A perspective review on the biosynthesis of plant-based secondary metabolites and their application as potent drugs

Many phytochemicals and their derived metabolites produced by plants are extensively employed in commercial goods,pharmaceutical products as well as in the environmental and medicalfields.However,these secondary metabolites obtained from plants are in low amounts,and it is difficult to synthesize them at the industrial level.Despite these challenges,they may be utilized for a variety of medicinal products that are either available in the market or are being researched and tested.Secondary metabolites are complex compounds that exhibit chirality.Further,under controlled conditions with elicitors,desired secondary metabolites may be produced from plant cell cultures.This review emphasizes the various aspects of secondary metabolites including their types,synthesis,and applications as medicinal products.The article aims to promote the use of plant secondary metabolites in the management and treatment of various diseases.

Secondary Metabolites of Entomopathogenic Fungi, Biological Alternative for the Control of Agricultural Pests and Disease: Present and Perspectives

The use of entomopathogenic fungi (EF) in recent years has been highly effective against the different orders of insects considered pests of agricultural importance and their conidia have been commonly applied, but it has been reported that these are sensitive to the environmental conditions. For this reason, biopesticides products have been formulated based on secondary metabolites, recently. These biomolecules participate as biological control agent, such as: cyclic depsipeptides, amino acids, polyketides, polyphenols and terpenoids, affecting their morphology, life cycle and insect behavior. The use of secondary metabolites of entomopathogenic fungi opens the possibility of application in a more efficient way for the control of agricultural pests in a compatible with the environment and human health;therefore, it is important to know, analyzing the type of molecules, their effects, and their different methods of application.

The role of sound stimulation in production of plant secondary metabolites

Sound vibration is one of natural stimuli trigging physiological changes in plants.Recent studies showed that sound waves stimulated production of a variety of plant secondary metabolites,including flavonoids,in order to enhance seed germination,flowering,growth or defense.In this review,we examine the potential role of sound stimulation on the biosynthesis of secondary metabolites and the followed cascade of physiological changes in plants,from the perspective of transcriptional regulation and epigenetic regulation for the first time.A systematic summary showed that a wide range of factors may regulate the production of secondary metabolites,including plant species,growth stage,sound types,sound frequency,sound intensity level and exposure time,etc.Biochemical and physiological changes due to sound stimulation were thoroughly summarized as well,for secondary metabolites can also act as a free radical scavenger,or a hormone signaling molecule.We also discussed the limits of previous studies,and the future application of sound waves in biosynthesis of plant secondary metabolites.

Study on Marine actinomycetes and analysis of their secondary metabolites

Actinomycetes are relatively prevalent bacteria in the ocean,constituting 9% of the total number of marine bacteria.The advancement of science and technology has led to a more profound exploration of marine actinomycetes.These studies hold immense significance in comprehending the distribution and adaptation of marine actinomycetes within the oceanic environment,as well as uncovering new secondary metabolites.Based on differing lifestyles,marine actinomycetes can be categorized as free-living or co-epiphytic.The activity and metabolism of actinomycetes vary across diverse marine settings,including the deep sea,benthic regions,and marine organisms.Due to their distinctive biological traits and genetic background,these marine actinomycetes inevitably generate metabolites possessing unique structures.Research methodologies concerning marine actinomycetes predominantly encompass traditional pure culture techniques,molecular biology approaches,and the integration of metagenomics and bioinformatics.The exploration of varied methodologies proves pivotal for the analysis of metabolite processes.Through the cultivation of marine actinomycetes,numerous compounds featuring novel structures and significant activities have been isolated,furnishing a substantial foundation for new drug investigations.These encompass,but are not restricted to,peptides,antibiotics,terpenoids,ketones,quinones,macrolides,and pigments.The potential applications of marine actinomyces and their secondary metabolites extend beyond antibacterial and anti-tumor effects,exhibiting promising prospects in antifungal and antiviral domains.This paper provides a comprehensive review of the classification,resources,research methodologies,and habitats of marine actinomycetes.Furthermore,it delves into the classification of secondary metabolites and their functional activities,facilitating a more exhaustive analysis of the secondary metabolites produced by marine actinomycetes.

