• Biomedical Science Letters
• /
• v.17 no.4
• /
• pp.273-281
• /
• 2011

Our previous study demonstrated that the Korean traditional medicine Gyeongshingangjeehwan (GGEx) inhibits obesity and insulin resistance in obese type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. We investigated whether GGEx may affect AMP-activated protein kinase ${\alpha}$ ($AMPK{\alpha}$) since $AMPK{\alpha}$ activation is known to stimulate fatty acid oxidation in skeletal muscle of obese rodents. After OLETF rats were treated with GGEx, we studied the effects of GGEx on $AMPK{\alpha}$ and acetyl-CoA carboxylase (ACC) phosphorylation, and the expression of $AMPK{\alpha}$, $PPAR{\alpha}$, and $PPAR{\alpha}$ target genes. The effects of GGEx on mRNA expression of the above genes were also measured in C2C12 skeletal muscle cells. Administration of GGEx to OLETF rats for 8 weeks increased phosphorylation of $AMPK{\alpha}$ and ACC in skeletal muscle. GGEx also elevated skeletal muscle mRNA levels of $AMPK{\alpha}1$ and $AMPK{\alpha}2$ as well as $PPAR{\alpha}$ and its target genes. Consistent with the in vivo data, similar activation of genes was observed in GGEx-treated C2C12 cells. These results suggest that GGEx stimulates skeletal muscle $AMPK{\alpha}$ and $PPAR{\alpha}$ activation, leading to alleviation of obesity and related disorders.

• Toxicological Research
• /
• v.23 no.2
• /
• pp.127-133
• /
• 2007

Metformin is a drug used to lower blood sugar levels in patients with type 2 diabetes via activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). The primary objective of this study was to investigate whether metformin at the pharmacologically effective concentrations affects the expressions of ${\gamma}$-glutamylcysteine synthetase and phase II antioxidant genes in the H4IIE cell. Treatment of the cells with either metformin or 5-aminoimidazole-4-carboxamide riboside (AICAR) abrogated tert-butylhydroxyquinone (t-BHQ) induction of ${\gamma}$-glutamylcysteine synthetase, a rate limiting enzyme of GSH synthesis. The ability of t-BHQ to induce glutathione S-transferases (GSTs), a major class of phase II detoxifying enzymes that playa critical role in protecting cells from oxidative stress or electrophiles, was also inhibited by the agents. Transcriptional gene repression by metformin was verified by the GSTA2 promoter luciferase assay. Moreover, either metformin or AICAR treatment significantly decreased t-BHQ-dependent induction of other GSTs (i.e., $GST{\mu}$ and $GST{\pi}$ forms). Taken together, our data indicate that metformin treatment may result in the repression of ${\gamma}$-glutamylcysteine synthetase and glutathione S-transferase genes possibly via AMPK activation.

• Biomolecules & Therapeutics
• /
• v.18 no.1
• /
• pp.77-82
• /
• 2010

Peroxisome proliferator-activated receptor $\gamma$ (PPAR${\gamma}$) is a ligand-activated transcription factor that is used as a target for anti-diabetic drug development. In a search for novel PPAR${\gamma}$ agonists, the $\beta$-carboxyethyl-rhodanine derivative SP1818 was identified. We report here the characteristics of SP1818 as a selective PPAR${\gamma}$ agonist. In transactivation assays, SP1818 selectively activated PPAR${\gamma}$, but the degree of PPAR${\gamma}$ stimulation was less than with $1{\mu}M$ rosiglitazone. SP1818 also stimulated glucose uptake in a concentration-dependent manner. The adipocyte differentiation markers adiponectin, scavenger receptor CD36 and aP2 were weakly induced by treatment with SP1818, and TRAP220 subunit was specifically recruited into PPAR${\gamma}$ activated by rosiglitazone but not PPAR${\gamma}$ activated by SP1818.

• International Journal of Oral Biology
• /
• v.42 no.2
• /
• pp.39-45
• /
• 2017

Metformin (1,1-dimethylbiguanide hydrochloride), derived from French lilac (Galega officinalis), is a first-line anti-diabetic drug prescribed for patients with type 2 diabetes. However, the role of metformin in odontoblastic cell differentiation is still unclear. This study therefore undertook to examine the effect of metformin on regulating odontoblast differentiation in MDPC-23 mouse odontoblastic cells derived from mouse dental papilla cells. As compared to controls, metformin significantly accelerated the mineralization, significantly increased and accelerated the expressions of ALP and Col I mRNAs, and significantly increased the accelerated expressions of DSPP and DMP-1 mRNAs, during differentiation of MDPC-23 cells. There was no alteration in cell proliferation of MDPC-23 cells, on exposure to metformin. These results suggest that the effect of metformin on MDPC-23 mouse odontoblastic cells derived from mouse dental papilla cells, facilitates the odontoblast differentiation and mineralization, without altering the cell proliferation.

