Potential Anti-Mycobacterium tuberculosis Activity of Plant Secondary Metabolites: Insight with Molecular Docking Interactions

Tuberculosis (TB) is a recurrent and progressive disease, with high mortality rates worldwide. The drug-resistance phenomenon of Mycobacterium tuberculosis is a major obstruction of allelopathy treatment. An adverse side effect of allelopathic treatment is that it causes serious health complications. The search for suitable alternatives of conventional regimens is needed, i.e., by considering medicinal plant secondary metabolites to explore anti-TB drugs, targeting the action site of M. tuberculosis. Nowadays, plant-derived secondary metabolites are widely known for their beneficial uses, i.e., as antioxidants, antimicrobial agents, and in the treatment of a wide range of chronic human diseases (e.g., tuberculosis), and are known to “thwart” disease virulence. In this regard, in silico studies can reveal the inhibitory potential of plant-derived secondary metabolites against Mycobacterium at the very early stage of infection. Computational approaches based on different algorithms could play a significant role in screening plant metabolites against disease virulence of tuberculosis for drug designing.

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Target screening of plant secondary metabolites in river waters by liquid chromatography coupled to high-resolution mass spectrometry (LC–HRMS)

Environmental Sciences Europe ◽

10.1186/s12302-020-00399-2 ◽

2020 ◽

Vol 32 (1) ◽

Author(s):

Mulatu Yohannes Nanusha ◽

Martin Krauss ◽

Carina D. Schönsee ◽

Barbara F. Günthardt ◽

Thomas D. Bucheli ◽

...

Keyword(s):

Secondary Metabolites ◽

Surface Waters ◽

High Resolution Mass Spectrometry ◽

Water Cycle ◽

Endocrine Disrupting Chemicals ◽

Plant Secondary Metabolites ◽

Biologically Active ◽

Plant Metabolites ◽

River Waters ◽

Target Screening

Abstract Background Substantial efforts have been made to monitor potentially hazardous anthropogenic contaminants in surface waters while for plant secondary metabolites (PSMs) almost no data on occurrence in the water cycle are available. These metabolites enter river waters through various pathways such as leaching, surface run-off and rain sewers or input of litter from vegetation and might add to the biological activity of the chemical mixture. To reduce this data gap, we conducted a LC–HRMS target screening in river waters from two different catchments for 150 plant metabolites which were selected from a larger database considering their expected abundance in the vegetation, their potential mobility, persistence and toxicity in the water cycle and commercial availability of standards. Results The screening revealed the presence of 12 out of 150 possibly toxic PSMs including coumarins (bergapten, scopoletin, fraxidin, esculetin and psoralen), a flavonoid (formononetin) and alkaloids (lycorine and narciclasine). The compounds narciclasine and lycorine were detected at concentrations up to 3 µg/L while esculetin and fraxidin occurred at concentrations above 1 µg/L. Nine compounds occurred at concentrations above 0.1 µg/L, the Threshold for Toxicological Concern (TTC) for non-genotoxic and non-endocrine disrupting chemicals in drinking water. Conclusions Our study provides an overview of potentially biologically active PSMs in surface waters and recommends their consideration in monitoring and risk assessment of water resources. This is currently hampered by a lack of effect data including toxicity to aquatic organisms, endocrine disruption and genotoxicity and demands for involvement of these compounds in biotesting.

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The Health Promoting Bioactivities of Lactuca sativa can be Enhanced by Genetic Modulation of Plant Secondary Metabolites

Metabolites ◽

10.3390/metabo9050097 ◽

2019 ◽

Vol 9 (5) ◽

pp. 97 ◽

Cited By ~ 4

Author(s):

Hammad Ismail ◽

Anna L. Gillespie ◽

Danielle Calderwood ◽

Haroon Iqbal ◽

Colene Gallagher ◽

...

