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Fulltext Organ-Specific Analysis of Morus alba Using a Gel-Free/Label-Free Proteomic Technique

Zhu W, Zhong Z, Liu S, Yang B, Komatsu S, Ge Z, et al.

Int J Mol Sci, 2019 Jan 16;20(2).
PMID: 30654535 DOI: 10.3390/ijms20020365

Morus alba is an important medicinal plant that is used to treat human diseases. The leaf, branch, and root of Morus can be applied as antidiabetic, antioxidant, and anti-inflammatory medicines, respectively. To explore the molecular mechanisms underlying the various pharmacological functions within different parts of Morus, organ-specific proteomics were performed. Protein profiles of the Morus leaf, branch, and root were determined using a gel-free/label-free proteomic technique. In the Morus leaf, branch, and root, a total of 492, 414, and 355 proteins were identified, respectively, including 84 common proteins. In leaf, the main function was related to protein degradation, photosynthesis, and redox ascorbate/glutathione metabolism. In branch, the main function was related to protein synthesis/degradation, stress, and redox ascorbate/glutathione metabolism. In root, the main function was related to protein synthesis/degradation, stress, and cell wall. Additionally, organ-specific metabolites and antioxidant activities were analyzed. These results revealed that flavonoids were highly accumulated in Morus root compared with the branch and leaf. Accordingly, two root-specific proteins named chalcone flavanone isomerase and flavonoid 3,5-hydroxylase were accumulated in the flavonoid pathway. Consistent with this finding, the content of the total flavonoids was higher in root compared to those detected in branch and leaf. These results suggest that the flavonoids in Morus root might be responsible for its biological activity and the root is the main part for flavonoid biosynthesis in Morus.

Matched MeSH terms: Secondary Metabolism
Gut bacteria of animals living in polluted environments exhibit broad-spectrum antibacterial activities

Akbar N, Siddiqui R, Sagathevan K, Khan NA

Int Microbiol, 2020 Nov;23(4):511-526.
PMID: 32124096 DOI: 10.1007/s10123-020-00123-3

Infectious diseases, in particular bacterial infections, are the leading cause of morbidity and mortality posing a global threat to human health. The emergence of antibiotic resistance has exacerbated the problem further. Hence, there is a need to search for novel sources of antibacterials. Herein, we explored gut bacteria of a variety of animals living in polluted environments for their antibacterial properties against multi-drug resistant pathogenic bacteria. A variety of species were procured including invertebrate species, Blaptica dubia (cockroach), Gromphadorhina portentosa (cockroach), Scylla serrata (crab), Grammostola rosea (tarantula), Scolopendra subspinipes (centipede) and vertebrate species including Varanus salvator (water monitor lizard), Malayopython reticulatus (python), Cuora amboinensis (tortoise), Oreochromis mossambicus (tilapia fish), Rattus rattus (rat), Gallus gallus domesticus (chicken) and Lithobates catesbeianus (frog). Gut bacteria of these animals were isolated and identified using microbiological, biochemical, analytical profiling index (API) and through molecluar identification using 16S rRNA sequencing. Bacterial conditioned media (CM) were prepared and tested against selected Gram-positive and Gram-negative pathogenic bacteria as well as human cells (HaCaT). The results revealed that CM exhibited significant broad-spectrum antibacterial activities. Upon heat inactivation, CM retained their antibacterial properties suggesting that this effect may be due to secondary metabolites or small peptides. CM showed minimal cytotoxicity against human cells. These findings suggest that gut bacteria of animals living in polluted environments produce broad-spectrum antibacterial molecule(s). The molecular identity of the active molecule(s) together with their mode of action is the subject of future studies which could lead to the rational development of novel antibacterial(s).

