Microbial Oxidation of the Fusidic Acid Side Chain by Cunninghamella echinulata

Biotransformation of fusidic acid (1) was accomplished using a battery of microorganisms including Cunninghamella echinulata NRRL 1382, which converted fusidic acid (1) into three new metabolites 2–4 and the known metabolite 5. These metabolites were identified using 1D and 2D NMR and HRESI-FTMS data. Structural assignment of the compounds was supported via computation of 1H- and 13C-NMR chemical shifts. Compounds 2 and 3 were assigned as the 27-hydroxy and 26-hydroxy derivatives of fusidic acid, respectively. Subsequent oxidation of 3 afforded aldehyde 4 and the dicarboxylic acid 5. Compounds 2, 4 and 5 were screened for antimicrobial activity against different Gram positive and negative bacteria, Mycobacterium smegmatis, M. intercellulare and Candida albicans. The compounds showed lower activity compared to fusidic acid against the tested strains. Molecular docking studies were carried out to assist the structural assignments and predict the binding modes of the metabolites

Toxoplasmocidal and Cytotoxic Activities Guided Isolation and Characterization of an Undescribed Bioflavonoid-di-<i>C</i>-glucoside from <i>Cycas rumphii</i> Miq. Cultivated in Egypt

Toxoplasmosis and cancer are serious worldwide diseases, and the available drugs cause serious side effects. Investigation for new alternative therapies from natural sources is now an increasing concern. Herein, we carried out, for the first time, an in vitro screening of Cycas rumphii Miq. leaves for toxoplasmocidal effect, using Viruluent RH Toxoplasma gondii, and cytotoxic activity against HEPG-2, HCT-116 and HELA cancer cell lines using MTT assay. Among the tested extracts, the ethyl acetate fraction was the most effective against T. gondii, with an EC50 of 3.51 ± 0.2 µg/mL compared to cotrimoxazole (4.18 ± 0.01 µg/mL) and was the most potent against the tested cell lines, especially HEPG-2, with an IC50 of 6.98 ± 0.5 µg/mL compared to doxorubicin (4.50 ± 0.2 µg/mL). Seven compounds were isolated from the ethyl acetate fraction by extensive chromatographic techniques and fully elucidated using different spectroscopies. Compound (7) is an undescribed 4′, 4′′′ biapigenin di-C-glucoside, which showed a strong cytotoxic activity. Four known biflavonoids (1, 2, 4 and 5) in addition to a phenolic acid ester (3) and a flavonoid glycoside (6) were also isolated. Compounds (1, 3 and 6) were reported for the first time from C. rumphii

Unravelling the In Vitro and In Vivo Anti-Helicobacter pylori Effect of Delphinidin-3-O-Glucoside Rich Extract from Pomegranate Exocarp: Enhancing Autophagy and Downregulating TNF-&alpha; and COX2

Fruits containing antioxidants, e.g., anthocyanins, exhibit antimicrobial activities. The emergence of drug resistance represents a major challenge in eradicating H. pylori. The current study aims to explore the effect of pomegranate exocarp anthocyanin methanol extract (PEAME) against H. pylori isolates recovered from antral gastric biopsies. The UPLC-PDA-MS/MS and 1H NMR analyses indicated delphinidin-3-O-glucoside as the major anthocyanin in the extract. The PEAME showed activity against all tested resistant isolates in vitro recording minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 128 and 256 &micro;g/mL, respectively. In vivo investigation included evaluation of the rat gastric mucosa for malondialdehyde (MDA), catalase activity, COX2, TNF-&alpha;, and key autophagy gene expression. The combination of pomegranate with metronidazole markedly reduced the viable count of H. pylori and the level of COX2, with alleviation of H. pylori-induced inflammation and oxidative stress (reduction of MDA, p-value &lt; 0.001; and increase in catalase activity, p-value &lt; 0.001). Autophagy gene expression was significantly upregulated upon treatment, whereas TNF-&alpha; was downregulated. In conclusion, we comprehensively assessed the effect of PEAME against H. pylori isolates, suggesting its potential in combination with metronidazole for eradication of this pathogen. The beneficial effect of PEAME may be attributed to its ability to enhance autophagy

Phytochemical Profile of the Ethanol Extract of <i>Malvaviscus arboreus</i> Red Flower and Investigation of the Antioxidant, Antimicrobial, and Cytotoxic Activities

