Four flavonoids from propolis ameliorate free fatty acids-induced non-alcoholic steatohepatitis in HepG2 cells: Involvement of enhanced AMPK activation, mTOR-NF-κBp65 interaction, and PTEN expression

Ye, Manhong; Fan, Shuhang; Li, Xiaoyuan; Yang, Shengmei; Ji, Chao; Ji, Fubiao; Zhou, Bin

doi:10.1016/j.jff.2023.105460

Cited by 8 publications

(4 citation statements)

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“…In addition, the results pointed out that naringenin, specifically, developed a stable complex with AMPK, indicating its potential as a viable candidate for NAFLD treatment [251].…”

Section: Nutrient-sensing Pathwaysmentioning

confidence: 96%

“…The pathological manifestations of NAFLD span from simple steatosis to the more intricate necroinflammatory fibrosing disorder recognized as steatohepatitis. Research findings indicate that flavonoids found in propolis possess the ability to alleviate steatohepatitis in HepG2 cells [ 251 ]. The hepatoprotective effects of flavonoids entail boosting AMPK activation, mTOR-NF-κBp65 interaction, and PTEN levels.…”

Section: Nutrient-sensing Pathwaysmentioning

confidence: 99%

“…The hepatoprotective effects of flavonoids entail boosting AMPK activation, mTOR-NF-κBp65 interaction, and PTEN levels. In addition, the results pointed out that naringenin, specifically, developed a stable complex with AMPK, indicating its potential as a viable candidate for NAFLD treatment [ 251 ].…”

Section: Nutrient-sensing Pathwaysmentioning

confidence: 99%

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Exploring the Prospective Role of Propolis in Modifying Aging Hallmarks

Scorza,

Goncalves,

Finsterer

et al. 2024

Cells

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Aging populations worldwide are placing age-related diseases at the forefront of the research agenda. The therapeutic potential of natural substances, especially propolis and its components, has led to these products being promising agents for alleviating several cellular and molecular-level changes associated with age-related diseases. With this in mind, scientists have introduced a contextual framework to guide future aging research, called the hallmarks of aging. This framework encompasses various mechanisms including genomic instability, epigenetic changes, mitochondrial dysfunction, inflammation, impaired nutrient sensing, and altered intercellular communication. Propolis, with its rich array of bioactive compounds, functions as a potent functional food, modulating metabolism, gut microbiota, inflammation, and immune response, offering significant health benefits. Studies emphasize propolis’ properties, such as antitumor, cardioprotective, and neuroprotective effects, as well as its ability to mitigate inflammation, oxidative stress, DNA damage, and pathogenic gut bacteria growth. This article underscores current scientific evidence supporting propolis’ role in controlling molecular and cellular characteristics linked to aging and its hallmarks, hypothesizing its potential in geroscience research. The aim is to discover novel therapeutic strategies to improve health and quality of life in older individuals, addressing existing deficits and perspectives in this research area.

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“…In addition, the results pointed out that naringenin, specifically, developed a stable complex with AMPK, indicating its potential as a viable candidate for NAFLD treatment [251].…”

Section: Nutrient-sensing Pathwaysmentioning

confidence: 96%

Section: Nutrient-sensing Pathwaysmentioning

confidence: 99%

See 1 more Smart Citation

Exploring the Prospective Role of Propolis in Modifying Aging Hallmarks

Scorza,

Goncalves,

Finsterer

et al. 2024

Cells

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“…Chrysin (Figure 1A) is a natural flavonoid with a wide range of biological activities that is widely present in honey, propolis, fruits, and various medicinal plants (Mani and Natesan, 2018). Many reports in the literature describe the potential of chrysin for the treatment of NAFLD, demonstrating its ability to ameliorate hepatic inflammation, hepatic fat accumulation, altered glucolipid metabolism, and insulin resistance (Pai et al, 2019;Song et al, 2020;Zhou et al, 2021;Liu et al, 2023;Ye et al, 2023). However, the oral bioavailability of chrysin is very low because of its poor water solubility and rapid metabolism in the gastrointestinal tract and liver.…”

Section: Introductionmentioning

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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