20 pages, 10249 KB  
Article
Investigating the Potential Anti-SARS-CoV-2 and Anti-MERS-CoV Activities of Yellow Necklacepod among Three Selected Medicinal Plants: Extraction, Isolation, Identification, In Vitro, Modes of Action, and Molecular Docking Studies
by Howaida I. Abd-Alla 1,*, Omnia Kutkat 2, Heba-tollah M. Sweelam 1, Wagdy M. Eldehna 3,4, Marwa A. Mostafa 5, Magda T. Ibrahim 6, Yassmin Moatasim 2, Mohamed GabAllah 2 and Ahmed A. Al-Karmalawy 7,*
1 Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki-Giza 12622, Egypt
2 The Center of Scientific Excellence for Influenza Viruses, Water Pollution Research Department, Environmental Research Institute, National Research Centre, Dokki-Giza 12622, Egypt
3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt
4 School of Biotechnology, Badr University in Cairo, Badr City 11829, Egypt
5 Bab El-Shaariya Hospital, Al-Azhar University, Cairo 11558, Egypt
6 Department of Pharmacognosy, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, Egypt
7 Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza 12566, Egypt
Metabolites 2022, 12(11), 1109; https://doi.org/10.3390/metabo12111109 - 13 Nov 2022
Cited by 19 | Viewed by 3911
Abstract
The anti-MERS-CoV activities of three medicinal plants (Azadirachta indica, Artemisia judaica, and Sophora tomentosa) were evaluated. The highest viral inhibition percentage (96%) was recorded for S. tomentosa. Moreover, the mode of action for both S. tomentosa and A. judaica [...] Read more.
The anti-MERS-CoV activities of three medicinal plants (Azadirachta indica, Artemisia judaica, and Sophora tomentosa) were evaluated. The highest viral inhibition percentage (96%) was recorded for S. tomentosa. Moreover, the mode of action for both S. tomentosa and A. judaica showed 99.5% and 92% inhibition, respectively, with virucidal as the main mode of action. Furthermore, the anti-MERS-CoV and anti-SARS-CoV-2 activities of S. tomentosa were measured. Notably, the anti-SARS-CoV-2 activity of S. tomentosa was very high (100%) and anti-MERS-CoV inhibition was slightly lower (96%). Therefore, the phytochemical investigation of the very promising S. tomentosa L. led to the isolation and structural identification of nine compounds (1–9). Then, both the CC50 and IC50 values for the isolated compounds against SARS-CoV-2 were measured. Compound 4 (genistein 4’-methyl ether) achieved superior anti-SARS-CoV-2 activity with an IC50 value of 2.13 µm. Interestingly, the mode of action of S. tomentosa against SARS-CoV-2 showed that both virucidal and adsorption mechanisms were very effective. Additionally, the IC50 values of S. tomentosa against SARS-CoV-2 and MERS-CoV were found to be 1.01 and 3.11 µg/mL, respectively. In addition, all the isolated compounds were subjected to two separate molecular docking studies against the spike (S) and main protease (Mpr°) receptors of SARS-CoV-2. Full article
(This article belongs to the Special Issue Natural Products: Chemical Profiling, Computational Studies and Bioactivities)
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12 pages, 603 KB  
Review
Nonalcoholic Fatty Liver Disease—A Concise Review of Noninvasive Tests and Biomarkers
by Tamara Bassal 1, Maamoun Basheer 1, Mariana Boulos 1 and Nimer Assy 1,2,*
1 Internal Medicine Department, Galilee Medical Center, Nahariya 2210001, Israel
2 Azrieli Faculty of Medicine in the Galilee, Bar-Ilan University, Safed 1311502, Israel
Metabolites 2022, 12(11), 1073; https://doi.org/10.3390/metabo12111073 - 5 Nov 2022
Cited by 19 | Viewed by 4667
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, with a continuously growing prevalence. The pathophysiology of the disease is complex and includes several mechanisms, with metabolic syndrome and insulin resistance playing a major role. It is crucial to diagnose [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, with a continuously growing prevalence. The pathophysiology of the disease is complex and includes several mechanisms, with metabolic syndrome and insulin resistance playing a major role. It is crucial to diagnose NAFLD before it advances to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis, presented by its complications which include ascites, portal hypertension, bleeding varices and encephalopathy. Another important complication of NAFLD and cirrhosis is hepatocellular carcinoma (HCC), a cancer with increasing incidence and poor prognosis. Even with the growing prevalence of NAFLD, diagnosis via liver biopsies is unrealistic, considering the costs and complications. Noninvasive tests, including serum biomarkers and elastography, are cost-effective and convenient, thereby replacing liver biopsies in diagnosing and excluding liver fibrosis. However, currently, these noninvasive tests have several limitations, such as variability, inadequate accuracy and risk factors for error. The limitations and variability of these tests comet the investigator to propose combining them in diagnostic algorithms to produce more accurate tools. Identifying patients with significant fibrosis is important for targeted therapies to prevent disease progression. Effective screening using noninvasive tests can be crucial for patient risk stratification and early diagnosis. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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18 pages, 1500 KB  
Article
A Novel Ketone-Supplemented Diet Improves Recognition Memory and Hippocampal Mitochondrial Efficiency in Healthy Adult Mice
by Erin R. Saito, Cali E. Warren, Cameron M. Hanegan, John G. Larsen, Johannes D. du Randt, Mio Cannon, Jeremy Y. Saito, Rachel J. Campbell, Colin M. Kemberling, Gavin S. Miller, Jeffrey G. Edwards and Benjamin T. Bikman *
Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA
Metabolites 2022, 12(11), 1019; https://doi.org/10.3390/metabo12111019 - 25 Oct 2022
Cited by 19 | Viewed by 11064
Abstract
Mitochondrial dysfunction and cognitive impairment are common symptoms in many neurologic and psychiatric disorders, as well as nonpathological aging. Ketones have been suggested as therapeutic for their efficacy in epilepsy and other brain pathologies such as Alzheimer’s disease and major depressive disorder. However, [...] Read more.