Matched MeSH terms: Secondary Metabolism
Fulltext Alpha-Mangostin-Rich Extracts from Mangosteen Pericarp: Optimization of Green Extraction Protocol and Evaluation of Biological Activity

Ghasemzadeh A, Jaafar HZE, Baghdadi A, Tayebi-Meigooni A

Molecules, 2018 Jul 25;23(8).
PMID: 30044450 DOI: 10.3390/molecules23081852

Since α-mangostin in mangosteen fruits was reported to be the main compound able to provide natural antioxidants, the microwave-assisted extraction process to obtain high-quality α-mangostin from mangosteen pericarp (Garcinia mangostana L.) was optimized using a central composite design and response surface methodology. The parameters examined included extraction time, microwave power, and solvent percentage. The antioxidant and antimicrobial activity of optimized and non-optimized extracts was evaluated. Ethyl acetate as a green solvent exhibited the highest concentration of α-mangostin, followed by dichloromethane, ethanol, and water. The highest α-mangostin concentration in mangosteen pericarp of 121.01 mg/g dry matter (DM) was predicted at 3.16 min, 189.20 W, and 72.40% (v/v). The verification of experimental results under these optimized conditions showed that the α-mangostin value for the mangosteen pericarp was 120.68 mg/g DM. The predicted models were successfully developed to extract α-mangostin from the mangosteen pericarp. No significant differences were observed between the predicted and the experimental α-mangostin values, indicating that the developed models are accurate. The analysis of the extracts for secondary metabolites showed that the total phenolic content (TPC) and total flavonoid content (TFC) increased significantly in the optimized extracts (OE) compared to the non-optimized extracts (NOE). Additionally, trans-ferulic acid and catechin were abundant among the compounds identified. In addition, the optimized extract of mangosteen pericarp with its higher α-mangostin and secondary metabolite concentrations exhibited higher antioxidant activities with half maximal inhibitory concentration (IC50) values of 20.64 µg/mL compared to those of the NOE (28.50 µg/mL). The OE exhibited the highest antibacterial activity, particularly against Gram-positive bacteria. In this study, the microwave-assisted extraction process of α-mangostin from mangosteen pericarp was successfully optimized, indicating the accuracy of the models developed, which will be usable in a larger-scale extraction process.

Matched MeSH terms: Secondary Metabolism
Fulltext Psychrotolerant Mesorhizobium sp. Isolated from Temperate and Cold Desert Regions Solubilizes Potassium and Produces Multiple Plant Growth Promoting Metabolites

Baba ZA, Hamid B, Sheikh TA, Alotaibi SH, El Enshasy HA, Ansari MJ, et al.

Molecules, 2021 Sep 23;26(19).
PMID: 34641302 DOI: 10.3390/molecules26195758

Soil potassium (K) supplement depends intensively on the application of chemical fertilizers, which have substantial harmful environmental effects. However, some bacteria can act as inoculants by converting unavailable and insoluble K forms into plant-accessible forms. Such bacteria are an eco-friendly approach for enhancing plant K absorption and consequently reducing utilization of chemical fertilization. Therefore, the present research was undertaken to isolate, screen, and characterize the K solubilizing bacteria (KSB) from the rhizosphere soils of northern India. Overall, 110 strains were isolated, but only 13 isolates showed significant K solubilizing ability by forming a halo zone on solid media. They were further screened for K solubilizing activity at 0 °C, 1 °C, 3 °C, 5 °C, 7 °C, 15 °C, and 20 °C for 5, 10, and 20 days. All the bacterial isolates showed mineral K solubilization activity at these different temperatures. However, the content of K solubilization increased with the upsurge in temperature and period of incubation. The isolate KSB (Grz) showed the highest K solubilization index of 462.28% after 48 h of incubation at 20 °C. The maximum of 23.38 µg K/mL broth was solubilized by the isolate KSB (Grz) at 20 °C after 20 days of incubation. Based on morphological, biochemical, and molecular characterization (through the 16S rDNA approach), the isolate KSB (Grz) was identified as Mesorhizobium sp. The majority of the strains produced HCN and ammonia. The maximum indole acetic acid (IAA) (31.54 µM/mL) and cellulase (390 µM/mL) were produced by the isolate KSB (Grz). In contrast, the highest protease (525.12 µM/mL) and chitinase (5.20 µM/mL) activities were shown by standard strain Bacillus mucilaginosus and KSB (Gmr) isolate, respectively.

