Citrus junos Tanaka peel ameliorates hepatic lipid accumulation in HepG2 cells and in mice fed a high-cholesterol diet

Abstract

Background Citrus junos Tanaka (yuja), a yellow-coloured citrus fruit has traditionally been consumed in Korea, Japan, and China and has been found effective in preventing certain diseases. However, the inhibitory effect of yuja on hepatic lipid accumulation has not been clearly elucidated thus far.MethodsThe inhibitory effect of yuja on hepatic lipid accumulation was investigated in both cell culture and mouse models. We investigated the inhibitory effect of ethanol extract of yuja peel (YE) using HepG2 cells. We next confirmed the effect of YE in mice fed a high cholesterol diet. Animals were divided into 4 groups (n = 8): a normal diet group (ND), a high-cholesterol diet group (HC), high-cholesterol diet plus 1% YE (YL), high-cholesterol diet plus 5% YE (YH).ResultSeventy percent ethanolic extracts of yuja peel (YE) reduced oleic acid-induced hepatic lipid accumulation in HepG2 cells. Treatment with YE at 100, 200 μg/mL up-regulated expression levels of cholesterol metabolism-related proteins such as AMPK, ACC, PPAR-α, and CPT1 and down-regulated the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase. The hypocholesterolemic effect of YE was further confirmed in mice fed a high-cholesterol diet. Compared to ND (normal diet) mice, HC (high-cholesterol diet) mice showed increased body weight, liver fat content, liver weight, and content of total cholesterol and low-density lipoprotein (LDL) cholesterol. On the contrary, administrations of YL (HC + 1% YE) or YH (HC + 5% YE) significantly reduced body weight, liver fat content, liver weight, total cholesterol, and LDL cholesterol compared to those of only HC fed mice group. As a result of in vitro data, protein expressions of PPAR-α and CPT1 were induced in mice fed YE diet compared to HC diet but HMGCR expression was decreased.ConclusionsYuja peel ameliorates hepatic lipid accumulation in both cell culture and mouse models and therefore, could serve as a useful supplement for hypercholesterolemia.

Assessment of the Cholesterol-Lowering Effect of MOMAST®: Biochemical and Cellular Studies

“…The cellular study was carried out on HepG2 cells because the hepatocyte is the major cell involved in the clearance of plasma LDL cholesterol expressing the most numbers of active LDLR on its surface [ 16 ]. In addition, since HepG2 expresses differentiated hepatic functions, these cells are worldwide recognized as a good model for assessing the hypocholesterolemic effects of bioactive compounds from different sources [ 17 , 18 , 19 , 20 , 21 ].…”

Identification and Extraction Optimization of Active Constituents in Citrus junos Seib ex TANAKA Peel and Its Biological Evaluation

“…Nakajima et al have reported that Citrus junos peel can attenuate dextran sulfate sodium-induced murine experimental colitis and that its anti-inflammatory effect is related to its bioactive components such as hesperidin and naringin [ 7 ]. Shin et al have found that 70% ethanolic extract of C. junos peel can reduce oleic acid-induced hepatic lipid accumulation in HepG2 cells with hypocholesterolemic effect in high-cholesterol diet mice models [ 8 ]. However, Shin et al did not give reasons for or show active markers about why 70% ethanol extract was used in their experiment.…”

New insights into Citrus genus: From ancient fruits to new hybrids

“…As far as biological activity is concerned, yuzu is certainly the most investigated among the selected Citrus species. The fruit has been examined for its antiaging (Adhikari et al., 2017; Shim et al., 2019), neuroprotective (Yang et al., 2013), lipid‐ and cholesterol‐lowering (Kim et al., 2013; Sharma et al., 2019; Shin et al., 2016), anti‐inflammatory (Abe et al., 2018), and osteogenic activities (Jeon et al., 2016) both as a plant complex and as a source of promising isolated bioactive compounds. Moreover, it is the only fruit that has been clinically investigated, whereas the other ones have been studied mostly by in vitro cell‐free and cell‐based assays.…”

“…The AD-Y group showed a normal glucose tolerance, insulin sensitivity, and secretion, suggesting a yuzu preventive role on cognitive dysfunction, impaired energy, and glucose homeostasis induced by β-amyloid infusion (Yang et al, 2013). Shin, Park, Sung, Chung, and Hwang (2016) recently investigated the potential role of yuzu peel 70% ethanol extract (YE) on hepatic lipid accumulation on an in vitro cell-based model (HepG2 cells), as well as on a mouse model (Table 3).…”

“…Shin, Park, Sung, Chung, and Hwang (2016) recently investigated the potential role of yuzu peel 70% ethanol extract (YE) on hepatic lipid accumulation on an in vitro cell‐based model (HepG2 cells), as well as on a mouse model (Table 3).…”