• Journal of Life Science
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• v.29 no.11
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• pp.1200-1207
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• 2019

Ultraviolet radiation exposure is a major cause of extrinsic skin aging, which leads to skin hyperpigmentation. Loganin, a major iridoid glycoside obtained from Corni fructus, has anti-inflammatory, anti-diabetic, and neuroprotective effects. In this study, we investigated the mechanisms underlying the anti-melanogenic effects of loganin in B16F10 melanocytes treated with ${\alpha}$-melanocyte stimulating hormone (${\alpha}-MSH$) and 3-isobutyl-1-methylxanthine (IBMX). Anti-melanogenic activity was measured by treating cells with loganin at concentrations between 1 and $20{\mu}m$. Cell viability assays confirmed that doses of loganin up to $20{\mu}m$ were not cytotoxic. Loganin significantly and dose-dependently decreased intracellular melanin production. We also investigated potential molecular signaling pathways for the anti-melanogenesis effects of loganin. Western blotting showed that treatment with ${\alpha}-MSH$ and IBMX increased the phosphorylation of cAMP response element-binding protein (CREB) and the gene expressions of microphthalmia-associated transcription factor (MITF) and tyrosinase. Addition of loganin suppressed these increases, while promoting the phosphorylation of extracellular signal regulated kinase (ERK) and the anti-melanogenesis response. Our data therefore indicated that loganin could attenuate the increased melanin synthesis induced by ${\alpha}-MSH$ and IBMX treatment of B16F10 melanocytes. This attenuation appears to occur by downregulation of CREB phosphorylation and MITF and tyrosinase gene expression and upregulation of ERK phosphorylation. These finding suggests that loganin could be a valuable candidate for treatment of skin diseases related to hyperpigmentation.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.546-551
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• 2001

We have previously shown that, in circular muscle cells of the lower esophageal sphincter (LES) isolated by enzymatic digestion, contraction in response to maximally effective doses of acetylcholine (ACh) or Inositol Triphosphate ($IP_3$) depends on the release of $Ca^{2+}$ from intracellular stores and activation of a $Ca6{2+}$-calmodulin (CaM)-dependent pathway. On the contrary, maintenance of LES tone, and response to low doses of ACh or $IP_3$ depend on a protein kinase C (PKC) mediated pathway. In the present investigation, we have examined requirements for $Ca6{2+}$ regulation of the interaction between CaM- and PKC-dependent pathways in LES contraction. Thapsigargin (TG) treatment for 30 min dose dependently reduced ACh-induced contraction of permeable LES cells in free $Ca6{2+}$ medium. ACh-induced contraction following the low level of reduction of $Ca6{2+}$ stores by a low dose of TG ($10^{-9}{\;}M$) was blocked by the CaM antagonist, CCS9343B but not by the PKC antagonists chelerythrine or H7, indicating that the contraction is CaM-dependent. After maximal reduction in intracellular $Ca{2+}$ from $Ca6{2+}$stores by TG ($10^{-6}{\;}M$), ACh-induced contraction was blocked by chelerythrine or H7, but not by CCS9343B, indicating that it is PKC-dependent. In normal $Ca^{2+}$medium, the contraction by ACh after TG ($10^{-9}{\;}M$) treatment was also CaM-dependent, whereas the contraction by ACh after TG ($10^{-9}{\;}M$) treatment was PKC-dependent. We examined whether PKC activation was inhibited by activated CaM. CCS 7343B Inhibited the CaM-induced contraction, but did not inhibit the DAC-induced contraction. CaM inhibited the DAC-induced contraction in the presence of CCS 9343B. This inhibition by CaM was $Ca{2+}$dependent. These data are consistent with the view that the switch from a PKC-dependent pathway to a CaM dependent pathway can occur and can be regulated by cytosolic $Ca{2+}$ in the LES.

• Journal of Ginseng Research
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• v.43 no.2
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• pp.196-208
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• 2019

Background: Nonalcoholic steatohepatitis (NASH) is one of the chronic inflammatory liver diseases and a leading cause of advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The main purpose of this study was to clarify the effects of GBCK25 fermented by Saccharomyces servazzii GB-07 and pectinase, on NASH severity in mice. Methods: Six-wk-old male mice were fed either a normal diet (ND) or a Western diet (WD) for 12 wks to induce NASH. Each group was orally administered with vehicle or GBCK25 once daily at a dose of 10 mg/kg, 20 mg/kg, 100 mg/kg, 200 mg/kg, or 400 mg/kg during that time. The effects of GBCK25 on cellular damage and inflammation were determined by in vitro experiments. Results: Histopathologic analysis and hepatic/serum biochemical levels revealed that WD-fed mice showed severe steatosis and liver injury compared to ND-fed mice. Such lesions were significantly decreased in the livers of WD-fed mice with GBCK25 administration. Consistently, mRNA expression levels of NASH-related inflammatory-, fibrogenic-, and lipid metabolism-related genes were decreased in the livers of WD-fed mice administered with GBCK25 compared to WD-fed mice. Western blot analysis revealed decreased protein levels of cytochrome P450 2E1 (CYP2E1) with concomitantly reduced activation of c-Jun N-terminal kinase (JNK) in the livers of WD-fed mice administered with GBCK25. Also, decreased cellular damage and inflammation were observed in alpha mouse liver 12 (AML12) cells and RAW264.7 cells, respectively. Conclusion: Administration of GBCK25 ameliorates NASH severity through the modulation of CYP2E1 and its associated JNK-mediated cellular damage. GBCK25 could be a potentially effective prophylactic strategy to prevent metabolic diseases including NASH.