Keyword(s):

Secondary Metabolites ◽

Lactuca Sativa ◽

Genetic Manipulation ◽

Sesquiterpene Lactones ◽

Plant Secondary Metabolites ◽

Rol Genes ◽

In Vitro Bioactivity ◽

New Paradigm ◽

Plant Metabolites

Plant secondary metabolites are protective dietary constituents and rol genes evidently increase the synthesis of these versatile phytochemicals. This study subjected a globally important vegetable, lettuce (Lactuca sativa) to a combination of untargeted metabolomics (LC-QTof-MS) and in vitro bioactivity assays. Specifically, we examined the differences between untransformed cultured lettuce (UnT), lettuce transformed with either rolABC (RA) or rolC (RC) and commercially grown (COM) lettuce. Of the 5333 metabolite features aligned, deconvoluted and quantified 3637, 1792 and 3737 significantly differed in RA, RC and COM, respectively, compared with UnT. In all cases the number of downregulated metabolites exceeded the number increased. In vitro bioactivity assays showed that RA and RC (but not COM) significantly improved the ability of L. sativa to inhibit α-glucosidase, inhibit dipeptidyl peptidase-4 (DPP-4) and stimulate GLP-1 secretion. We putatively identified 76 lettuce metabolites (sesquiterpene lactones, non-phenolic and phenolic compounds) some of which were altered by several thousand percent in RA and RC. Ferulic acid levels increased 3033–9777%, aminooxononanoic acid increased 1141–1803% and 2,3,5,4′tetrahydroxystilbene-2-O-β-d-glucoside increased 40,272–48,008%. Compound activities were confirmed using commercially obtained standards. In conclusion, rol gene transformation significantly alters the metabolome of L.sativa and enhances its antidiabetic properties. There is considerable potential to exploit rol genes to modulate secondary metabolite production for the development of novel functional foods. This investigation serves as a new paradigm whereby genetic manipulation, metabolomic analysis and bioactivity techniques can be combined to enable the discovery of novel natural bioactives and determine the functional significance of plant metabolites.

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Manipulation of Rumen Fermentation and Methane Gas Production by Plant Secondary Metabolites (Saponin, Tannin and Essential Oil) – A Review of Ten-Year Studies

Annals of Animal Science ◽

10.2478/aoas-2018-0037 ◽

2019 ◽

Vol 19 (1) ◽

pp. 3-29 ◽

Cited By ~ 7

Author(s):

Saied Jafari ◽

Mahdi Ebrahimi ◽

Yong M. Goh ◽

Mohamed A. Rajion ◽

Mohamed F. Jahromi ◽

...

Keyword(s):

Secondary Metabolites ◽

Reduction Potential ◽

Plant Secondary Metabolites ◽

Rumen Fermentation ◽

Gas Production ◽

Feed Additives ◽

Source Type ◽

Wide Range ◽

Fermentation Parameters ◽

Ruminant Feed

AbstractA wide range of plant secondary metabolites (PSM) have been shown to have the potential to modulate the fermentation process in the rumen. The use of plants and plant extracts as natural feed additives has become an interesting topic not only among nutritionists but also other scientists. Although a large number of phytochemicals (e.g. saponins, tannins and essential oils) have recently been investigated for their methane (CH4) reduction potential, there have not yet been major breakthroughs that could be applied in practice. However, the effectiveness of these PSM depends on the source, type and the level of their presence in plant products. The aim of the present review was to assess ruminal CH4 emission through a comparison of integrating related studies from published papers, which described various levels of different PSM sources being added to ruminant feed. Apart from CH4, other related rumen fermentation parameters were also included in this review.

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Simultaneous Identification and Quantification of Three Xanthones and Two Polyisoprenylated Benzophenones in Eight Indian Garcinia Species Using a Validated UHPLC-PDA Method

Journal of AOAC International ◽

10.1093/jaoac/102.5.1423 ◽

2019 ◽

Vol 102 (5) ◽

pp. 1423-1434

Author(s):

Azazahemad A Kureshi ◽

Chirag Dholakiya ◽

Tabaruk Hussain ◽

Amit Mirgal ◽

Siddhesh P Salvi ◽

...