• Journal of Mushroom
• /
• v.12 no.4
• /
• pp.330-340
• /
• 2014

Coprinellus micaceus, belongs to family Psathyrellaceae of Agaricales, Basidiomycota, has been used for edible purposes in the world. This study was initiated to evaluate the antioxidant, anti-diabetic, anti-cholinesterase, anti-tyrosinase, and nitric oxide inhibitory activities of fruiting bodies from C. micaceus extracted with methanol and hot water. The HPLC analysis of phenolic compounds from the mushroom extracts identified 4 phenolic compounds including procatechuic acid, chlorogenic acid, (-)-epicatechin, and naringin. In 1,1-diphenyl-2-picrylhydrazyl(DPPH) free radical scavenging assay, the scavenging activities of methanol and hot water extracts were lower than that of positive control, BHT. The chelating effects of methanol and hot water extracts were significantly higher than that of BHT, the positive control at the all concentrations tested. In the reducing power assay, methanol and hot water extracts exhibited the lower activities compared with positive control at the 0.125-0.2 mg/ml. The methanol and hot water extracts of the mushroom inhibited the ${\alpha}$-glucosidase activity by 62.26% and 67.59%, respectively at the 2.0 mg/ml, while acarbose, the positive control, inhibited the ${\alpha}$-glucosidase activity by 81.81% at the same concentration. In the acetylcholinesterase(AChE) inhibitory activity assay, methanol and hot water extracts of the mushroom inhibited the AChE by 94.64% and 74.19%, respectively at 1.0 mg/ml, whereas the galanthamine, standard drug, inhibited the AChE activity by 97.80% at the same concentration. The tyrosinase inhibitory activities of methanol and hot water extracts were 91.33% and 91.99% at 2.0 mg/ml, while the inhibitory activity of kojic acid, the positive control, was 99.61% at the same concentration. Nitric oxide(NO) production in lipopolysaccahride (LPS) activated RAW 264.7 cells were inhibited by the methanol and hot water extracts in a concentration dependent manner. Therefore, it is concluded that fruiting bodies of C. micaceus contained natural antioxidant, anti-acetylcholinesterase and ${\alpha}$-glucosidase inhibitory, anti-inflammatory, anti-tyrosinase substances which might be used for promoting human health.

• Journal of the East Asian Society of Dietary Life
• /
• v.24 no.1
• /
• pp.101-108
• /
• 2014

This study was conducted in order to compare the biological activities of water extracts and sugar immersion extracts of green pepper (Capsicum annuum L.), purslane (Portulaca oleracea L.) and shiitake (Lentinula edodes (Berk.) Pegler) by measuring total polyphenol and flavonoid contents, antioxidant activities and inhibitory effects on ${\alpha}$-amylase and ${\alpha}$-glucosidase. The contents of total polyphenols and flavonoids were higher in water extracts than in sugar immersion extracts. The anti-oxidative activities of water and sugar immersion extracts were measured using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging activity assay and reducing power assay. All extracts scavenged radicals in a concentration-dependent manner, and water extracts showed stronger radical scavenging activity and reducing power than sugar immersion extract. However, they all exhibited lower activities than ascorbic acid. Compared to the anti-diabetic drug acarbose, which was used as a positive control, the two types of extracts exhibited low ${\alpha}$-glucosidase inhibitory activities, although the activity of sugar immersion extracts were 2-fold higher than that of water extracts. ${\alpha}$-Amylase inhibitory action was not observed for any of the extracts. Finally, by cytotoxicity test, we confirmed that sugar immersion extracts were safer than water extracts. These results indicate that water extracts and sugar immersion extracts of green pepper, purslane and shiitake have different advantages in terms of their antioxidant and anti-diabetic effects, respectively.