Metabolic and transcriptomic analyses elucidate a novel insight into the network for biosynthesis of carbohydrate and secondary metabolites in the stems of a medicinal orchid Dendrobium nobile

Dendrobium nobile is an important medicinal and nutraceutical herb.Although the ingredients of D.nobile have been identified as polysaccharides,alkaloids,amino acids,flavonoids and bibenzyls,our understanding of the metabolic pathways that regulate the synthesis of these compounds is limited.Here,we used transcriptomic and metabolic analyses to elucidate the genes and metabolites involved in the biosynthesis of carbohydrate and several secondary metabolites in the stems of D.nobile.A total of 1005 metabolites and 31,745 genes were detected in the stems of D.nobile.The majority of these metabolites and genes were involved in the metabolism of carbohydrates(fructose,mannose,glucose,xylulose and starch),while some were involved in the metabolism of secondary metabolites(alkaloids,β-tyrosine,ferulic acid,4-hydroxybenzoate and chrysin).Our predicted regulatory network indicated that five genes(AROG,PYK,DXS,ACEE and HMGCR) might play vital roles in the transition from carbohydrate to alkaloid synthesis.Correlation analysis identified that six genes(ALDO,PMM,BGLX,EGLC,XYLB and GLGA) were involved in carbohydrate metabolism,and two genes(ADT and CYP73A) were involved in secondary metabolite biosynthesis.Our analyses also indicated that phosphoenol-pyruvate(PEP) was a crucial bridge that connected carbohydrate to alkaloid biosynthesis.The regulatory network between carbohydrate and secondary metabolite biosynthesis established will provide important insights into the regulation of metabolites and biological systems in Dendrobium species.

Effect of Different Concentrations of Pesticide-Imidacloprid on the Main Secondary Metabolites of Fruit and Polysaccharide of Chinese Wolfberry

[Objective] The aim was to seek the appropriate utilization methods for imidacloprid pesticide in the production of Chinese wolfberry,as well as to provide scientific basis for the rational use of imidacloprid pesticide. [Method] The effect of different concentrations and spraying times of 10% WP of imidacloprid on the main secondary metabolites such as carotenoid and flavone,as well as the polysaccharide and total sugar content was studied in field. [Result] The effect of different concentrations of imidacloprid on the secondary metabolites and the content of polysaccharide of Chinese wolfberry was significant. After imidacloprid spraying,the contents of flavone,polysaccharide and total sugar on the 1st,7th and 14th d showed increasing trend,while the content of carotenoid showed decreasing trend. With the dilution times increasing,the content of the flavone,polysaccharide and total sugar showed increasing trend,while the content of carotenoid decreased,in which the highest content of the secondary metabolites and polysaccharide appeared in 1 800 times. [Conclusion] The dilution ratio of 1 800 times should be selected as the appropriate dosage of 10% WP of imidacloprid.

Changes of main secondary metabolites in leaves of Ginkgo biloba in response to ozone fumigation

To investigate the effect of elevated 03 on the accumulation of main secondary metabolites in leaves of Ginkgo biloba L., four-year- old trees were exposed in open-top chambers with ambient air and the air with twice ambient 03 concentration in Shenyang in 2006. Elevated 03 increased the concentrations of terpenes, but decreased the concentrations of phenolics in G. biloba leaves. The results showed that secondary compounds from G. biloba leaves responded to the elevated 03 exposure in a different way when compared to previous studies which showed elevated 03 increased the concentrations of phenolics but had no effect on the terpenes in leaves of other deciduous trees. Furthermore, reduced synthesis of phenolics may decrease the resistance of G. biloba to 03 and other environmental factors. On the other hand, the induced synthesis of terpenes may enhance the antioxidant abilities in G. biloba leaves at the end of 03 fumigation.

