Eun Ju Shin

Ethanol extract of the Prunus mume fruits stimulates glucose uptake by regulating PPAR-γ in C2C12 myotubes and ameliorates glucose intolerance and fat accumulation in mice fed a high-fat diet.

In this study, we performed in vitro and in vivo studies to examine whether a 70% ethanol extract of Prunus mume fruits (EMS) exhibits anti-diabetic effects. Treatment with EMS increased glucose uptake in C2C12 myotubes, and also increased PPAR-γ activity or PPAR-γ mRNA expression. To confirm these in vitro results, we next conducted an animal experiment. A high-fat diet significantly increased the body weight, fat accumulation, and glucose levels in mice. Under the same conditions, 5% EMS attenuated the high-fat diet-induced increase in body weight and fat accumulation and improved the impaired fasting glucose level and glucose tolerance. High performance liquid chromatography analysis demonstrated that EMS contained chlorogenic acid, caffeic acid, rutin, luteolin-7-glucoside, naringin, apigenin-7-glucoside, and hesperidin. Taken together, these findings suggest that EMS exerts an anti-diabetic effect both in vitro and in vivo, which is mediated, at least in part, by the activation of PPAR-γ.

Boehmeria nivea Attenuates the Development of Dextran Sulfate Sodium-Induced Experimental Colitis

We examined the therapeutic effect of an ethanol extract derived from Boehmeria nivea (Linn.) Gaudich in a mouse model of experimental colitis. Treatment with 70% ethanol extract derived from B. nivea (EBN) at a dose of 100, 200, or 500u2009mg/(kg·d) improved colon shortening, body weight, the disease activity index (DAI), and histopathological score of DSS-induced colitis mice. DSS significantly increased the levels of cyclooxygenase-(COX-) 2 in colon tissue relative to that of the untreated control group. EBN administered at 100, 200, or 500u2009mg/(kg·d) reduced COX-2 levels in the DSS-treated mice. In addition, EBN decreased the DSS-induced secretion of the inflammatory cytokine interleukin-6 (IL-6) and chemokine monocyte chemotactic protein-1 (MCP-1). Taken together, these data suggest that B. nivea extract is effective in preventing colitis.

Poly-γ-Glutamic Acid Induces Apoptosis via Reduction of COX-2 Expression in TPA-Induced HT-29 Human Colorectal Cancer Cells

Poly-γ-glutamic acid (PGA) is one of the bioactive compounds found in cheonggukjang, a fast-fermented soybean paste widely utilized in Korean cooking. PGA is reported to have a number of beneficial health effects, and interestingly, it has been identified as a possible anti-cancer compound through its ability to promote apoptosis in cancer cells, although the precise molecular mechanisms remain unclear. Our findings demonstrate that PGA inhibits the pro-proliferative functions of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), a known chemical carcinogen in HT-29 human colorectal cancer cells. This inhibition was accompanied by hallmark apoptotic phenotypes, including DNA fragmentation and the cleavage of poly (ADP-ribose) polymerase (PARP) and caspase 3. In addition, PGA treatment reduced the expression of genes known to be overexpressed in colorectal cancer cells, including cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Lastly, PGA promoted activation of 5 adenosine monophosphate-activated protein (AMPK) in HT-29 cells. Taken together, our results suggest that PGA treatment enhances apoptosis in colorectal cancer cells, in part by modulating the activity of the COX-2 and AMPK signaling pathways. These anti-cancer functions of PGA make it a promising compound for future study.

Schisandra chinensis berry extract protects against steatosis by inhibiting histone acetylation in oleic acid–treated HepG2 cells and in the livers of diet-induced obese mice

We hypothesized that hepatic steatosis could be mitigated by the hypolipidemic activity of Schisandra chinensis berry ethanol extract (SCE) via the inhibition of histone acetyltransferase (HAT) activity. HepG2 cells treated with oleic acid (OA) in the presence of SCE exhibited reduced OA-induced lipid accumulation, which was likely mediated by reductions in SREBP-1c expression. SCE attenuated the acetylation of total lysine and H3K9 that was otherwise increased by OA. Male obese mice fed with either a low-fat diet or Western diet exhibited reduced body and liver weights when supplemented with 1% SCE. The SCE-mediated attenuation of hepatic lipid accumulation was accompanied by a decrease in the expression of lipogenic genes. SCE also attenuated the expression of acetylated lysine and non-acetylated forms of H3K9 acetylation in the livers of these mice. Taken together, these results suggest that SCE has potential for further development as a novel therapeutic agent for the prevention of steatosis.

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

BackgroundCitrus 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 (nu2009=u20098): 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, 200xa0μg/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 (HCu2009+u20091% YE) or YH (HCu2009+u20095% 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.

Anti-tumour effects of beta-sitosterol are mediated by AMPK/PTEN/HSP90 axis in AGS human gastric adenocarcinoma cells and xenograft mouse models

Graphical abstract Figure. No Caption available. ABSTRACT We investigated the anti‐cancer effects of beta‐sitosterol (BS), a plant‐derived sterol in AGS human gastric adenocarcinoma cells and xenograft mouse models. BS significantly reduced cell viability by inducing apoptosis in AGS adenocarcinoma cells. This was accompanied by the formation of apoptotic bodies, as detected by Annexin V, caspase 3/7 activity, and MitoPotential assay. BS stimulated phosphatase and tensin homolog (PTEN) and phospho‐AMP‐activated protein kinase (p‐AMPK) expression. Pharmacological inhibitors or siRNA were used to further analyse the relationship between the two proteins. AMPK was found to represent a likely upstream regulator of PTEN. Additionally, two‐dimensional gel electrophoresis was used to identify related proteins in the treatment of BS. The decrease of Hsp90 protein by BS was observed. Induction of PTEN protein and reduction of Hsp90 was mediated by AICAR, an AMPK activator, indicating that AMPK is necessary for PTEN and Hsp90 expression. Additionally, BS was found to be effective through the regulation of cancer biomarker. Furthermore, BS suppressed tumour growth without toxicity in the AGS xenograft mouse models‐. Taken together, the present results demonstrate that BS exerts anti‐cancer effects in AGS cells and xenograft mouse models by mediating AMPK, PTEN, and Hsp90.