Mitochondrial dysfunction and cognitive impairment are common symptoms in many neurologic and psychiatric disorders, as well as nonpathological aging. Ketones have been suggested as therapeutic for their efficacy in epilepsy and other brain pathologies such as Alzheimer’s disease and major depressive disorder. However, their effects on cognitive function in healthy individuals is less established. Here, we explored the mitochondrial and performative outcomes of a novel eight-week ketone-supplemented ketogenic (KETO) diet in healthy adult male and female mice. In a novel object recognition test, KETO mice spent more time with the novel, compared to familiar, object, indicating an improvement in recognition memory. High-resolution respirometry on permeabilized hippocampal tissue returned significant reductions in mitochondrial O2 consumption. No changes in ATP production were observed, yielding a significantly higher ATP:O2 ratio, a measure of mitochondrial efficiency. Together, these findings demonstrate the KETO diet improves hippocampal mitochondrial efficiency. They add to a growing body of evidence that suggests ketones and ketogenic diets are neuroprotective and metabolically and cognitively relevant, even in healthy adults. They also suggest that ketogenic lifestyle changes may be effective strategies for protecting against cognitive decline associated with aging and disease. Full article
(This article belongs to the Special Issue The Metabolomic Landscape of Carbohydrate Restriction)
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18 pages, 2839 KB  
Article
Dietary Effect of Clostridium autoethanogenum Protein on Growth, Intestinal Histology and Flesh Lipid Metabolism of Largemouth Bass (Micropterus salmoides) Based on Metabolomics
by Pinxian Yang 1,2,3,†, Xiaoqin Li 1,2,3,†, Wenxiang Yao 1,2,3, Menglu Li 1,2,3, Yuanyuan Wang 1,2,3 and Xiangjun Leng 1,2,3,*
1 National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai 201306, China
2 Centre for Research on Environmental Ecology and Fish Nutrition (CREEFN) of the Ministry of Agriculture and Rural Affairs, Shanghai Ocean University, Shanghai 201306, China
3 Shanghai Collaborative Innovation for Aquatic Animal Genetics and Breeding, Shanghai Ocean University, Shanghai 201306, China
† These authors contributed equally to this work.
Metabolites 2022, 12(11), 1088; https://doi.org/10.3390/metabo12111088 - 9 Nov 2022
Cited by 18 | Viewed by 3198
Abstract
Clostridium autoethanogenum protein (CAP) is a new single-cell protein explored in aquatic feeds in recent years. This study investigated the dietary effects of CAP replacing fishmeal (FM) on the growth, intestinal histology and flesh metabolism of largemouth bass (Micropterus salmoides). In [...] Read more.
Clostridium autoethanogenum protein (CAP) is a new single-cell protein explored in aquatic feeds in recent years. This study investigated the dietary effects of CAP replacing fishmeal (FM) on the growth, intestinal histology and flesh metabolism of largemouth bass (Micropterus salmoides). In a basal diet containing 700 g/kg of FM, CAP was used to substitute 0%, 15%, 30%, 45%, 70% and 100% of dietary FM to form six isonitrogenous diets (Con, CAP-15, CAP-30, CAP-45, CAP-70, CAP-100) to feed largemouth bass (80.0 g) for 12 weeks. Only the CAP-100 group showed significantly lower weight gain (WG) and a higher feed conversion ratio (FCR) than the control (p < 0.05). A broken-line analysis based on WG and FCR showed that the suitable replacement of FM with CAP was 67.1–68.0%. The flesh n-3/n-6 polyunsaturated fatty acid, intestinal protease activity, villi width and height in the CAP-100 group were significantly lower than those in the control group (p < 0.05). The Kyoto Encyclopedia of Genes and Genomes analysis showed that the metabolic pathway in flesh was mainly enriched in the “lipid metabolic pathway”, “amino acid metabolism”, “endocrine system” and “carbohydrate metabolism”. In conclusion, CAP could successfully replace 67.1–68.0% of dietary FM, while the complete substitution decreased the growth, damaged the intestinal morphology and down-regulated the lipid metabolites. Full article
(This article belongs to the Special Issue Metabolic Research in Aquatic Animal Nutrition, Physiology and Disease)
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29 pages, 2666 KB  
Review
Isotope-Assisted Metabolic Flux Analysis: A Powerful Technique to Gain New Insights into the Human Metabolome in Health and Disease
by Bilal Moiz 1, Andrew Li 1, Surya Padmanabhan 1, Ganesh Sriram 2,* and Alisa Morss Clyne 1,*
1 Department of Bioengineering, University of Maryland, College Park, MD 20742, USA
2 Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, MD 20742, USA
Metabolites 2022, 12(11), 1066; https://doi.org/10.3390/metabo12111066 - 4 Nov 2022
Cited by 18 | Viewed by 5888
Abstract
Cell metabolism represents the coordinated changes in genes, proteins, and metabolites that occur in health and disease. The metabolic fluxome, which includes both intracellular and extracellular metabolic reaction rates (fluxes), therefore provides a powerful, integrated description of cellular phenotype. However, intracellular fluxes cannot [...] Read more.