Matched MeSH terms: Secondary Metabolism
Fulltext Biophysical characterization of antibacterial compounds derived from pathogenic fungi Ganoderma boninense

Abdullah S, Oh YS, Kwak MK, Chong K

J Microbiol, 2021 Feb;59(2):164-174.
PMID: 33355891 DOI: 10.1007/s12275-021-0551-8

There have been relatively few studies which support a link between Ganoderma boninense, a phytopathogenic fungus that is particularly cytotoxic and pathogenic to plant tissues and roots, and antimicrobial compounds. We previously observed that liquid-liquid extraction (LLE) using chloroformmethanol-water at a ratio (1:1:1) was superior at detecting antibacterial activities and significant quantities of antibacterial compounds. Herein, we demonstrate that antibacterial secondary metabolites are produced from G. boninense mycelia. Antibacterial compounds were monitored in concurrent biochemical and biophysical experiments. The combined methods included high performance thin-layer chromatography (HPTLC), gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), fourier transform infrared (FTIR), and nuclear magnetic resonance (NMR) spectroscopy. The antibacterial compounds derived from mycelia with chloroform-methanol extraction through LLE were isolated via a gradient solvent elution system using HPTLC. The antibacterial activity of the isolated compounds was observed to be the most potent against Staphylococcus aureus ATCC 25923 and multidrug-resistant S. aureus NCTC 11939. GC-MS, HPLC, and FTIR analysis confirmed two antibacterial compounds, which were identified as 4,4,14α-trimethylcholestane (m/z = 414.75; lanostane, C30H54) and ergosta-5,7,22-trien-3β-ol (m/z = 396.65; ergosterol, C28H44O). With the aid of spectroscopic evaluations, ganoboninketal (m/z = 498.66, C30H42O6), which belongs to the 3,4-seco-27-norlanostane triterpene family, was additionally characterized by 2D-NMR analysis. Despite the lack of antibacterial potential exhibited by lanostane; both ergosterol and ganoboninketal displayed significant antibacterial activities against bacterial pathogens. Results provide evidence for the existence of bioactive compounds in the mycelia of the relatively unexplored phytopathogenic G. boninense, together with a robust method for estimating the corresponding potent antibacterial secondary metabolites.

Matched MeSH terms: Secondary Metabolism
Fulltext Inactivating pathogenic bacteria in greywater by biosynthesized Cu/Zn nanoparticles from secondary metabolite of Aspergillus iizukae; optimization, mechanism and techno economic analysis

Noman E, Al-Gheethi A, Talip BA, Mohamed R, Kassim AH

PLoS One, 2019;14(9):e0221522.
PMID: 31513594 DOI: 10.1371/journal.pone.0221522

The inactivation of antibiotic resistant Escherichia coli (Gram negative) and Staphylococcus aureus (Gram positive) seeded in greywater by bimetallic bio-nanoparticles was optimized by using response surface methodology (RSM). The bimetallic nanoparticles (Cu/Zn NPs) were synthesized in secondary metabolite of a novel fungal strain identified as Aspergillus iizukae EAN605 grown in pumpkin medium. Cu/Zn NPs were very effective for inhibiting growth of E. coli and S. aureus. The maximum inactivation was optimized with 0.028 mg mL-1 of Cu/Zn NPs, at pH 6 and after 60 min, at which the reduction of E. coli and S. aureus was 5.6 vs. 5.3 and 5.2 vs. 5.4 log reduction for actual and predicted values, respectively. The inactivation mechanism was described based on the analysis of untreated and treated bacterial cells by Field emission scanning electron microscopy (FESEM), Energy Dispersive X-Ray Spectroscopy (EDS), Atomic Force Microscopy (AFM) revealed a damage in the cell wall structure due to the effect of Cu/Zn NPs. Moreover, the Raman Spectroscopy showed that the Cu/Zn NPs led to degradation of carbohydrates and amino structures on the bacteria cell wall. The Fourier transform infrared spectroscopy (FTIR) analysis confirmed that the destruction take place in the C-C bond of the functional groups available in the bacterial cell wall. The techno economic analysis revealed that the biosynthesis Cu/Zn NPs is economically feasible. These findings demonstrated that Cu/Zn NPs can effectively inhibit pathogenic bacteria in the greywater.