Flowers are rich sources of bioactive antimicrobial, antioxidant, and anticancer components. This study aimed to determine the constituents of the ethanol extract of Malvaviscus arboreus red flower (ERF) by GC-MS analysis and HPLC identification of phenolic compounds and flavonoids, in addition to the 1HNMR fingerprint. The antimicrobial, antioxidant, and cytotoxic activities of the ERF were investigated. The GC-MS analysis revealed twenty-one components, while HPLC analysis revealed the presence of phenolic and flavonoid compounds. The ERF showed antifungal and antibacterial activity. The highest antibacterial activity was found against Vibrio damsela where a time-kill assay revealed a decline in the amount of viable V. damsela. For fungi, the highest activity was observed against Aspergillus terreus. Using the SRB test on HepG2, the anti-proliferative efficacy of the ERF was evaluated. Cell cycle analysis was utilized to determine autophagic cell death. The ERF prevented the proliferation of the HepG2 cell line with an IC50 of 67.182 µg/µL. The extract primarily promoted apoptosis in HepG2 cells by accumulating hypodiploid cells in the sub-G0/G1 phase, increased caspase 3/7 activity, and caused considerable autophagic cell death in apoptosis-deficient cells. Finally, the observed elevation of cancer cell death indicated that ERF had substantial anticancer potential against HepG2 cells

New pacidamycins biosynthetically: probing N- and C-terminal substrate specificity of an unusual NRPS

Feeding phenylalanine analogues to Streptomyces coeruleorubidus reveals the remarkable steric and electronic flexibility of this biosynthetic pathway and leads to the generation of a series of new halopacidamycins

Evaluation of <i>Zamia floridana</i> A. DC. Leaves and Its Isolated Secondary Metabolites as Natural Anti-Toxoplasma and Anti-Cancer Agents Using In Vitro and In Silico Studies

Toxoplasmosis and cancer are life-threatening diseases with worldwide distribution. However, currently used chemosynthetic treatments are not devoid of their own intrinsic problems. Natural metabolites are gaining attention due to their lower side effects. In this study, we investigated for the first time Zamia floridana leaves extract and its different fractions for their toxoplasmocidal activity, using Virulent RH Toxoplasma gondii, and cytotoxic activity against MCF-7 and HCT-116 cancer cell lines using MTT assay. The n-butanol fraction was the most potent fraction against T. gondii with an EC50 of 7.16 ± 0.4 µg/mL compared to cotrimoxazole (4.18 ± 0.3 µg/mL). In addition, the n-BuOH fraction showed a significant cytotoxicity against MCF-7 and HCT-116 with IC50 of 12.33 ± 1.1 and 17.88 ± 1.4 µg/mL, respectively, compared to doxorubicin (4.17 ± 0.2 and 5.23 ± 0.3 µg/mL, respectively), with higher safety index against normal cell line (WISH). Therefore, the n-BuOH fraction was investigated for its phytochemicals using extensive chromatographic techniques, which led to the isolation of six compounds that were fully characterized using different spectroscopic techniques. Three biflavonoids (1, 2 and 4) in addition to two phenolic acid derivatives (3 and 5) and a flavonoid glycoside (6) were isolated. Compounds (1, 3, 5 and 6) were reported for the first time from Z. floridana. In silico docking studies for toxoplasmocidal and cytotoxic effects of these compounds revealed that compounds (1, 2, 4 and 6) have promising inhibition potential of either thymidylate synthase-dihydrofolate reductase (TS-DHFR) or cyclin dependent kinase 2 (CDK2) target proteins. This study is considered the first report of chemical and biological investigation of Z. floridana leaves

Antihyperlipidemic effect of bread fortified with potato peel powder against Triton X-100-induced hyperlipidemia in male albino rats

