Phenylethanoid glycosides are naturally occurring water-soluble compounds with remarkable biological properties that are widely distributed in the plant kingdom. Verbascoside is a phenylethanoid ...glycoside that was first isolated from mullein but is also found in several other plant species. It has also been produced by in vitro plant culture systems, including genetically transformed roots (so-called ‘hairy roots’). Verbascoside is hydrophilic in nature and possesses pharmacologically beneficial activities for human health, including antioxidant, anti-inflammatory and antineoplastic properties in addition to numerous wound-healing and neuroprotective properties. Recent advances with regard to the distribution, (bio)synthesis and bioproduction of verbascoside are summarised in this review. We also discuss its prominent pharmacological properties and outline future perspectives for its potential application.
The natural flavonoids, especially their glycosides, are the most abundant polyphenols in foods and have diverse bioactivities. The biotransformation of flavonoid aglycones into their glycosides is ...vital in flavonoid biosynthesis. The main biological strategies that have been used to achieve flavonoid glycosylation in the laboratory involve metabolic pathway engineering and microbial biotransformation. In this review, we summarize the existing knowledge on the production and biotransformation of flavonoid glycosides using biotechnology, as well as the impact of glycosylation on flavonoid bioactivity. Uridine diphosphate glycosyltransferases play key roles in decorating flavonoids with sugars. Modern metabolic engineering and proteomic tools have been used in an integrated fashion to generate numerous structurally diverse flavonoid glycosides. In vitro, enzymatic glycosylation tends to preferentially generate flavonoid 3- and 7-O-glucosides; microorganisms typically convert flavonoids into their 7-O-glycosides and will produce 3-O-glycosides if supplied with flavonoid substrates having a hydroxyl group at the C-3 position. In general, O-glycosylation reduces flavonoid bioactivity. However, C-glycosylation can enhance some of the benefits of flavonoids on human health, including their antioxidant and anti-diabetic potential.
Over the past two decades, extensive studies have revealed that inflammation represents a major risk factor for various human diseases. Chronic inflammatory responses predispose to pathological ...progression of chronic illnesses featured with penetration of inflammatory cells, dysregulation of cellular signaling, excessive generation of cytokines, and loss of barrier function. Hence, the suppression of inflammation has the potential to delay, prevent, and to treat chronic diseases. Flavonoids, which are widely distributed in humans daily diet, such as vegetables, fruits, tea and cocoa, among others, are considered as bioactive compounds with anti-inflammatory potential. Modification of flavonoids including hydroxylation, o-methylation, and glycosylation, can alter their metabolic features and affect mechanisms of inflammation. Structure-activity relationships among naturally occurred flavonoids hence provide us with a preliminary insight into their anti-inflammatory potential, not only attributing to the antioxidant capacity, but also to modulate inflammatory mediators. The present review summarizes current knowledge and underlies mechanisms of anti-inflammatory activities of dietary flavonoids and their influences involved in the development of various inflammatory-related chronic diseases. In addition, the established structure-activity relationships of phenolic compounds in this review may give an insight for the screening of new anti-inflammatory agents from dietary materials.
Phenylethanoid glycosides (PhGs) are generally water‐soluble phenolic compounds that occur in many medicinal plants. Until June 2020, more than 572 PhGs have been isolated and identified. PhGs ...possess antibacterial, anticancer, antidiabetic, anti‐inflammatory, antiobesity, antioxidant, antiviral, and neuroprotective properties. Despite these promising benefits, PhGs have failed to fulfill their therapeutic applications due to their poor bioavailability. The attempts to understand their metabolic pathways to improve their bioavailability are investigated. In this review article, we will first summarize the number of PhGs compounds which is not accurate in the literature. The latest information on the biological activities, structure–activity relationships, mechanisms, and especially the clinical applications of PhGs will be reviewed. The bioavailability of PhGs will be summarized and factors leading to the low bioavailability will be analyzed. Recent advances in methods such as bioenhancers and nanotechnology to improve the bioavailability of PhGs are also summarized. The existing scientific gaps of PhGs in knowledge are also discussed, highlighting research directions in the future.
Targeting PI3K/AKT signaling pathway in obesity Savova, Martina S.; Mihaylova, Liliya V.; Tews, Daniel ...
Biomedicine & pharmacotherapy,
March 2023, 2023-Mar, 2023-03-00, 20230301, 2023-03-01, Letnik:
159
Journal Article
Recenzirano
Odprti dostop
Obesity is a disorder with an increasing prevalence, which impairs the life quality of patients and intensifies societal health care costs. The development of safe and innovative prevention ...strategies and therapeutic approaches is thus of great importance. The complex pathophysiology of obesity involves multiple signaling pathways that influence energy metabolism in different tissues. The phosphatidylinositol 3-kinases (PI3K)/protein kinase B (AKT) pathway is critical for the metabolic homeostasis and its function in insulin-sensitive tissues is described in the context of health, obesity and obesity-related complications. The PI3K family participates in the regulation of diverse physiological processes including but not limited to cell growth, survival, differentiation, autophagy, chemotaxis, and metabolism depending on the cellular context. AKT is downstream of PI3K in the insulin signaling pathway, and promotes multiple cellular processes by targeting a plethora of regulatory proteins that control glucose and lipid metabolism. Natural products are essential for prevention and treatment of many human diseases, including obesity. Anti-obesity natural compounds effect multiple pathophysiological mechanisms involved in obesity development. Numerous recent preclinical studies reveal the advances in using plant secondary metabolites to target the PI3K/AKT signaling pathway for obesity management. In this paper the druggability of PI3K as a target for compounds with anti-obesity potential is evaluated. Perspectives on the strategies and limitations for clinical implementation of obesity management using natural compounds modulating the PI3K/AKT pathway are suggested.
