New Alpha-Amylase Inhibitory Metabolites from Pericarps of Garcinia mangostana.

Two new benzophenones: garcimangophenones A (6) and B (7) and five formerly reported metabolites were purified from the pericarps EtOAc fraction of Garcinia mangostana ((GM) Clusiaceae). Their structures were characterized by various spectral techniques and by comparing with the literature. The α-amylase inhibitory (AAI) potential of the isolated metabolites was assessed. Compounds 7 and 6 had significant AAI activity (IC50 9.3 and 12.2 µM, respectively) compared with acarbose (IC50 6.4 µM, reference α-amylase inhibitor). On the other hand, 5 had a moderate activity. Additionally, their activity towards the α-amylase was assessed utilizing docking studies and molecular dynamics (MD) simulations. The docking and predictive binding energy estimations were accomplished using reported crystal structure of the α-amylase (PDB ID: 5TD4). Compounds 7 and 6 possessed highly negative docking scores of -11.3 and -8.2 kcal/mol, when complexed with 5TD4, respectively while acarbose had a docking score of -16.1 kcal/mol, when complexed with 5TD4. By using molecular dynamics simulations, the compounds stability in the complexes with the α-amylase was analyzed, and it was found to be stable over the course of 50 ns. The results suggested that the benzophenone derivative 7 may be potential α-amylase inhibitors. However, further investigations to support these findings are required.

Fusaroxazin, a novel cytotoxic and antimicrobial xanthone derivative from Fusarium oxysporum.

Oxazines and their derivatives are an uncommon natural heterocyclic compounds, which contain oxygen and nitrogen atoms and possess various bioactivities. A novel 1,4-oxazine-xanthone derivative, fusarioxazin (4) and three known sterols (1-3) were separated from Fusarium oxysporum EtOAc extract associated with Vicia faba L. (broad bean, Fabaceae) roots. Their structural assignment was accomplished using various spectroscopic tools and comparing with literature data. The cytotoxic and antimicrobial potentials of the novel metabolite (4) were evaluated. It possessed a significant antibacterial activity towards S. aureus (IZD 14.8 mm and MIC 5.3 µg/mL) and B. cereus (IZD 18.9 mm and MIC 3.7 µg/mL), in comparison to ciprofloxacin (IZDs 16.9 and 20.5 mm; MICs 3.9 and 2.3 µg/mL, respectively). Furthermore, it displayed a promising cytotoxic effect toward HCT-116 (IC50 2.1 µM), MCF-7 (IC50 1.8 µM), and A549 (IC50 3.2 µM) comparable to doxorubicin (IC50s 0.68, 0.54, and 0.39 µM, respectively).

Anti-inflammatory ergosterol derivatives from the endophytic fungus Fusarium chlamydosporum.

Two new ergosterol derivatives namely, chlamydosterols A [(22E,24R)-ergosta-7,22-diene-3ß,5α,6ß-triol 6-decanoate] (1) and B [5α,6ß,25-trihydroxy-(22E,24R)-ergosta-7,22-dien-3-one] (5) and three known ergosterols: ergosta-7,22-dien-3ß-ol (2), ergosta-5,7,22-triene-3ß-ol (3), and ergosta-7,22-diene-3ß,5α,6ß-triol (4) were separated from the EtOAc extract of the endophytic fungus Fusarium chlamydosporum isolated from Anvillea garcinii (Asteraceae) leaves growing in Saudi Arabia. Their structural assignment was accomplished by various spectroscopic analyses, as well as comparing with the published data. The 5-lipoxygenase (5-LOX) inhibitory potential of the isolated metabolites was assessed. Compounds 1 and 3 displayed moderate 5-LOX inhibitory potential with IC50s 3.06 and 3.57 µM, respectively compared to indomethacin (IC50 1.13 µM).

Naturally Occurring Isocoumarins Derivatives from Endophytic Fungi: Sources, Isolation, Structural Characterization, Biosynthesis, and Biological Activities.

Recently, the metabolites separated from endophytes have attracted significant attention, as many of them have a unique structure and appealing pharmacological and biological potentials. Isocoumarins represent one of the most interesting classes of metabolites, which are coumarins isomers with a reversed lactone moiety. They are produced by plants, microbes, marine organisms, bacteria, insects, liverworts, and fungi and possessed a wide array of bioactivities. This review gives an overview of isocoumarins derivatives from endophytic fungi and their source, isolation, structural characterization, biosynthesis, and bioactivities, concentrating on the period from 2000 to 2019. Overall, 307 metabolites and more than 120 references are conferred. This is the first review on these multi-facetted metabolites from endophytic fungi.

