Citrus flavone tangeretin is a potential insulin sensitizer targeting hepatocytes through suppressing MEK-ERK1/2 pathway

Guo, Jiajie; Chen, Jinfeng; Ren, Wei Ying; Zhu, Yun; Zhao, Qian; Zhang, Kaini; Su, Dongming; Qiu, Chen; Zhang, Wei; Li, Kai

doi:10.1016/j.bbrc.2020.05.212

Cited by 24 publications

(19 citation statements)

References 28 publications

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“…Similar results were found with a swertisin rich flavonoid fraction both in insulin resistance hepatic cells [35] and in high fat diet (HFD)-fed and streptozotocin (STZ)-induced type 2 diabetic rats [36], as well as with the flavonoid tangeretin in (db/db) diabetic mice [37]. The hepatic insulin sensitizing effect of tangeretin [37] and cocoa flavonoids [55] has also been associated with their ability to suppress the MAPKs pathway. On the contrary, the flavonoid myricetin up-regulated p-IR, p-IRS1 and p-AKT in the liver of HFD-fed and STZ-induced type 2 diabetic rats by inhibiting the activity and expression of PTP1B, the tyrosine phosphatase that negatively regulates the insulin signal transduction [38].…”

Section: Effects Of Flavonoids On Insulin Signaling In T2dsupporting

confidence: 72%

“…Likewise, a cocoa flavonoid extract (1 µg/mL) and its main flavonoid epicatechin (EC) (10 µM) were able to diminish the insulin desensitization in glucose-induced insulin-resistant HepG2 cells by reducing IRS-1 serine phosphorylation and increasing tyrosine phosphorylated lev-els of IR, IRS-1 and IRS-2, and stimulating both the PI3K/AKT pathway and AMP-activated protein kinase (AMPK) [34]. Similar results were found with a swertisin rich flavonoid fraction both in insulin resistance hepatic cells [35] and in high fat diet (HFD)-fed and streptozotocin (STZ)-induced type 2 diabetic rats [36], as well as with the flavonoid tangeretin in (db/db) diabetic mice [37]. The hepatic insulin sensitizing effect of tangeretin [37] and cocoa flavonoids [55] has also been associated with their ability to suppress the MAPKs pathway.…”

Section: Effects Of Flavonoids On Insulin Signaling In T2dsupporting

confidence: 61%

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Dietary Flavonoids and Insulin Signaling in Diabetes and Obesity

Ramos

2021

Cells

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Type 2 diabetes (T2D) and obesity are relevant worldwide chronic diseases. A common complication in both pathologies is the dysregulation of the insulin-signaling pathway that is crucial to maintain an accurate glucose homeostasis. Flavonoids are naturally occurring phenolic compounds abundant in fruits, vegetables and seeds. Rising evidence supports a role for the flavonoids against T2D and obesity, and at present, these compounds are considered as important potential chemopreventive agents. This review summarizes in vitro and in vivo studies providing data related to the effects of flavonoids and flavonoid-rich foods on the modulation of the insulin route during T2D and obesity. Notably, few human studies have evaluated the regulatory effect of these phenolic compounds at molecular level on the insulin pathway. In this context, it is also important to note that the mechanism of action for the flavonoids is not fully characterized and that a proper dosage to obtain a beneficial effect on health has not been defined yet. Further investigations will contribute to solve all these critical challenges and will enable the use of flavonoids to prevent, delay or support the treatment of T2D and obesity.

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Section: Effects Of Flavonoids On Insulin Signaling In T2dsupporting

confidence: 72%

Section: Effects Of Flavonoids On Insulin Signaling In T2dsupporting

confidence: 61%

Dietary Flavonoids and Insulin Signaling in Diabetes and Obesity

Ramos

2021

Cells

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“…After 8 weeks, the dosed mice on the HFD exhibited significantly lower weight gain, glucose tolerance, total‐C levels, and decreased secretion of proinflammatory adipocytokines and cytokines compared with the nonsupplemented HFD mice. Wild‐type C57BL/6J mice on a normal diet with intragastric dose s of TAN for 30 days produced significantly lower serum glucose levels and serum insulin levels in nonfasted animals on day 31 (Guo et al., 2020). Blood glucose tolerance test s after 16‐hr fasting showed significantly lower glucose levels for 25 and 50 mg/kg dosed animals compared with nontreated animals, but insulin resistance was significantly different only for the mice dosed with 50 mg/kg (Guo et al., 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Wild‐type C57BL/6J mice on a normal diet with intragastric dose s of TAN for 30 days produced significantly lower serum glucose levels and serum insulin levels in nonfasted animals on day 31 (Guo et al., 2020). Blood glucose tolerance test s after 16‐hr fasting showed significantly lower glucose levels for 25 and 50 mg/kg dosed animals compared with nontreated animals, but insulin resistance was significantly different only for the mice dosed with 50 mg/kg (Guo et al., 2020). In a further study, 30 days of oral administration of TAN (100 mg/kg body weight) to streptozotocin‐induced diabetic rats resulted in significant reductions in plasma glucose and glycosylated hemoglobin (HbA1c; Sundaram et al., 2014).…”