The present investigation aimed to improve the nutritional and healthy values and evaluate the influence of bread fortified with dried potato peels (BPP) on Triton X-100-induced hyperlipidemia in male albino rats. The findings demonstrated that BPP lowered hepatic triglycerides and total cholesterol while increasing high-density lipoprotein (HDL-C). BPP exhibited potential lipid-lowering and hepatoprotective actions that were generated by the reduction of oxidative damage and preservation of the non-enzymatic and enzymatic antioxidant systems compromised by hyperlipidemic condition. Furthermore, BPP considerably enhanced the mRNA expression of AMPKα (AMP-activated protein kinase-alpha), suppressed the expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase alpha (ACCα), and decreased the mRNA expression of the adipogenic transcription factor SREBP-1c (sterol regulatory element-binding protein-1c), which are essential regulators of hepatocyte lipid metabolism. A histopathological assessment of the liver confirmed the results. In conclusion, this investigation revealed a positive impact of bread fortified with BPP therapy in preventing hyperlipidemia

Ameliorative Effects of Aspergillus awamori against the Initiation of Hepatocarcinogenesis Induced by Diethylnitrosamine in a Rat Model: Regulation of Cyp19 and p53 Gene Expression

Hepatocellular carcinoma (HCC) is the most common cancer in humans. Despite advances in its treatment, liver cancer remains one of the most difficult cancers to treat. This study aimed to investigate the ameliorative action and potential mechanism of Aspergillus awamori (ASP) administration against the initiation process of liver carcinogenesis induced by diethylnitrosamine (DEN) in male Wistar rats. Seventy-two male rats were divided equally into eight groups as follows, Group 1: untreated control; Group 2: DEN (200 mg/kg bw) intra-peritoneally for the initiation of HCC; Groups 3–5: DEN + ASP at a dose of 1, 0.5, and 0.25 mg/kg bw and groups 6–8: ASP at a dose of 1, 0.5, and 0.25 mg/kg bw. Supplementation of A. awamori significantly lightened the adverse impacts induced by DEN via restoring the leukogram to normal, lowering the elevated serum aspartate aminotransferase (AST), alanine transaminase (ALT), and γ-glutamyl transferase (GGT), and alkaline phosphatase (ALP). Furthermore, it enhanced the hepatic antioxidant capacity through increasing the reduced glutathione (GSH) level and catalase (CAT) activity with a marked reduction in malondialdehyde (MDA) level. In addition, it decreased the positive GST-P foci. Likewise, a significant alteration of DEN-associated hepatocarcinogenesis occurred through inhibiting cytochrome P450 (Cyp19) and activating p53 gene expression. In conclusion, supplementation of A. awamori counteracts the negative effects of DEN, inhibits the early development of GST-P-positive foci and could be used as a new alternative strategy for its chemo-preventive effect in liver cancer. To the best of our knowledge, the present study is the first to report the hepato-protective effect of A. awamori in induced hepatocarcinogenesis

Assessment of Bioactive Phytochemicals and Utilization of <i>Rosa canina</i> Fruit Extract as a Novel Natural Antioxidant for Mayonnaise

The oxidation of food emulsions causes rancidity, which reduces their shelf life. To prevent rancidity, synthetic antioxidants are widely used in the food industry. However, due to their potential health risks, researchers are exploring natural alternatives. This study aimed to investigate whether Rosa canina fruit extract (RCFE) could be used as a natural antioxidant to extend the shelf life of mayonnaise. Mayonnaise containing varying concentrations of RCFE [0.125% (T1), 0.25% (T2), 0.50% (T3), 0.75% (T4)] was compared to a mayonnaise control sample (C1) and a mayonnaise sample containing 0.02% BHT (C2) for 60 days of storage at 4 °C. RCFE was found to have high levels of total phenols content (52.06 ± 1.14 mg GAE g−1), total flavonoids content (26.31 ± 1.03 mg QE g−1), and free radical scavenging activity. The GC–MS analysis of RCFE revealed 39 different peaks, whereas the HPLC analysis showed the presence of 13 polyphenolic compounds in RCFE. The pH values of T2, T3, and T4 mayonnaise samples substantially declined as storage progressed; however, the reduction was less than that of C1 and C2. After 60 days, mayonnaise samples T2, T3, and T4 had greatly reduced peroxide and free fatty acid levels compared to C1 and C2. The mayonnaise enriched with RCFE (T3 and T4) had the most potent antioxidative ability and the lowest value of lipid hydroperoxides (peroxide value, POV) and the lowest value of thiobarbituric-acid-reactive substances (TBARS). The sensory evaluation revealed that the T3 sample exhibited the highest overall acceptability. In conclusion, this study recommends that RCFE could be used as a natural preservative to enhance the shelf life of functional foods