Identification and Bioactivities of Secondary Metabolites Derived from Endophytic Fungi Isolated from Ethnomedicinal Plants of Tujia in Hubei Province:A Review

Tujia is a national minority,inhabiting in the mountainous Wuling area in China.Since 1978,Tujia medicine has been studied,summarized and developed,leading to numerous achievements by Chinese researchers,such as the publishing of approximately 30 monographs of Tujia medicine.These publications are focused on summarizing and improving the theory of Tujia medicine and developing clinical therapies from this system of medicine.The shortage of natural medicinal plants used in Tujia medicine has created the need to discover new resources to replace them and protect endangered natural plant species.Endophytic fungi are one of the conservation options,are considered a source of new bioactive natural products,and are a renewable and inexhaustible source of new drugs and agrochemicals.This review summarizes 260 compounds from endophytic fungi that have been previously isolated from the medicinal plants of Tujia.These compounds include steroids,terpenoids,meroterpenoids,polyketides,alkaloids,peptides,aliphatic compounds,aromatic compounds,and heterocyclic compounds.

Secondary metabolites of rice sheath blight pathogen Rhizoctonia solani Kühn and their biological activities

Eight compounds were isolated from the fermentation cultures of rice sheath blight pathogen Rhizoctonia solani Kuhn. They were identified as ergosterol （1）, 6β-hydroxysitostenone （2）, sitostenone （3）, m-hydroxyphenylacetic acid （4）, methyl m-hydroxyphenylacetate （5）, m-hydroxymethylphenyl pentanoate （6）, （Z）-3-methylpent-2-en-1,5-dioic acid （7） and 3-methoxyfuran-2-carboxylic acid （8） by means of physicochemical and spectroscopic analysis. Among them, 2, 3, 5-8 were isolated from R. solani for the first time. All the compounds were evaluated for their biological activities. 4-6 and 8 showed their inhibitory activities on the radical and germ elongation of rice seeds. 1,4 and 7 showed moderate antibacterial activity to some bacteria. 4, 7 and 8 exhibited weak inhibitory activities on spore germination of Magnaporthe oryzae. 8 showed moderate antioxidant activity with the 1,1-diphenyl-2-picryhydrazyl （DPPH） andβ-carotene-linoleic acid assays. This is the first time to reveal compounds 5, 6 and 8 from rice sheath blight pathogen R. solani to have in vitro phytotoxic activity.

The Bioactive Secondary Metabolites from Talaromyces species

The focus of this review is placed on the chemical structures from the species of the genus Talaromyces reported with reference to their biological activities.221 secondary metabolites,including 43 alkaloids and peptides,88 esters,31 polyketides,19 quinones,15 steroid and terpenoids,and 25 other structure type compounds,have been included,and 66 references are cited.

Plant-derived secondary metabolites as the main source of efflux pump inhibitors and methods for identification

The upsurge of multiple drug resistance(MDR)bacteria substantially diminishes the effectiveness of antibiotic arsenal and therefore intensifies the rate of therapeutic failure.The major factor in MDR is efflux pump-mediated resistance.A unique pump can make bacteria withstand a wide range of structurally diverse compounds.Therefore,their inhibition is a promising route to eliminate resistance phenomenon in bacteria.Phytochemicals are excellent alternatives as resistance-modifying agents.They can directly kill bacteria or interact with the crucial events of pathogenicity,thereby decreasing the ability of bacteria to develop resistance.Numerous botanicals display noteworthy efflux pumps inhibitory activities.Edible plants are of growing interest.Likewise,some plant families would be excellent sources of efflux pump inhibitors(EPIs)including Apocynaceae,Berberidaceae,Convolvulaceae,Cucurbitaceae,Fabaceae,Lamiaceae,and Zingiberaceae.Easily applicable methods for screening plant-derived EPIs include checkerboard synergy test,berberine uptake assay and ethidium bromide test.In silico highthroughput virtual detection can be evaluated as a criterion of excluding compounds with efflux substrate-like characteristics,thereby improving the selection process and extending the identification of EPIs.To ascertain the efflux activity inhibition,real-time PCR and quantitative mass spectrometry can be applied.This review emphasizes on efflux pumps and their roles in transmitting bacterial resistance and an update plant-derived EPIs and strategies for identification.