Section: Discussionmentioning

confidence: 99%

Physiological effects of tangeretin and heptamethoxyflavone on obese C57BL/6J mice fed a high‐fat diet and analyses of the metabolites originating from these two polymethoxylated flavones

Nery

Ferreira

Gonçalves

et al. 2021

Food Science & Nutrition

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Two compounds from citrus peel, tangeretin (TAN) and 3′,4′,3,5,6,7,8‐heptamethoxyflavone (HMF), were investigated for their abilities to repair metabolic damages caused by an high‐fat diet (HFD) in C57BL/6J mice. In the first 4 weeks, mice were fed either a standard diet (11% kcal from fat) for the control group, or a HFD (45% kcal from fat) to establish obesity in three experimental groups. In the following 4 weeks, two groups receiving the HFD were supplemented with either TAN or HMF at daily doses of 100 mg/kg body weight, while the two remaining groups continued to receive the standard healthy diet or the nonsupplemented HFD. Four weeks of supplementation with TAN and HMF resulted in intermediate levels of blood serum glucose, leptin, resistin, and insulin resistance compared with the healthy control and the nonsupplemented HFD groups. Blood serum peroxidation (TBARS) levels were significantly lower in the TAN and HMF groups compared with the nonsupplemented HFD group. Several differences occurred in the physiological effects of HMF versus TAN. TAN, but not HMF, reduced adipocyte size in the mice with pre‐existent obesity, while HMF, but not TAN, decreased fat accumulation in the liver and also significantly increased the levels of an anti‐inflammatory cytokine, IL‐10. In an analysis of the metabolites of TAN and HMF, several main classes occurred, including a new set of methylglucuronide conjugates. It is suggested that contrasts between the observed physiological effects of TAN and HMF may be attributable to the differences in numbers and chemical structures of TAN and HMF metabolites.

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“…Studies have found that phlegm syndrome is the main syndrome of patients with lung cancer, and in recent years, C. reticulata and P. ternata are the main drugs for the treatment of cancer, especially lung cancer (18)(19)(20)(21). Pharmacological studies also showed that Erchen decoction, mainly composed of C. reticulata and P. Ternata, could reverse the multidrug resistance of tumor cells, and its effect was mainly related to the decreased expression of multidrug resistanceassociated protein (MRP)1 and P-glycoprotein (P-gp) through Jun N-terminal kinase (JNK) signal transduction pathway (22,23). However, due to the Chinese herbal medicine working by regulating multiple proteins, it is still difficult to effectively, scientifically and comprehensively explain the mechanism of action of C. reticulata and P. ternata in the treatment of lung cancer.…”

Section: Introductionmentioning

confidence: 99%

Network pharmacology study of Citrus reticulata and Pinellia ternata in the treatment of non-small cell lung cancer

Jiang

et al. 2022

Cell Mol Biol (Noisy-le-grand)

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It has been recognized that Citrus reticulata and Pinellia ternata have a good therapeutic effect on NSCLC. However, the potential mechanism of C. reticulata and P. ternata in the treatment of NSCLC based on network pharmacology analysis is not clear. The “Drug-Component-Target-Disease” network was constructed by Cytoscape, and the protein interaction (PPI) network was constructed by STRING. Our study indicated that 18 active ingredients of C. reticulata and P. Ternata were screened from the TCMSP database, and 56 target genes of C. reticulata and P. Ternata for the treatment of NSCLC were identified, and we constructed the “Drug-Component-Target-Disease” network. In this study, we screened 56 PPI core genes to establish a PPI network. We concluded that the network pharmacology mechanism of the effect of C. reticulata and P. Ternata on NSCLC may be closely related to the protein expressed by TP53, ESR1, FOS, NCOA3 and MAPK8, and these may play the therapeutic roles by regulating the IL-17 signaling pathway, antigen processing and presentation, microRNAs in cancer and endocrine resistance.

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Citrus flavone tangeretin is a potential insulin sensitizer targeting hepatocytes through suppressing MEK-ERK1/2 pathway

Cited by 24 publications

References 28 publications

Dietary Flavonoids and Insulin Signaling in Diabetes and Obesity

Dietary Flavonoids and Insulin Signaling in Diabetes and Obesity

Physiological effects of tangeretin and heptamethoxyflavone on obese C57BL/6J mice fed a high‐fat diet and analyses of the metabolites originating from these two polymethoxylated flavones

Network pharmacology study of Citrus reticulata and Pinellia ternata in the treatment of non-small cell lung cancer

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