Cell metabolism represents the coordinated changes in genes, proteins, and metabolites that occur in health and disease. The metabolic fluxome, which includes both intracellular and extracellular metabolic reaction rates (fluxes), therefore provides a powerful, integrated description of cellular phenotype. However, intracellular fluxes cannot be directly measured. Instead, flux quantification requires sophisticated mathematical and computational analysis of data from isotope labeling experiments. In this review, we describe isotope-assisted metabolic flux analysis (iMFA), a rigorous computational approach to fluxome quantification that integrates metabolic network models and experimental data to generate quantitative metabolic flux maps. We highlight practical considerations for implementing iMFA in mammalian models, as well as iMFA applications in in vitro and in vivo studies of physiology and disease. Finally, we identify promising new frontiers in iMFA which may enable us to fully unlock the potential of iMFA in biomedical research. Full article
(This article belongs to the Special Issue Frontiers in Metabolic Flux Analysis on Human Disease)
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13 pages, 1952 KB  
Article
Enhancement of Cadmium Phytoremediation Potential of Helianthus annuus L. with Application of EDTA and IAA
by Naila Shah 1,2, Muhammad Qadir 1, Muhammad Irshad 1,*, Anwar Hussain 1, Muhammad Hamayun 1, Waheed Murad 1, Ajmal Khan 3,* and Ahmed Al-Harrasi 3,*
1 Department of Botany, Garden Campus, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan
2 Department of Botany, Government Girls College, Mardan 23200, Pakistan
3 Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al-Mauz, Nizwa 616, Oman
Metabolites 2022, 12(11), 1049; https://doi.org/10.3390/metabo12111049 - 31 Oct 2022
Cited by 18 | Viewed by 3017
Abstract
The aim of the current study was to assess the cadmium (Cd) phytoremediation potential of Helianthus annuus L. that was exposed to 50, 100, and 150 mg/kg of cadmium for 15, 30, and 60 days with application of EDTA (Ethylenediaminetetraacetic acid) in the [...] Read more.
The aim of the current study was to assess the cadmium (Cd) phytoremediation potential of Helianthus annuus L. that was exposed to 50, 100, and 150 mg/kg of cadmium for 15, 30, and 60 days with application of EDTA (Ethylenediaminetetraacetic acid) in the soil and IAA (indole acetic acid) as a foliar spray. The results indicated that the concentration, duration of exposure, and amount of Cd affect the phytoremediation potential. The maximum Cd was observed at 60 days (32.05, 16.86, and 10.63%) of Cd application, compared to 15 (2.04, 0.60, and 1.17%) or 30 days (8.41, 3.93, and 4.20%, respectively), in a dose-dependent manner. The application of EDTA in the soil and foliar IAA enhanced the Cd accumulation in the plants at 15, 30, and 60 days of exposure, with maximum accumulation at 60 days. Exposed plants with foliar IAA application showed 64.82%, 33.77%, and 25.84% absorption at 50, 100, and 150 mg/kg, respectively. Apart from higher absorption, the cadmium translocation to the edible part of the plants ceased, i.e., the seeds had 0% accumulation. The interesting fact was recorded that efficient phytoremediation was recorded at 15 days of exposure, whereas maximum phytoremediation was recorded at 60 days of exposure. To minimize the stress, the host also produced stress-related metabolites (i.e., flavonoids, phenolics, proline, and sugar) and antioxidants (i.e., catalases and ascorbate peroxidases). From the current evidence, it could be assumed that the use of EDTA and IAA, along with hyperaccumulating plants, could be a possible green method to remediate Cd-contaminated soil efficiently in a short period of time. Full article
(This article belongs to the Special Issue Identification of Plant Metabolites: Characterization and Biological Activities)
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10 pages, 541 KB  
Article
Carbohydrate Intake and Closed-Loop Insulin Delivery System during Two Subsequent Pregnancies in Type 1 Diabetes
by Ana Munda 1, Chiara Kovacic 2 and Drazenka Pongrac Barlovic 1,2,*
1 Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
2 Medical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia
Metabolites 2022, 12(11), 1137; https://doi.org/10.3390/metabo12111137 - 18 Nov 2022
Cited by 17 | Viewed by 3078
Abstract
Carbohydrate intake is one of the main determinants of glycemic control. In pregnancy, achievement of tight glycemic control is of utmost importance; however, data on the role of hybrid closed-loop systems (HCLs) in pregnancy are scarce. Therefore, we aimed to assess glycemic control [...] Read more.
