For centuries plants have been intensively utilized as reliable sources of food, flavoring, agrochemical and pharmaceutical ingredients. However, plant natural habitats are being rapidly lost due to ...climate change and agriculture. Plant biotechnology offers a sustainable method for the bioproduction of plant secondary metabolites using plant in vitro systems. The unique structural features of plant-derived secondary metabolites, such as their safety profile, multi-target spectrum and "metabolite likeness," have led to the establishment of many plant-derived drugs, comprising approximately a quarter of all drugs approved by the Food and Drug Administration and/or European Medicinal Agency. However, there are still many challenges to overcome to enhance the production of these metabolites from plant in vitro systems and establish a sustainable large-scale biotechnological process. These challenges are due to the peculiarities of plant cell metabolism, the complexity of plant secondary metabolite pathways, and the correct selection of bioreactor systems and bioprocess optimization. In this review, we present an integrated overview of the possible avenues for enhancing the biosynthesis of high-value marketable molecules produced by plant in vitro systems. These include metabolic engineering and CRISPR/Cas9 technology for the regulation of plant metabolism through overexpression/repression of single or multiple structural genes or transcriptional factors. The use of NMR-based metabolomics for monitoring metabolite concentrations and additionally as a tool to study the dynamics of plant cell metabolism and nutritional management is discussed here. Different types of bioreactor systems, their modification and optimal process parameters for the lab- or industrial-scale production of plant secondary metabolites are specified.
Osteoarthritis (OA) is an age‐related joint degenerative disease associated with pain, joint deformity, and disability. The disease starts with cartilage damage but then progressively involves ...subchondral bone, causing an imbalance between osteoclast‐driven bone resorption and osteoblast‐driven remodeling. Here, we summarize the data for the role of oxidative stress and inflammation in OA pathology and discuss how these two processes are integrated during OA progression, as well as their contribution to abnormalities in cartilage/bone metabolism and integrity. At the cellular level, oxidative stress and inflammation are counteracted by transcription factor nuclear factor erythroid p45–related factor 2 (NRF2), and we describe the regulation of NRF2, highlighting its role in OA pathology. We also discuss the beneficial effect of some phytonutrients, including the therapeutic potential of NRF2 activation, in OA.
Cosmeceuticals are hybrids between cosmetics and pharmaceuticals which are being designed for a dual purpose: (1) To provide desired esthetical effects and (2) simultaneously treat dermatological ...conditions. The increased demand for natural remedies and the trends to use natural and safe ingredients resulted in intensive cultivation of medicinal plants. However, in many cases the whole process of plant cultivation, complex extraction procedure, and purification of the targeted molecules are not economically feasible. Therefore, the desired production of natural cosmetic products in sustainable and controllable fashion in the last years led to the intensive utilization of plant cell culture technology. The present review aims to highlight examples of biosynthesis of active ingredients derived through plant in vitro systems with potential cosmeceutical application. The exploitation of different type of extracts used in a possible cosmeceutical formulation, as well as, their activity tested in in vitro/in vivo models is thoroughly discussed. Furthermore, opportunities to manipulate the biosynthetic pathway, hence engineering the biosynthesis of some secondary metabolites, such as anthocyanins, have been highlighted.
Diverse groups of factors are leading to increased weight gain and obesity, such as certain genetic phenotypes, neuroendocrine disturbances, the administration of some drugs, behavioral, social and ...environmental factors. The progressively escalating rates of overweight and obesity worldwide have led to an introduction of a new term “globesity”. Excessive accumulation of body fat and especially of visceral adipose tissue is the main predisposing factor for the development of metabolic syndrome and other obesity related co-morbidities. At the present moment only few pharmacotherapeuticals are used for long-term treatment of obesity acting on narrow target spectra, e.g. pancreatic and gastric lipase inhibition, acting as adrenomimetics or activating the satiety centers in hypothalamus. Plant-based medications that accelerate weight loss, proved to be safe, effective and widely available, would be a preferable alternative for anti-obesity treatments. As plant extracts are multi-component systems they could also act by more than one mechanism, including decreased lipid absorption, decreased energy intake, increased energy expenditure, decreased pre-adipocyte differentiation and proliferation, decreased lipogenesis and increased lipolysis.
The current review gives a summary of the risk factors for obesity development and its characteristics consequences. Current treatment options, combining lifestyle changes and conventional treatment with commercial anti-obesity drugs have been described as well. Special emphasis on in vitro, in vivo and human studies, of potential medicinal plant extracts and phytochemicals, such as polyphenols, terpenoids, alkaloids, saponins, able to modulate the molecular pathways and gene/protein expressions related to obesity, have been highlighted.
