Kukoamine A attenuates insulin resistance and fatty liver through downregulation of Srebp-1c

Li, Guangyun; Zhou, Fang; Chen, Ying; Zhang, Weiguo; Wang, Ning

doi:10.1016/j.biopha.2017.02.024

Cited by 38 publications

(38 citation statements)

References 33 publications

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“…Our results thus suggested that acacetin attenuated lipogenesis and had an anti-obesity effect in obese mice mainly by blocking the action of C/EBPs and SREBP-1c. Notably, SREBP-1c and C/EBPs bind to the promoter of FAS to promote lipogenesis and to increase aP2 and LPL expression in adipocytes ( Li G. et al, 2017 ; Mota de Sa et al, 2017 ). aP2 is expressed in mature adipose tissue where it regulates lipid and glucose metabolism ( Wang et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Acacetin from Traditionally Used Saussurea involucrata Kar. et Kir. Suppressed Adipogenesis in 3T3-L1 Adipocytes and Attenuated Lipid Accumulation in Obese Mice

Liou

Chen

et al. 2017

Front. Pharmacol.

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Acacetin, a flavone that can be isolated from the Saussurea involucrata plant, has anti-tumor and anti-inflammatory properties that ameliorate airway hyperresponsiveness in asthmatic mice. This study investigated whether acacetin has anti-adipogenic effects in 3T3-L1 adipocytes and whether it regulates the inflammatory response in adipocytes and macrophages. It also investigated whether acacetin ameliorates lipid accumulation in high-fat diet- (HFD) induced obese mice. Differentiated 3T3-L1 cells were treated with acacetin. The glycerol levels in the culture medium were measured, and the expression of proteins and genes involved in adipogenesis and lipolysis were assayed by Western blot and real-time PCR, respectively. Inflammatory cytokine signaling pathway activity was assessed in macrophages that were treated with acacetin and cultured with differentiated medium from 3T3-L1 cells. Intraperitoneal injections of acacetin were administered to HFD-induced obese mice twice a week for 10 weeks. Acacetin significantly increased the levels of glycerol in the culture medium and significantly inhibited lipid accumulation in adipocytes. Acacetin reduced the expression of adipogenesis-related transcription factors, including the expression of the CCAAT/enhancer-binding protein; it also increased sirtuin 1 expression and AMPK phosphorylation in adipocytes. In macrophages cultured with differentiated media from 3T3-L1 adipocytes, acacetin reduced the levels of inflammatory mediators and the activity of the mitogen-activated protein kinase and NF-κB pathways. In obese mice, acacetin reduced both body weight and visceral adipose tissue weight. These results demonstrate that acacetin inhibited adipogenesis in adipocytes and in obese mice. Acacetin also reduced the inflammatory response of macrophages that were stimulated with differentiated media from 3T3-L1 cells.

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Section: Discussionmentioning

confidence: 99%

Acacetin from Traditionally Used Saussurea involucrata Kar. et Kir. Suppressed Adipogenesis in 3T3-L1 Adipocytes and Attenuated Lipid Accumulation in Obese Mice

Liou

Chen

et al. 2017

Front. Pharmacol.

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“…The sterol regulatory element-binding proteins (SREBPs) regulate lipid homeostasis and are present in three isoforms: SREBP-1a , SREBP-1c , and SREBP-2 , with the second form being the predominant one [ 43 ]. Researches show that the transcriptional activity and levels of SREBP-1c are strongly associated with hepatic TG accumulation, insulin resistance, and metabolic dysfunction [ 44 , 45 , 46 ]. This study found that MDG-1 could significantly improve insulin resistance; we suspect that this improvement could be accounted for through the down-regulation of SREBP expression.…”

Section: Discussionmentioning

confidence: 99%

MDG-1, a Potential Regulator of PPARα and PPARγ, Ameliorates Dyslipidemia in Mice