Carbohydrate intake is one of the main determinants of glycemic control. In pregnancy, achievement of tight glycemic control is of utmost importance; however, data on the role of hybrid closed-loop systems (HCLs) in pregnancy are scarce. Therefore, we aimed to assess glycemic control achieved through the use of HCLs, and its association with carbohydrate intake in type 1 diabetes pregnancy. We included data from women with a sensor-augmented pump (SAP) during their first pregnancy and HCL use during the subsequent pregnancy. Student’s paired t-test was used to compare data between both pregnancies. Six women were identified, with age 30.2 ± 3.6 vs. 33.0 ± 3.6 years, diabetes duration 23 ± 5 vs. 26 ± 5 years, and baseline HbA1c 6.7 ± 0.7% (50.1 ± 7.7 mmol/mol) vs. 6.3 ± 0.6% (45.2 ± 6.5 mmol/moll) in the first and second pregnancies, respectively. Time with glucose in the range 3.5–7.8 mmol/L was 69.1 ± 6.7 vs. 78.6 ± 7.4%, p = 0.045, with the HCLs compared to SAP. Higher meal frequency, but not the amount of carbohydrate consumption, was associated with more time spent in the target range and lower glycemic variability. HCLs and meal frequency were associated with better glycemic control in a small series of pregnant women with type 1 diabetes. Whether this translates to better perinatal outcomes remains to be seen. Full article
(This article belongs to the Special Issue Functional Foods and Diabetes)
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15 pages, 2332 KB  
Article
Effect of Breastmilk Microbiota and Sialylated Oligosaccharides on the Colonization of Infant Gut Microbial Community and Fecal Metabolome
by Juan Ding 1,†, Runze Ouyang 2,3,4,†, Sijia Zheng 2,3,4,†, Yanfeng Wang 2,3,4, Yan Huang 3, Xiao Ma 5, Yuxin Zou 6, Rong Chen 7, Zhihong Zhuo 8, Zhen Li 9, Qi Xin 10, Lina Zhou 2,3,4, Surong Mei 11, Jingyu Yan 2, Xin Lu 2,3,4, Zhigang Ren 12,*, Xinyu Liu 2,3,4,* and Guowang Xu 2,3,4
1 Department of Quality Control, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
2 CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
3 University of Chinese Academy of Sciences, Beijing 100049, China
4 Liaoning Province Key Laboratory of Metabolomics, Dalian 116023, China
5 Department of Nursing, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
6 Liaocheng People’s Hospital, Liaocheng 252000, China
7 Dalian Municipal Women and Children’s Medical Center (Group), Dalian 116011, China
8 Department of Pediatric, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
9 Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
10 Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China
11 State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
12 Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
† These authors contributed equally to this work.
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Metabolites 2022, 12(11), 1136; https://doi.org/10.3390/metabo12111136 - 18 Nov 2022
Cited by 17 | Viewed by 4586
Abstract
The complex microbiota and sialylated oligosaccharides in breastmilk are important bioactive components that affect the gut microbiota. However, the effect of breastmilk microbiota and sialylated oligosaccharides on the gut microbiota during the neonatal period has been largely overlooked. Here, 16S rRNA gene sequencing [...] Read more.