Keyword(s):

Secondary Metabolites ◽

Mobile Phase ◽

Plant Secondary Metabolites ◽

Gradient Elution ◽

Garcinia Cambogia ◽

Wide Range ◽

Photodiode Array ◽

Simultaneous Identification ◽

Gradient Elution Mode ◽

Identification And Quantification

Abstract Background: Xanthones and polyisoprenylated benzophenones (PIBs) are two important classes of plant secondary metabolites with a wide range of bioactivities. Garcinia species synthesize numerous xanthones and PIBs. As per the literature, no data claiming simultaneous identification and quantification of three xanthones, α-mangostin, β-mangostin, γ-mangostin, and two PIBs, xanthochymol, isoxanthochymol, were found. Methods: A validated ultra-HPLC (UHPLC)-photodiode array (PDA) method for the simultaneous identification and quantification of five compounds in different extracts of eight Indian Garcinia species was developed. The compounds were separated on a Waters ACQUITY™ UPLC H-Class column using a mobile phase consisting of solvents 0.1% formic acid in water (A) and methanol (B) in gradient elution mode. The total run time was 9 min. Results: From fruit rinds of eight Indian Garcinia species, namely Garcinia cambogia, G. cowa, G. indica, G. loniceroides, G. mangostana, G. morella, G. pedunculata, and G. xanthochymus, extracts were prepared using solvents of varying polarity. These extracts were analyzed for five biologically important compounds, namely α-mangostin, β-mangostin, γ-mangostin, xanthochymol, and isoxanthochymol. The results revealed that there is a wide variation in concentration of these compounds in extracts of Garcinia species. Conclusions: The developed and validated UHPLC-PDA method could be used for simultaneous identification and quantification of these five compounds for bioprospection of other Garcinia species.

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Plant secondary metabolites as defenses, regulators and primary metabolites- The blurred functional trichotomy

10.31219/osf.io/6ba7r ◽

2020 ◽

Author(s):

Matthias Erb ◽

Daniel J. Kliebenstein

Keyword(s):

Secondary Metabolites ◽

Plant Growth ◽

Plant Secondary Metabolites ◽

Trophic Levels ◽

Primary Metabolism ◽

Plant Metabolites ◽

Small Molecular Weight ◽

Primary Metabolites ◽

Environmental Selection ◽

Plant Environment

The plant kingdom produces hundreds of thousands of small molecular weight organic compounds. Based on their assumed functions, the research community has classified them into three overarching groups: primary metabolites which are directly required for plant growth, secondary (or specialized) metabolites which mediate plant-environment interactions and hormones which regulate organismal processes, including metabolism. For decades, this functional trichotomy has shaped theory and experimentation in plant biology. However, evidence is accumulating that the boundaries between the different types of metabolites are blurred. An increasing number of mechanistic studies demonstrate that secondary metabolites are multifunctional and can act as potent regulators of plant growth and defense. Secondary metabolites are also re-integrated into primary metabolism, thus behaving like primary metabolites sensu lato. Several adaptive scenarios may have favored this functional diversity for secondary metabolites, including signaling robustness and cost-effective storage and recycling. Secondary metabolite multi-functionality can provide new explanations for ontogenetic patterns of defense production and can refine our understanding of plant-herbivore interactions, in particular by accounting for the discovery that adapted herbivores misuse plant secondary metabolites for multiple purposes, some of which mirror their functions in plants. In conclusion, recent work unveils the limits of our current classification system for plant metabolites and suggests that viewing them as integrated components of metabolic networks that are dynamically shaped by environmental selection pressures and transcend multiple trophic levels can improve our understanding of plant metabolism and plant-environment interactions.

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Phloroglucinol-Gold and -Zinc Oxide Nanoparticles: Antibiofilm and Antivirulence Activities towards Pseudomonas aeruginosa PAO1

Marine Drugs ◽

10.3390/md19110601 ◽

2021 ◽

Vol 19 (11) ◽

pp. 601

Author(s):

