Hesperidin is a bioflavonoid occurring in high concentrations in citrus fruits. Its use has been associated with a great number of health benefits, including antioxidant, antibacterial, antimicrobial, anti-inflammatory and anticarcinogenic properties. The food industry uses large quantities of citrus fruit, especially for the production of juice. It results in the accumulation of huge amounts of by-products such as peels, seeds, cell and membrane residues, which are also a good source of hesperidin. Thus, its extraction from these by-products has attracted considerable scientific interest with aim to use as natural antioxidants. In this review, the extraction and determination methods for quantification of hesperidin in fruits and by-products are presented and discussed as well as its stability and biological activities.

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Hesperidin: A Review on Extraction Methods, Stability and Biological Activities

The antioxidant, anti-inflammatory and antibacterial activities of hesperetin, hesperidin and hesperidin glucoside with different solubility were compared in vitro. Hesperetin was prepared by enzymatic hydrolysis from hesperidin, and hesperidin glucoside composed of hesperidin mono-glucoside was prepared from hesperidin through enzymatic transglycosylation. Solubility of the compounds was different: the partition coefficient (log P) was 2.85 ± 0.02 for hesperetin, 2.01 ± 0.02 for hesperidin, and −3.04 ± 0.03 for hesperidin glucoside. Hesperetin showed a higher effect than hesperidin and hesperidin glucoside on radical scavenging activity in antioxidant assays, while hesperidin and hesperidin glucoside showed similar activity. Cytotoxicity was low in the order of hesperidin glucoside, hesperidin, and hesperetin in murine macrophage RAW264.7 cells. Treatment of the cells with each compound reduced the levels of inflammatory mediators, nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Hesperetin was most effective at relatively low concentrations, however, hesperidin glucoside was also effective at higher concentration. Hesperetin showed higher antibacterial activity than hesperidin in both Gram-positive and -negative bacteria, and hesperidin glucoside showed similarly higher activity with hesperetin depending on the bacterial strain. In conclusion, hesperetin in the form of aglycone showed more potent biological activity than hesperidin and hesperidin glucoside. However, hesperidin glucoside, the highly soluble form, has been shown to increase the activity compared to poorly soluble hesperidin.

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A Comparative Study of Hesperetin, Hesperidin and Hesperidin Glucoside: Antioxidant, Anti-Inflammatory, and Antibacterial Activities In Vitro

This paper evaluated the chemical and biological properties of bee pollen samples from Romania. Firstly, the bee pollen alcoholic extracts (BPEs) were obtained from raw bee pollen harvested by Apis mellifera carpatica bees. The chemical composition of BPE was obtained by determination of total phenol content and total flavonoid content, UHPLC-DAD-ESI/MS analysis of phenolic compounds, and GC-MS analysis of fatty acids, esters, and terpenes. Additionally, the antioxidant activity was evaluated by the Trolox Equivalent Antioxidant Capacity method. Furthermore, the biological properties of BPE were evaluated (antimicrobial and cytotoxic activity). The raw BP samples studied in this paper had significant phenolic acid and flavonoid content, and moderate fatty acid, ester, and terpene content. P1, P2, and P4 have the highest TPC and TFC levels, and the best antioxidant activity. All BPEs studied had antimicrobial activity on pathogenic strains isolated from the clinic or standard strains. A synergistic antimicrobial effect of the BPEs was observed along with the soluble compounds of L. rhamnosus MF9 and E. faecalis 2M17 against some pathogenic (clinical) strains and, considering the tumour proliferation inhibitory activity, makes BP a potential prebiotic and antitumour agent for the gut environment.

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Bee Pollen Extracts: Chemical Composition, Antioxidant Properties, and Effect on the Growth of Selected Probiotic and Pathogenic Bacteria

Plants are a reservoir of phytochemicals, which are known to possess several beneficial health properties. Along with all the secondary metabolites, polyphenols have emerged as potential replacements for synthetic additives due to their lower toxicity and fewer side effects. However, controlling microbial growth using these preservatives requires very high doses of plant-derived compounds, which limits their use to only specific conditions. Their use at high concentrations leads to unavoidable changes in the organoleptic properties of foods. Therefore, the biochemical modification of natural preservatives can be a promising alternative to enhance the antimicrobial efficacy of plant-derived compounds/polyphenols. Amongst these modifications, low concentration of ascorbic acid (AA)–Cu (II), degradation products of ascorbic acid (DPAA), Maillard reaction products (MRPs), laccase–mediator (Lac–Med) and horse radish peroxidase (HRP)–H2O2 systems standout. This review reveals the importance of plant polyphenols, their role as antimicrobial agents, the mechanism of the biochemical methods and the ways these methods may be used in enhancing the antimicrobial potency of the plant polyphenols. Ultimately, this study may act as a base for the development of potent antimicrobial agents that may find their use in food applications.

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Recent Advancements in Enhancing Antimicrobial Activity of Plant-Derived Polyphenols by Biochemical Means

With incidence of antimicrobial resistance rising globally, there is a continuous need for development of new antimicrobial molecules. Phenolic compounds having a versatile scaffold that allows for a broad range of chemical additions; they also exhibit potent antimicrobial activities which can be enhanced significantly through functionalization. Synthetic routes such as esterification, phosphorylation, hydroxylation or enzymatic conjugation may increase the antimicrobial activity of compounds and reduce minimal concentrations needed. With potent action mechanisms interfering with bacterial cell wall synthesis, DNA replication or enzyme production, phenolics can target multiple sites in bacteria, leading to a much higher sensitivity of cells towards these natural compounds. The current review summarizes some of the most important knowledge on functionalization of natural phenolic compounds and the effects on their antimicrobial activity.