Effects of Barium Stress in Brassica juncea and Cakile maritima:The Indicator Role of Some Antioxidant Enzymes and Secondary Metabolites

Soil contamination by toxic trace metal elements,like barium(Ba),may stimulate various undesirable changes in the metabolic activity of plants.The plant responses are fast and with,direct or indirect,generation of reactive oxygen species(ROS).To cope with the stress imposed by the ROS production,plants developed a dual cellular system composed of enzymatic and non-enzymatic players that convert ROS,and their by-products,into stable nontoxic molecules.To assess the Ba stress response of two Brassicaceae species(Brassica juncea,a glycophyte,and Cakile maritime,a halophyte),plants were exposure to different Ba concentrations(0,100,200,300 and 500µM).The plants response was evaluated through their morphology and development,the determination of plant leaves antioxidant enzymatic activities and by the production of plants secondary metabolites.Results indicated that the two Brassicaceae species have the ability to survive in an environment containing Ba(even at 500µM).The biomass production of C.maritima was slightly affected whereas an increase in biomass B.juncea was noticed.The stress imposed by Ba activated the antioxidant defense system in the two species,noticed by the changes in the leaves activity of catalase(CAT),ascorbate peroxidase(APX)and guaicol peroxidase(GPX),and of the secondary metabolites,through the production of total phenols and flavonoids.The enzymatic response was not similar within the two plant species:CAT and APX seem to have a more important role against the oxidative stress in C.maritima while in B.juncea is GPX.Overall,total phenols and flavonoids production was more significant in the plants aerial part than in the roots,of the both species.Although the two Brassicaceae species response was different,in both plants catalytic and non-catalytic transformation of ROS occurs,and both were able to overcome the Ba toxicity and prevent the cell damage.

Secondary Metabolites from the Endophytic Fungus Xylaria sp.hg1009

A detailed chemical investigation of the secondary metabolites produced by the endophytic fungus Xylaria sp.isolated from the stems of Isodon sculponeatus afforded six new compounds,xylariahgins A-F(1-6),two new natural products(7 and 8),along with two known compounds(9 and 10)(Fig.1).The structures of all compounds were unambiguously established by analyzing their spectroscopic data or referring to pertinent literature.Compounds 1-8 were tested for their cytotoxic activity against five human tumor cell lines.

The comparative analysis and identification of secondary metabolites between Tibet wild and cultivated pomegranates(Punica granatum L.)in China

Secondary metabolites are closely related to the nutritional quality and health functions of plants.We investigated the secondary metabolites of both wild(n=23)and cultivated(n=27)pomegranate plants(Punica granatum L.)growing in China.The total flavonoid(TF)and tannin(TT)contents from the peel and juice were determined and the secondary metabolites in the peel(ZLP)and juice(ZLZ)of‘Zela 4’were identified using liquid chromatography–electrospray ionization tandem mass spectrometry(LC–ESI-MS/MS).Analysis of variance(P<0.05)showed that there were significant differences in the TF content of peel(TF(P))and juice(TF(J)),and the TT content of peel(TT(P))and juice(TT(J))among different pomegranate accessions.Pearson correlation analysis showed that latitude and altitude might be the main environmental factors affecting TF and TT contents in pomegranates.In this study,279 secondary metabolites were identified in the ZLP and ZLZ.In addition,we report for the first time 227 secondary metabolites in pomegranates.Using orthogonal partial least squares discriminant analysis,90 differential metabolites were identified in ZLP and ZLZ.In addition,we screened eight specific germplasms(high-TF(P),‘Junyong 3’;low-TF(P),‘Yanzhihong’;high-TF(J),‘Zela 4’;low-TF(J),‘Yudazi’,high-TT(P),‘Junyong 4’;low-TT(P),‘Anba 1’;high-TT(J),‘Yeba 1’;and low-TT(J),‘Baihuayushizi’).The results of our study provide a reference for the development and utilization of wild pomegranate resources and pomegranate breeding in China.