The complex microbiota and sialylated oligosaccharides in breastmilk are important bioactive components that affect the gut microbiota. However, the effect of breastmilk microbiota and sialylated oligosaccharides on the gut microbiota during the neonatal period has been largely overlooked. Here, 16S rRNA gene sequencing and metabolomics analysis were applied to the breastmilk and feces of 69 newborns to clarify the link between breastmilk components and the newborn gut. Results showed that Staphylococcus, Enterococcus, and Bacteroides were commonly shared and positively correlated between breastmilk and the neonatal intestine and they were the main bacteria of breastmilk that interacted with the newborn fecal metabolome. Breastmilk Staphylococcus mainly interacted with amino acids, whereas Bacteroides was involved in the tryptophan, nucleotide, and vitamin metabolism. Breastmilk sialylated oligosaccharides were related to Bacteroides and amino acids of the newborn fecal metabolites. Moreover, Bacteroides was related to the interaction between breastmilk 3′-sialyllactose and newborn fecal metabolites in the mediation effect models. Finally, we pointed out that breastmilk Bacteroides was important in the milk–gut interaction, and it was negatively associated with waist circumference in infants aged 1 year. Our study provides a scientific basis for understanding the role of breastmilk in the development of newborn gut microbiota and metabolome. Full article
(This article belongs to the Section Nutrition and Metabolism)
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19 pages, 9004 KB  
Article
Structural Diversity, LC-MS-MS Analysis and Potential Biological Activities of Brevibacillus laterosporus Extract
by Muhammad Zayed 1, Islam M. El-Garawani 2,*, Sabha M. El-Sabbagh 1, Bassem Amr 1, Sultan M. Alsharif 3, Ahmed A. Tayel 4, Mohamed F. AlAjmi 5, Hasnaa M. S. Ibrahim 6, Qiyang Shou 7,*, Shaden A. M. Khalifa 8, Hesham R. El-Seedi 6,9,10,11,* and Nora Elfeky 1
1 Department of Botany and Microbiology, Faculty of Science, Menoufia University, Menoufia 32511, Egypt
2 Department of Zoology, Faculty of Science, Menoufia University, Menoufia 32511, Egypt
3 Biology Department, Faculty of Science, Taibah University, Al Madinah 887, Saudi Arabia
4 Department of Fish Processing and Biotechnology, Faculty of Aquatic and Fisheries Sciences, Kafrelsheikh University, Kafrelsheikh 33516, Egypt
5 Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
6 Department of Chemistry, Faculty of Science, Menoufia University, Menoufia 32511, Egypt
7 Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310058, China
8 Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-106 91 Stockholm, Sweden
9 International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
10 Pharmacognosy Group, Department of Pharmaceutical Biosciences, Uppsala University, Biomedical Centre, SE 751-24 Uppsala, Sweden
11 International Joint Research Laboratory of Intelligent Agriculture and Agri-Products Processing, Jiangsu Education Department, Jiangsu University, Nanjing 210024, China
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Metabolites 2022, 12(11), 1102; https://doi.org/10.3390/metabo12111102 - 11 Nov 2022
Cited by 17 | Viewed by 4123
Abstract
Lake Mariout is Egypt’s degraded coastal marine habitat that encompasses a variety of wastes. The biodiversity and hard environmental conditions allow the co-existence of organisms with high resistance and rich metabolism, making them potential candidates for screening and isolating novel microbial strains. A [...] Read more.
Lake Mariout is Egypt’s degraded coastal marine habitat that encompasses a variety of wastes. The biodiversity and hard environmental conditions allow the co-existence of organisms with high resistance and rich metabolism, making them potential candidates for screening and isolating novel microbial strains. A bacterial isolate (BF202) cultured from the marine sediments of Alexandria’s Mariout Lake (Egypt) was tested for its antimicrobial and anticancer potential. The phylogenetic analysis of the isolated strain’s 16S rDNA and gyrB revealed that BF202 belongs to Brevibacillus laterosporus (B. laterosporus). Antibiosis of B. laterosporus was confirmed against microbial pathogens including Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, and Staphylococcus aureus. The highest antibacterial activity was detected on glucose peptone medium after 18 h of incubation at 35 °C, and at pH of 7.0 in the presence of mannose and ammonium carbonate as carbon and nitrogen sources, respectively. The cytotoxicity of the methanolic extract against breast cancer (MCF-7) and normal Vero cell lines, using the MTT test, revealed IC50 values of 7.93 and 23.79 µg/mL, respectively. To identify apoptotic and necrotic cells, a flow cytometric analysis using annexin V-FITC/PI dual-labeling was utilized and recorded a higher number of necrotic cells compared to apoptotic ones. Similarly, the cell cycle S-phase arrest was reported. The LC-MS-MS investigation of B. laterosporus extract and the molecular networking database analysis demonstrated five strategic diketopiperazine compounds with antimicrobial and anticancer activities. Taken together, this research shows that the crude extract of B. laterosporus might be an effective agent against drug-resistant bacteria and malignant disorders due to its richness in diketopiperazines. Full article
(This article belongs to the Special Issue Mass Spectrometry-Based Metabolomics as Tools in Pharmaceutical and Biological Analysis)
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19 pages, 2807 KB  
Article
Euclea divinorum Hiern: Chemical Profiling of the Leaf Extract and Its Antioxidant Activity In Silico, In Vitro and in Caenorhabditis elegans Model
by Hanin A. Bogari 1,†, Rasha M. H. Rashied 2,†, Mohamed A. O. Abdelfattah 3, Rania T. Malatani 1, Roaa M. Khinkar 1, Rawan H. Hareeri 4, Michael Wink 5 and Mansour Sobeh 5,6,*
1 Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
2 School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, New Administrative Capital, Cairo 11835, Egypt
3 College of Engineering and Technology, American University of the Middle East, Kuwait
4 Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
5 Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany
6 AgroBioSciences, Mohammed VI Polytechnic University, Ben-Guerir 43150, Morocco
† These authors contributed to this work equally.
Metabolites 2022, 12(11), 1031; https://doi.org/10.3390/metabo12111031 - 27 Oct 2022
Cited by 17 | Viewed by 3586
Abstract
Euclea divinorum Hiern is a medicinal plant widely distributed in the northeast parts of South Africa. This plant has been used to treat miscarriage and to alleviate gastrointestinal problems. It can also be used externally for the treatment of ulcers and gonorrhea. In [...] Read more.