Display omitted
•The PI3K/AKT pathway is critical for energy metabolism in insulin-sensitive tissues.•The PI3K/AKT druggability against obesity needs more detailed mechanistic research.•Up- or downregulation of PI3K/AKT is beneficial in obesity depending on the context.•Natural compounds are promising PI3K/AKT modulators in obesity models.
More than a century has passed since the first attempt to cultivate plant cells in vitro. During this time, plant cell cultures have become increasingly attractive and cost-effective alternatives to ...classical approaches for the mass production of plant-derived metabolites. Furthermore, plant cell culture is the only economically feasible way of producing some high-value metabolites (e.g., paclitaxel) from rare and/or threatened plants. This review summarizes recent advances in bioprocessing aspects of plant cell cultures, from callus culture to product formation, with particular emphasis on the development of suitable bioreactor configurations (e.g., disposable reactors) for plant cell culture-based processes; the optimization of bioreactor culture environments as a powerful means to improve yields; bioreactor operational modes (fed-batch, continuous, and perfusion); and biomonitoring approaches. Recent trends in downstream processing are also considered.
Continuously growing demand for plant derived therapeutic molecules obtained in a sustainable and eco-friendly manner favors biotechnological production and development of innovative extraction ...techniques to obtain phytoconstituents. What is more, improving and optimization of alternative techniques for the isolation of high value natural compounds are issues having both social and economic importance. In this critical review, the aspects regarding plant biotechnology and green downstream processing, leading to the production and extraction of increased levels of fine chemicals from both plant cell, tissue, and organ culture or fresh plant materials and the remaining by-products, are discussed.
We imaged, with ALMA and ARGOS/LUCI, the molecular gas and dust and stellar continuum in XID2028, which is an obscured quasi-stellar object (QSO) at z = 1.593, where the presence of a massive outflow ...in the ionised gas component traced by the OIII5007 emission has been resolved up to 10 kpc. This target represents a unique test case to study QSO feedback in action at the peak epoch of AGN-galaxy co-evolution. The QSO was detected in the CO(5 − 4) transition and in the 1.3 mm continuum at ~30 and ~20σ significance, respectively; both emissions are confined in the central (<2 kpc) radius area. Our analysis suggests the presence of a fast rotating molecular disc (v ~ 400 km s−1) on very compact scales well inside the galaxy extent seen in the rest-frame optical light (~10 kpc, as inferred from the LUCI data). Adding available measurements in additional two CO transitions, CO(2 − 1) and CO(3 − 2), we could derive a total gas mass of ~1010 M⊙, thanks to a critical assessment of CO excitation and the comparison with the Rayleigh–Jeans continuum estimate. This translates into a very low gas fraction (<5%) and depletion timescales of 40–75 Myr, reinforcing the result of atypical gas consumption conditions in XID2028, possibly because of feedback effects on the host galaxy. Finally, we also detect the presence of high velocity CO gas at ~5σ, which we interpret as a signature of galaxy-scale molecular outflow that is spatially coincident with the ionised gas outflow. XID2028 therefore represents a unique case in which the measurement of total outflowing mass, of ~500–800 M⊙ yr−1 including the molecular and atomic components in both the ionised and neutral phases, was attempted for a high-z QSO.
Display omitted
•Evidence linking ROS overproduction to obesity-induced inflammation are present.•NRF2 activation is crucial for physiological adipocyte differentiation.•In context of obesity in ...humans the modulation of NRF2 needs further clarification.•NRF2 activation could be potential approach in obesity treatment.
The expanding dimensions of the global health crisis of overweight population has defined the term “globesity”. Among the most common pathological conditions connected with excessive adiposity are hyperglycemia, insulin resistance, dyslipidemia and hypertension which result in chronic non-communicable diseases (NCD) such as metabolic syndrome (MetS), type 2 diabetes (T2D), and nonalchoholic steatohepatitis (NASH). The contribution of inflammatory-immune reactions in obesity and its related co-morbidities is unequivocal. Increased levels of free fatty acids (FFA), reactive oxygen species (ROS) and reactive nitrogen species (RNS) overloads the homeostatic system resulting in pro-inflammatory adipokines secretion, immune-activation and chronic inflammation in obesity. The cellular mechanisms of defense against oxidative stress are orchestrated by the transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2). Excessive oxidative stress in the cell activates NRF2 which upregulates genes encoding major cytoprotective enzymes such as NAD(P)H:quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO1), and glutathione S-transferases (GST). The present review aims to clarify the interconnections between chronic inflammation, oxidative overload and NRF2-mediated cytoprotection as potential therapeutic approach in obesity.
PDF