Effect of salinity on the growth,biological activity and secondary metabolites of some marine fungi

The study investigated the effects of salinity on growth, antimicrobial activities and secondary metabolites of 47 marine filamentous fungi isolated from the East China Sea near the western shore of the Taiwan Straits. The results indicate that NaCl promoted the growth up to 91.5% of test strains. However, only 14.9% of them showed a significant increase of antimicrobial activity against Candida albicans. When incubated in different concentrations of NaCl, the colony growth, antimicrobial activities and composition of secondary metabolites of the strain Ty01b-8 of Penicillium sp. varied. Treatment with KCl also showed a similar effect. An alkaloid isolated from the fermentation broth of Ty01b-8 was identified as chrysogine, inhibition activity of which against Hela cells was 15.05% at 20μg/ml, and yield was 4.4 and 4.9 times higher in 3 percent and 6 percent NaCl treatments, respectively, compared with the non-salt culture condition. These findings prove that salinity is an important factor influencing growth and secondary metabolites of some marine fungi, which can be used to screen for new metabolites from marine fungi, and to enhance their metabolites production in industrial fermentation.

Evaluation of quantitative variation of secondary metabolites in Bergenia ciliata(Haw.)using high performance thin layer chromatography

Dear Editor： Therapeutically active metabolite contents in a med- icinal plant vary in nature, which may impact on its therapeutic efficacy. Bergenia （Saxifragaceae） is an evergreen perennial herb widely distributed in Central and East Asia with about 30 species reported worldwide. It grows at a range of altitudes from the Khasia hills at 400 feet to the temperate Himalayas from Kashmir to Bhutan at 7,000-10,000 feet. Its distribution over a wide range of altitudinal zones makes it a good candidate for studying variations in its metabolic profiles under different climatic conditions. Bergenin （C-glycoside of 4-O-methyl gallic acid） has been identified as a potent active secondary metabolite in Bergenia and other therapeutically active constituents including, among others, gallic acid （3,4,5 trihydroxybenzoic acid）, （＋） catechin, and gallicin （Fig. 1）.

Bioactivity Determination and Control Effect Evaluation of Three Plant Secondary Metabolites against Semiaphis heraclei

[Objective] The paper was to clarify the bioactivity of trans-2-hexenal,oregano oil and thyme oil against Semiaphis heraclei and the synergistic effect of orange peel essential oil and organosilicon on the aphidicidal activity of the three agents.[Method] With S.heraclei,the dominant species of aphids in Lonicera japonica thunb.,as the test insect,the bioactivity and control effect were evaluated by the method of leaf dipping and foliar spraying.[Result] The indoor toxicity of thyme oil was the highest,with the LC_(50) of 1.793 mg/L.Adding additives significantly increased the toxicity of the agents to S.heraclei.Among them,trans-2-hexenal+OSi,oregano oil+OSi and thyme oil+OSi had obvious synergistic effects,with the toxicity coefficients of 1.80,1.48 and 1.45,respectively.Field test showed that the corrected control effect of thyme oil was the highest after con-ventional spraying,and the toxicities of the three agents were higher than that of the control group at 7 d post spraying.Under the condition of 20%reduction of three agents and adding organosilicon,the control effect was increased by about 10% at 1 d post spraying,which was higher than that of the control group at 4 d post spraying,and reached over 98% at 14 d post spraying.[Conclusion] Thyme oil has the highest toxicity and control effect on S.heraclei.Three agents combined with organosilicon have the obvious effect of reducing the quantity and increasing the efficiency,which has the potential for further development.