Euclea divinorum Hiern is a medicinal plant widely distributed in the northeast parts of South Africa. This plant has been used to treat miscarriage and to alleviate gastrointestinal problems. It can also be used externally for the treatment of ulcers and gonorrhea. In this study, we investigated the phytochemical composition of E. divinorum leaf extract using LC-MS and explored its antioxidant properties in vitro and in vivo. The total polyphenolic content of the extract was determined by the Folin–Ciocalteu method. DPPH and FRAP assays were employed to confirm the plant’s antioxidant potential in vitro. A survival assay in the Caenorhabditis elegans model was used to evaluate the extract’s ability to counteract juglone-induced oxidative stress. Moreover, a docking study was performed for the extract’s metabolites, in order to predict possible molecular targets that could explain the antioxidant effect of the plant on a molecular level. This in silico approach was accomplished on three different proteins; xanthine oxidase enzyme, heat shock protein 90 (Hsp90), and induced nitric oxide synthase (iNOS). Docking scores of the resulting poses and their interactions with binding sites’ residues were explored for each protein and were compared to those of simultaneously docked respective co-crystallized and reference substrates. The extract furnished promising antioxidant activities in vitro and in vivo in the C. elegans model that might be attributed to the presence of 46 compounds, which showed several interactions and low binding scores with the tested enzymes. In conclusion, E. divinorum is a promising, safe, and effective antioxidant candidate that could be used to ameliorate oxidative stress-related disorders. Full article
(This article belongs to the Special Issue Identification and Therapeutic Properties of Secondary Metabolites of Medicinal Plants)
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20 pages, 2760 KB  
Article
Anti-Candida albicans Activity of Ononin and Other Secondary Metabolites from Platonia Insignis MART
by Anderson França da Silva 1,2, Josivan Regis Farias 1,3, Danielle Cristine Gomes Franco 1,3, Andrea Araruna Galiza 1,2, Elizangela Pestana Motta 1,3, Aluísio da Silva Oliveira 1,3, Cleydlenne Costa Vasconcelos 2, Maria do Socorro de Sousa Cartágenes 3,4, Claudia Quintino da Rocha 5, Mayara Cristina Pinto da Silva 1,3, Alberto Jorge Oliveira Lopes 6, Flavia Raquel Fernandes do Nascimento 1,3, Cristina Andrade Monteiro 7 and Rosane Nassar Meireles Guerra 1,2,3,*
1 Laboratory of Immunophysiolgy, Federal University of Maranhão, São Luís 65080-805, Brazil
2 Program in Biotechnology-RENORBIO, Federal University of Maranhão, São Luís 65080-805, Brazil
3 Program in Health Sciences, Federal University of Maranhão, São Luís 65080-805, Brazil
4 Laboratory of Experimental Study of Pain, Department of Physiological Sciences, Federal University of Maranhão, São Luís 65080-805, Brazil
5 Department of Chemistry, Federal University of Maranhão, São Luís 65080-805, Brazil
6 Federal Institute of Science Education and Technology of Maranhão-Campus Santa Inês, Santa Inês 65300-000, Brazil
7 Department of Biology, Federal Institute of Science Education and Technology of Maranhão, São Luís 65030-005, Brazil
Metabolites 2022, 12(11), 1014; https://doi.org/10.3390/metabo12111014 - 24 Oct 2022
Cited by 17 | Viewed by 3412
Abstract
Candida albicans is a human pathogen that is part of the healthy microbiome. However, it is often associated with opportunistic fungal infections. The treatment of these infections is challenging because prolonged exposure to antifungal drugs can culminate in fungal resistance during therapy, and [...] Read more.
Candida albicans is a human pathogen that is part of the healthy microbiome. However, it is often associated with opportunistic fungal infections. The treatment of these infections is challenging because prolonged exposure to antifungal drugs can culminate in fungal resistance during therapy, and there is a limited number of available drugs. Therefore, this study investigated the antifungal activity of ononin by in silico and in vitro assays, and in Tenebrio molitor as an alternative in vivo model of infection caused by C. albicans. Ononin is an isoflavone glycoside derived from formononetin that has various biological activities. According in silico evaluation, ononin showed the best electron affinity in molecular docking with CaCYP51, with a binding free energy of −10.89 kcal/mol, superior to that of the antifungal drugs fluconazole and posaconazole. The ononin + CaCYP51 complex formed hydrogen bonds with Tyr132, Ser378, Phe380, and Met508, as well as hydrophobic connections with Tyr118, Leu121, Phe126, Leu131, Ile304, and Leu309, and interactions with the heme group. Ononin exerted anti-Candida albicans activity, with MIC between 3.9 and 7.8 µg/mL, and inhibited young and mature biofilms, with a reduction in cell density and metabolic activity of 50 to 80%. The compound was not cytotoxic to sheep red blood cells at concentrations up to 1000 µg/mL. Larvae of the mealworm T. molitor were used as an alternative in vivo model of C. albicans infection. Ononin was able to prolong larval survival at concentrations of 0.5, 1, and 5 mg/kg, and was not toxic up to a concentration of 20 mg/kg. Moreover, ononin reduced the fungal charge in treated animals. In conclusion, our results suggest that ononin has anti-Candida albicans activity and is a potential candidate for the development of new therapeutic alternatives. Full article
(This article belongs to the Special Issue The Natural Products in the Treatment and Prevention of Diseases)
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15 pages, 4385 KB  
Article
A New Mechanism for Ginsenoside Rb1 to Promote Glucose Uptake, Regulating Riboflavin Metabolism and Redox Homeostasis
by Yihan Liu 1,†, Yuchan Deng 1,†, Fengyu Wang 1, Xiaoyi Liu 1, Jiaqi Wang 1, Jian Xiao 2, Cunli Zhang 1,* and Qiang Zhang 1,2,*
1 Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Xianyang 712100, China
2 Shaanxi Key Laboratory of Phytochemistry, College of Chemistry and Chemical Engineering, Baoji University of Arts and Sciences, Baoji 721013, China
† These authors have contributed equally to this work.
