Baicalein improves glucose metabolism in insulin resistant HepG2 cells

Zheng, Yang; Wei, Huang; Zhang, Jingsheng; Xie, Ming; Wang, Xiaowan

doi:10.1016/j.ejphar.2019.04.005

Cited by 71 publications

(44 citation statements)

References 33 publications

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“…In addition, kaempferol also can reduce myocardial ischemia-reperfusion injury/MAPK-induced oxidative stress and inflammation by reducing AGE-RAGE, thereby improving myocardial injury in diabetic rats [ 23 ]. Yang discovered that baicalein (10 −6 and 10 −5 mol/L) may promote glucose uptake and glycolysis through the InsR/IRS-1/PI3K/AKT pathway and inhibit gluconeogenesis in liver cells, thus have strong anti-IR hepatocyte activity [ 24 ]. Therefore, the above active components indicate the effectiveness and diversity of chemical ingredients in HLJDD for treating T2DM.…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanism of the Effect of Huanglian Jiedu Decoction on Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

Yin

Fan

et al. 2020

Journal of Diabetes Research

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Background. Huanglian Jiedu Decoction (HLJDD) is a Traditional Chinese Medicine (TCM) formula comprising four herbal medicines. This decoction has long been used in China for clinically treating T2DM. However, the molecular mechanism of HLJDD treat for T2DM is still not fully known. Hence, this study was designed to reveal the synergistic mechanism of HLJDD formula in the treatment of T2DM by using network pharmacology method and molecular docking. Methods. Retrieving and screening of active components of different herbs in HLJDD and corresponding T2DM-related target genes across multiple databases. Subsequently, STRING and Cytoscape were applied to analysis and construct PPI network. In addition, cluster and topological analysis were employed for the analysis of PPI networks. Then, the GO and KEGG enrichment analysis were performed by using ClueGO tool. Finally, the differentially expressed analysis was used to verify whether the expression of key target genes in T2DM and non-T2DM samples was statistically significant, and the binding capacity between active components and key targets was validated by molecular docking using AutoDock. Results. There are 65 active components involved in 197 T2DM-related targets that are identified in HLJDD formula. What is more, 39 key targets (AKT1, IL-6, FOS, VEGFA, CASP3, etc.) and 3 clusters were obtained after topological and cluster analysis. Further, GO and KEGG analysis showed that HLJDD may play an important role in treating T2DM and its complications by synergistically regulating many biological processes and pathways which participated in signaling transduction, inflammatory response, apoptotic process, and vascular processes. Differentially expressed analysis showed that AKT1, IL-6, and FOS were upregulated in T2DM samples and a significant between sample differential expression. These results were validated by molecular docking, which identified 5 high-affinity active components in HLJDD, including quercetin, wogonin, baicalein, kaempferol, and oroxylin A. Conclusion. Our research firstly revealed the basic pharmacological effects and relevant mechanisms of the HLJDD in the treatment of T2DM and its complications. The prediction results might facilitate the development of HLJDD or its active compounds as alternative therapy for T2DM. However, more pharmacological experiments should be performed for verification.

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Section: Discussionmentioning

confidence: 99%

Molecular Mechanism of the Effect of Huanglian Jiedu Decoction on Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

Yin

Fan

et al. 2020

Journal of Diabetes Research

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“…The baicalein mechanism of action could upregulate AMPK signaling pathways, which can attenuate insulin resistance and inhibit inflammation [187]. The treatment of baicalein in HepG2 cells (0.001 umol/L and 0.01 umol/L) enhanced glucose uptake and glycolysis and suppressed [188]. In addition, baicalein prevents oxidative stress and inflammation in diabetic cardiomyopathy rats through the regulation of PI3K/AKT signaling [189].…”