Matched MeSH terms: Secondary Metabolism
New insights into the phytochemical composition, enzyme inhibition and antioxidant properties of desert cotton (Aerva javanica (Bum.f) Shult. -Amaranthaceae)

Saleem H, Zengin G, Khan KU, Ahmad I, Waqas M, Mahomoodally FM, et al.

Nat Prod Res, 2021 Feb;35(4):664-668.
PMID: 30919661 DOI: 10.1080/14786419.2019.1587427

This study sets out to probe into total bioactive contents, UHPLC-MS secondary metabolites profiling, antioxidant (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum and metal chelating) and enzyme inhibitory (acetylcholinesterase- AChE, butyrylcholinesterase- BChE, α-amylase, α glucosidase, and tyrosinase) activities of methanol extract of Aerva javanica, also known as desert cotton or Kapok bush. Aerva javanica contains considerable phenolic (44.79 ± 3.12 mg GAE/g) and flavonoid (28.86 ± 0.12 mg QE/g) contents which tends to correlate with its significant antioxidant potential for ABTS, FRAP and CUPRAC assays with values of 101.41 ± 1.18, 124.10 ± 1.71 and 190.22 ± 5.70 mg TE/g, respectively. The UHPLC-MS analysis identified the presence of 45 phytochemicals belonging to six major groups: phenolic, flavonoids, lignin, terpenes, glycoside and alkaloid. Moreover, the plant extract also showed potent inhibitory action against AChE (3.73 ± 0.22 mg GALAE/g), BChE (3.31 ± 0.19 mg GALAE/g) and tyrosinase (126.05 ± 1.77 mg KAE/g). The observed results suggest A. javanica could be further explored as a natural source of bioactive compounds.

Matched MeSH terms: Secondary Metabolism
Fulltext Efficacy of metabolites of a Streptomyces strain (AS1) to control growth and mycotoxin production by Penicillium verrucosum, Fusarium verticillioides and Aspergillus fumigatus in culture

Danial AM, Medina A, Sulyok M, Magan N

Mycotoxin Res, 2020 May;36(2):225-234.
PMID: 31960351 DOI: 10.1007/s12550-020-00388-7

The objectives of this study were to determine the efficacy of metabolites of a Streptomyces strain AS1 on (a) spore germination, (b) mycelial growth, (c) control of mycotoxins produced by Penicillium verrucosum (ochratoxin A, OTA), Fusarium verticillioides (fumonisins, FUMs) and Aspergillus fumigatus (gliotoxin) and (d) identify the predominant metabolites involved in control. Initial screening showed that the Streptomyces AS1 strain was able to inhibit the mycelial growth of the three species at a distance, due to the release of secondary metabolites. A macroscopic screening system showed that the overall Index of Dominance against all three toxigenic fungi was inhibition at a distance. Subsequent studies showed that the metabolite mixture from the Streptomyces AS1 strain was very effective at inhibiting conidial germination of P. verrucosum, but less so against conidia of A. fumigatus and F. verticillioides. The efficacy was confirmed in studies on a conducive semi-solid YES medium in BioScreen C assays. Using the BioScreen C and the criteria of Time to Detection (TTD) at an OD = 0.1 showed good efficacy against P. verrucosum when treated with the Streptomyces AS1 extract at 0.95 and 0.99 water activity (aw) when compared to the other two species tested, indicating good efficacy. The effective dose for 50% control of growth (ED50) at 0.95 and 0.99 aw were approx. 0.005 ng/ml and 0.15 μg/ml, respectively, with the minimum inhibitory concentration (MIC) at both aw levels requiring > 40 μg/ml. In addition, OTA production was completely inhibited by 2.5 μg/ml AS1 extract at both aw levels in the in vitro assays. Ten metabolites were identified with four of these being predominant in concentrations > 2 μg/g dry weight biomass. These were identified as valinomycin, cyclo(L-Pro-L-Tyr), cyclo(L-Pro-L-Val) and brevianamide F.

