Isolation, purification and structure elucidation of three newbioactive secondary metabolites from Streptomyces lividans AM

Microorganisms are a huge mine of bioactive metabolites,and actinomycetes are one of the very active groups in this area.In this article,we are concerned about the full taxonomical characterization of Streptomyces lividans AM,isolated from Egyptian soil.This isolate produced three new bioactive metabolites,namely:1-Nona-decanoyl,4-oleyl disuccinate(1),filoboletic acid;(9Z,11E)-8,13-dihydroxy octadeca-9,11-dienoic acid(2),and sitosteryl-3β-D-glucoside(3).Extensive 1D and 2D NMR and HR-mass spectrometry were used to elucidate the structures of the three compounds.Moreover,ten known compounds were also identified.The antimicrobial activity of the producing organism and newly reported compounds(1–3)was investigated against a selected group of pathogenic microorganisms.A full taxonomical characterization of the strain was described as well.

Anti‑leishmanial and Anti‑inflammatory Agents from Endophytes:A Review

Leishmaniases and chronic inflammatory diseases are the cause of millions of deaths in the world each year.The treatment of leishmaniasis is facing serious drawbacks particularly due to the limited number of effective medicines,the resistance,and the toxicity of available drugs.On the other hand,many drugs are used for the management of inflammatory disorders.However,the most commonly prescribed although efficient is highly toxic with multiples side effects.New leads compounds for the development of new anti-leishmanial and anti-inflammatory drugs are needed.Over the past decade,several studies on the potential of endophytes to produce bioactive metabolites have been reported.We are presenting in the present review the status of research from 2000 to 2019 on the anti-leishmanial and anti-inflammatory metabolites isolated from endophytes from diverse habitats.An emphasis was put on existing gaps in the literature to inspire and guide future investigations.We hope that this review will help accelerate the drug discovery against leishmaniases and inflammation-associated disorders.

Endophytic fungi:a source of potential anticancer compounds

Bioactive metabolites produced by different endophytic fungi have wide range of applications in pharmaceutical and herbal medicine research.In contrast to plants,they are barely investigated to their boundless possibilities as storehouses of novel bioactive metabolites.They produce diverse metabolites by different biosynthetic pathways with the host plant.Enthusiasm for endophytes as a characteristic asset for new drugs was roused by the disclosure of paclitaxel-producing endophytic fungi.Anticancer activity is by and large connected with the cytotoxicity of the compounds present in the endophytic fungi.Phylogenetic classification of endophytic fungi is of great interest to mycologists as they can produce novel bioactive compounds with antitumor activity.This article audits anticancer compounds derived from endophytic fungi disengaged from the separate host plant.The endophytic fungi have been grouped by their host plants and anticancer compound synthesized.

Dietary fatty acids and bioactive fatty acid metabolites in alcoholic liver disease

Alcoholic liver disease(ALD)comprises a spectrum of liver pathology,including steatosis,steatohepatitis,and cirrhosis.Previous work from our group and others suggests that dietary fat,both the amount and composition,plays a pivotal role in ALD development and progression;however,the impact of specific dietary fatty acids on ALD pathogenesis is not fully elucidated.Preclinical rodent models of ALD revealed the deleterious effects of omega-6 polyunsaturated fatty acids(n-6 PUFAs),specifically linoleic acid(LA),and this may be partially attributed to the increased levels of pro-inflammatory oxidized LA metabolites.There is limited understanding regarding the role of omega-3 polyunsaturated fatty acids(n-3 PUFAs,such as alpha-linolenic acid,eicosapentaenoic acid,and docosahexaenoic acid),and bioactive n-3 PUFAderived lipid molecules in ALD.Given that majority of n-6 and n-3 PUFAs-derived metabolites are potent endogenous signaling molecules,knowledge regarding the changes in these lipid mediators may shed new light on the mechanisms contributing to ALD pathogenesis and reveal novel therapeutic targets and biomarkers of this disease.The current review summarizes relevant scientific literature regarding the role of dietary fat,distinct fatty acids,and bioactive fatty acid metabolites in ALD,and highlights recent advances in the field.