Wang

Shi

Joyce

et al. 2017

IJMS

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Hyperlipidemia is a serious epidemic disease caused by lipid metabolism disorder, which is harmful to human health. MDG-1, a β-d-fructan polysaccharide extracted from Ophiopogon japonicus, has been shown to improve abnormal blood lipid levels and alleviate diabetes. However, the underlying mechanism on hyperlipidemia is largely unknown. In this study, male C57BL/6 mice were randomly separated into three groups, respectively: low-fat diet (Con), high-fat diet (HFD), and high-fat diet plus 5‰ MDG-1 (HFD + MDG-1). Body weight was measured and the serum lipid levels were analyzed. Using gene microarray, various core pathways, together with levels of gene expression within hepatocytes, were analyzed. RT-PCR was used to confirm the identity of the differentially expressed genes. MDG-1 could prevent obesity in HFD-induced mice and improve abnormal serum lipids. Besides, MDG-1 could regulate hyperlipidemia symptoms, specifically, and decrease fasting blood glucose, improve glucose tolerance, and ameliorate insulin resistance. According to results from gene microarray, most of the identified pathways were involved in the digestion and absorption of fat, biosynthesis, and catabolism of fatty acids as well as the secretion and biological synthesis of bile acids. Furthermore, MDG-1 may act upon peroxisome proliferator-activated receptors (PPAR) α and γ, activating PPARα whilst inhibiting PPARγ, thus having a potent hypolipidemic effect.

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“…Kuk A dosage selection was based on the previous report. 26,27 Kuk A and indomethacin were dissolved in normal saline prior to administration. The rats in groups 1 and 2 were orally administered with normal saline, while the rats in groups 3-5 were treated with indomethacin and Kuk B by oral gavage for 5 days prior to carrageenan injection.…”

Section: Experimental Animalsmentioning

confidence: 99%

“…5 Kukoamine A (Kuk A; Figure 1) is a naturally occurring bioactive spermine alkaloid found in the root back of Lycium chinense, and previous studies have indicated the therapeutic potentials of Kuk A, highlighting its antihypertensive, antiinflammatory, antisepsis, antioxidant, anticancer and neuroprotective properties. [6][7][8] Although Kuk A has many pharmacological effects associated with it, there are no evidences in the literature on its effects on acute inflammation. Thus, this study investigated the in vitro and in vivo anti-inflammatory activities of KuK A on lipopolysaccharide (LPS)-stimulated inflammation in RAW 264.7 cells and carrageenan-induced inflammation in rats.…”

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confidence: 99%

Anti-Inflammatory Activities of Kukoamine A From the Root Bark of Lycium chinense Miller

Wang

et al. 2020

Natural Product Communications

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Kukoamine A (Kuk A) is a naturally occurring bioactive spermine alkaloid found in the root bark of Lycium chinense, and it exerts various therapeutic effects including antioxidant, neuroprotective, anti-inflammatory, and antidiabetic effects. This study evaluated the anti-inflammatory properties of Kuk A against lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophage cells and carrageenan-induced paw edema in rats. Pretreatment of cells with Kuk A significantly inhibited the production of reactive oxygen species, nitric oxide, prostaglandin E2, cyclooxygenase-2 activity, tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6 in LPS-treated cells. In addition, pretreatment of rats with Kuk A significantly decreased inflammatory response to carrageenan-induced paw edema by alleviating proinﬂammatory cytokines in the serum, malondialdehyde levels in the liver and increasing the activities of liver antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) of carrageenan-treated rats. These results suggest the protective role of Kuk A in acute inflammatory reaction and could be useful in the treatment of inflammatory-related disorders.

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Kukoamine A attenuates insulin resistance and fatty liver through downregulation of Srebp-1c

Cited by 38 publications

References 33 publications

Acacetin from Traditionally Used Saussurea involucrata Kar. et Kir. Suppressed Adipogenesis in 3T3-L1 Adipocytes and Attenuated Lipid Accumulation in Obese Mice

Acacetin from Traditionally Used Saussurea involucrata Kar. et Kir. Suppressed Adipogenesis in 3T3-L1 Adipocytes and Attenuated Lipid Accumulation in Obese Mice

MDG-1, a Potential Regulator of PPARα and PPARγ, Ameliorates Dyslipidemia in Mice

Anti-Inflammatory Activities of Kukoamine A From the Root Bark of Lycium chinense Miller

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