Insulin Sensitivity of Adipocytes is Improved by Pomegranate Mesocarp Through Reduced Oxidative Stress and Inflammation.

OBJECTIVE: Inflammatory phenomena and increase in oxidative stress in cell physiopathology progression render therapeutic strategies based on nutritional antioxidants necessary. It was thus aimed at assessing the effectiveness of the pomegranate mesocarp extract (PME) on differentiation of preadipocytes to adipocytes in the presence/absence of hydrogen peroxide (H2O2), a model mimicking insulin resistance. METHOD: The effect of PME on lipid accumulation, protein expression of antioxidant, inflammatory and adipogenic biomarkers, reactive oxygen species production, activity of antioxidant enzymes and secretion of IL-6 has been evaluated during the differentiation of preadipocytes to adipocytes, in the presence or absence of H2O2. RESULTS: H2O2 reduced the expression of the regulator of insulin sensitivity PPARγ and suppressed adipocyte differentiation. PME counteracted the effect of H2O2. The latter induced a higher level of fat accumulation by promoting the expressions of the adipogenic markers PPARγ, C/EBPα, FABP4 and CD36 as compared to the control and the H2O2-treated differentiating cells. During the progression of adipogenesis, highest increase (p < 0.05) in IL-6 secretion, by 3.16 and 3.85 folds, was observed on day 2 of differentiation in control and H2O2-treated cells, respectively, compared to day 0. PME significantly decreased (p < 0.01) the secretion of the cytokine in addition to suppressing the expression of NFκB. PME also prevented the reduction of superoxide dismutase, catalase and glutathione peroxidase activities that occurred during adipogenesis, by at most 33%, 119% and 42%, respectively. CONCLUSION: These findings indicate that PME efficiently improves insulin sensitivity and can significantly counteract oxidative stress and inflammation.

Multigene phylogeny, bioactive properties, enzymatic and dye decolorization potential of selected marine fungi from brown algae and sponges of Mauritius.

Marine fungi represent an important proportion of the microbial diversity in the oceans. They are attractive candidates for biotechnological purposes and industrial applications. Despite an increasing interest in mycology, marine fungi associated with sponges and algae have been poorly studied in Mauritius. The objectives of this study were to: 1) use multigene phylogenetic analyses to identify isolated marine fungi; 2) determine the differences in the antimicrobial and antioxidant properties of the fungal extracts; and 3) assess their enzyme activities and dye decolorization potential. Five fungal isolates viz Aspergillus chevalieri, Aspergillus iizukae, Aspergillus ochraceus, Exserohilum rostratum and Biatriospora sp. were identified based on phylogenetic analyses. There was no significant difference in the antimicrobial properties of the liquid and solid media extracts unlike the antioxidant properties (p < 0.05). The solid media extract of Aspergillus chevalieri (F2-SF) had a minimum inhibitory concentration of 0.156 mg/ml against Staphylococcus aureus while Aspergillus ochraceus (F25-SF) had a minimum inhibitory concentration of 0.313 and 2.5 mg/ml against Enterococcus faecalis and Salmonella typhi. The solid media extract of Biatriospora sp. (F34-SF) had a minimum inhibitory concentration of 0.195 and 1.563 mg/ml against Bacillus cereus, Escherichia coli and Enterobacter cloacae. An IC50 of 78.92 ± 4.71 µg/ml in the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging assay, ferric reducing antioxidant power (FRAP) value of 11.17 ± 0.20 mM Fe2+/g dry weight extract (DWE) and total phenolic content 360.35 ± 10.31 mg GAE/g DWE was obtained with the solid media extract of Aspergillus chevalieri (F2-SF). Aspergillus ochraceus (F25-SF) and Biatriospora sp. (F34-SF) solid media extracts showed lower IC50 values in the DPPH assay and higher total phenolic content as compared to the liquid media extracts. Aspergillus chevalieri was a good producer of the enzymes DNAse and lipase and had maximum percentage dye decolorization of 79.40 ± 17.72% on Congo red. An enzymatic index ≥ 2 was found for the DNAse and lipase and the maximum percentage dye decolorization of 87.18 ± 3.80% was observed with Aspergillus ochraceus on Methylene blue. Regarding Biatriospora sp., it was a moderate producer of the three enzymes amylase, DNAse and protease and had a maximum dye decolorization potential of 56.29 ± 6.51% on Crystal violet. This study demonstrates that Mauritian marine fungi possess good bioactive properties, enzymatic and dye decolorization potentials, that can potentially be considered for use in pharmaceutical and industrial applications.

Metabolite Profiling of Antioxidant Rich Fractions of Punica granatum L. Mesocarp and CD36 Expression Regulation.