Elucidation of the melitidin biosynthesis pathway in pummelo

Specialized plant metabolism is a rich resource of compounds for drug discovery.The acylated flavonoid glycoside melitidin is being developed as an anti-cholesterol statin drug candidate,but its biosynthetic route in plants has not yet been fully characterized.Here,we describe the gene discovery and functional characterization of a new flavonoid gene cluster(UDP-glucuronosyltransferases(Cg UGTs),1,2rhamnosyltransferase(Cg1,2Rha T),acyltransferases(Cg ATs))that is responsible for melitidin biosynthesis in pummelo(Citrus grandis(L.)Osbeck).Population variation analysis indicated that the tailoring of acyltransferases,specific for bitter substrates,mainly determine the natural abundance of melitidin.Moreover,3-hydroxy-3-methylglutaryl-Co A reductase enzyme inhibition assays showed that the product from this metabolic gene cluster,melitidin,may be an effective anti-cholesterol statin drug candidate.Co-expression of these clustered genes in Nicotiana benthamiana resulted in the formation of melitidin,demonstrating the potential for metabolic engineering of melitidin in a heterologous plant system.This study establishes a biosynthetic pathway for melitidin,which provides genetic resources for the breeding and genetic improvement of pummelo aimed at fortifying the content of biologically active metabolites.

Medicinal mushrooms in prevention and control of diabetes mellitus

Diabetes mellitus is a life-threatening chronic metabolic disease caused by lack of insulin and/or insulin dysfunction,characterized by high levels of glucose in the blood(hyperglycemia).Millions worldwide suffer from diabetes and its complications.Significantly,it has been recognized that type 2 diabetes is an important preventable disease and can be avoided or delayed by lifestyle intervention.Presently,there are many chemical and biochemical hypoglycemic agents(synthetic drugs),that are used in treating diabetes and are effective in controlling hyperglycemia.However,as they may have harmful side-effects and fail to significantly alter the course of diabetic complications,natural anti-diabetic drugs from medicinal plants have attracted a great deal of attention.Medicinal mushrooms have been valued as a traditional source of natural bioactive compounds over many centuries and have been targeted as potential hypoglycemic and anti-diabetic agents.Bioactive metabolites including polysaccharides,proteins,dietary fibres,and many other biomolecules isolated from medicinal mushrooms and their cultured mycelia have been shown to be successful in diabetes treatment as biological antihyperglycemic agents.In this review we discuss the biological nature of diabetes and,in particular,explore some promising mushrooms that have experimental anti-diabetic properties,preventing or reducing the development of diabetes mellitus.The importance of medicinal mushrooms as agents of medical nutrition therapy and how their metabolites can be used as supportive candidates for prevention and control of diabetes is explored.Future prospects for this field of study and the difficulties and constraints that might affect the development of rational drug products from medicinal mushrooms are discussed.

Medicinal mushrooms in supportive cancer therapies:an approach to anti-cancer effects and putative mechanisms of action

Medicinal mushrooms have been valued as natural sources of bioactive compounds since times immemorial and have been recognized as potential immunomodulating and anti-cancer agents.Their consumption has consistently been shown to have beneficial effects on human health.Cancer is a generic term for several types of diseases that can be chronic and are responsible for a large number of deaths worldwide.Although there has been considerable progress in modern cancer therapy research,difficulties in understanding the molecular behavior of various types of cancers and the numerous side effects experienced by patients from treatments means that this whole subject area is still problematic.Thus,biological immunotherapy using natural bioactive compounds as supportive treatments in conventional cancer therapies has become in vogue.Bioactive metabolites isolated from medicinal mushrooms have shown potential successes in cancer treatment as biological immunotherapeutic agents that stimulate the immune system against cancer cells.They also act as an effective source of anti-cancer agents,capable of interfering with cellular signal transduction pathways linked to cancer development and progression.In this review we compile available data on the characteristics of medicinal mushrooms that appear to be particularly effective as biological immunotherapeutic agents.Major consideration is given to biological constituents and the putative mechanisms of action by which bioactive compounds act on the human body.Consideration is also given to the benefits that have been claimed for the use of mushrooms in treating cancer and the future prospects of using medicinal mushrooms as potent supportive candidate bioagents for treatment of cancers is discussed.

A new endophytic insect-associated Daldinia species, recognised from a comparison of secondary metabolite profiles and molecular phylogeny

Xylariaceous endophytes are commonly encountered in plants,and it has recently been found out that insect vectors play a major role in their life cycle,as well as in the apparent host-specificity of the fungal stromata.In this study,a new insect-associated,endophytic anamorph species of Daldinia is recognised from a comparison of (a)morphological and ecological data;(b)molecular phylogenetic data based on rDNA,alpha-actin and beta-tubulin genes;and (c)secondary metabolite profiles based on high performance liquid chromatography/diode array/mass spectrometry(HPLC-DAD/MS)and gas chromatography/mass spectrometry(GC-MS)in comparison with authentic strains of Daldinia and other Xylariaceae.The new species,Daldinia hawksworthii,is a symbiont of the willow woodwasp,Xiphydria prolongata,which is in turn preferentially associated with Salix.A comparison of HPLCDAD/MS profiles from standardised cultures revealed the presence of a specific compound,which was not encountered in any of the ca.250 Daldinia strains studied for comparison.This compound was isolated after fermentation of the fungus in 10 l scale by preparative chromatography.Structure elucidation by NMR spectroscopy revealed a novel pyrone,for which the name dalsymbiopyrone is proposed.The compound showed weak antimicrobial and cytotoxic effects and might be a signal molecule involved in the trilateral ecological interaction between the host plant,the insect,and its fungal symbiont.