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•Obesity pathology, risk factors and complications.•Current anti-obesity treatment options.•Novel targets in obesity research.•Medicinal plants and plant-derived compounds with anti-obesity potential.•Evaluation of efficacy and toxicity data from in vitro, iv vivo and clinical studies.
Rosmarinic acid (RA) is widely distributed in plant species of Lamiaceae and Boraginaceae families, among others. Structurally RA is an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid with ...well explored biosynthetic pathway, physiological functions in plants and (potential) biological activities. Great number of herbal preparations and food supplements, containing RA, are marketed with claims for beneficial health effects. Furthermore, due to the inhibition of lipid peroxidation and bacterial growth, RA is approved for use as natural antioxidant and/or preservative in food industry.
The present review will explore the contemporary biotechnological approaches for RA mass-production and will attempt to summarize its main biological properties based on recent studies. Future applications in food industry and potential functional food development will be proposed. Implications for technological and chemical modification of RA aiming to improve its bioavailability will be presented.
The advances in biotechnological production of RA provide effective and “green” approach which worth further implementation to a large-scale application. Numerous in vitro and in vivo studies confirm many of the claimed health-promoting effects of RA, as well as, its value as food additive. Despite the recent improvements in RA stability and bioavailability, its use in food products should be thoroughly evaluated until a tight balance between safety and efficiency is set.
•Genetic manipulation and elicitation effectively enhance rosmarinic acid production in vitro.•Production of rosmarinic acid by green cell factories and eco-friendly processing is proposed.•Rosmarinic acid is a molecule of high value for pharmacy, cosmetics and food industry.•The biological activities of rosmarinic acid worth further development into functional food products.
During the past decade metabolomics has emerged as one of the fastest developing branches of “-omics” technologies. Metabolomics involves documentation, identification, and quantification of ...metabolites through modern analytical platforms in various biological systems. Advanced analytical tools, such as gas chromatography–mass spectrometry (GC/MS), liquid chromatography–mass spectroscopy (LC/MS), and non-destructive nuclear magnetic resonance (NMR) spectroscopy, have facilitated metabolite profiling of complex biological matrices. Metabolomics, along with transcriptomics, has an influential role in discovering connections between genetic regulation, metabolite phenotyping and biomarkers identification. Comprehensive metabolite profiling allows integration of the summarized data towards manipulation of biosynthetic pathways, determination of nutritional quality markers, improvement in crop yield, selection of desired metabolites/genes, and their heritability in modern breeding. Along with that, metabolomics is invaluable in predicting the biological activity of medicinal plants, assisting the bioactivity-guided fractionation process and bioactive leads discovery, as well as serving as a tool for quality control and authentication of commercial plant-derived natural products. Metabolomic analysis of human biofluids is implemented in clinical practice to discriminate between physiological and pathological state in humans, to aid early disease biomarker discovery and predict individual response to drug therapy. Thus, metabolomics could be utilized to preserve human health by improving the nutritional quality of crops and accelerating plant-derived bioactive leads discovery through disease diagnostics, or through increasing the therapeutic efficacy of drugs via more personalized approach. Here, we attempt to explore the potential value of metabolite profiling comprising the above-mentioned applications of metabolomics in crop improvement, medicinal plants utilization, and, in the prognosis, diagnosis and management of complex diseases.
This study aimed to investigate the availability of flavonoids, anthocyanins, and phenolic acids in mutant bean seeds, focusing on M7 mutant lines, and their corresponding initial and local ...cultivars. HPLC-DAD-MS/MS and HPLC-MS/MS were used to analyze twenty-eight genotypes of common bean. The obtained results suggest that the mutations resulted in four newly synthesized anthocyanins in the mutant bean seeds, namely, delphinidin 3-O-glucoside, cyanidin 3-O-glucoside, pelargonidin 3-O-glucoside, and petunidin 3-O-glucoside, in 20 accessions with colored seed shapes out of the total of 28. Importantly, the initial cultivar with white seeds, as well as the mutant white seeds, did not contain anthocyanins. The mutant lines were classified into groups based on their colors as novel qualitative characteristics. Five phenolic acids were further quantified: ferulic, p-coumaric, caffeic, sinapic, and traces of chlorogenic acids. Flavonoids were represented by epicatechin, quercetin, and luteolin, and their concentrations in the mutant genotypes were several-fold superior compared to those of the initial cultivar. All mutant lines exhibited higher concentrations of phenolic acids and flavonoids. These findings contribute to the understanding of the genetics and biochemistry of phenolic accumulation and anthocyanin production in common bean seeds, which is relevant to health benefits and might have implications for common bean breeding programs and food security efforts.
