.53 µM.

Xanthone-enriched fraction of Garcinia mangostana and α-mangostin improve the spatial learning and memory of chronic cerebral hypoperfusion rats.

OBJECTIVES: Xanthones isolated from the pericarp of Garcinia mangostana has been reported to exhibit neuroprotective effect. METHODS: In this study, the effect of xanthone-enriched fraction of Garcinia mangostana (XEFGM) and α-mangostin (α-MG) were investigated on cognitive functions of the chronic cerebral hypoperfusion (CCH) rats. KEY FINDINGS: HPLC analysis revealed that XEFGM contained 55.84% of α-MG. Acute oral administration of XEFGM (25, 50 and 100 mg/kg) and α-MG (25 and 50 mg/kg) before locomotor activity and Morris water maze (MWM) tests showed no significant difference between the groups for locomotor activity. CONCLUSIONS: However, α-MG (50 mg/kg) and XEFGM (100 mg/kg) reversed the cognitive impairment induced by CCH in MWM test. α-MG (50 mg/kg) was further tested upon sub-acute 14-day treatment in CCH rats. Cognitive improvement was shown in MWM test but not in long-term potentiation (LTP). BDNF but not CaMKII was found to be down-regulated in CCH rats; however, both parameters were not affected by α-MG. In conclusion, α-MG ameliorated learning and memory deficits in both acute and sub-acute treatments in CCH rats by improving the spatial learning but not hippocampal LTP. Hence, α-MG may be a promising lead compound for CCH-associated neurodegenerative diseases, including vascular dementia and Alzheimer's disease.

LC-QTOF-MS analysis of xanthone content in different parts of Garcinia mangostana and its influence on cholinesterase inhibition.

Mangosteen is one of the best tasting tropical fruit widely cultivated in Southeast Asia. This study aimed to quantify xanthone content in different parts of Garcinia mangostana by LC-QTOF-MS and determine its influence on their cholinesterase inhibitory activities. The total xanthone content in G. mangostana was in the following order: pericarp > calyx > bark > stalk > stem > leaves > aril. The total xanthone content of pericarp was 100 times higher than the aril. Methanol extracts of the pericarp and calyx demonstrated the most potent inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 0.90 and 0.37 µg/mL, respectively. Statistical analysis showed a strong correlation between xanthone content and cholinesterase inhibition. Nonmetric multidimensional scaling analysis revealed α-mangostin and γ-mangostin of pericarp as the key metabolites contributing to cholinesterase inhibition. Due to the increasing demand of mangosteen products, repurposing of fruit waste (pericarp) has great potential for enhancement of the cognitive health of human beings.

Highly potent cholinesterase inhibition of geranylated xanthones from Garcinia fusca and molecular docking studies.

Three new oxygenated xanthones, fuscaxanthones L-N (1-3), and 14 known xanthones 4-17, together with the other known metabolites 18-20 were isolated from the stem barks of Garcinia fusca Pierre. Their chemical structures were determined based on NMR and MS spectroscopic data analysis, as well as single X-ray crystallography. The geranylated compounds, cowanin (13), cowagarcinone E (15), norcowanin (16) and cowanol (17) exhibited potent inhibitions against acetylcholinesterase (AChE) (IC50 0.33-1.09 µM) and butyrylcholinesterase (BChE) (IC50 0.048-1.84 µM), which were more active than the reference drug, galanthamine. Compound 15 was highly potent BChE inhibitor (IC50 0.048 µM) and was 76-fold more potent than the drug. Structure-activity relationship studies indicated that the C-2 prenyl and C-8 geranyl substituents in the tetraoxygenated scaffold are important for high activity. Molecular docking studies revealed that the leads 13 and 15-17 showed similar binding orientations on both enzymes and very well-fitted at the double binding active sites of PAS and CAS with strong hydrophobic interactions from both isoprenyl side chains.

Antiproliferative activity of caged xanthones from the leaves of Garcinia wightii T. Anderson.

