Apigenin reduces the excessive accumulation of lipids induced by palmitic acid via the AMPK signaling pathway in HepG2 cells

Abstract

In recent years, increasing attention has been paid to diseases caused by excessive accumulation of lipids in the liver with therapeutic agents derived from natural products offering an alternative treatment to conventional therapies. Among these therapeutic agents, apigenin, a natural flavonoid, has been proven to exert various beneficial biological effects. In the present study, the antiadipogenic effects of apigenin in HepG2 cells was investigated. It was demonstrated that the treatment of cells with different concentrations of apigenin for 24 h significantly decreased the palmitic acid-induced increases in total cholesterol (TC) and triglyceride (TG) levels as well as intracellular lipid accumulation. In addition, apigenin increased the phosphorylated-AMP-activated protein kinase (AMPK) levels but decreased the expression levels of 3-hydroxy-3-methylglutaryl CoA reductase, sterol regulatory element-binding protein (SREBP)-1, fatty acid synthase, and SREBP-2 in a concentration-dependent manner. The present findings suggested that apigenin might improve lipid metabolism by activating the AMPK/SREBP pathway to reduce lipid accumulation in the liver.

Anti‐acne vulgaris effects of chlorogenic acid by anti‐inflammatory activity and lipogenesis inhibition

“…To identify which upstream signalling pathway is responsible for the CGA‐mediated suppression of SREBPs, we investigated the signalling pathways of JNK, AMPK and AKT based on the following three reasons: (1) Activation of JNK pathways increases SREBPs proteins and lipogenesis in epidermal cells 25 . (2) Epigallocatechin‐3‐Gallate can inhibit SREBP1 expression in sebocytes via the AMPK signalling pathway 12 .…”

Chamomile as a potential remedy for obesity and metabolic syndrome

“…In monotypic human THP-1 cells, apigenin inhibited the activation of NF-κB-induced synthesis of cytokines TNF-α and IL-1β (Zhang et al, 2014[ 148 ]). In HepG2 hepatocytes treated with palmitic acid, the flavonoid reduced excessive lipid accumulation, enhanced phosphorylation of AMP-activated protein kinase (AMPK) and decreased levels of 3-hydroxy-3-methylglutaryl CoA reductase (Lu et al, 2019[ 75 ]). Apigenin also prevented lipid accumulation in HepG2 cells exposed to high glucose levels, and these effects were accompanied by increased phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (Zang et al, 2006[ 145 ]), confirming that apigenin has a beneficial effect on dyslipidemia and diabetes by regulating energy metabolism.…”

“…The AMP-activated kinase is a cellular energy sensor responding to low ATP levels (e.g., as in a state of caloric restriction) and its activation restores energy homeostasis and stimulates FOXO1 and Nrf2 signaling pathways that provide cellular stress resistance and adaptation (Salminen and Kaarniranta, 2012[ 114 ]). Activation of AMPK was found in adipose tissue of luteolin-treated mice (Zhang et al, 2016[ 147 ][ 149 ]) and in HepG2 cells treated with apigenin and palmitate (Lu et al, 2019[ 75 ]). It seems that phytochemicals can indirectly activate AMPK by acting as mimetics of caloric restriction or via their pro-oxidant mechanism.…”

“…The antioxidant effects seem to attribute not only phenolic compounds but also to essential oils (Querio et al, 2018[ 105 ]). Modulation of signaling pathways related to energy metabolism, inflammation, stress responses and adipogenesis were also found under treatment with chamomile extracts or its individual components (Weidner et al, 2013[ 140 ]; Pallauf et al, 2017[ 98 ]; Lu et al, 2019[ 75 ]; Ma et al, 2020[ 80 ]). Some studies report that chamomile inhibits carbohydrate digestion and glucose absorption in the intestine (Villa-Rodriguez et al, 2018[ 136 ]; de Franco et al, 2020[ 21 ]).…”

Recent insights into the biological functions of apigenin

“…Here, we summarize the key findings of the biological and pharmacological actions of apigenin (Table 1 (Tab. 1) ; References in Table 1: Ahmad et al, 2019[ 1 ]; Ai et al, 2017[ 2 ]; Amiri et al, 2018[ 3 ]; Britto et al, 2017[ 4 ]; Charalabopoulos et al, 2019[ 5 ]; Chen et al, 2017[ 7 ], 2019[ 8 ], 2020[ 6 ]; Choi et al, 2018[ 9 ]; Dean et al, 2018[ 10 ]; Feng et al, 2017[ 11 ]; Ganai, 2017[ 13 ]; Han et al, 2017[ 15 ]; Hassan et al, 2017[ 16 ]; He et al, 2020[ 17 ]; Huang et al, 2020[ 19 ]; Jiang et al, 2018[ 20 ]; Jiao et al, 2019[ 21 ]; Jing et al, 2019[ 22 ]; Kang et al, 2018[ 23 ]; Ketkaew et al, 2017[ 24 ]; Lee et al, 2019[ 26 ]; Li et al, 2017[ 28 ], 2019[ 29 ], 2020[ 27 ]; Liu et al, 2018[ 30 ]; Lu et al, 2019[ 31 ]; Malik et al, 2017[ 32 ]; Mirzoeva et al, 2018[ 33 ]; Mrazek et al, 2019[ 34 ]; Nelson et al, 2017[ 36 ]; Pang et al, 2019[ 37 ]; Qiu et al, 2019[ 38 ]; Quan et al, 2020[ 39 ]; Rašković et al, 2017[ 40 ]; Ren et al, 2018[ 41 ]; Safari et al, 2018[ 42 ]; Sánchez-Marzo et al, 2019[ 44 ]; Sang et al, 2017[ 45 ]; Sharma et al, 2018[ 48 ]; Siddique and Jyoti, 2017[ 49 ]; Stump et al, 2017[ 50 ]; Thangaiyan et al, 2018[ 52 ]; Tong et al, 2019[ 53 ]; Wang et al, 2017[ 54 ], 2018[ 56 ], 2019[ 55 ]; Wu et al, 2017[ 57 ]; Xu et al, 2018[ 58 ]; Zare et al, 2019[ 59 ]; Zhang et al, 2017[ 61 ], 2018[ 63 ], 2019[ 62 ], 2020[ 60 ]; Zhao et al, 2019[ 64 ]; Zhong et al, 2017[…”