Metabolites 2022, 12(11), 1011; https://doi.org/10.3390/metabo12111011 - 23 Oct 2022
Cited by 17 | Viewed by 3331
Abstract
Glucose absorption promoters perform insulin mimic functions to enhance blood glucose transport to skeletal muscle cells and accelerate glucose consumption, thereby reducing blood glucose levels. In our screening exploration of food ingredients for improving glucose transportation and metabolism, we found that the saponins [...] Read more.
Glucose absorption promoters perform insulin mimic functions to enhance blood glucose transport to skeletal muscle cells and accelerate glucose consumption, thereby reducing blood glucose levels. In our screening exploration of food ingredients for improving glucose transportation and metabolism, we found that the saponins in American ginseng (Panaxquinquefolius L.) showed potential activity to promote glucose uptake, which can be used for stabilizing levels of postprandial blood glucose. The aim of this study was to identify key components of American ginseng with glucose uptake-promoting activity and to elucidate their metabolic regulatory mechanisms. Bio-guided isolation using zebrafish larvae and 2-NBDG indicator identified ginsenoside Rb1 (GRb1) as the most potential promotor of glucose uptake. Using UPLC-QTOF-MS/MS combined with RT-qPCR and phenotypic verification, we found that riboflavin metabolism is the hinge for GRb1-mediated facilitation of glucose transport. GRb1-induced restoration of redox homeostasis was mediated by targeting riboflavin transporters (SLC52A1 and SLC52A3) and riboflavin kinase (RFK). Full article
(This article belongs to the Special Issue Functional Foods and Diabetes)
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12 pages, 310 KB  
Review
Familial Hypercholesterolemia and Lipoprotein(a): A Gordian Knot in Cardiovascular Prevention
by Amalia Despoina Koutsogianni 1, Petros Spyridonas Adamidis 1, Fotios Barkas 2, Evangelos Liberopoulos 3, Ta-Chen Su 4, Shizuya Yamashita 5, George Liamis 1 and Manfredi Rizzo 6,*
1 Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
2 Department of Hygiene and Epidemiology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
3 1st Propaedeutic Department of Medicine, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, 10679 Athens, Greece
4 Departments of Environmental and Occupational Medicine and Internal Medicine, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei 10617, Taiwan
5 Department of Cardiology, Rinku General Medical Center, Rinku Ourai Kita 2-23, Osaka 598-8577, Japan
6 Department of Internal Medicine and Medical Specialties, School of Medicine, University of Palermo, 90133 Palermo, Italy
Metabolites 2022, 12(11), 1065; https://doi.org/10.3390/metabo12111065 - 4 Nov 2022
Cited by 16 | Viewed by 3391
Abstract
Familial hypercholesterolemia (FH) is the most frequent genetic disorder resulting in increased low-density lipoprotein cholesterol (LDL-C) levels from childhood, leading to premature atherosclerotic cardiovascular disease (ASCVD) if left untreated. FH diagnosis is based on clinical criteria and/or genetic testing and its prevalence is [...] Read more.
