Dihydromyricetin ameliorates atherosclerosis in LDL receptor deficient mice

Liu, Ting Ting; Zhang, Yi; Tang, Kun; Chen, XueMeng; Zhang, Wei; Xu, Xiao Le

doi:10.1016/j.atherosclerosis.2017.05.003

Cited by 88 publications

(55 citation statements)

References 37 publications

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“…Our results indicated that DHM could suppress the production of proinflammatory cytokines, which plays a key role in protecting against LPS‐induced inflammation. These findings are consistent with previous studies that reported the potent regulation of DHM on the production of inflammatory cytokines in the liver injury, diabetic, and atherosclerosis models . IL‐10 is an important anti‐inflammatory cytokine that can inhibit the proinflammatory cytokines and limit the inflammatory response in the lung .…”

Section: Resultssupporting

confidence: 92%

Protective effect of dihydromyricetin on LPS-induced acute lung injury

Wang

Xiao

Yang

et al. 2018

Journal of Leukocyte Biology

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Dihydromyricetin (DHM), a bioactive flavonoid component isolated from Ampelopsis grossedentata, is known to have anti-inflammatory effect, but the effect of DHM on acute lung injury (ALI) is largely unknown. Here, we investigated the effect of DHM on ALI and the underlying mechanism by bioinformatic analyses and animal experiments. We found that pretreatment with DHM ameliorated lung pathological changes and suppressed the inflammation response in lung tissues after LPS challenge. The potential targets of DHM were predicted by DDI-CPI and DRAR-CPI tools and analyzed using the STRING server to predict the functionally related signaling pathways, such as MAPK signaling. Molecular docking calculations indicated that DHM could be embedded tightly into the binding pocket of ERK, JNK, and p38. Furthermore, the activation of MAPK signaling induced by LPS was inhibited by DHM. In conclusion, these findings suggest that DHM may exert its protective effect on ALI by inhibiting MAPK signaling. The present study supports a potential clinical application for DHM in treating ALI and provides a novel design that combines in silico methods with in vivo experiments for drug research.

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Section: Resultssupporting

confidence: 92%

Protective effect of dihydromyricetin on LPS-induced acute lung injury

Wang

Xiao

Yang

et al. 2018

Journal of Leukocyte Biology

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“…Thus far, the studies regarding the athero-protective effects of apigenin and the underlying molecular mechanisms are limited to a certain extent [14,15]. Many kinds of flavonoid can exert athero-protection through regulation of lipid and cholesterol metabolism and macrophage ABCA1 expression [45][46][47], which makes us wonder whether apigenin can inhibit atherogenesis by maintaining cholesterol homeostasis. The results showed that treatment of lipid-laden macrophages with apigenin markedly increased cholesterol efflux and decreased cholesterol content by amplifying ABCA1 expression in a concentration-and time-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Apigenin Retards Atherogenesis by Promoting ABCA1-Mediated Cholesterol Efflux and Suppressing Inflammation

Ren

Jiang

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: The development of atherosclerosis is accompanied by escalating inflammation and lipid accumulation within blood vessel walls. ABCA1 plays a crucial role in mediating cholesterol efflux from macrophages, which protects against atherogenesis. This research was designed to explore the effects and underlying mechanisms of apigenin (4’, 5, 7-trihydroxyflavone) on ABCA1-mediated cellular cholesterol efflux and LPS-stimulated inflammation in RAW264.7 macrophages and apoE^-/- mice. Methods: Expression of genes or proteins was examined by RT-PCR or western blot analysis. Liquid scintillation counting was used to detect percent cholesterol efflux. Cellular cholesterol content was measured using HPLC assay. The secretion levels of pro-inflammatory cytokines were quantified by ELISA assay. Atherosclerotic lesion sizes were determined with Oil Red O staining. The contents of macrophages and smooth muscle cells in atherosclerotic lesion were evaluated using immunohistochemistry. Plasma TC, TG, HDL-C and LDL-C levels in apoE^-/- mice were evaluated using commercial test kits. Results: Apigenin potently increased ABCA1 expression through miR-33 repression in a dose- and time-dependent manner. Treatment with apigenin significantly increased ABCA1-mediated cholesterol efflux, and reduced TC, FC and CE levels in macrophage-derived foam cells. In LPS-treated macrophages, the expression levels of TLR-4, MyD88 and p-IκB-α as well as nuclear NF-κB p65 were decreased by the addition of apigenin. Moreover, apigenin markedly decreased secretion levels of several pro-inflammatory cytokines. Lastly, in LPS-challenged apoE^-/- mice, apigenin administration augmented ABCA1 expression, decreased the contents of macrophages and smooth muscle cells in atherosclerotic lesion, reduced miR-33, TLR-4, and NF-κB p65 levels, improved plasma lipid profile and relieved inflammation, which results in less atherosclerotic lesion size. Conclusions: Taken together, these results suggest that apigenin may attenuate atherogenesis through up-regulating ABCA1-mediated cholesterol efflux and inhibiting inflammation.

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“…Dihydromyricetin (DMY), the most abundant and bioactive flavonoid in vine tea, could reach the content of more than 30%, which is rarely seen and unique in plant kingdom (Wang, Xiong, Reddy Perumalla, Fang, & Sun Calvin 2016). The antioxidant (Liao et al, 2014), anti-inflammation (Hou et al, 2015b;Liu et al, 2017), and antibacterial (Wu, Bai, Zhong, Huang, & Gao, 2017) effects of DMY were already demonstrated in vitro. The anti-alcoholic intoxication of DMY on the animal models was also reported (Shen et al, 2012).…”

Section: Introductionmentioning

confidence: 99%