Paeonol Ameliorates Glucose and Lipid Metabolism in Experimental Diabetes by Activating Akt

Xu, Futian; Xiao, Haipeng; Liu, Renbin; Yang, Yan; Zhang, Meng; Chen, Lihao; Chen, Zhiquan; Liu, Peiqing; Huang, Heqing

doi:10.3389/fphar.2019.00261

Cited by 25 publications

(19 citation statements)

References 49 publications

(63 reference statements)

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“…PN, an MC-derived ingredient, reduces lipid accumulation in the livers of high-fat diet-induced diabetic mice and improves glucose and lipid metabolism by increasing the phosphorylation level of Akt and expression of glucokinase and low-density lipoprotein receptor in human liver cancer-derived HepG2 cells [29]. In this study, PN reduced lipid accumulation by suppressing early differentiation into mature adipocytes by inhibiting Dex-induced GR promoter activity (Figures 4, 6 and 7) and the expression of the PPAR-γ gene, which is one of the late-stage markers of adipocytes.…”

Section: Discussionmentioning

confidence: 99%

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Paeonol, an Ingredient of Kamishoyosan, Reduces Intracellular Lipid Accumulation by Inhibiting Glucocorticoid Receptor Activity in 3T3-L1 Cells

et al. 2020

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Excessive triglyceride accumulation in lipid-metabolizing tissues is associated with an increased risk of a variety of metabolic diseases. Kamishoyosan (KSS) is a Kampo composed of 10 constituent herbs, and contains moutan cortex (MC) and paeonol (PN) as the major ingredient of MC. Here, we demonstrate the molecular mechanism underlying the effect of KSS on the differentiation of mouse preadipocytes (3T3-L1 cells). KSS inhibited the accumulation of triglycerides in a dose-dependent manner in 3T3-L1 cells that were induced to differentiate into adipocytes. We also found that MC and PN were responsible for the anti-adipogenetic effect of KSS and significantly suppressed the expression of CCAAT/enhancer-binding proteins-δ (C/EBP-δ) mRNA 3 days after the induction of differentiation. Thus, PN may contribute to the anti-adipogenetic property of MC in 3T3-L1 cells. In addition, PN inhibited dexamethasone (Dex)-induced glucocorticoid receptor (GR) promoter activity. Taken together, these results suggest that PN suppresses C/EBP-δ expression by inhibiting Dex-induced GR promoter activity at the early stage of differentiation and, consequently, delays differentiation into mature adipocytes. Our results suggest that the habitual intake of Kampo-containing PN contributes to the prevention of the onset of metabolic diseases by decreasing the excessive accumulation of triglycerides in lipid-metabolizing tissues.

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Section: Discussionmentioning

confidence: 99%

“…One of the compounds included in KSS, geniposide, reduces lipid accumulation in 3T3-L1 cells during differentiation [28]. Another compound, paeonol, reduces lipid accumulation in HepG2 cells [29].…”

Section: Introductionmentioning

confidence: 99%

Paeonol, an Ingredient of Kamishoyosan, Reduces Intracellular Lipid Accumulation by Inhibiting Glucocorticoid Receptor Activity in 3T3-L1 Cells

et al. 2020

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“…The HepG2 cells, generously gifted by Professor Hongbo Hu (China Agricultural University, Beijing, China), were cultured in DMEM containing 10% (v/v) fetal bovine serum and 1% (v/v) penicillin‐streptomycin in a humidified incubator at 37 °C with 5% CO 2 . The PA was prepared according to the method in previous report (Xu et al., 2019). Briefly, the PA was dissolved in pure drinking water (Hangzhou Wahaha Group Co., Ltd., Hangzhou, China) at 70 °C, combined with bovine serum albumin (BSA).…”

Section: Methodsmentioning

confidence: 99%

Coniferaldehyde ameliorates the lipid and glucose metabolism in palmitic acid‐induced HepG2 cells via the LKB1/AMPK signaling pathway