Familial hypercholesterolemia (FH) is the most frequent genetic disorder resulting in increased low-density lipoprotein cholesterol (LDL-C) levels from childhood, leading to premature atherosclerotic cardiovascular disease (ASCVD) if left untreated. FH diagnosis is based on clinical criteria and/or genetic testing and its prevalence is estimated as being up to 1:300,000–400,000 for the homozygous and ~1:200–300 for the heterozygous form. Apart from its late diagnosis, FH is also undertreated, despite the available lipid-lowering therapies. In addition, elevated lipoprotein(a) (Lp(a)) (>50 mg/dL; 120 nmol/L), mostly genetically determined, has been identified as an important cardiovascular risk factor with prevalence rate of ~20% in the general population. Novel Lp(a)-lowering therapies have been recently developed and their cardiovascular efficacy is currently investigated. Although a considerable proportion of FH patients is also diagnosed with high Lp(a) levels, there is a debate whether these two entities are associated. Nevertheless, Lp(a), particularly among patients with FH, has been established as a significant cardiovascular risk factor. In this narrative review, we present up-to-date evidence on the pathophysiology, diagnosis, and treatment of both FH and elevated Lp(a) with a special focus on their association and joint effect on ASCVD risk. Full article
(This article belongs to the Special Issue The Role of Lipid Metabolism in Dyslipidemias and Atherosclerosis)
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17 pages, 1497 KB  
Article
Development and Validation of Risk Prediction Models for Gestational Diabetes Mellitus Using Four Different Methods
by Ning Wang 1,2,†, Haonan Guo 3,†, Yingyu Jing 3,†, Lin Song 4, Huan Chen 3, Mengjun Wang 4,5, Lei Gao 1, Lili Huang 6, Yanan Song 1, Bo Sun 4,*, Wei Cui 2,3,* and Jing Xu 1,2,*
1 Department of Endocrinology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
2 International Center for Obesity and Metabolic Disease Research of Xi’an Jiaotong University, Xi’an 710061, China
3 Department of Endocrinology and Second Department of Geriatrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
4 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China
5 Department of Endocrinology, 521 Hospital of Norinco Group, Xi’an 710065, China
6 Department of Medical Ultrasound, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
† Ning Wang, Haonan Guo, and Yingyu Jing contributed equally to this work.
Metabolites 2022, 12(11), 1040; https://doi.org/10.3390/metabo12111040 - 29 Oct 2022
Cited by 16 | Viewed by 4085
Abstract
Gestational diabetes mellitus (GDM), a common perinatal disease, is related to increased risks of maternal and neonatal adverse perinatal outcomes. We aimed to establish GDM risk prediction models that can be widely used in the first trimester using four different methods, including a [...] Read more.
Gestational diabetes mellitus (GDM), a common perinatal disease, is related to increased risks of maternal and neonatal adverse perinatal outcomes. We aimed to establish GDM risk prediction models that can be widely used in the first trimester using four different methods, including a score-scaled model derived from a meta-analysis using 42 studies, a logistic regression model, and two machine learning models (decision tree and random forest algorithms). The score-scaled model (seven variables) was established via a meta-analysis and a stratified cohort of 1075 Chinese pregnant women from the Northwest Women’s and Children’s Hospital (NWCH) and showed an area under the curve (AUC) of 0.772. The logistic regression model (seven variables) was established and validated using the above cohort and showed AUCs of 0.799 and 0.834 for the training and validation sets, respectively. Another two models were established using the decision tree (DT) and random forest (RF) algorithms and showed corresponding AUCs of 0.825 and 0.823 for the training set, and 0.816 and 0.827 for the validation set. The validation of the developed models suggested good performance in a cohort derived from another period. The score-scaled GDM prediction model, the logistic regression GDM prediction model, and the two machine learning GDM prediction models could be employed to identify pregnant women with a high risk of GDM using common clinical indicators, and interventions can be sought promptly. Full article
(This article belongs to the Special Issue Metabolomics in the Interventions of Metabolic Diseases and Physical Activity)
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20 pages, 3780 KB  
Article
Analysis of Galangin and Its In Vitro/In Vivo Metabolites via Ultra-High-Performance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry
by Feng Zhao 1,†, Yinling Ma 2,†, Jintuo Yin 1, Ying Li 2, Yanli Cao 2 and Lantong Zhang 1,*
1 School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China
2 National Clinical Drug Monitoring Center, Department of Pharmacy, Hebei Province General Center, Shijiazhuang 050051, China
† These authors contributed equally to this work.
Metabolites 2022, 12(11), 1032; https://doi.org/10.3390/metabo12111032 - 28 Oct 2022
Cited by 16 | Viewed by 3146
Abstract
Galangin, a naturally available flavonoid, induces a variety of pharmacological activities and biological effects via several mechanisms. However, in vivo metabolism of galangin has not been fully explored, which means knowledge of its pharmacodynamics and application potential is limited. The objective of this [...] Read more.
Galangin, a naturally available flavonoid, induces a variety of pharmacological activities and biological effects via several mechanisms. However, in vivo metabolism of galangin has not been fully explored, which means knowledge of its pharmacodynamics and application potential is limited. The objective of this study was to establish an ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry method for the rapid profiling and identification of galangin metabolites in vitro and in vivo using unique online information-dependent acquisition with multiple mass defect filtering combined with dynamic background subtraction in positive ion mode. A total of 27 metabolites were detected and characterized, among which eight metabolites in liver microsomes and four metabolites in intestinal microflora were characterized, and 27 metabolites from rat plasma, bile, urine, feces, and a number of different tissue samples were characterized. Thirteen major metabolic pathways including hydrogenation, hydroxylation, glycosylation, methylation, acetylation, glucuronidation, and sulfation were observed to be attributable to the biotransformation of the metabolites. This study provides evidence for the presence of in vitro and in vivo metabolites and the pharmacokinetic mechanism of galangin. Moreover, the study promotes the further development and utilization of galangin and the plant from which it is derived, Alpinia officinarum Hance. Full article
(This article belongs to the Collection Feature Papers Related to "Metabolomic Profiling Technology" Section)
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Graphical abstract