Endophytes and associated marine derived fungi—ecological and chemical perspectives

The potential of endophytes and algal or invertebrate associated marine derived fungi as promising sources of structurally unprecedented bioactive natural products is undeniable and continues to attract broad attention.This review highlights new bioactive fungal metabolites reported in 2011 until April 2012,as well as known compounds for which novel biological activities have been disclosed.All compounds are grouped according to their reported biological activities which include cytotoxic,anti-infective,as well as radical scavenging,enzyme inhibition,anti-fouling and anti-parasitic activities.Overall,178 fungal metabolites,including 138 new natural products are presented.Furthermore,new insights into fungal-host interaction,chemical communication,and chemo-ecological roles of fungal metabolites,as well as new strategies for bioprospecting are presented.

Modulatory Effects of Mushrooms on the Inflammatory Signaling Pathways and Pro-inflammatory Mediators

Background:Mushrooms include a wide variety of bioactive compounds that have been linked to therapeutic and nutritional benefits,making them a potential source of new medications and functional foods.Objective:The goal of this study is to offer a complete overview of the mushroom’s modulatory effects on inflam-matory signaling pathways,which leads to the inhibition of inflammation in various types of immune cells and animal models.Methods:This study reviewed the inhibitory effects of mushrooms on the inflammation process through the modulation of the pro-inflammatory mediators and associated signaling pathways.A literature search in PubMed and Google Scholar was conducted for the relevant original research and review articles on the anti-inflammatory effects of mushrooms.Related articles published in English were selected,studied and discussed.Results:As revealed by the selected articles,bioactive molecules which include peptides,polysaccharides,ter-penes,sterols,fatty acids,and phenols have been extracted from the powder,concentrate,and different solvent extracts of edible mushrooms.These bioactive molecules have shown significant efficacy in inhibiting the major pro-inflammatory biomarkers and associated pathways in in vivo and in vitro settings.Conclusion:This review demonstrated that mushrooms significantly inhibit the production of pro-inflammatory mediators and can be developed for clinical use as anti-inflammatory agents.Further research is required to establish the comparative efficacy between mushrooms and NSAID especially in the in vivo inhibitory activity against the production of cyclooxygenase and pro-inflammatory cytokines.

Angiotensin-converting enzyme inhibitors from plants: A review of their diversity, modes of action, prospects, and concerns in the management of diabetes-centric complications

Angiotensin-converting enzyme(ACE)inhibitors are antihypertensive medications often used in the treatment of diabetes-related complications.Synthetic ACE inhibitors are known to cause serious side effects like hypotension,renal insufficiency,and hyperkalaemia.Therefore,there has been an intensifying search for natural ACE inhibitors.Many plants or plant-based extracts are known to possess ACEinhibitory activity.In this review,articles focusing on the natural ACE inhibitors extracted from plants were retrieved from databases like Google Scholar,Pub Med,Scopus,and Web of Science.We have found more than 50 plant species with ACE-inhibitory activity.Among them,Angelica keiskei,Momordica charantia,Muntingia calabura,Prunus domestica,and Peperomia pellucida were the most potent,showing comparatively lower half-maximal inhibitory concentration values.Among the bioactive metabolites,peptides(e.g.,Tyr-Glu-Pro,Met-Arg-Trp,and Gln-Phe-Tyr-Ala-Val),phenolics(e.g.,cyanidin-3-Osambubioside and delphinidin-3-O-sambubioside),flavonoids([-]-epicatechin,astilbin,and eupatorin),terpenoids(ursolic acid and oleanolic acid)and alkaloids(berberine and harmaline)isolated from several plant and fungus species were found to possess significant ACE-inhibitory activity.These were also known to possess promising antioxidant,antidiabetic,antihyperlipidemic and anti-inflammatory activities.Considering the minimal side effects and lower toxicity of herbal compounds,development of antihypertensive drugs from these plant extracts or phytocompounds for the treatment of diabetesassociated complications is an important endeavour.This review,therefore,focuses on the ACE inhibitors extracted from different plant sources,their possible mechanisms of action,present status,and any safety concerns.