Gai

Zhou

Zhang

et al. 2020

Journal of Food Science

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Impaired lipid and glucose metabolism in the liver is a crucial characteristic of nonalcoholic fatty liver disease (NAFLD). Coniferaldehyde (CA), a kind of phenolic compound found in many edible plants, has multiple biological and pharmacological functions. However, since the effect and molecular mechanism of CA on hepatic lipid and glucose metabolism disorders in NAFLD remain unknown, this study investigated its impact on the lipid and glucose metabolism of palmitic acid (PA)‐induced HepG2 cells. Compared with the HepG2 cells treated only with PA, supplementation with 25, 50, and 100 µM CA reduced the levels of intracellular triglyceride (by 7.11%, 19.62%, and 31.57%) and total cholesterol (by 8.46%, 23.32%, and 27.17%), and enhanced glucose uptake (by 40.91%, 57.49%, and 61.32%) and intracellular glycogen content (by 12.75%, 41.27%, and 53.77%). Moreover, CA supplementation downregulated the expression of sterol regulatory element‐binding protein‐1, fatty acid synthase, and stearoyl‐CoA desaturase 1 related to lipogenesis while upregulating the expression of carnitine palmitoyltransferase 1α related to fatty acid oxidation. CA supplementation also upregulated the glucose transporter 2 protein expression and phosphorylation of glycogen synthase kinase 3β while downregulating the phosphorylation of glycogen synthase. Most importantly, most of these effects of CA were reversed by pretreatment with AMP‐activated protein kinase (AMPK) inhibitor and small interfering RNA‐liver kinase B1 (LKB1). In conclusion, CA ameliorated the lipid and glucose metabolism in PA‐induced HepG2 cells via the LKB1/AMPK signaling pathway. Practical Application In this study, coniferaldehyde appeared to be effective in ameliorating hepatic lipid and glucose metabolism disorders in nonalcoholic fatty liver disease by reducing the levels of intracellular triglyceride and total cholesterol and enhancing glucose uptake and intracellular glycogen content via the LKB1/AMPK signaling pathway in vitro. Therefore, our findings provide new evidence in support of that supplementation with coniferaldehyde or food rich in coniferaldehyde might be considered as a viable dietary intervention strategy for preventing and treating nonalcoholic fatty liver disease.

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“…Paeonol, a phenolic compound isolated from Paeonia suffruticosa, has been shown to have a wide range of pharmacological activities including antioxidant and anti-inflammatory properties [9] that may be beneficial in various diseases such as diabetes [10], cancer [11], gastric ulcer [12], liver fibrosis [13], and myocardial infarction [14]. Paeonol has been proven to have a protection against antineoplastic-induced toxicities such as cisplatin-induced nephrotoxicity [15] and epirubicininduced cardiac toxicity [16]; however, to date, this role has not been investigated in MTX-induced cardiac toxicity.…”

Section: Introductionmentioning

confidence: 99%

Paeonol Attenuates Methotrexate-Induced Cardiac Toxicity in Rats by Inhibiting Oxidative Stress and Suppressing TLR4-Induced NF-κB Inflammatory Pathway

Al‐Taher

Morsy

Rifaai

et al. 2020

Mediators of Inflammation

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Methotrexate (MTX) is a commonly used chemotherapeutic agent. Oxidative stress and inflammation have been proved in the development of MTX toxicity. Paeonol is a natural phenolic compound with various pharmacological activities including antioxidant and anti-inflammatory properties. The aim of the present study was to evaluate the protective effect of paeonol against MTX-induced cardiac toxicity in rats and to evaluate the various mechanisms that underlie this effect. Paeonol (100 mg/kg) was administered orally for 10 days. MTX cardiac toxicity was induced at the end of the fifth day of the experiment, with or without paeonol pretreatment. MTX-induced cardiac damage is evidenced by a distortion in the normal cardiac histological structure, with significant oxidative and nitrosative stress shown as a significant increase in NADPH oxidase-2, malondialdehyde, and nitric oxide levels along with a decrease in reduced glutathione concentration and superoxide dismutase activity compared to the control group. MTX-induced inflammatory effects are evidenced by the increased cardiac toll-like receptor 4 (TLR4) mRNA expression and protein level as well as increased cardiac tumor necrosis factor- (TNF-) α and interleukin- (IL-) 6 levels along with increased nuclear factor- (NF-) κB/p65 immunostaining. MTX increased apoptosis as shown by the upregulation of cardiac caspase 3 immunostaining. Paeonol was able to correct the oxidative and nitrosative stress as well as the inflammatory and apoptotic parameters and restore the normal histological structure compared to MTX alone. In conclusion, paeonol has a protective effect against MTX-induced cardiac toxicity through inhibiting oxidative and nitrosative stress and suppressing the TLR4/NF-κB/TNF-α/IL-6 inflammatory pathway, as well as causing an associated reduction in the proapoptotic marker, caspase 3.

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Paeonol Ameliorates Glucose and Lipid Metabolism in Experimental Diabetes by Activating Akt

Cited by 25 publications

References 49 publications

Paeonol, an Ingredient of Kamishoyosan, Reduces Intracellular Lipid Accumulation by Inhibiting Glucocorticoid Receptor Activity in 3T3-L1 Cells

Paeonol, an Ingredient of Kamishoyosan, Reduces Intracellular Lipid Accumulation by Inhibiting Glucocorticoid Receptor Activity in 3T3-L1 Cells

Coniferaldehyde ameliorates the lipid and glucose metabolism in palmitic acid‐induced HepG2 cells via the LKB1/AMPK signaling pathway

Paeonol Attenuates Methotrexate-Induced Cardiac Toxicity in Rats by Inhibiting Oxidative Stress and Suppressing TLR4-Induced NF-κB Inflammatory Pathway

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