Wogonin ameliorates hyperglycemia and dyslipidemia via PPARα activation in db/db mice

Bak, Eun‐Jung; Kim, Jinmoon; Choi, Yun Hui; Kim, Ji Hye; Lee, Dong‐Eun; Woo, Gye Hyeong; Heon, Jeong; Yoo, Yun‐Jung

doi:10.1016/j.clnu.2013.03.013

Cited by 63 publications

(47 citation statements)

References 32 publications

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“…Recently, several studies have shown that PPARα is expressed in the adipose tissues of humans and rodents [31,32] . In both type 1 and type 2 diabetes models, PPARα expression was significantly downregulated in some tissues [15,33] , consistent with our results showing that expression levels of PPARα protein and mRNA in adipose tissues of diabetic mice were statistically significantly decreased compared to those of control mice (Figure 3B-3D). Our results further confirm that wogonin treatment increased PPARα expression (Figure 3), inhibited PPARα phosphorylation ( Figure 4A-4C), enhanced PPARα transactivation (Supplementary Figure 2), and restored mRNA expression of the PPARα target ACOX ( Figure 4D) in the adipose tissue of diabetic mice and/or in 3T3-L1 adipocytes.…”

Section: Discussionsupporting

confidence: 80%

“…PPARα phosphorylation has been suggested to have a negative association with PPARα activity; decreased phosphorylation leads to increased PPARα activity [21] . Hence, our results indicate that wogonin could activate PPARα, in [15] . Furthermore, our results showed that PPARα knockdown abrogated the inhibitory effects of wogonin on OPN expression in 3T3-L1 adipocytes ( Figure 5), suggesting that PPARα mediated the OPN lowering effects of wogonin.…”

Section: Discussionmentioning

confidence: 85%

“…Wogonin possesses anti-oxidant and anti-inflammatory pro perties [26,27] and is assumed to have anti-diabetic activity. Recent studies have indeed shown that wogonin treatment in db/db mice prevented weight gain, improved glucose tolerance, decreased serum insulin and cholesterol levels, and suppressed the accumulation of lipid droplets in the liver [15] . These pro-metabolic effects are associated with the enhanced expression of PPARα and adiponectin [15] .…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have indeed shown that wogonin treatment in db/db mice prevented weight gain, improved glucose tolerance, decreased serum insulin and cholesterol levels, and suppressed the accumulation of lipid droplets in the liver [15] . These pro-metabolic effects are associated with the enhanced expression of PPARα and adiponectin [15] . In this study, we demonstrate an inhibitory effect of wogonin on OPN expression in adipocytes in vivo and in vitro (Figure 1 and 2).…”

Section: Discussionmentioning

confidence: 99%

“…We have recently found that wogonin is a potent antioxidant capable of inhibiting lipotoxicity-induced apoptosis of vascular smooth muscle cells (VSMCs) via suppression of intracellular DAG generation [14] . Intriguingly, wogonin exhibits beneficial effects on glucose and lipid metabolism in db/db mice [15] , indicating that wogonin is a new candidate for the treatment of diabetes. However, the underlying molecular mechanism of wogonin action remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Wogonin suppresses osteopontin expression in adipocytes by activating PPARα

Zhang

Tang

et al. 2015

Acta Pharmacol Sin

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Aim: Wogonin (5,7-dihydroxy-8-methoxyflavone), a major bioactive compound of the flavonoid family, is commonly extracted from the traditional Chinese medicine Scutellaria baicalensis and possesses antioxidant and anti-inflammatory activities and is assumed to have anti-diabetes function. Indeed, a current study has shown that it can possibly treat metabolic disorders such as those found in db/db mice. However, the underlying molecular mechanism remains largely unclear. The aim of this study was to investigate the impact of wogonin on osteopontin (OPN) expression in adipose tissue from type 1 diabetic mice and in 3T3-L1 adipocytes. Methods: Type 1 diabetes was induced by streptozotocin (STZ) injection. 3T3-L1 preadipocytes were converted to 3T3-L1 adipocytes through treatment with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine (IBMX). Western blot analysis and RT-PCR were performed to detect protein expression and mRNA levels, respectively. Results: Wogonin treatment suppressed the increase in serum OPN levels and reduced OPN expression in adipose tissue from STZinduced type 1 diabetic mice. Administration of wogonin enhanced PPARα expression and activity. Silencing of PPARα diminished the inhibitory effects of wogonin on OPN expression in 3T3-L1 adipocytes. Furthermore, the levels of c-Fos and phosphorylated c-Jun were reduced in wogonin-treated adipose tissue and 3T3-L1 adipocytes. In addition, wogonin treatment dramatically mitigated p38 MAPK phosphorylation. Pharmacological inhibition of p38 MAPK by its specific inhibitor SB203580 increased PPARα activity and decreased OPN expression. Conclusion: Our results suggest that wogonin downregulated OPN expression in adipocytes through the inhibition of p38 MAPK and the sequential activation of the PPARα pathway. Given the adverse effects of high OPN levels on metabolism, our results provide evidence for the potential administration of wogonin as a treatment for diabetes.

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