• Korean Journal of Pharmacognosy
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• v.53 no.3
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• pp.145-152
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• 2022

Type II diabetes mellitus (T2DM) is a chronic metabolic disease caused by insulin resistance, and abnormally elevated hepatic gluconeogenesis is characterized. Phillyrin, one of the major active constituents of Forsythia suspense, is known to possess the anti-inflammatory and anti-oxidant effects. However, the anti-diabetes mellitus effect of phillyrin and its molecular mechanisms are unclear. The aim of the current study was to investigate the role of phillyrin on gluconeogenesis in insulin resistant HepG2 cells. Phillyrin suppressed high glucose (HG)-induced glucose production. In addition, phillyrin reduced HG-induced the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), major genes in hepatic gluconeogenesis. Phillyrin treatment attenuated HG-induced nucleus protein levels of FOXO1 and HDAC5 and increased the phosphorylation of Akt, AMPK, HDAC5, and FOXO1. The block of AMPK and Akt activity did not exert the inhibitory effect of phillyrin on gluconeogenesis in insulin resistant HepG2. Taken together, these results suggest that phillyrin inhibits gluconeogenesis of hepatocytes to improve glucose metabolism, through the regulation of LKB1/AMPK/HDAC5 and PI3K/AKT/FOXO1 pathway. These results indicate that phillyrin may be useful in improving hepatic gluconeogenesis associated with insulin resistant and T2DM.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.479-491
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• 2023

Background: Hepatocellular carcinoma (HCC) has a high incidence and is one of the highest mortality cancers when advanced stage is proceeded. However, Anti-cancer drugs available for treatment are limited and new anti-cancer drugs and new ways to treat them are minimal. We examined that the effects and possibility of Red Ginseng (RG, Panax ginseng Meyer) as new anti-cancer drug on HCC by combining network pharmacology and molecular biology. Materials and Methods: Network pharmacological analysis was employed to investigate the systems-level mechanism of RG focusing on HCC. Cytotoxicity of RG was determined by MTT analysis, which were also stained by annexin V/PI staining for apoptosis and acridine orange for autophagy. For the analyze mechanism of RG, we extracted protein and subjected to immunoblotting for apoptosis or autophagy related proteins. Results: We constructed compound-target network of RG and identified potential pathways related to HCC. RG inhibited growth of HCC through acceleration of cytotoxicity and reduction of wound healing ability of HCC. RG also increased apoptosis and autophagy through AMPK induction. In addition, its ingredients, 20S-PPD (protopanaxadiol) and 20S-PPT (protopanaxatriol), also induced AMPK mediated apoptosis and autophagy. Conclusion: RG effectively inhibited growth of HCC cells inducing apoptosis and autophagy via ATG/AMPK in HCC cells. Overall, our study suggests possibility as new anti-cancer drug on HCC by proof for the mechanism of the anti-cancer action of RG.

• Journal of Nutrition and Health
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• v.56 no.6
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• pp.641-654
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• 2023

Purpose: Sour cherry (Prunus cerasus L.) contains abounding phytochemicals, such as polyphenols and anthocyanins, and has antioxidative effects. Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator in enhancing the lipid metabolism. This study hypothesized that the intake of sour cherry affects AMPK signaling. Therefore, this study examined whether sour cherry regulates AMPK to balance the hepatic lipid metabolism and exert ameliorating effects. Methods: Male C57BL/6J mice had obesity induced with a 45% fat diet. The mice were divided into four groups: control (CON), high-fat diet (HFD), low percentage sour cherry powder (LSC), and high percentage sour cherry powder (HSC). The mice in the sour cherry groups were fed 1% sour cherry or 5% sour cherry in their respective diets for 12 weeks. Results: The body weight, visceral fat weight, and lipid droplet size significantly decreased in the treatment groups. The serum and hepatic triglyceride and total cholesterol levels improved significantly in the HSC group. The low-density lipoprotein cholesterol levels were also reduced significantly, whereas the high-density lipoprotein cholesterol levels were increased significantly in both treatment groups. The sterol regulator binding protein-1c and fatty acid synthase expression levels as fatty acid synthesis-related enzymes were significantly lower in the treatment groups than in the high-fat diet group. Furthermore, the adipose triglyceride lipase and hormone-sensitive lipase expression levels as lipolytic enzyme activity and AMPK/acetyl-CoA carboxylase/carnitine palmitoyltransferase-1 as fatty acid β-oxidation-related pathway were upregulated significantly in both sour cherry groups. Conclusions: These results show that sour cherry intake improves hepatic lipid synthesis and chronic diseases by activating AMPK signaling. Therefore, this study suggests that phytochemical-rich sour cherry can be developed as a healthy functional food.

