Advances on the in vivo and in vitro glycosylations of flavonoids

Ji, Yuan; Li, Bingzhi; Qiao, Meng; Li, Jingmin; Han, Xu; Zhang, Lihui; Zhang, Xing

doi:10.1007/s00253-020-10667-z

Cited by 59 publications

(42 citation statements)

References 88 publications

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“…While the utilisation of relatively simple sugars like sucrose makes GH enzymes preferable for simple changes, such as those targeting pharmacokinetics, further understanding and streamlining of donor and receptor data is required for widespread GH applications [ 62 ]. A study conducted by Ye et al led to the characterisation of 11 glycotransferases, which can not only efficiently glycosylate flavonoids, but also chalcones, triterpenoids and licorice compounds, widening the scope of enzymatic synthesis of natural products for various applications [ 63 ]. With C-glycosides synthesis, C-glycosyltransferases are an important tool, as synthetic approaches still struggle with the synthesis of bis-C-glycosides, which are the main interest for potential pharmaceutical applications [ 55 ].…”

Section: Glycosylation Biosynthetic Pathwaysmentioning

confidence: 99%

Synthetic Biology towards Improved Flavonoid Pharmacokinetics

et al. 2021

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Flavonoids are a structurally diverse class of natural products that have been found to have a range of beneficial activities in humans. However, the clinical utilisation of these molecules has been limited due to their low solubility, chemical stability, bioavailability and extensive intestinal metabolism in vivo. Recently, the view has been formed that site-specific modification of flavonoids by methylation and/or glycosylation, processes that occur in plants endogenously, can be used to improve and adapt their biophysical and pharmacokinetic properties. The traditional source of flavonoids and their modified forms is from plants and is limited due to the low amounts present in biomass, intrinsic to the nature of secondary metabolite biosynthesis. Access to greater amounts of flavonoids, and understanding of the impact of modifications, requires a rethink in terms of production, more specifically towards the adoption of plant biosynthetic pathways into ex planta synthesis approaches. Advances in synthetic biology and metabolic engineering, aided by protein engineering and machine learning methods, offer attractive and exciting avenues for ex planta flavonoid synthesis. This review seeks to explore the applications of synthetic biology towards the ex planta biosynthesis of flavonoids, and how the natural plant methylation and glycosylation pathways can be harnessed to produce modified flavonoids with more favourable biophysical and pharmacokinetic properties for clinical use. It is envisaged that the development of viable alternative production systems for the synthesis of flavonoids and their methylated and glycosylated forms will help facilitate their greater clinical application.

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Section: Glycosylation Biosynthetic Pathwaysmentioning

confidence: 99%

Synthetic Biology towards Improved Flavonoid Pharmacokinetics

et al. 2021

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“…Different sugar moieties can be found in its structure, such as glucose, galactose, rhamnose, arabinose, and rutinose [8]. Glycosylation has a tremendous impact on the biological properties of flavonoid derivatives [61]. Flavonoids are poorly soluble in aqueous solutions, in which they also have the tendency to for insoluble polymers.…”

Section: Structure and Function Of Glycosyl Flavonoidsmentioning

confidence: 99%

Therapeutic Potential of Glycosyl Flavonoids as Anti-Coronaviral Agents

2021

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The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread all over the world, creating a devastating socio-economic impact. Even though protective vaccines are starting to be administered, an effective antiviral agent for the prevention and treatment of COVID-19 is not available yet. Moreover, since new and deadly CoVs can emerge at any time with the potential of becoming pandemics, the development of therapeutic agents against potentially deadly CoVs is a research area of much current interest. In the search for anti-coronaviral drugs, researchers soon turned their heads towards glycosylated flavonoids. Glycosyl flavonoids, widespread in the plant kingdom, have received a lot of attention due to their widely recognized antioxidant, anti-inflammatory, neuroprotective, anticarcinogenic, antidiabetic, antimicrobial, and antiviral properties together with their capacity to modulate key cellular functions. The wide range of biological activities displayed by glycosyl flavonoids, along with their low toxicity, make them ideal candidates for drug development. In this review, we examine and discuss the up-to-date developments on glycosyl flavonoids as evidence-based natural sources of antivirals against coronaviruses and their potential role in the management of COVID-19.

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“…[25,26] Compounds 2 and 3 are quercetin glucosides. Many flavonoids are known to exist in nature in the form of their glycosides rather than as aglycones, and glycosylated flavonoids have been demonstrated to be less toxic than their aglycones, [27,28] which could explain the non-toxic effects of compounds 2 and 3, at least, in part.…”

Section: Structural Elucidation Of Isolated Compoundsmentioning

confidence: 99%

Isolation and Characterisation of Two Quercetin Glucosides with Potent Anti‐Reactive Oxygen Species (ROS) Activity and an Olean‐12‐en Triterpene Glucoside from the Fruit of Abelmoschus esculentus (L.) Moench

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Heerden

et al. 2021

Chemistry & Biodiversity

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Abelmoschus esculentus (Okra) is used in the traditional treatment of cancer, hyperlipidaemia and hyperglycaemia. We, therefore, investigated its composition and potential cytotoxic or antioxidant properties that might underlie its phytotherapeutic applications. Its methanolic fruit extract yielded compounds 1, 2 and 3, identified through NMR, UV and MS analyses as olean-12-en-3-O-β-D-glucopyranoside, isoquercitrin (quercetin glucoside) and 5,7,3',4'-tetrahydroxy-flavonol-3-O-[β-D-glucopyranosyl-(1!6)]-β-D-glucopyranoside (quercetin diglucoside), respectively. Following 48 h exposure, oleanene glucoside was mildly toxic to the HeLa and the MRC5-SV2 cancer cells, isoquercitrin was not toxic except at 100 μg/ml in HeLa, and quercetin diglucoside elicited no toxicity. In a 2',7'-dichlorofluorescein diacetate (DCFDA) assay of intracellular levels of reactive oxygen species (ROS), hydrogen peroxide increased ROS levels, an effect not affected by oleanene glucoside but protected against by isoquercitrin and quercetin diglucoside, with IC 50 values, respectively, of 2.7 � 0.5 μg/ml and 1.9 � 0.2 μg/ml (3 h post-treatment) and 2.0 � 0.8 μg/ml and 1.5 � 0.4 μg/ml (24 h post-treatment.) This is the first report of this oleanene skeleton triterpenoid in the plant. The work provides some insight into why the plant is included in remedies for cancers, cardiovascular complications and diabetes, and reveals it as a potential source of novel therapeutics.

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Advances on the in vivo and in vitro glycosylations of flavonoids

Cited by 59 publications

References 88 publications

Synthetic Biology towards Improved Flavonoid Pharmacokinetics

Synthetic Biology towards Improved Flavonoid Pharmacokinetics

Therapeutic Potential of Glycosyl Flavonoids as Anti-Coronaviral Agents

Isolation and Characterisation of Two Quercetin Glucosides with Potent Anti‐Reactive Oxygen Species (ROS) Activity and an Olean‐12‐en Triterpene Glucoside from the Fruit of Abelmoschus esculentus (L.) Moench

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