Two new caged xanthones, wightiic acid (1) 16-O-methyl wightiic acid (2), along with eight known compounds, gaudichaudic acid E (3), isogaudichaudic acid E (4), ursolic acid (5) stigmasterol (6), lupeol (7), glutinol (8), lupenone (9) and stigmasteryl linoleate (10) were isolated from Garcinia wightii T. Anderson. The structures of the compounds were elucidated by spectroscopic means, including 1D and 2D NMR, HR-ESIMS, and the absolute configuration of the new compounds 1 and 2 were determined by analysis of ECD data. Anti-proliferation activities of the four caged xanthones (1-4) were evaluated by MTT assay on MCF-7 and SKBR-3 human breast cancer cells and A-375 human melanoma cells by MTT assay. All the tested compounds exhibited dose dependent antiproliferative activity. Wightiic acid (1) showed remarkable activity with IC50 value of 4.7 µM and 5.2 µM respectively in A-375 and MCF-7 cells. The compound isogaudichaudic acid E (4) induced potent antiproliferation against SKBR-3 cells with an IC50 value of 6.1 µM.

Bioactive fractions from Securidaca inappendiculata alleviated collagen-induced arthritis in rats by regulating metabolism-related signaling.

Securidaca inappendiculata is a xanthone rich medicinal plant that has been used in the treatment of inflammation and autoimmune diseases like rheumatoid arthritis (RA) for centuries; however, the material base and mechanism of action responsible for its anti-arthritis effect still remains elusive. The objective of this study is to evaluate the therapeutic effects of xanthone-enriched extract of the plant against collagen-induced arthritis (CIA) in rats and explore the underlying mechanisms. The xanthone-deprived fraction (XDF) and xanthone-rich fraction (XRF) were obtained by using a resin adsorption coupled with acid-base treatment method, and their chemical composition difference was characterized by UPLC-MS/MS analysis. Effects of the two on CIA were analyzed using radiographic, histological, and immunohistochemical analyses. The results indicated that XRF alleviated joint structures destructions with the higher efficacy than XDF, and decreased levels of TNF-α, IL-6, and anti-cyclic citrullinated peptide antibody in CIA rats significantly. Furthermore, XRF inhibited nicotinamide phosphoribosyl transferase (NAMPT) mediated fat biosynthesis and utilization indicated by clinical evidences and metabonomics analysis, which thereby disrupted energy-metabolism feedback. In addition, Toll-like Receptor 4 and High Mobility Group Protein 1 expressions were downregulated in XRF-treated CIA rats. Collective evidences suggest NAMPT could be an ideal target for RA treatments and reveal a novel antirheumatic mechanism of S. inappendiculata by regulating NAMPT controlled fat metabolism.

Antidiabetic xanthones with α-glucosidase inhibitory activities from an endophytic Penicillium canescens.

Worldwide, 463 million people are affected by diabetes of which the majority is diagnosed with Type 2 Diabetes (T2D). T2D can ultimately lead to retinopathy, nephropathy, nerve damage, and amputation of the lower extremities. α-Glucosidase, responsible for converting starch to monosaccharides, is a key therapeutic target for the management of T2D. However, due to substantial side effects of currently marketed drugs, there is an urgent need for the discovery of new α-glucosidase inhibitors. In our ongoing efforts to identify novel α-glucosidase inhibitors from Nature, we are investigating the potential of endophytic filamentous fungi as sustainable sources of hits and/or leads for future antihyperglycemic drugs. Here we report one previously unreported xanthone (5) and two known xanthones (7 and 11) as α-glucosidase inhibitors, isolated from an endophytic Penicillium canescens, recovered from fruits of Juniperus polycarpos. The three xanthones 5, 7, and 11 showed inhibitory activities against α-glucosidase with IC50 values of 38.80 ± 1.01 µM, 32.32 ± 1.01 µM, and 75.20 ± 1.02 µM, respectively. Further pharmacological characterization revealed a mixed-mode inhibition for 5, a competitive inhibition for 7, while 11 acted as a non-competitive inhibitor.