• Herbal Formula Science
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• v.32 no.1
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• pp.99-109
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• 2024

Objectives : In this study, we investigated the cytoprotective effect of Eriobotrya japonica L. (EJ) extract against Arachidonic acid (AA)+iron-induced oxidative stress. Methods : To confirm the cytoprotective effect of EJ against AA+iron-induced oxidative stress in HepG2 cells, it was evaluated by MTT assay, immunoblot anaylsis, and Calcein-AM/propidium iodide (PI) staining. Additionally, the mechanism of action of the cytoprotective effect was evaluated through molecular mechanisms. Results : EJ (100 ㎍/mL) inhibited Arachidonic acid (AA)+iron-induced cell death in a concentration-dependent manner. It also inhibited AA+iron-induced mitochondrial dysfunction and ROS production. EJ activated the LKB1-AMPK signaling pathway. Conclusions : In conclusion, EJ has the ability to protect liver cells from oxidative stress, indicating that it is related to AMPK-LKB1 signaling pathways.

• Journal of Life Science
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• v.27 no.2
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• pp.155-163
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• 2017

Mori Folium, the leaf of Morus alba, is a traditional medicinal herb that shows various pharmacological activities such as antiinflammatory, antidiabetic, antimelanogenesis, antioxidant, antibacterial, antiallergic, and immunomodulatory activities. However, the mechanisms of their inhibitory effects on adipocyte differentiation and adipogenesis remain poorly understood. In the present study, we investigated the inhibition of adipocyte differentiation and adipogenesis by ethanol extracts of Mori Folium (EEMF) in 3T3-L1 preadipocytes. Treatment with EEMF suppressed the terminal differentiation of 3T3-L1 preadipocytes in a dose-dependent manner, as confirmed by a decrease in the lipid droplet number and lipid content through Oil Red O staining. EEMF significantly reduced the accumulation of cellular triglyceride, which is associated with a significant inhibition of pro-adipogenic transcription factors, including sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-${\gamma}$ ($PPAR{\gamma}$), and CCAAT/enhancer-binding proteins ${\alpha}$ ($C/EBP{\alpha}$) and ${\beta}$ ($C/EBP{\beta}$). In addition, EEMF potentially downregulated the expression of adipocyte-specific genes, including adipocyte fatty acid binding protein (aP2) and leptin. Furthermore, EEMF treatment effectively increased the phosphorylation of the AMP-activated protein kinase (AMPK) and acetyl CoA carboxylase (ACC); however, treatment with a potent inhibitor of AMPK, compound C, significantly restored the EEMF-induced inhibition of pro-adipogenic transcription factors and adipocyte-specific genes. These results together indicate that EEMF has preeminent effects on the inhibition of adipogenesis through the AMPK signaling pathway, and further studies will be needed to identify the active compounds in Mori Folium.

• Journal of the Korean Magnetic Resonance Society
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• v.11 no.2
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• pp.122-128
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• 2007

Three sterol sulfates were isolated from AMPK activity-guided fraction of a marine sponge Acanthodoryx fibrosa. Their structures were determined by an extensive NMR analysis, MS data, and two compounds were confirmed as unusual phosphorylated sterol sulfates by comparing with NMR data of the known compounds. Compound 3 was given to be a new dephosphated sterol sulfate derivative. Compound 1 moderately showed AMPK activation effect on L6 myoblast cell through Western blot analysis.