Matched MeSH terms: Secondary Metabolism
Fulltext Isolation, Purification, and Characterization of Five Active Diketopiperazine Derivatives from Endophytic Streptomyces SUK 25 with Antimicrobial and Cytotoxic Activities

Alshaibani M, Zin NM, Jalil J, Sidik N, Ahmad SJ, Kamal N, et al.

J Microbiol Biotechnol, 2017 07 28;27(7):1249-1256.
PMID: 28535606 DOI: 10.4014/jmb.1608.08032

In our search for new sources of bioactive secondary metabolites from Streptomyces sp., the ethyl acetate extracts from endophytic Streptomyces SUK 25 afforded five active diketopiperazine (DKP) compounds. The aim of this study was to characterize the bioactive compounds isolated from endophytic Streptomyces SUK 25 and evaluate their bioactivity against multiple drug resistance (MDR) bacteria such as Enterococcus raffinosus, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter spp., and their cytotoxic activities against the human hepatoma (HepaRG) cell line. The production of secondary metabolites by this strain was optimized through Thornton's medium. Isolation, purification, and identification of the bioactive compounds were carried out using high-performance liquid chromatography, high-resolution mass liquid chromatography-mass spectrometry, Fourier transform infrared spectroscopy, and nuclear magnetic resonance, and cryopreserved HepaRG cells were selected to test the cytotoxicity. The results showed that endophytic Streptomyces SUK 25 produces four active DKP compounds and an acetamide derivative, which were elucidated as cyclo-(L-Val-L-Pro), cyclo-(L-Leu-L-Pro), cyclo-(L-Phe-L-Pro), cyclo-(L-Val-L-Phe), and N-(7-hydroxy-6-methyl-octyl)-acetamide. These active compounds exhibited activity against methicillin-resistant S. aureus ATCC 43300 and Enterococcus raffinosus, with low toxicity against human hepatoma HepaRG cells. Endophytic Streptomyces SUK 25 has the ability to produce DKP derivatives biologically active against some MDR bacteria with relatively low toxicity against HepaRG cells line.

Matched MeSH terms: Secondary Metabolism
Novel targets of pentacyclic triterpenoids in Staphylococcus aureus: A systematic review

Chung PY

Phytomedicine, 2020 Jul 15;73:152933.
PMID: 31103429 DOI: 10.1016/j.phymed.2019.152933

