Baicalein Enhances the Effect of Acarbose on the Improvement of Nonalcoholic Fatty Liver Disease Associated with Prediabetes via the Inhibition of <i>De Novo</i> Lipogenesis

Xing, Yan; Ren, Xinxiu; Li, Xia; Sui, Liping; Shi, Xuan; Sun, Yu; Quan, Chunshan; Xiu, Zhilong

doi:10.1021/acs.jafc.1c04194

Cited by 23 publications

(24 citation statements)

References 48 publications

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“…It is evidence that indicated that BAL inhibits hepatic de novo lipogenesis via suppressing SREBP1c and ChREBP activities, thereby reversing the high expressions of FASN, ACC and SCD expression in oleic acid-induced hepatocytes and highfat-diet (HFD) induced mice (Xing et al, 2021), we got the similar results in fructose-induced rats. These evidences suggested that excessive HFD or fructose consumption both enhance the activities of key regulators in hepatic DNL, SREBP1c and ChREBP in liver, and which were suppressed by BAL treatment.…”

Section: Discussionsupporting

confidence: 56%

“…In addition, Oil red O (ORO) Staining was also used to investigate the hepatic lipid accumulation in fructose-fed rats. As previous descriptions with a little adjustment (Li L. et al, 2021), liver tissues were fixed with 4% paraformaldehyde and put the tissues in 15-30% sucrose solution for dehydrating twice at 4 °C. After that, embedding agent were used to embed.…”

Section: Histological Examinationmentioning

confidence: 99%

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Baicalein Prevents Fructose-Induced Hepatic Steatosis in Rats: In the Regulation of Fatty Acid De Novo Synthesis, Fatty Acid Elongation and Fatty Acid Oxidation

Zhang²,

Wang³

et al. 2022

Front. Pharmacol.

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Non-alcoholic fatty liver disease (NAFLD), ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), hepatic fibrosis and even hepatocellular carcinoma, is a liver disease worldwide without approved therapeutic drugs. Baicalein (BAL), a flavonoid compound extracted from the Traditional Chinese Medicine (TCM) Scutellariae Radix (Scutellaria baicalensis Georgi.), has been used in TCM clinical practice for thousands of years to treat liver diseases due to its “hepatoprotective effect”. However, the underlying liver-protecting mechanisms remain largely unknown. Here, we found that oral administration of BAL significantly decreased excess serum levels of triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST) as well as hepatic TG in fructose-fed rats. Attenuation of the increased vacuolization and Oil Red O staining area was evident on hepatic histological examination in BAL-treated rats. Mechanistically, results of RNA-sequencing, western-blot, real-time quantitative PCR (RT-qPCR) and hepatic metabolomics analyses indicated that BAL decreased fructose-induced excessive nuclear expressions of mature sterol regulatory element-binding protein 1c (mSREBP1c) and carbohydrate response element-binding protein (ChREBP), which led to the decline of lipogenic molecules [including fatty acid synthase (FASN), stearoyl-CoA desaturase 1 (SCD1), elongation of very long chain fatty acids 6 (ELOVL6), acetyl-CoA carboxylase (ACC)], accompanying with the alternation of hepatic fatty acids composition. Meanwhile, BAL enhanced fatty acid oxidation by activating AMPK/PGC1α signaling axis and PPARα signal pathway, which elicited high expression of carnitine palmitoyl transferase 1α (CPT1α) and Acyl-CoA oxidase 1 (ACO1) in livers of fructose-fed rats, respectively. BAL ameliorated fructose-induced hepatic steatosis, which is associated with regulating fatty acid synthesis, elongation and oxidation.

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Section: Discussionsupporting

confidence: 56%

Section: Histological Examinationmentioning

confidence: 99%

Baicalein Prevents Fructose-Induced Hepatic Steatosis in Rats: In the Regulation of Fatty Acid De Novo Synthesis, Fatty Acid Elongation and Fatty Acid Oxidation

Zhang²,

Wang³

et al. 2022

Front. Pharmacol.

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“…Therefore, the hypothesis that whether the effective control of liver fatty acid synthase and the promotion of fatty acid β-oxidase activity are potential means to alleviate the abnormal accumulation of lipid droplets and TG can be supported by evidence in recent studies . Studies have shown that, in the study of food ingredients, it was found that the combination of baicalein and acarbose could inhibit de novo lipogenesis and the expression of synthase . Interestingly, our results also provided theoretical support for this hypothesis; specifically, Ery inhibited the activity of FAS, ACC, and SREBP-1c and promoted the expression of PPAR α, CPT1A , CPT2 , and ACO in the NAFLD model in vivo and in vitro.…”

Section: Discussionsupporting

confidence: 76%

“…20 Studies have shown that, in the study of food ingredients, it was found that the combination of baicalein and acarbose could inhibit de novo lipogenesis and the expression of synthase. 17 Interestingly, our results also provided theoretical support for this hypothesis; specifically, Ery inhibited the activity of FAS, ACC, and SREBP-1c and promoted the expression of PPARα, CPT1A, CPT2, and ACO in the NAFLD model in vivo and in vitro.…”