• Journal of the Korean Magnetic Resonance Society
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• v.16 no.1
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• pp.1-10
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• 2012

A new scalaran class sesterterpenoid with five known ones was isolated from a marine sponge Smenospongia species collected from the Gageo island, Korea. Chemical structure of all of compounds was determined on the basis of a combination of extensive 1D and 2D NMR experiments and MS data. The new compound exhibited a new functional group on a common scalaran sesterterpene skeleton, identified as 12-deacetoxy-23-deacetoxyscalarin. The compound 1 moderately showed the effect of the activation of AMP-activated protein kinase (AMPK) in L6 myoblast cell.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.2
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• pp.195-199
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• 2014

Although the Herba Cirsii is known to posses beneficial health effects, the anti-diabetic effects and the mechanism of action have not been elucidated. In the present study we have shown that Herba Cirsii Extract (HCE) can stimulate glucose uptake in OP9 adipocytes. Unlike insulin, HCE did not stimulate the Ser473 phosphorylation and activation of Akt. The increasing effects of HCE on glucose uptake were inhibited by PD680509 and compound C pretreatment, which means that the glucose uptake effects by HCE were carried out by extracelluar signal-regulated kinase1/2(ERK1/2) and AMP-activated protein kinase (AMPK) activation. Further studies revealed that HCE stimulated glucose transport occurs through a mechanism involving ERK1/2 activation and AMPK activation.

• Journal of the Korean Magnetic Resonance Society
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• v.12 no.1
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• pp.33-39
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• 2008

Four sesterterpenoids were isolated from AMPK activity-guided fraction of marine sponge Sarcotragus species. Their planar structures were determined from combination of extensive 1D and 2D NMR experiments and MS data, and the configuration at the chiral centers were assigned by comparison with the $^1H$ and $^{13}C$ chemical shifts of the known compounds. Among four compounds, compound 2 was found to be a new sarcotrine derivative. Though not strong, compounds 1-4 moderately showed AMPK activation effect on L6 myoblast cell through Western Blot analysis.

• Journal of Nutrition and Health
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• v.55 no.4
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• pp.462-475
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• 2022

Purpose: Allomyrina dichotoma larvae are one of the approved edible insects with nutritional value and various functional and medicinal properties. Previously we have demonstrated that the Allomyrina dichotoma larval extract (ADLE) ameliorates hepatic insulin resistance in high-fat diet (HFD)-induced diabetic mice through the activation of adenosine monophosphate-activated protein kinase (AMPK). This study investigated the effects of ADLE on insulin resistance in the skeletal muscle and explored mechanisms for enhancing the glucose uptake in palmitate (PAL)-treated C2C12 myotubes. Methods: To induce insulin resistance, the differentiated C2C12 myotubes were treated with PAL (0.5 mM) for 24 hours, and then treated with a 0.5 mg/ml concentration of ADLE, and the resultant effects were measured. The expression levels of glucose transporter-4 (GLUT4), AMPK, and the mitochondrial metabolism-related proteins were analyzed by western blotting. The mRNA expression levels of lipogenesis- related genes were determined by quantitative reverse-transcriptase PCR. Results: The exposure of C2C12 myotubes to 0.5 mg/ml of ADLE increased cell viability significantly compared to PAL-treated cells. ADLE upregulated the protein expression of GLUT4 and enhanced glucose uptake in the PAL-treated cells. ADLE increased the phosphorylated AMPK in both the PAL-treated C2C12 myotubes and HFD-treated skeletal muscle. The reduced expression levels of peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC1α) and uncoupling protein 3 (UCP3) due to the PAL and HFD treatment were reversed by the ADLE treatment. The citrate synthase activity was also significantly increased with the PAL and ADLE co-treatment. Moreover, the mRNA and protein expressions of fatty acid synthesis-related factors were reduced in the PAL and HFD-treated muscle cells, and this effect was significantly attenuated by the ADLE treatment. Conclusion: ADLE activates AMPK, which in turn induces mitochondrial metabolism and reduces fatty acid synthesis in C2C12 myotubes. Therefore, ADLE could be useful for preventing or treating insulin resistance of skeletal muscles in diabetes.