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Future Antimicrobials: Natural and Functionalized Phenolics

According to the latest report released by the World Health Organization, bacterial resistance to well-known and widely available antibacterial drugs has become a significant and severe global health concern and a grim challenge to tackle in order to cure infections associated with multidrug-resistant pathogenic microorganisms efficiently. Consequently, various strategies have been orchestrated to cure the severe complications related to multidrug-resistant bacteria effectively. Some approaches involved the retardation of biofilm formation and multidrug-resistance pumps in bacteria as well as the discovery of new antimicrobial agents demonstrating different mechanisms of action. In this regard, natural products namely alkaloids, terpenoids, steroids, anthraquinone, flavonoids, saponins, tannins, etc., have been suggested to tackle the multidrug-resistant bacterial strains owing to their versatile pharmacological effects. Amongst these, flavonoids, also known as polyphenolic compounds, have been widely evaluated for their antibacterial property due to their tendency to retard the growth of a wide range of pathogenic microorganisms, including multidrug-resistant bacteria. The hydroxylation of C5, C7, C3′, and C4′; and geranylation or prenylation at C6 have been extensively studied to increase bacterial inhibition of flavonoids. On the other hand, methoxylation at C3′ and C5 has been reported to decrease flavonoids’ antibacterial action. Hence, the latest information on the antibacterial activity of flavonoids is summarized in this review, with particular attention to the structure–activity relationship of this broad class of natural compounds to discover safe and potent antibacterial agents as natural products.

https://www.mdpi.com/1420-3049/27/4/1149/pdf?version=1644377368

Antibacterial Effects of Flavonoids and Their Structure-Activity Relationship Study: A Comparative Interpretation

Flavonoids are a group of naturally occurring polyphenolic secondary metabolites which have been reported to demonstrate a wide range of pharmacological properties, most importantly, antidiabetic and anti-inflammatory effects. The relationship between hyperglycaemia and inflammation and vascular complications in diabetes is now well established. Flavonoids possessing antidiabetic properties may alleviate inflammation by reducing hyperglycaemia through different mechanisms of action. It has been suggested that the flavonoids’ biochemical properties are structure-dependent; however, they are yet to be thoroughly grasped. Hence, the main aim of this review is to understand the antidiabetic and anti-inflammatory properties of various structurally diverse flavonoids and to identify key positions responsible for the effects, their correlation, and the effect of different substitutions on both antidiabetic and anti-inflammatory properties. The general requirement of flavonoids for exerting both anti-inflammatory and antidiabetic effects is found to be the presence of a C2–C3 double bond (C-ring) and hydroxyl groups at the C3’, C4’, C5, and C7 positions of both rings A and B of a flavonoid skeleton. Furthermore, it has been demonstrated that substitution at the C3 position of a C-ring decreases the anti-inflammatory action of flavonoids while enhancing their antidiabetic activity. Correlation is discussed at length to support flavonoids possessing essential pharmacophores to demonstrate equipotent effects. The consideration of these structural features may play an important role in synthesizing better flavonoid-based drugs possessing dual antidiabetic and anti-inflammatory effects. A meta-analysis further established the role of flavonoids as antidiabetic and anti-inflammatory agents.

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Flavonoids as Antidiabetic and Anti-Inflammatory Agents: A Review on Structural Activity Relationship-Based Studies and Meta-Analysis

This study explored a series of reported 5-lipoxygenase-activating protein (FLAP) inhibitors to understand their structural requirements and identify potential new inhibitor scaffolds through automated unbiased procedures. Docking studies have revealed that inhibitor binding affinity can be influenced by several key binding interactions with Phe114 and Lys116 from chain B and Val21, Phe25, His28 and Lys29 from chain C in the FLAP-binding site. A ligand-based alignment three-dimensional (3D)-quantitative structure–activity relationship (QSAR) was adopted, resulting in a robust model with a statistically significant noncross-validated coefficient ([Formula: see text]), a cross-validated correlation coefficient ([Formula: see text]) and a predictive squared correlation coefficient ([Formula: see text]). Overall, the analysis revealed the important electrostatic and steric attributes responsible for the FLAP inhibitory activity, which appeared to correlate well with the docking results. In addition, two statistically significant two-dimensional (2D)-QSAR models ([Formula: see text], [Formula: see text] and [Formula: see text], [Formula: see text]) were developed by a genetic function approximation (GFA). HypoGen 1, a proposed pharmacophore model, was used for database mining to identify potential new FLAP inhibitors. The bioactivity of the retrieved hits was then evaluated in silico based on the validated QSAR models, followed by pharmacokinetics and toxicity predictions.

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Identification of Novel 5-Lipoxygenase-Activating Protein (FLAP) Inhibitors by an Integrated Method of Pharmacophore Virtual Screening, Docking, QSAR and ADMET Analyses

Nur Farisya Shamsudin

Papers

Antibacterial Effects of Flavonoids and Their Structure-Activity Relationship Study: A Comparative Interpretation

Flavonoids as Antidiabetic and Anti-Inflammatory Agents: A Review on Structural Activity Relationship-Based Studies and Meta-Analysis

Identification of Novel 5-Lipoxygenase-Activating Protein (FLAP) Inhibitors by an Integrated Method of Pharmacophore Virtual Screening, Docking, QSAR and ADMET Analyses