Section: Anti-diabetic Effects Of Selected Flavonoidsmentioning

confidence: 99%

Flavonoids and Their Anti-Diabetic Effects: Cellular Mechanisms and Effects to Improve Blood Sugar Levels

et al. 2019

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Diabetes mellitus (DM) is a prevailing global health metabolic disorder, with an alarming incidence rate and a huge burden on health care providers. DM is characterized by the elevation of blood glucose due either to a defect in insulin synthesis, secretion, binding to receptor, or an increase of insulin resistance. The internal and external factors such as obesity, urbanizations, and genetic mutations could increase the risk of developing DM. Flavonoids are phenolic compounds existing as secondary metabolites in fruits and vegetables as well as fungi. Their structure consists of 15 carbon skeletons and two aromatic rings (A and B) connected by three carbon chains. Flavonoids are furtherly classified into 6 subclasses: flavonols, flavones, flavanones, isoflavones, flavanols, and anthocyanidins. Naturally occurring flavonoids possess anti-diabetic effects. As in vitro and animal model’s studies demonstrate, they have the ability to prevent diabetes and its complications. The aim of this review is to summarize the current knowledge addressing the antidiabetic effects of dietary flavonoids and their underlying molecular mechanisms on selected pathways: Glucose transporter, hepatic enzymes, tyrosine kinase inhibitor, AMPK, PPAR, and NF-κB. Flavonoids improve the pathogenesis of diabetes and its complications through the regulation of glucose metabolism, hepatic enzymes activities, and a lipid profile. Most studies illustrate a positive role of specific dietary flavonoids on diabetes, but the mechanisms of action and the side effects need more clarification. Overall, more research is needed to provide a better understanding of the mechanisms of diabetes treatment using flavonoids.

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“…It had been reported that GQD could significantly decrease fasting blood glucose, glycosylated serum protein, glycosylated hemoglobin, and fasting serum insulin and promote myocardial glycolysis in diabetic rats [ 9 , 10 ]. Isoflavonoids (3′-hydroxy puerarin, puerarin, daidzin, daidzein, genistin, and genistein), flavonoids (baicalin, baicalein, wogonoside, wogonin, liquiritin, and liquiritigenin), alkaloids (berberine, jatrorrhizine, palmatine, and coptisine), and glycyrrhetic acid have been identified within the preparation [ 11 – 13 ], and these components are correlated to the antidiabetic, antioxidant, and immunoregulative effects [ 14 – 17 ]. Notably, the administration of GQD has also yielded a potential hypoglycemic effect associated with multitarget therapy.…”

Section: Introductionmentioning

confidence: 99%

Herbal Formula Gegen‐Qinlian Decoction for Type 2 Diabetes Mellitus: A Meta‐Analysis of Randomized Controlled Trials

Lin

Cheng

Qin

2020

Evidence-Based Complementary and Alternative Medicine

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Background. Herbal formula Gegen-Qinlian Decoction (GQD) has been widely used in China for the treatment of type 2 diabetes mellitus (T2DM), but its efficacy and safety are unclear. Method. The studies were identified from the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure database, Wanfang database, and VIP database using the keywords “Gegenqinlian” or “Gegen-Qinlian” or “Gegen-Qin-Lian” or “Ge Gen Qin Lian.” Relevant studies were selected according to predefined inclusion and exclusion criteria. Study selection, data extraction, and validation were carried out by, at least, two reviewers with disagreements being settled by discussion. Results. After literature search, a total of 26 randomized controlled trials were included with a total of 2553 patients. There was evidence that compared with metformin, the combination of GQD and metformin significantly reduced the fasting plasma glucose levels (MD −1.79, 95% CI (−2.31, −1.27), p < 0.00001 ); 2-hour postprandial plasma glucose levels (MD −1.72, 95% CI (−2.12, −1.31), p < 0.00001 ); and glycosylated hemoglobin levels (MD −1.26, 95% CI (−1.80, −0.72), p < 0.00001 ), and no serious side effects were identified. Conclusion. These data suggest that GQD may be an effective herbal formula in treating T2DM without serious side effects. The addition of GQD also enhances the hypoglycemic effects of metformin. However, the evidence remains weak due to methodological flaws, which may amplify the therapeutic benefit of GQD.

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Baicalein improves glucose metabolism in insulin resistant HepG2 cells

Cited by 71 publications

References 33 publications

Molecular Mechanism of the Effect of Huanglian Jiedu Decoction on Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

Molecular Mechanism of the Effect of Huanglian Jiedu Decoction on Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

Flavonoids and Their Anti-Diabetic Effects: Cellular Mechanisms and Effects to Improve Blood Sugar Levels

Herbal Formula Gegen‐Qinlian Decoction for Type 2 Diabetes Mellitus: A Meta‐Analysis of Randomized Controlled Trials

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