The unique structure of Mycobacterium tuberculosis cell envelope provides impermeable barrier against environmental stimuli. In the situation that this barrier is disturbed Mycobacteria react at the ...transcriptional and translational level to redirect metabolic processes and to maintain integrity of the cell. In this work we aimed to explore the early metabolic response of M. tuberculosis to tanshinones, which are active antimycobacterial compounds of Salvia miltiorrhiza Bunge root. The investigation of the expression of sigma factors revealed the significant shifts in the general bacterial regulatory network, whereas LC-MS metabolomics evidenced the changes in the composition of bacterial cell envelope and indicated altered metabolic pathways. Tanshinones acted via the disruption of the cell envelope surface and generation of reactive oxygen species. Bacteria responded with overproduction of inner region of outer membrane, fluctuations in the production of glycerophosphoinositolglycans, as well as changes in the levels of mycobactins, accompanied by enrichment of metabolic pathways related to redox balance and repair of damages caused by tanshinones.
Plants from the
genus are used across the world as traditional remedies. In the present study, extracts from the aerial part of the scarcely investigated
L., collected from two habitats in ...Bulgaria-the Balkan Mountains (Vau-1) and the Rhodopi Mountains (Vau-2), were analyzed by nuclear magnetic resonance (NMR) spectroscopy. The secondary metabolite, arbutin, was identified as a major constituent in both extracts, and further quantified by high-performance liquid chromatography (HPLC), while catalpol, aucubin and verbascoside were detected at lower amounts. The effect of the extracts and of pure arbutin on the survival of neutrophils isolated from murine bone marrow (BM) were determined by colorimetric assay. The production of cytokines-tumor necrosis factor (TNF)-α and interferon (IFN)-γ was evaluated by flowcytometry. While Vau-1 inhibited neutrophil vitality in a dose-dependent manner, arbutin stimulated the survival of neutrophils at lower concentrations, and inhibited cell density at higher concentrations. The Vau-1 increased the level of intracellular TNF-α, while Vau-2 and arbutin failed to do so, and expanded the frequency of mature double TNF-α
/IFN-γ
neutrophils within the BM pool.
Obesity is a global health burden for which we do not yet have effective treatments for prevention or therapy. Plants are an invaluable source of bioactive leads possessing anti-adipogenic potential. ...Ethnopharmacological use of Ononis spinosa L. roots (OSR) for treatment of obesity and metabolic disorders requires а scientific rationale. The current study examined the anti-adipogenic capacity of OSR and its secondary metabolites ononin (ONON) and maackiain (MACK) in human adipocytes as an in vitro model of obesity. Both ONON and MACK diminished lipid accumulation during adipocyte differentiation. Molecular docking analysis exposed the potential interactions between MACK or ONON and target regulatory adipogenic proteins. Furthermore, results from an RT-qPCR analysis disclosed significant upregulation of AMPK by MACK and ONON treatment. In addition, ONON increased SIRT1, PI3K and ACC mRNA expression, while MACK notably downregulated CEBPA, AKT, SREBP1, ACC and ADIPOQ. The protein level of PI3K, C/EBPα, PPARγ and adiponectin was reduced upon MACK treatment in a concentration-dependent manner. Similarly, ONON suppressed PI3K, PPARγ and adiponectin protein abundance. Finally, our study provides evidence that ONON exerts anti-adipogenic effect by upregulation of SIRT1 and inhibition of PI3K, PPARγ and adiponectin, while MACK induced strong inhibitory effect on adipogenesis via hampering PI3K, PPARγ/C/EBPα signaling and anti-lipogenic effect through downregulation of SREBP1 and ACC. Even though OSR does not hamper adipogenic differentiation, it could be exploited as a source of natural leads with anti-adipogenic potential. The multidirectional mechanism of action of MACK warrant further validation in the context of in vivo obesity models.
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•Ononis spinosa root extract did not obstruct adipogenesis.•Secondary metabolites from Ononis spinosa hampered adipocyte differentiation.•Ononin inhibited adipogenesis through SIRT1/PPARγ and PI3K signaling.•Maackiain inhibited adipo- and lipogenesis via PI3K/PPARγ and SREBP1 inhibition.
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