Dataset Information

Taxifolin and Sorghum Ethanol Extract Protect against Hepatic Insulin Resistance via the miR-195/IRS1/PI3K/AKT and AMPK Signalling Pathways.

ABSTRACT: This study aimed to evaluate the effects of taxifolin and sorghum ethanol extract on free fatty acid (FFA)-induced hepatic insulin resistance. FFA treatment decreased glucose uptake by 16.2% compared with that in the control, whereas taxifolin and sorghum ethanol extract increased the glucose uptake. Additionally, taxifolin and sorghum ethanol extract increased the expression of p-PI3K, p-IRS1, p-AKT, p-AMPK, and p-ACC in FFA-induced hepatocytes. Furthermore, FFA treatment increased the expression of miR-195. However, compared with the FFA treatment, treatment with taxifolin and sorghum ethanol extract decreased miR-195 expression in a dose-dependent manner. Taxifolin and sorghum ethanol extract enhanced p-IRS1, p-PI3K, p-AMPK, p-AKT, and p-ACC expression by suppressing miR-195 levels in miR-195 mimic- or inhibitor-transfected cells. These results indicate that taxifolin and sorghum ethanol extract attenuate insulin resistance by regulating miR-195 expression, which suggests that taxifolin and sorghum ethanol extract may be useful antidiabetic agents.

SUBMITTER: Lee H

PROVIDER: S-EPMC8465682 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Taxifolin and Sorghum Ethanol Extract Protect against Hepatic Insulin Resistance via the miR-195/IRS1/PI3K/AKT and AMPK Signalling Pathways.

Lee Hana H Jeong Won-Tae WT So Yoon-Sup YS Lim Heung-Bin HB Lee Junsoo J

Antioxidants (Basel, Switzerland) 20210824 9

This study aimed to evaluate the effects of taxifolin and sorghum ethanol extract on free fatty acid (FFA)-induced hepatic insulin resistance. FFA treatment decreased glucose uptake by 16.2% compared with that in the control, whereas taxifolin and sorghum ethanol extract increased the glucose uptake. Additionally, taxifolin and sorghum ethanol extract increased the expression of p-PI3K, p-IRS1, p-AKT, p-AMPK, and p-ACC in FFA-induced hepatocytes. Furthermore, FFA treatment increased the expressi ...[more]

PMID: 34572963

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Project description:IntroductionThe root of Paeonia suffruticosa Andrews (P. suffruticosa Andr.), is a traditional Chinese medicine. Numerous studies have shown that it possesses anti-inflammatory, antioxidant, and anti-aging effects due to its rich content of bioactive compounds such as polyphenols and paeonol. Thus, it finds extensively applied in the fields of medicine and cosmetics. However, there are few reports on the photoprotective effects of P. suffruticosa Andr. root bark, this study aims to investigate its research in this area.MethodsThis study utilized P. suffruticosa Andr. root bark sourced from Kunming, Yunnan Province, China. The P. suffruticosa Andr. root extract (PSAE) was obtained using AB-8 resin. The photoprotective effect of PSAE was assessed using HaCaT cells, HFF cells, and a 3D Reconstructed Human full T-Skin™ model. Mechanistic investigations were performed using RT-qPCR, WB, IF, H&E staining, Masson's trichrome staining and IHC staining. Finally, an assessment of the effects on humans was conducted.ResultsThe total phenolic content in the obtained PSAE was 48.9%. Antioxidant activity studies demonstrated that PSAE effectively inhibits DPPH radicals, superoxide anions, hydroxyl radicals, and ABTS radicals, while also enhancing the inhibition rates of collagenase and hyaluronidase. In vitro studies on photoaging resistance revealed that PSAE significantly reduced the UV-induced increases in reactive oxygen species (ROS) levels and senescence-associated β-galactosidase (SA-β-gal) activity. Mechanistic studies indicated that PSAE suppressed the overexpression of IRS1 and its downstream effectors, including PI3K, AKT, and mTOR induced by UV irradiation. A human efficacy assessment was conducted by evaluating parameters such as transepidermal water loss (TEWL), epidermal moisture content, roughness and elasticity, confirming the efficacy of PSAE in humans.DiscussionIn summary, PSAE attenuates UV-induced oxidative damage, genetic damage, and collagen degradation associated with photoaging by modulating the IRS/PI3K/FOXO signaling pathway. This study elucidated the mechanism through which PSAE, thereby providing strong support for its application in cosmetic anti-aging formulations.

Project description:Cadmium, a ubiquitous environmental pollutant, has been implicated in the disruption of various metabolic pathways, contributing to the development of insulin resistance, glucose intolerance, and associated metabolic disorders. This study aimed to investigate the cadmium chloride (CdCl2) exposure on metabolic pathways and to assess the potential therapeutic efficacy of the taxifolin-enriched extract in mitigating these disruptions by modulating biochemical pathways. Taxifolin-enriched extract (TEE) was prepared from Pinus roxburghii bark using a green extraction method. About 60 Wistar albino rats were divided into six groups: the control group (n = 10), the CdCl2 group (30 mg/kg) (n = 10), and four groups (each comprises n = 10) treated with 30 mg/kg CdCl2 in combination with metformin (100 mg/kg), ascorbic acid, taxifolin (30 mg/kg), and TEE (30 mg/kg), respectively. After the treatment period of 1 month, a comprehensive assessment of metabolic biomarkers and gene expressions that regulate the metabolism of carbohydrates and lipids was conducted to evaluate the impact of CdCl2 exposure and the potential protective effects of TEE. The results revealed that CdCl2 exposure significantly increased (P < 0.001) serum levels of α-glucosidase, α-amylase, insulin, G6PC, hexokinases, TGs, LDL, HMG-CoA reductase, and pro-inflammatory cytokines such as IL-6 and TNF-α. Conversely, CdCl2 exposure led to a reduction in HDL, antioxidant enzyme levels, phosphofructokinases, and glucose-6-phosphatase dehydrogenase. However, the administration of TEE alongside CdCl2 substantially mitigated (P < 0.001) these fluctuations in metabolic and inflammatory biomarker levels induced by CdCl2 exposure. Both TEE and taxifolin treatment effectively lowered the elevated levels of α-amylase, α-glucosidase, G6PC, insulin, TGs, HMG-CoA reductase, leptin, ALT, AST, blood urea nitrogen, creatinine, and pro-inflammatory cytokines while simultaneously enhancing levels of HDL cholesterol and antioxidant enzymes. Moreover, CdCl2 exposure suppressed mRNA expression of critical metabolic biomarkers such as glucose transporter 2 (GLUT2), insulin-like growth factor 1 (IGF-1), lactate dehydrogenase, and HMG-CoA lyases while upregulating the mRNA expression of angiotensin receptor 2 and vasopressin, key metabolic biomarkers involved in glucose metabolism and insulin regulation. TEE demonstrated the potential to restore normal metabolic functions and reduce the adverse impacts caused by CdCl2 exposure by mitigating disturbances in several metabolic pathways and restoring gene expression of critical metabolic biomarkers related to glucose metabolism and insulin regulation. Nevertheless, further investigation is warranted to comprehensively understand the underlying mechanisms and optimize the appropriate dosage and duration of TEE treatment for achieving the most effective therapeutic outcomes.

Dataset Information

Taxifolin and Sorghum Ethanol Extract Protect against Hepatic Insulin Resistance via the miR-195/IRS1/PI3K/AKT and AMPK Signalling Pathways.

Publications

Taxifolin and Sorghum Ethanol Extract Protect against Hepatic Insulin Resistance via the miR-195/IRS1/PI3K/AKT and AMPK Signalling Pathways.

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