α-Amylase inhibition of xanthones from Garcinia mangostana pericarps and their possible use for the treatment of diabetes with molecular docking studies.

Chromatographic separation of the methanol extract of Garcinia mangostana (mangosteen, Guttiferae) dried pericarps led to the isolation and structural characterization of a new xanthone, namely garcimangostin A (5), together with garcixanthone A (1), gartanin (2), normangostin (3), and garcinone C (4). Their structural characterization was achieved using various NMR spectroscopic tools as well as HRMS. Their α-amylase inhibitory (AAI) potential was assessed. It is noteworthy that 5 had the most potent inhibitory effect with % inhibition 94.1 compared to acarbose (96.7%). Moreover, the molecular modeling studies were estimated. The observed scoring results correlated to those results of the AAI assay. Interestingly, 5 was completely fitting with acarbose structure and a superimposition of acarbose complexed structure with 5 in the enzyme binding site was observed. The AAI activity of 5 could be attributed to the xanthone moiety insertion in the active site of the enzyme via H-bonds network and pi-pi interactions. PRACTICAL APPLICATIONS: Garcinia mangostana is a widely consumed fruit for its unique pleasant aroma and sweet taste. Also, it contains valuable nutritious compounds that are advantageous for human body. It is used as various traditional medicines for treating several ailments such as skin infection, hyperkeratosis, eczema, wounds, psoriasis, amebic dysentery, cholera, diarrhea, and suppuration. The findings of this work can demonstrate the significant AAI potential of G. mangostana xanthones. Therefore, mangosteen as a functional food could help in lowering the postprandial glucose absorption and identifying lead compounds from α-amylase inhibition for the treatment and/or prevention of diabetes and obesity.

Vitex agnus-castus safeguards the lung against lipopolysaccharide-induced toxicity in mice.

Vitex agnus-castus (VAC, Verbenaceae) is widely used in Chinese traditional medicine as an antiinflammatory agent. This study aimed to explore the efficacy of the VAC extract to protect against lipopolysaccharide (LPS)-induced acute lung injury. The results have shown that VAC had a potent protective activity against LPS-induced acute lung damage. It significantly decreased pulmonary edema as there was a significant decrease in lung wet/dry ratio and in protein content. VAC also decreased the lactate dehydrogenase's activity in the bronchoalveolar fluid. VAC ameliorated LPS-induced inflammatory cells infiltration into the lung tissue and reversed the histopathological lesions of the lung. Furthermore, VAC counteracted LPS-induced oxidative stress as it attenuated the lipid peroxidation marker, malondialdehyde, in the lung. VAC increased the antioxidant activity as evident by elevated superoxide dismutase activity and increased reduced glutathione content in the lung tissue. Collectively, VAC has a protective activity against LPS-induced acute lung damage through its antioxidant potential. PRACTICAL APPLICATIONS: Vitex agnus-castus has been used in various traditional medicines for treating various ailments as digestive complains, acne, rheumatic pains, menstrual irregularities, premenstrual syndrome, infertility, and hyperprolactinemia. Its leaves are used as a spice and the fruits are used as a substitute for pepper. VAC food supplements are used by women against psychic and somatic premenstrual symptoms. The findings of this study can demonstrate the potent protective activity of the VAC extract against LPS-induced acute lung damage due to its antioxidative effects. Therefore, VAC could be developed as a health functional food to improve acute lung damage and many diseases caused by oxidative damage.

Cucumol B, a new triterpene benzoate from Cucumis melo seeds with cytotoxic effect toward ovarian and human breast adenocarcinoma.

