Chrysin: A polyedric flavone as a tool to explore new phytotherapeutic applications and drug design

Falbo, Federica; Aiello, Francesca

doi:10.1002/ardp.202200347

Cited by 6 publications

(4 citation statements)

References 44 publications

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“…Therefore, its chemical modification may be a viable strategy to improve its drug-forming properties. From a chemical point of view, the 5-O and 7-O positions of chrysin are key points for its easy modification, and the oxygen atom-free B and C rings allow it to act as a hydrophobic center in many biological interactions (Falbo and Aiello, 2023). In recent years, researchers have developed several chrysin derivatives with modification of the 7-O position that exhibit anti-inflammatory (Cho et al, 2004), antioxidant (Zhu et al, 2016), antitumor (Liu et al, 2020), and antidiabetic (Zhang et al, 2021) activity.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and biological evaluation of the novel chrysin prodrug for non-alcoholic fatty liver disease treatment

Zhang,

Gao,

et al. 2024

Front. Pharmacol.

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Background: Chrysin (5,7-dihydroxyflavone) is a natural flavonoid that has been reported as a potential treatment for non-alcoholic fatty liver disease (NAFLD). However, extensive phase II metabolism and poor aqueous solubility led to a decrease in the chrysin concentration in the blood after oral administration, limiting its pharmacological development in vivo.Methods: In the present study, we synthesized a novel chrysin derivative prodrug (C-1) to address this issue. We introduced a hydrophilic prodrug group at the 7-position hydroxyl group, which is prone to phase II metabolism, to improve water solubility and mask the metabolic site. Further, we evaluated the ameliorative effects of C-1 on NAFLD in vitro and in vivo by NAFLD model cells and db/db mice.Results:In vitro studies indicated that C-1 has the ability to ameliorate lipid accumulation, cellular damage, and oxidative stress in NAFLD model cells. In vivo experiments showed that oral administration of C-1 at a high dose (69.3 mg/kg) effectively ameliorated hyperlipidemia and liver injury and reduced body weight and liver weight in db/db mice, in addition to alleviating insulin resistance. Proteomic analysis showed that C-1 altered the protein expression profile in the liver and particularly improved the expression of proteins associated with catabolism and metabolism. Furthermore, in our preliminary pharmacokinetic study, C-1 showed favorable pharmacokinetic properties and significantly improved the oral bioavailability of chrysin.Conclusion: Our data demonstrated that C-1 may be a promising agent for NAFLD therapy.

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Section: Discussionmentioning

confidence: 99%

Synthesis and biological evaluation of the novel chrysin prodrug for non-alcoholic fatty liver disease treatment

Zhang,

Gao,

et al. 2024

Front. Pharmacol.

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“…There are many compounds of medicinal value in flavonoids. These compounds are used to prevent and cure cardiovascular and cerebrovascular diseases, such as reducing the brittleness of blood vessels, improving the permeability of blood vessels, reducing blood lipid and cholesterol and so on [ 39 – 41 ]. In this study, the number of flavonoid metabolic pathways ranked second in E .…”

Section: Discussionmentioning

confidence: 99%

Ephedrine and pseudoephedrine in Ephedra saxatilis on the vertical altitude gradient changed in southern Tibet Plateau, China

Lu,

Zhang,

Wang

et al. 2023

PLoS ONE

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Ephedra is one of the world’s most important plants, used in medicine, plants and ecology. Most Ephedra grows in plain areas and is stable. But the plateau environment is special, with the change of altitude, the variety difference of plateau Ephedra saxatilis is very obvious. E. saxatilis metabolism on the Tibetan Plateau is not only affected by altitude, but also environmental conditions such as climate conditions and different soil components. However, the change mechanism of E. saxatilis alkaloids in special ecological environment is still unclear. Therefore, we analyzed the metabolic and altitude of E. saxatilis species in the Tibetan Plateau. Through the functional analysis of Kyoto Metabolism and Metabolomic Encyclopedia (KEGG), we can determine that the number of E. saxatilis metabolites decreases with the increase of altitude, and there are differences in metabolism among the three mountains. This was confirmed by univariate analysis of the top five metabolic pathways. Based on the analysis of soil and metabolomics, it was found that soil water content was also a factor affecting E. saxatilis metabolism. According to the difference of vertical height gradient, ephedrine and pseudephedrine showed the same change in vertical altitude under different mountains. Ephedrine increased as the altitude gradient increased, and pseudoephedrine decreased as the altitude gradient decreased. Our results provide valuable information for further study of metabolic mechanism and efficacy stability. It provides useful reference for the research of E. saxatilis planting in special area.

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“…Flavonoids are the most abundant type of polyphenols and have been investigated as complementary therapeutics for a variety of diseases [ 12 ]. Chrysin, also known as 5,7-dihydroxyflavone, is found in a variety of plants, such as propolis, bitter melon, and walnut pellicle; it exerts antioxidant, anti-inflammatory, and anti-apoptotic effects, but has demonstrated toxicity and safety issues [ 13 , 14 ]. CM1, a hydroxyethyl derivative of chrysin, is generated by the exposure of chrysin methanolic solution to ionising radiation and has an anti-inflammatory effect on primary dendritic cells and dextran sodium salt (DSS)-induced colitis in mice [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

CM1, a Chrysin Derivative, Protects from Endotoxin-Induced Lethal Shock by Regulating the Excessive Activation of Inflammatory Responses

Lee,

Ko,

Choi

et al. 2024

Nutrients

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Sepsis, a leading cause of death worldwide, is a harmful inflammatory condition that is primarily caused by an endotoxin released by Gram-negative bacteria. Effective targeted therapeutic strategies for sepsis are lacking. In this study, using an in vitro and in vivo mouse model, we demonstrated that CM1, a derivative of the natural polyphenol chrysin, exerts an anti-inflammatory effect by inducing the expression of the ubiquitin-editing protein TNFAIP3 and the NAD-dependent deacetylase sirtuin 1 (SIRT1). Interestingly, CM1 attenuated the Toll-like receptor 4 (TLR4)-induced production of inflammatory cytokines by inhibiting the extracellular-signal-regulated kinase (ERK)/MAPK and nuclear factor kappa B (NF-κB) signalling pathways. In addition, CM1 induced the expression of TNFAIP3 and SIRT1 on TLR4-stimulated primary macrophages; however, the anti-inflammatory effect of CM1 was abolished by the siRNA-mediated silencing of TNFAPI3 or by the genetic or pharmacologic inhibition of SIRT1. Importantly, intravenous administration of CM1 resulted in decreased susceptibility to endotoxin-induced sepsis, thereby attenuating the production of pro-inflammatory cytokines and neutrophil infiltration into the lung compared to control mice. Collectively, these findings demonstrate that CM1 has therapeutic potential for diverse inflammatory diseases, including sepsis.

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Chrysin: A polyedric flavone as a tool to explore new phytotherapeutic applications and drug design

Cited by 6 publications

References 44 publications

Synthesis and biological evaluation of the novel chrysin prodrug for non-alcoholic fatty liver disease treatment

Synthesis and biological evaluation of the novel chrysin prodrug for non-alcoholic fatty liver disease treatment

Ephedrine and pseudoephedrine in Ephedra saxatilis on the vertical altitude gradient changed in southern Tibet Plateau, China

CM1, a Chrysin Derivative, Protects from Endotoxin-Induced Lethal Shock by Regulating the Excessive Activation of Inflammatory Responses

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