Fazlurrahman Khan ◽

Min-Gyun Kang ◽

Du-Min Jo ◽

Pathum Chandika ◽

Won-Kyo Jung ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Zinc Oxide ◽

Virulence Factors ◽

Antimicrobial Agents ◽

Early Stage ◽

Nanoparticle Synthesis ◽

Synthesis Of Nanoparticles ◽

Human Pathogenic Bacterium ◽

Wide Range ◽

Materials Used

With the advancement of nanotechnology, several nanoparticles have been synthesized as antimicrobial agents by utilizing biologically derived materials. In most cases, the materials used for the synthesis of nanoparticles from natural sources are extracts. Natural extracts contain a wide range of bioactive components, making it difficult to pinpoint the exact component responsible for nanoparticle synthesis. Furthermore, the bioactive component present in the extract changes according to numerous environmental factors. As a result, the current work intended to synthesize gold (AuNPs) and zinc oxide (ZnONPs) nanoparticles using pure phloroglucinol (PG). The synthesized PG-AuNPs and PG-ZnONPs were characterized using a UV–Vis absorption spectrophotometer, FTIR, DLS, FE-TEM, zeta potential, EDS, and energy-dispersive X-ray diffraction. The characterized PG-AuNPs and PG-ZnONPs have been employed to combat the pathogenesis of Pseudomonas aeruginosa. P. aeruginosa is recognized as one of the most prevalent pathogens responsible for the common cause of nosocomial infection in humans. Antimicrobial resistance in P. aeruginosa has been linked to the development of recalcitrant phenotypic characteristics, such as biofilm, which has been identified as one of the major obstacles to antimicrobial therapy. Furthermore, P. aeruginosa generates various virulence factors that are a major cause of chronic infection. These PG-AuNPs and PG-ZnONPs significantly inhibit early stage biofilm and eradicate mature biofilm. Furthermore, these NPs reduce P. aeruginosa virulence factors such as pyoverdine, pyocyanin, protease, rhamnolipid, and hemolytic capabilities. In addition, these NPs significantly reduce P. aeruginosa swarming, swimming, and twitching motility. PG-AuNPs and PG-ZnONPs can be used as control agents for infections caused by the biofilm-forming human pathogenic bacterium P. aeruginosa.

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Target screening of plant secondary metabolites in river waters by liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS)

10.21203/rs.3.rs-36114/v2 ◽

2020 ◽

Author(s):

Mulatu Yohannes Nanusha ◽

Martin Krauss ◽

Carina D. Schönsee ◽

Barbara F. Günthardt ◽

Thomas D. Bucheli ◽

...

Keyword(s):

Secondary Metabolites ◽

Surface Waters ◽

High Resolution Mass Spectrometry ◽

Water Cycle ◽

Endocrine Disrupting Chemicals ◽

Plant Secondary Metabolites ◽

Biologically Active ◽

Plant Metabolites ◽

River Waters ◽

Target Screening

Abstract Background: Substantial efforts have been made to monitor potentially hazardous anthropogenic contaminants in surface waters while for plant secondary metabolites (PSMs) almost no data on occurrence in the water cycle are available. These metabolites enter river waters through various pathways such as leaching, surface run-off and rain sewers or input of litter from vegetation and might add to the biological activity of the chemical mixture. To reduce this data gap we conducted a LC-HRMS target screening in river waters from two different catchments for 150 plant metabolites which were selected from a larger database considering their expected abundance in the vegetation, their potential mobility, persistence and toxicity in the water cycle and commercial availability of standards. Results: The screening revealed the presence of 12 out of 150 possibly toxic PSMs including coumarins (bergapten, scopoletin, fraxidin, esculetin and psoralen), a flavonoid (formononetin) and alkaloids (lycorine and narciclasine). The compounds narciclasine and lycorine were detected at concentrations up to 3 µg/L while esculetin and fraxidin occurred at concentrations above 1 µg/L. Nine compounds occurred at concentrations above 0.1 µg/L, the Threshold for Toxicological Concern (TTC) for non-genotoxic and non-endocrine disrupting chemicals in drinking water. Conclusions: Our study provides an overview of potentially biologically active PSMs in surface waters and recommends their consideration in monitoring and risk assessment of water resources. This is currently hampered by a lack of effect data including toxicity to aquatic organisms, endocrine disruption and genotoxicity and demands for involvement of these compounds in biotesting.

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Activities of Tannins – from in Vitro Studies to Clinical Trials

Natural Product Communications ◽

10.1177/1934578x1501001118 ◽

2015 ◽

Vol 10 (11) ◽

pp. 1934578X1501001 ◽

Cited By ~ 7

Author(s):

Elwira Sieniawska

Keyword(s):

Clinical Trials ◽

Secondary Metabolites ◽

Human Health ◽

Laboratory Tests ◽

Plant Secondary Metabolites ◽

In Vitro Studies ◽

Literature Research ◽

Wide Range

Tannins are considered as valuable plant secondary metabolites providing many benefits for human health. In this review information was gathered about bioactivity in vitro and in vivo, as well as about conducted clinical trials. The literature research was based on ScienceDirect, Scopus, and Cochrane databases and presents a wide range of tested activities of tannins. The described clinical trials verify laboratory tests and show the effective health benefits taken from supplementation with tannins.