OBJECTIVE: It was aimed at determining which polyphenolic compound(s) in pomegranate mesocarp extract (PME) is liable for the antioxidant, anti-glycation and anti-CD36 activities. METHODS: The PME was fractionated using liquid-liquid extraction method. The fractions were tested for their polyphenolic content, antioxidant potency, anti-glycation activity and anti-CD36 potential. The metabolite compositions of PME and derived fractions were investigated in an untargeted manner using metabolomics in relation to its antioxidant and anti-glycation activities. RESULTS: The ethyl acetate and n-butanol fractions of the pomegranate mesocarp demonstrated highest antioxidant and anti-glycation potencies. These fractions, represented by gallic and ellagic acids monomers, were enriched in tannins and phenolic acids. Orthogonal partial least squares discriminate analysis (OPLS-DA) modeling of ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) metabolite profiles from the different pomegranate mesocarp fractions indicated that gallic and ellagic acids were potential contributors to the antioxidant and anti-glycation effects of the pomegranate mesocarp. At cellular level, the polyphenolic-rich crude extract as well as the ethyl acetate, n-butanol and aqueous residual fractions suppressed the protein expression of CD36. The anti-CD36 activity of these extracts and fractions was attributed to the presence of punicalagin, the ellagitannins that occurred in equal amount in the different fractions. CONCLUSION: This work demonstrated the protective effect of the non-edible part of the pomegranate fruit and showed that gallic and ellagic acids account for the antioxidant and anti-glycation activities while punicalagin is liable for the anti-CD36 activity of PME.

Metabarcoding assessment of fungal diversity in brown algae and sponges of Mauritius.

Marine fungi are largely associated with second most inhabitants of the marine ecosystem such as sponges and algae. They are important colonizers and play vital ecological roles, such as nutrient cycling, organic matter decomposition, and symbiosis with other organisms. High throughput sequencing methods have been used successfully to reveal unknown fungal communities associated with a number of hosts particularly in the marine environment. However, the diversity of marine fungi associated with sponges and brown algae in Mauritius remains largely unknown. Traditional methods based on culturing do not provide reliable estimate of fungal diversity as only those that are able to grow under laboratory conditions are dominant; in addition, a large proportion of fungi, cultured in vitro remain most of the time unidentifiable, given that there are no sporulating structures to be examined morphologically. To overcome these limitations, we employed Illumina sequencing to unravel fungi species present in the sponges, Iotrochota sp. and Biemna sp. and the brown algae Turbinaria conoides, Sargassum pfeifferae, and Sargassum obovatum, collected from the north of Mauritius. Diversity analyses revealed that Biemna sp. had the highest diversity from the sampled sponges with fungi from 24 orders being recovered while from brown algae; Turbinaria conoides had the highest diversity with recovery of fungal taxa of the orders Botryosphaeriales, Chaetothyriales, Eurotiales, Hypocreales, and Mucorales with the latter four orders being common in both sampled algae and sponges. Beta diversity analyses revealed clustering only in the algae, Turbinaria conoides, and Sargassum pfeifferae and not in the co-occurring sponges, indicating that sampling location did not have much influence on fungal diversity. Our findings provide the first amplicon sequencing based insights of the fungal communities associated with macro-algae and sponges in Mauritius and supplements research on the fungal community existing in the oceans around the world.

Regulation of cancer cell signaling pathways as key events for therapeutic relevance of edible and medicinal mushrooms.

Mushrooms, both edible and medicinal have received considerable attention against cancer due to their polysaccharides, polysaccharides-protein complexes and low molecular weight secondary metabolites content. Every year, millions of people die because of this disease. Existing cancer therapies are poised with questions of efficacy, toxicity and adverse effects, hence justifying the search for finding new, alternative and efficient means to fend off the disease. Mushrooms and their derived active molecules can prevent oncogenesis and tumour metastasis via directly inhibiting tumour cells growth or indirectly improving immunity functions and by acting as chemotherapy adjuvants. While the mechanisms of such effects are not fully known, the roles of the bioactive compounds on cell signaling pathways involved in the promotion and progression of the disease appear to be key, particularly in view of their role(s) in multiple cellular processes, including cell survival, proliferation, and differentiation. This review discusses the aberrant cell signaling pathways involved in inhibition of tumour cell growth as target for mushrooms and their bioactive compounds as well as the associated challenges for the molecules therein to be successfully considered as preventive/therapeutic agents against cancer.

Novel assay to measure chromosome instability identifies Punica granatum extract that elevates CIN and has a potential for tumor- suppressing therapies.

Human artificial chromosomes (HACs) have provided a useful tool to study kinetochore structure and function, gene delivery, and gene expression. The HAC propagates and segregates properly in the cells. Recently, we have developed an experimental high-throughput imaging (HTI) HAC-based assay that allows the identification of genes whose depletion leads to chromosome instability (CIN). The HAC carries a GFP transgene that facilitates quantitative measurement of CIN. The loss of HAC/GFP may be measured by flow cytometry or fluorescence scanning microscope. Therefore, CIN rate can be measured by counting the proportion of fluorescent cells. Here, the HAC/GFP-based assay has been adapted to screen anticancer compounds for possible induction or elevation of CIN. We analyzed 24 cytotoxic plant extracts. Punica granatum leaf extract (PLE) indeed sharply increases CIN rate in HT1080 fibrosarcoma cells. PLE treatment leads to cell cycle arrest, reduction of mitotic index, and the increased numbers of micronuclei (MNi) and nucleoplasmic bridges (NPBs). PLE-mediated increased CIN correlates with the induction of double-stranded breaks (DSBs). We infer that the PLE extract contains a component(s) that elevate CIN, making it a candidate for further study as a potential cancer treatment. The data also provide a proof of principle for the utility of the HAC/GFP-based system in screening for natural products and other compounds that elevate CIN in cancer cells.