BACKGROUND: Staphylococcus aureus is an important pathogen both in community-acquired and healthcare-associated infections, and has successfully evolved numerous strategies for resisting the action to practically all antibiotics. Resistance to methicillin is now widely described in the community setting (CMRSA), thus the development of new drugs or alternative therapies is urgently necessary. Plants and their secondary metabolites have been a major alternative source in providing structurally diverse bioactive compounds as potential therapeutic agents for the treatment of bacterial infections. One of the classes of natural secondary metabolites from plants with the most bioactive compounds are the triterpenoids, which comprises structurally diverse organic compounds. In nature, triterpenoids are often found as tetra- or penta-cyclic structures.
AIM: This review highlights the anti-staphylococcal activities of pentacyclic triterpenoids, particularly α-amyrin (AM), betulinic acid (BA) and betulinaldehyde (BE). These compounds are based on a 30-carbon skeleton comprising five six-membered rings (ursanes and lanostanes) or four six-membered rings and one five-membered ring (lupanes and hopanes).
METHODS: Electronic databases such as ScienceDirect, PubMed and Scopus were used to search scientific contributions until March 2018, using relevant keywords. Literature focusing on the antimicrobial and antibiofilms of effects of pentacyclic triterpenoids on S. aureus were identified and summarized.
RESULTS: Pentacyclic triterpenoids can be divided into three representative classes, namely ursane, lupane and oleananes. This class of compounds have been shown to exhibit analgesic, immunomodulatory, anti-inflammatory, anticancer, antioxidant, antifungal and antibacterial activities. In studies of the antimicrobial activities and targets of AM, BA and BE in sensitive and multidrug-resistant S. aureus, these compounds acted synergistically and have different targets from the conventional antibiotics.
CONCLUSION: The inhibitory mechanisms of S. aureus in novel targets and pathways should stimulate further researches to develop AM, BA and BE as therapeutic agents for infections caused by S. aureus. Continued efforts to identify and exploit synergistic combinations by the three compounds and peptidoglycan inhibitors, are also necessary as alternative treatment options for S. aureus infections.

Matched MeSH terms: Secondary Metabolism
Fulltext Can the intake of antiparasitic secondary metabolites explain the low prevalence of hemoparasites among wild Psittaciformes?

Masello JF, Martínez J, Calderón L, Wink M, Quillfeldt P, Sanz V, et al.

Parasit Vectors, 2018 Jun 19;11(1):357.
PMID: 29921331 DOI: 10.1186/s13071-018-2940-3

BACKGROUND: Parasites can exert selection pressure on their hosts through effects on survival, on reproductive success, on sexually selected ornament, with important ecological and evolutionary consequences, such as changes in population viability. Consequently, hemoparasites have become the focus of recent avian studies. Infection varies significantly among taxa. Various factors might explain the differences in infection among taxa, including habitat, climate, host density, the presence of vectors, life history and immune defence. Feeding behaviour can also be relevant both through increased exposure to vectors and consumption of secondary metabolites with preventative or therapeutic effects that can reduce parasite load. However, the latter has been little investigated. Psittaciformes (parrots and cockatoos) are a good model to investigate these topics, as they are known to use biological control against ectoparasites and to feed on toxic food. We investigated the presence of avian malaria parasites (Plasmodium), intracellular haemosporidians (Haemoproteus, Leucocytozoon), unicellular flagellate protozoans (Trypanosoma) and microfilariae in 19 Psittaciformes species from a range of habitats in the Indo-Malayan, Australasian and Neotropical regions. We gathered additional data on hemoparasites in wild Psittaciformes from the literature. We considered factors that may control the presence of hemoparasites in the Psittaciformes, compiling information on diet, habitat, and climate. Furthermore, we investigated the role of diet in providing antiparasitic secondary metabolites that could be used as self-medication to reduce parasite load.
RESULTS: We found hemoparasites in only two of 19 species sampled. Among them, all species that consume at least one food item known for its secondary metabolites with antimalarial, trypanocidal or general antiparasitic properties, were free from hemoparasites. In contrast, the infected parrots do not consume food items with antimalarial or even general antiparasitic properties. We found that the two infected species in this study consumed omnivorous diets. When we combined our data with data from studies previously investigating blood parasites in wild parrots, the positive relationship between omnivorous diets and hemoparasite infestation was confirmed. Individuals from open habitats were less infected than those from forests.
CONCLUSIONS: The consumption of food items known for their secondary metabolites with antimalarial, trypanocidal or general antiparasitic properties, as well as the higher proportion of infected species among omnivorous parrots, could explain the low prevalence of hemoparasites reported in many vertebrates.

Matched MeSH terms: Secondary Metabolism

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