Plant Secondary Metabolites： Biosynthesis, Classification, Function and Pharmacological Properties

Secondary metabolites, also known as phytochemicals, natural products or plant constituents are responsible for medicinal properties of plants to which they belong. The role they play in the plant is not, to date, well known or understood, but it may be beyond the protection. Their classification is based on chemical structure, composition, their solubility in various solvents, or the pathway by which they are synthesized. The main classification system includes three major groups： terpenoids, alkaloids and phenolics. For each one, we find subclasses with complexity in structure. In this review, we deal with the description of second metabolites, their biosynthesis, function, and the current pharmacological findings. Natural products are an important source of drug candidates in pharmaceutical industry, more deeply we understand them, the easier it is for scientists to intervene in alleviating different kind of diseases. The recent references have been consulted for presenting updated information, but also showing the new potentialities of plant second metabolites in drug research and development.

Evaluation of Some Secondary Metabolites and Determination of the Antioxidant Potential of Different Extracts from the Plant of <i>Pteridium aquilinum</i>

The present study aims to make an evaluation of some secondary metabolites and determination of the antioxidant potential of P. aquilinum plant extracts obtained by means of a simple and rapid TLC method. The latter revealed the presence of terpenes, sterols, steroids, flavonoids, polyphenols, saponins, sugars and amino acids. The evaluation of the potential antioxidant was assessed on phenolic and flavonoid compounds. These compounds’ dosages revealed different levels, but the highest antioxidant activity was found in the hydro-ethanol extract followed by the aqueous extract. Among the two families of evaluated antioxidants, phenolic compounds were found to be higher in the hydro-ethanolic extract (75.18 mgEAG/gMS), followed by the aqueous extract (66.78 mgEAG/gMS) and lower in the ethanolic extract (12.39 mgEAG/gMS). Whereas flavonoids, less significantly elevated, showed values of 2.58 mgECa/gMS for the hydro-ethanolic extract, 2.24 mgECa/gMS for the aqueous extract and 1.58 mgECa/gMS for the ethanolic extract. However, the antiradical activity was also evaluated. Contrary to the antioxidant activity, the most important antiradical activity was observed on the hydroethanolic extract with a rate of 3.61 mg/mL, then a weak activity on the aqueous and ethanolic extracts respectively 6.18 mg/mL and 15.81 mg/mL, then less important on the aqueous and hydro-ethanolic extracts respectively at levels of 6.18 mg/mL and 3.61 mg/mL.

Influence of Environmental Conditions on Morphogenesis and on Changes of Primary and Secondary Metabolites in Asclepias syriaca L, Derived in Vitro

The object of this study was to adapt in vitro system for morphogenesis and regeneration of microshoots of common milkweed （Asclepias syriaca L.） applying different concentrations of hydrogen ion （H＋） and cytokinin 6-benzylaminopurine （BAP）. The influence of BAP and hydrogen ion （H＋） on the level of primary （chlorophyll a, chlorophyll b and carotenoids） and secondary （flavonoids and hydrolyzable and condensed tannins） metabolites in in vitro grown Asclepias syriaca L, were evaluated. Six different concentrations of BAP （0, 1, 2, 3, 4 and 5 ~tmol/L） and three different concentrations of hydrogen ion （pH 4.5, 5.0 and 5.5） were applied to the woody plant medium （WPM） medium used for microshoots propagation. The most effective morphogenesis of Asclepias syriaca L. was observed in culture medium supplemented with 2 p, mol/L BAP. However, synthesis of primary and secondary metabolites was the most intensive when cytokinin concentration reached the value of 3 gmol/L BAP. It was determined that the activity of hydrogen ion （H＋）, measured as the pH of culture medium, had a significant effect on secondary metabolites in the shoots in vitro.