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In silico studies evidenced the role of structurally diverse plant secondary metabolites in reducing SARS-CoV-2 pathogenesis

Scientific Reports ◽

10.1038/s41598-020-77602-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Hariprasad Puttaswamy ◽

Hittanahallikoppal Gajendramurthy Gowtham ◽

Monu Dinesh Ojha ◽

Ajay Yadav ◽

Gourav Choudhir ◽

...

Keyword(s):

Secondary Metabolites ◽

Active Site ◽

Plant Secondary Metabolites ◽

Natural Occurrence ◽

Primary Concern ◽

In Vivo Evaluation ◽

Target Proteins ◽

In Silico Studies

AbstractPlants are endowed with a large pool of structurally diverse small molecules known as secondary metabolites. The present study aims to virtually screen these plant secondary metabolites (PSM) for their possible anti-SARS-CoV-2 properties targeting four proteins/ enzymes which govern viral pathogenesis. Results of molecular docking with 4,704 ligands against four target proteins, and data analysis revealed a unique pattern of structurally similar PSM interacting with the target proteins. Among the top-ranked PSM which recorded lower binding energy (BE), > 50% were triterpenoids which interacted strongly with viral spike protein—receptor binding domain, > 32% molecules which showed better interaction with the active site of human transmembrane serine protease were belongs to flavonoids and their glycosides, > 16% of flavonol glycosides and > 16% anthocyanidins recorded lower BE against active site of viral main protease and > 13% flavonol glycoside strongly interacted with active site of viral RNA-dependent RNA polymerase. The primary concern about these PSM is their bioavailability. However, several PSM recorded higher bioavailability score and found fulfilling most of the drug-likeness characters as per Lipinski's rule (Coagulin K, Kamalachalcone C, Ginkgetin, Isoginkgetin, 3,3′-Biplumbagin, Chrysophanein, Aromoline, etc.). Natural occurrence, bio-transformation, bioavailability of selected PSM and their interaction with the target site of selected proteins were discussed in detail. Present study provides a platform for researchers to explore the possible use of selected PSM to prevent/ cure the COVID-19 by subjecting them for thorough in vitro and in vivo evaluation for the capabilities to interfering with the process of viral host cell recognition, entry and replication.

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Chemical and biological assays for quantification of major plant secondary metabolites

BSAP Occasional Publication ◽

10.1017/s146398150004245x ◽

2006 ◽

Vol 34 ◽

pp. 235-249 ◽

Cited By ~ 2

Author(s):

Harinder P.S. Makkar

Keyword(s):

Polyethylene Glycol ◽

Secondary Metabolites ◽

Picric Acid ◽

Plant Secondary Metabolites ◽

Gas Production ◽

Qualitative Assessment ◽

Plant Sample ◽

Cyanogenic Glycosides ◽

Chromatographic Paper ◽

Wide Range

SummaryDuring grazing, animals interact with many compounds in the diet. Plant secondary metabolites (PSM) such as tannins, saponins, cyanogenic glycosides, mimosine. could have wide ranging effects –beneficial or harmful, depending on the nature, quantity in the plant, and amount and rate of ingestion of the PSM. A wide range of methods is available to quantify these PSM. The methods presented for tannins are based on the oxidation-reduction, metal complexing, polyethylene glycol binding and protein precipitation/binding principles of tannins. A tannin bioassay based onin vitrogas production using a medium containing rumen microbes, and incubation of the plant sample with and without polyethylene glycol (a tannin-inactivating agent) is also discussed. Saponins have haemolitic activity, and a qualitative and a quantitative assay are based on this property are described, in addition to a spectrophotometric assay. Cyanogenic glycosides are measured using picric acid methods with and without distillation. The methods described for mimosine determination are based on its reaction with ferric chloride and diazotised p-nitroaniline. Alkaloids are a chemically heterogeneous group of compounds. Therefore, it is difficult to assay alkaloids using a single method. An approach, for qualitative assessment of alkaloids in feeds and forages, based on the use of various spray reagents on the developed TLC plate or a paper chromatographic paper is presented.

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