The natural flavone acacetin protects against high-fat diet-induced lipid accumulation in the liver via the endoplasmic reticulum stress/ferroptosis pathway

Zhe, Jiang; Sun, Hao; Miao, Jiaen; Sheng, Qiyu; Xu, Jia; Gao, Zhe; Xie, Zhaoxiong; Song, Yufei; Chen, Kuihao

doi:10.1016/j.bbrc.2022.12.014

Cited by 20 publications

(7 citation statements)

References 43 publications

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“…Flavones and flavonols are flavonoids, a group of natural plant compounds. Research has suggested that certain flavones, such as apigenin, scutellarin, tangeretin, and acacetin, may improve MAFLD by regulating lipid metabolism, reducing oxidative stress and inflammation, and enhancing autophagy [37][38][39][40]. Similarly, luteolin, a flavone, alleviates MAFLD in rats by helping to repair intestinal mucosal barrier damage and addressing microbiota imbalances in the gut-liver axis [41,42].…”

Section: Discussionmentioning

confidence: 99%

The Reduced Gut Lachnospira Species Is Linked to Liver Enzyme Elevation and Insulin Resistance in Pediatric Fatty Liver Disease

Tsai,

Chiu,

Kek

et al. 2024

IJMS

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The objective of this study was to investigate gut dysbiosis and its metabolic and inflammatory implications in pediatric metabolic dysfunction-associated fatty liver disease (MAFLD). This study included 105 children and utilized anthropometric measurements, blood tests, the Ultrasound Fatty Liver Index, and fecal DNA sequencing to assess the relationship between gut microbiota and pediatric MAFLD. Notable decreases in Lachnospira spp., Faecalibacterium spp., Oscillospira spp., and Akkermansia spp. were found in the MAFLD group. Lachnospira spp. was particularly reduced in children with MAFLD and hepatitis compared to controls. Both MAFLD groups showed a reduction in flavone and flavonol biosynthesis sequences. Lachnospira spp. correlated positively with flavone and flavonol biosynthesis and negatively with insulin levels and insulin resistance. Body weight, body mass index (BMI), and total cholesterol levels were inversely correlated with flavone and flavonol biosynthesis. Reduced Lachnospira spp. in children with MAFLD may exacerbate insulin resistance and inflammation through reduced flavone and flavonol biosynthesis, offering potential therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

The Reduced Gut Lachnospira Species Is Linked to Liver Enzyme Elevation and Insulin Resistance in Pediatric Fatty Liver Disease

Tsai,

Chiu,

Kek

et al. 2024

IJMS

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“…These detrimental lipid metabolites may further exacerbate ERS, forming a vicious cycle. [44,45] Additionally, ERS may impact key molecules in insulin signaling pathway, such as the insulin receptor and insulin receptor substrate 1. This impact may lead to abnormalities in insulin receptor and its downstream signaling pathways, further contributing to the occurrence and development of insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Research status and hotspots in the field of endoplasmic reticulum stress and liver disease: A bibliometric study

Wang,

Huang,

Wang

et al. 2024

Medicine

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Recently, the study of endoplasmic reticulum stress (ERS) and liver disease has attracted much attention, but bibliometric analysis on this field is scarce. Therefore, to address this gap, we conducted a bibliometric analysis to explore the research status, hotspots, and trends in this field. We searched the Web of Science Core Collection database for publications on ERS and liver disease from 2007 to 2022. Bibliometric online analysis platform, VOSviewer, and CiteSpace were used to perform bibliometric analysis. Two thousand seven hundred fifty-one publications were retrieved form the Web of Science Core Collection database. The USA was the most productive and influential country. Seoul National University, International Journal of Molecular Sciences, and Kaufman RJ were the most productive institution, journal, and author. “Endoplasmic reticulum stress,” “nonalcoholic fatty liver disease,” “inflammation,” “oxidative stress” and “insulin resistance” were the high-frequency keywords, “necrosis factor alpha” was the keywords with the strongest citation bursts, and “nonalcoholic fatty liver,” “fibrosis” and “lipid droplet” were the keywords that were still bursting in 2022. The number of publications on ERS and liver disease has increased over the past years. The USA was the most productive and influential country. China has become the country with the largest number of annual publications, but it still needs to work on the quality. ERS and nonalcoholic fatty liver disease, especially the insulin resistance and lipotoxicity in hepatocytes may be the research hotspots and trends in this field of ERS and liver disease.

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“…Acacetin, another flavonoid, has been shown to protect against NAFLD by regulating inflammation and AMPK-related lipid metabolism [ 167 ]. A further study showed that acacetin could reduce HFD-induced liver lipid accumulation by inhibiting ER stress-dependent ferroptosis, suggesting that acacetin may be a potential therapeutic drug for NAFLD [ 168 ]. In addition, acacetin could also inhibit ER stress and hepatocyte apoptosis by targeting PPARγ, which has a significant protective effect on APAP-induced liver injury [ 169 ].…”

Section: Nac Treat Liver Disease By Targeting Ferroptosismentioning

confidence: 99%

Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications

Wu,

Zhu,

Liu

et al. 2024

Antioxidants

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Ferroptosis is an emerging type of regulated cell death usually accompanied by the accumulation of ferrous ions (Fe2+) and lipid peroxides. As the metabolic hub of the body, the liver is crucial for iron storage and lipid metabolism. The liver seems to be closely related to ferroptosis through iron and lipid metabolism. Liver disease greatly threatens host health, and exploring effective interventions is essential. Mounting studies have demonstrated that ferroptosis is one of the possible pathogenic mechanisms involved in liver disease. Targeting ferroptosis may provide a promising opportunity for treating liver disease. However, drugs targeting ferroptosis are extremely limited. Therefore, it is an urgent need to develop new and safe ferroptosis regulators. Natural active compounds (NAC), especially those derived from traditional Chinese medicine, have recently shown great therapeutic potential in liver disease via modulating ferroptosis-related genes or pathways. Here, we outline the molecular mechanism of ferroptosis and systematically summarize the regulatory function of NAC on ferroptosis in liver disease. Finally, we discuss the application prospects and potential problems concerning NAC as ferroptosis regulators for managing liver disease.

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The natural flavone acacetin protects against high-fat diet-induced lipid accumulation in the liver via the endoplasmic reticulum stress/ferroptosis pathway

Cited by 20 publications

References 43 publications

The Reduced Gut Lachnospira Species Is Linked to Liver Enzyme Elevation and Insulin Resistance in Pediatric Fatty Liver Disease

The Reduced Gut Lachnospira Species Is Linked to Liver Enzyme Elevation and Insulin Resistance in Pediatric Fatty Liver Disease

Research status and hotspots in the field of endoplasmic reticulum stress and liver disease: A bibliometric study

Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications

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