Section: ■ Discussionsupporting

confidence: 72%

“…This has a similar function to some effective food ingredients such as baicalein and acarbose combinations, hesperetin, and acerola polysaccharides. These drugs can alleviate the occurrence of NAFLD by reducing the level of TG. − The formation of lipid droplets and TG is dependent on the functions of fatty acid synthase and fatty acid β-oxidase. Therefore, the hypothesis that whether the effective control of liver fatty acid synthase and the promotion of fatty acid β-oxidase activity are potential means to alleviate the abnormal accumulation of lipid droplets and TG can be supported by evidence in recent studies .…”

Section: Discussionmentioning

confidence: 99%

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Erythritol Improves Nonalcoholic Fatty Liver Disease by Activating Nrf2 Antioxidant Capacity

Jin

Wei

et al. 2021

J. Agric. Food Chem.

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Nonalcoholic fatty liver disease (NAFLD) is a kind of serious fat disorder that has become a critical problem to human society. Therefore, finding drugs that are safe and effective has become more and more important. Erythritol (Ery) is a polyol sweetener with a variety of biological functions. However, whether Ery has a relieving effect on NAFLD has not been reported yet. Therefore, we induced HepG2 cells with oleic acid and palmitic acid as our in vitro model. Moreover, we choose wild-type mice with tyloxapol and high-fat diet and nuclear factor E2-related factor 2 (Nrf2) knockout mice with high-fat diet as our in vivo model. We found that Ery could reverse the lipid accumulation, oxidative stress, and endoplasmic reticulum stress caused by the NAFLD model. The mechanism studies showed that Ery promoted the translocation of Nrf2 from cytoplasm to nucleus, and the molecular simulation docking results of Ery and Nrf2 showed that there was a hydrogen bond between them. Moreover, Ery could promote the production of HO-1 and NQO1 antioxidant proteins and inhibit the expression of endoplasmic reticulum stress proteins GPR78, p-PERK, and CHOP. On the contrast, when Nrf2 was knocked out in mice, Ery lost its protective effect on NAFLD. In conclusion, we found that the potential mechanism of Ery’s protective effect is that it plays an antioxidant role by activating the Nrf2 signaling pathway, thereby inhibiting endoplasmic reticulum stress and lipid accumulation in NAFLD.

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Baicalein, a dietary flavonoid, enhances the insulin‐sensitizing effect of metformin to prevent type 2 diabetes via the regulation of lipid metabolism and gut microenvironment

Xing,

Liu,

Zhang

et al. 2024

Food Frontiers

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Baicalein is a natural flavonoid abundant in various foods and dietary plants, including Tuber aestivum and Oroxylum indicum. In this study, we investigated the role of baicalein in enhancing the insulin‐sensitizing effect of metformin in mice with prediabetes. Baicalein, when combined with 25% of normal‐dose metformin, achieved a diabetes‐reversion rate of 80%, which was 1.86‐fold that of normal‐dose metformin. Mechanistically, baicalein enhanced the insulin‐sensitizing effect of metformin on lipid metabolism by inhibiting de novo lipogenesis through the AMP‐activated protein kinase/SREBP‐1c/FASN pathway and by inducing fatty‐acid β‐oxidation through the upregulation of ACSL1, CPT1A, EHHADH, and acyl‐CoA dehydrogenases (ACADL/ACADM/ACADS). Meanwhile, baicalein enhanced the insulin‐sensitizing effect of metformin via the modulation of the gut microenvironment by enriching probiotics, especially Akkermansia by 53.4‐fold, depleting opportunistic pathogens, and strengthening the intestinal barrier. The improved gut microenvironment led to the alleviation of chronic endotoxemia, as evidenced by decreased levels of lipopolysaccharide and proinflammatory cytokines. Furthermore, baicalein enhanced the effect of metformin on decreasing the circulating level of branched‐chain amino acids (BCAAs), which further improved insulin sensitivity by normalizing the mTORC1/p70S6K/IRS1 signaling pathway and de novo lipogenesis. Moreover, the role of baicalein in enhancing the insulin‐sensitizing effect of metformin was verified by an oleic acid‐induced steatosis model and a BCAA‐induced insulin resistance model in hepatocytes. Our study laid a theoretical foundation for developing baicalein into a dietary supplement for diabetes prevention. The diverse mechanisms of food‐derived flavonoids can be applied in the development of dietary supplements to enhance the efficacy of oral hyperglycemic agents currently used in clinics.

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Baicalein Enhances the Effect of Acarbose on the Improvement of Nonalcoholic Fatty Liver Disease Associated with Prediabetes via the Inhibition of De Novo Lipogenesis

Cited by 23 publications

References 48 publications

Baicalein Prevents Fructose-Induced Hepatic Steatosis in Rats: In the Regulation of Fatty Acid De Novo Synthesis, Fatty Acid Elongation and Fatty Acid Oxidation

Baicalein Prevents Fructose-Induced Hepatic Steatosis in Rats: In the Regulation of Fatty Acid De Novo Synthesis, Fatty Acid Elongation and Fatty Acid Oxidation

Erythritol Improves Nonalcoholic Fatty Liver Disease by Activating Nrf2 Antioxidant Capacity

Baicalein, a dietary flavonoid, enhances the insulin‐sensitizing effect of metformin to prevent type 2 diabetes via the regulation of lipid metabolism and gut microenvironment

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