Astilbin lowers the effective caffeine dose for decreasing lipid accumulation via activating AMPK in high‐fat diet‐induced obese mice

Abstract

BACKGROUND: Caffeine has an anti-obesity effect, although chronic excessive caffeine consumption also causes caffeinism, which is marked by increased anxiety or depression, amongst other symptoms. The present study aimed to investigate whether the addition of flavonoids such as astilbin can reduce the caffeine dose needed to inhibit obesity. RESULTS: ICR mice (n = 80) were fed with normal diet, high-fat diet (HFD), HFD supplemented with astilbin, caffeine, or astilbin + caffeine for 12 weeks. When diets supplemented with astilbin, 0.3 g kg −1 diet caffeine had the same effect as 0.6 g kg −1 diet caffeine alone, and 0.6 g kg −1 diet caffeine combined with astilbin most effectively inhibited HFD-induced obesity. Astilbin improved the anti-obesity effects of caffeine on lipid accumulation via the activation of AMP-activated protein kinase ⊍ (AMPK⊍). (i) Activated AMPK⊍ decreased lipid biosynthesis by suppressing the activity or mRNA expression of 3-hydroxy-3-methylglutaryl-CoA reductase, sterol regulatory element binding protein 1c and its target gene fatty acid synthase. (ii) Activated AMPK⊍ also up-regulated lipolysis by enhancing the expression of adipose triglyceride lipase and increasing the phosphorylation of hormone-sensitive lipase. (iii) Finally, activated AMPK⊍ increased carnitine acyltransferase and acyl-CoA oxidase activities, which further promoted fatty acid ⊎-oxidation. CONCLUSION: The results obtained in the present study indicate that astilbin may decrease the effective dose of caffeine needed for an anti-obesity effect and also suggest that it suppresses fat accumulation via the activation of AMPK.

Astilbin fromSmilax glabraRoxb. alleviates high-fat diet-induced metabolic dysfunction

“…Several studies showed that astilbin can reduce body weight and protect the liver in mice. 14,15 However, the impact of this flavonoid on the intestinal microbiota and the gut-liver axis was not investigated. In this study, we used astilbin extracted from S. glabra Roxb.…”

“…12,13 Astilbin is the main active substance in the rhizome of S. glabra Roxb., which has various functions such as anti-inflammatory activity and antioxidant effect. 14 Astilbin has been reported to reduce body weight and protect against liver injury in obese mice, 15 but most of these studies were observational and the effect of astilbin consumption on gut microbes has not been reported yet.…”

Astilbin Activates the Reactive Oxidative Species/PPARγ Pathway to Suppress Effector CD4+ T Cell Activities via Direct Binding With Cytochrome P450 1B1

“…The mechanisms of astilbin-mediated anti-inflammation and immunosuppression are involved with downregulating the activities of macrophages, dendritic cells ( Ding et al, 2014 ), and effector T cells and inducing regulatory B cells ( Xu et al, 2020 ) and T cells ( Han et al, 2020 ). Astilbin suppresses the function of inflammatory cells by inhibiting the PI3K/AKT, TLR4/MyD88/NF-κB ( Li et al, 2019 ), and MAPK signaling pathways and promoting the expression of SOCS3 and activating AMPK, leading to less production of IL-1β, IL-6, TNF-α, IFN-γ, and MMPs ( Sharma et al, 2020 ; Yang et al, 2021 ). Astilbin is also verified to have strong capacity for scavenging reactive oxidative species (ROS) directly or indirectly ( Wang et al, 2019 ).…”