• Development and Reproduction
• /
• v.22 no.2
• /
• pp.133-142
• /
• 2018

Patients with type II diabetes mellitus are more susceptible to colorectal cancer (CRC) incidence than non-diabetics. The anti-diabetic drug metformin is most commonly prescribed for the treatment of this disease and has recently shown antitumor effect in preclinical studies. The aberrant mutational activation in the components of RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathway is very frequently observed in CRC. We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA. Therefore, we hypothesized that simultaneous inhibition of two pathways by combining metformin with BEZ235 could be more effective in the suppression of proliferation than single agent treatment in HCT15 CRC cells. Here, we investigated the combinatory effect of metformin and BEZ235 on the cell survival in HCT15 CRC cells. Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6. This combination treatment synergistically reduced cell viability. The combination index (CI) values ranged from 0.44 to 0.88, indicating synergism for the combination. These results offer a preclinical rationale for the potential therapeutic option for the treatment of CRC.

• Journal of Life Science
• /
• v.23 no.3
• /
• pp.399-405
• /
• 2013

This study was carried out to analyze the effects on antioxidative, antidiabetic, and anti-inflammatory activities of Parthenocissus tricuspidata (PT) stem extracts. The total phenolic contents of hot water and ethanol extracts from PT stems were 61.5 mg TAE/g and 122.1 mg TAE/g, respectively. The antioxidative activities of hot water and ethanol extracts from PT stem were measured by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and superoxide dismutase (SOD) assay. The DPPH radical scavenging activities of ethanol extract and butanol fraction were approximately 95% and 92% at 1 mg/ml, respectively, and the SOD activities of ethanol extract and butanol fraction were about 91% and 97% at 1 mg/ml, respectively. The DPPH radical scavenging and SOD activities of ethanol extract and butanol fraction from PT stem increased remarkably increased in a dose-dependent manner and were higher than in the hot water extracts. Compared to the acarbose, a known anti-diabetic drug, which was used as a positive control, the ${\alpha}$-glucosidase inhibitory capacity of PT stem showed a strong inhibitory rate in ethanol extract and in butanol and hexane fractions. We investigated the effect of hot water extract from PT stem on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells. Hot water extract from PT stem inhibited LPS-induced NO production up to 40% at a treatment of 1 mg/ml. These results suggest that PT stem extracts have an effect on antioxidative, antidiabetic, and anti-inflammatory activities and thus have great potential as antidiabetic materials and a source for natural health products.

• Korean Journal of Pharmacognosy
• /
• v.46 no.2
• /
• pp.105-108
• /
• 2015

To establish the anti-diabetic(α-glucosidase inhibitory) activity of D. lotus leaf extract, isolate and identify the constituents responsible for the activity. The methanolic extract of leaves was partitioned between water, n-butanol and ethyl acetate. Bio-assay guided fractionation, based on inhibition of ;${\alpha}$-glucosidase, allowed isolation and identification of the active components. Liquid chromatography/mass spectrometry(LC/MS), ¹ H-NMR and ¹³ C-NMR spectra analyses demonstrated that the active compound was myricetin-3-O-;${\alpha}$-L-rhamnoside(1). Compound 1 demonstrated a strong inhibition on the α-glucosidase, in vitro and ;${\alpha}$-glucosidase inhibitory value was calculated as 98.08%, when that of a reference drug, acarbose was estimated as 83.03%. The present study indicates compound 1 could be considered as an ;${\alpha}$-glucosidase inhibitor and developed as an important antidiabetes agent for type II diabetes therapy.

• Korean Journal of Pharmacognosy
• /
• v.35 no.1 s.136
• /
• pp.98-103
• /
• 2004

To investigate the antioxidant activitys of Biofuntional Foods Prescriptions (BFP), we were measured radical scavenging activity with 1,1-diphenyl-2-picryl-hydrazyl (DPPH) method and anti-lipid peroxidative efficacy on human LDL with thiobarbituric acid reactive substances (TBARS) assay. The DPPH and TBARS assay were revealed that Two BFP had significantly activity when compared to that of contrast drug. The antidiabetic effect of Dicollow-B (Rx B) were investigated in streptozotocin-induced diabetic Spraque-Dawley (SD) rats. When each 100,200 kg/mg fraction of Rx B was administrated. the blood glucose showed 155.7 mg/dl, 124.7 mg/dl and inhibitive activity of the serum total cholesterol showed 67.8 mg/dl, 61.5 mg/dl and the serum triglyce of hyperglycemic rats revealed 66.3 mg/dl, 62.3mg/dl. Those were decreased do dependently when compared with control group. The effect of Rx B on The body weight was not dose-dependently decreased dosedependently when by the administration of 100 mg/kg or 200 mg/kg fractions. But it was dose-dependantly decreased from $22.2{\times}4.9$ g to $18.9{\times}4.4$ g by the administration of 400 mg/kg fraction.