Towards policies that capture the expected value of biomolecular diversity for drug discovery, human health, and well-being.

This paper aims to help policy makers with a characterization of the intrinsic value of biodiversity and its role as a critical foundation for sustainable development, human health, and well-being. Our objective is to highlight the urgent need to overcome economic, disciplinary, national, cultural, and regional barriers, in order to work out innovative measures to create a sustainable future and prevent the mutual extinction of humans and other species. We emphasize the pervasive neglect paid to the cross-dependency of planetary health, the health of individual human beings and other species. It is critical that social and natural sciences are taken into account as key contributors to forming policies related to biodiversity, conservation, and health management. We are reaching the target date of Nagoya treaty signatories to have accomplished measures to prevent biodiversity loss, providing a unique opportunity for policy makers to make necessary adjustments and refocus targets for the next decade. We propose recommendations for policy makers to explore novel avenues to halt the accelerated global loss of biodiversity. Beyond the critical ecological functions biodiversity performs, its enormous untapped the repertoire of natural molecular diversity is needed for solving accelerating global healthcare challenges.

Antiproliferative activity of Syzygium coriaceum, an endemic plant of Mauritius, with its UPLC-MS metabolite fingerprint: A mechanistic study.

Flowering plants from the Syzygium genus have long been used in different ethnomedicinal systems worldwide and have been under scrutiny for their biological activities. Syzygium coriaceum, an endemic plant of Mauritius has been poorly studied for its potential application against cancer. Herein, Syzygium coriaceum leaf extract has been investigated for its anticancer effect against hepatocellular carcinoma (HepG2) cells. The anticancer activity was assessed using cell proliferation assays, flow cytometry, JC-1 mitochondrial membrane potential assay, and the COMET assay. Un-targeted metabolite profiling via ultra-performance liquid chromatography coupled to high-resolution qTOF-MS (UPLC-MS) and aided by molecular networking was employed to identify the crude extract metabolites. S. coriaceum treatment induced a dose-dependent increase in lactate dehydrogenase leakage into the culture media, peaking up to 47% (p ≤ 0.0001), compared to untreated control. Moreover, at 40 µg/mL, S. coriaceum led to 88.1% (p ≤ 0.0001) drop in mitochondrial membrane potential and 5.7% (p ≤ 0.001) increased in the number of the cell population in G0/G1 phase as well as increased (p < 0.05) the proportion of cells undergoing apoptotic/necrotic cell death. More so, at 10 µg/mL, S. coriaceum induced DNA damage which was 19 folds (p < 0.001) higher than that of untreated control cells. Metabolite profiling indicated the presence of 65 metabolites, out of which 59 were identified. Tannins, flavonoids, nitrogenous compounds, and organic acids were the most predominant classes of compounds detected. Our findings showed that the presence of tannins and flavonoids in S. coriaceum leaf extract could account for the multiple mechanisms of actions underlying the antiproliferative effect against HepG2 cells.

Terminalia bentzoë, a Mascarene Endemic Plant, Inhibits Human Hepatocellular Carcinoma Cells Growth In Vitro via G0/G1 Phase Cell Cycle Arrest.

Tropical forests constitute a prolific sanctuary of unique floral diversity and potential medicinal sources, however, many of them remain unexplored. The scarcity of rigorous scientific data on the surviving Mascarene endemic taxa renders bioprospecting of this untapped resource of utmost importance. Thus, in view of valorizing the native resource, this study has as its objective to investigate the bioactivities of endemic leaf extracts. Herein, seven Mascarene endemic plants leaves were extracted and evaluated for their in vitro antioxidant properties and antiproliferative effects on a panel of cancer cell lines, using methyl thiazolyl diphenyl-tetrazolium bromide (MTT) and clonogenic cell survival assays. Flow cytometry and comet assay were used to investigate the cell cycle and DNA damaging effects, respectively. Bioassay guided-fractionation coupled with liquid chromatography mass spectrometry (MS), gas chromatography-MS, and nuclear magnetic resonance spectroscopic analysis were used to identify the bioactive compounds. Among the seven plants tested, Terminaliabentzoë was comparatively the most potent antioxidant extract, with significantly (p < 0.05) higher cytotoxic activities. T. bentzoë extract further selectively suppressed the growth of human hepatocellular carcinoma cells and significantly halted the cell cycle progression in the G0/G1 phase, decreased the cells' replicative potential and induced significant DNA damage. In total, 10 phenolic compounds, including punicalagin and ellagic acid, were identified and likely contributed to the extract's potent antioxidant and cytotoxic activities. These results established a promising basis for further in-depth investigations into the potential use of T. bentzoë as a supportive therapy in cancer management.