Phytochemical investigation of the methanolic extract of Cucumis melo L. (Cucurbitaceae) seeds furnished a new triterpene benzoate derivative: cucumol B (1) and four known flavonoids: quercetin-3-O-ß-D-glucopyranosyl-(1→6)-α-L-rhamnopyranoside (2), quercetin-3-O-ß-D-glucopyranoside (3), quercetin (4), and luteolin (5). Their structures were identified by UV, IR, 1D (13C and 1H), 2D (HSQC, 1H-1H COSY, HMBC, and NOESY) NMR, and HRESIMS spectral as well as comparing with literature data. Compound 1 has been assessed for the in vitro cytotoxic effect against SKOV-3, MCF-7, and HCT-116 cell lines. It had selective and potent effect toward SKOV-3 and MCF-7 cell lines with IC50s 2.05 and 0.41 µM, respectively, in comparison to doxorubicin (IC50s 0.32 and 0.05 µM). However, it showed moderate activity toward HCT-116 cell line with IC50 8.27 µM.

Garcixanthone A, a new cytotoxic xanthone from the pericarps of Garcinia mangostana.

A new prenylated xanthone, garcixanthone A (5), together with eight known compounds, mangostanaxanthones I (1) and II (2), garcinone E (3), ß-mangostin (4), 8-hydroxycudraxanthone G (6), garcinone C (7), cudraxanthone G (8), and (-)-epicatechin (9) were isolated from the EtOAc-soluble fraction of the air-dried pericarps of Garcinia mangostana (family Clusiaceae). Their structures were verified on the basis of spectroscopic data interpretation as well as comparison with the literature. The cytotoxic and antimicrobial activities of the new compound were assessed using sulforhodamine B (SRB) and agar disk diffusion assays, respectively. Compound 5 showed significant cytotoxic potential against epithelial lung carcinoma (A549) and breast carcinoma (MCF7) cell lines with IC50s 3.0 and 4.2 µM, respectively, compared to doxorubicin (0.74 and 0.41 µM, respectively).

Anti-inflammatory terpenoids from Cyperus rotundus rhizomes.

Phytochemical investigation of the methanolic extract of Cyperus rotundus L. (Cyperaceae) rhizomes afforded a new norterpenoid with an unprecedented carbon skeleton, namely cyperalin A (1) and sugetriol triacetate (2). Their structures were identified by using advanced spectroscopic technique such as UV, IR, 1D (1H and 13C), 2D (1H-1HCOSY, HSQC, HMBC, and NOESY) NMR, and HRESIMS as well as comparison with literature data. The isolated compounds were evaluated for their anti-inflammatory activity. Compound 1 displayed the highest inhibitory activity of PGE2, COX-2, and LOX-5 with IC50s 0.22, 1.03, and 1.37 µM, respectively compared to indomethacin (IC50s 0.15, 0.69, and 0.81 µM, respectively). Moreover, 2 demonstrated significant activity with IC50s 0.57 (PGE2), 1.74 (COX-2) and 2.03 (LOX-5) µM.

Protective effect of quercetin against gentamicin-induced nephrotoxicity in rats.

Gentamicin (GM) is an antibiotic widely used in treating severe gram-negative infections. However, its clinical use is limited by its nephrotoxicity. Several lines of evidence indicate that free radicals are important mediators of gentamicin nephrotoxicity. Therefore, the aim of this work was to investigate the possible protective effect of the flavonoid quercetin, an antioxidant, on gentamicin-induced nephrotoxicity. For this purpose, rats were divided into four groups. First group served as a control and injected with the normal saline, second group was injected with quercetin (50 mg/kg/d, per os) for 7 d, third group was injected with gentamicin (80 mg/kg/d, intraperitoneally) for 7 d and the fourth group of animals was injected with quercetin plus gentamicin simultaneously for 7 d. Total protein levels were estimated in 24-h urine samples to assess kidney dysfunction. The rats were sacrificed on the seventh day and kidneys were collected for histopathological studies. Blood urea nitrogen (BUN) and creatinine levels were measured in the blood. Moreover, glutathione (GSH), lipid peroxide (TBARS) levels, superoxide dismutase (SOD) and catalase (CAT) activities were determined in renal tissues. GM-treated rats showed early kidney dysfunction as urinary total protein, BUN and serum creatinine levels were significantly increased. The significant decrease in GSH levels, SOD, CAT activities and increase in TBARS levels, indicated that GM-induced nephrotoxicity was mediated through oxidative stress reactions. Histopathological examination of GM-treated rats revealed degenerative changes in glomeruli and tubules. On the other hand, simultaneous administration of quercetin plus gentamicin protected kidney tissues against nephrotoxic effects of gentamicin as evidenced from amelioration of histopathological changes and normalization of kidney biochemical parameters.