• Journal of Life Science
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• v.29 no.2
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• pp.191-197
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• 2019

Parkinson's disease (PD) is a progressive neurodegenerative disease that mainly affects motor system with clinical features such as bradykinesia, rigidity, tremor and abnormal posture. PD is characterized by the death of dopaminergic neurons in the substantia nigra pars compacta, which is associated with accumulation of oxidative stress and dysregulation of intracellular signaling pathway. Quercetin-3-O-glucuronide (Q3GA), a major metabolite of quercetin, has been reported to have neuroprotective effects. In this study, we examined the neuroprotective effect of Q3GA against 1-methyl-4-phenyl pyridinium ($MPP^+$)-induced neurotoxicity of PD and the underlying molecular mechanisms in SH-SY5Y cells. MTT and LDH assay showed that Q3GA significantly decreased $MPP^+$-induced cell death, which is accompanied by a reduction in poly (ADP-ribose) polymerase (PARP) cleavage. Furthermore, it attenuated $MPP^+$-induced intracellular reactive oxygen species (ROS) with the reduction of Bax/ Bcl-2 ratio. Moreover, Q3GA significantly increased the phosphorylation of Akt and cAMP response element binding protein (CREB), but it has no effects on the phosphorylation of extracellular signal-regulated kinase (ERK). Taken together, these results demonstrate that Q3GA significantly attenuates $MPP^+$-induced neurotoxicity through ROS reduction and Akt/CREB signaling pathway in SH-SY5Y cells. Our findings suggest that Q3GA might be one of the potential candidates for the prevention and/or treatment of PD.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.6
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• pp.904-911
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• 2019

Objective: The study was conducted to evaluate the effects of night light regimen on growth performance, antioxidant status and health of Lingnan Yellow broiler chickens from 1 to 21 days of age. Methods: A completely randomized factorial design involved 2 photoperiods (constant lighting [CL], 24 L:0 D and intermittent lighting [INL], 17 L:3 D:1 L:3 D)${\times}2$ light intensities (10 lx and 30 lx). A total of one thousand six hundred and eighty 1-d-old Lingnan Yellow broiler chicks were randomly divided into 4 treatments with 6 replicates (70 birds per replicate). The experiment lasted for 21 d. Results: Photoperiods and light intensities had no effect on average daily gain, feed conversion ratio, and mortality of the broiler chickens (p>0.05). The INL had a significant effect on average daily feed intake (p<0.05) of broiler chickens compared with CL. Photoperiod and light intensity had an interactive effect on melatonin (MT) concentration (p<0.05). At CL, reducing light intensity increased MT concentration; INL birds had higher MT but MT concentration was not affected by light intensity. There was an interactive effect on glutathione peroxidase (GPx) and catalase (CAT) in serum and total antioxidant capability (T-AOC) in liver between photoperiod and light intensity. With the decrease of light intensity, the activities of GPx and CAT in serum and T-AOC in liver increased in CL group (p<0.05). Broiler chickens reared under INL had better antioxidant status and 10 lx treatments had higher activities of CAT in serum than 30 lx (p<0.05). Different photoperiods and light intensities had no effect on malondialdehyde. There was an interaction between photoperiod and light intensity on serum creatine kinase (CK) concentration (p<0.05). At CL, the elevated light intensity resulted in an increase in CK content; INL birds had lower CK concentration especially in low light intensity group. Besides, INL and low light intensity significantly reduced the concentration of serum corticosterone and heat shock protein 70 (p<0.05). Serum immunoglobulin M contents were increased in broiler chickens reared under the INL compared with CL group (p<0.05). Conclusion: Results above suggest that the night light regimen of INL and 10 lx could be beneficial to the broiler chickens from 1 to 21 days of age due to the better health status and electricity savings.

• Korean Journal of Plant Resources
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• v.35 no.2
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• pp.372-379
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• 2022

This study investigated the effect of lemon balm (Melissa officinalis) extract on improving blood triglycerides according to the extraction solvent using 3T3-L1 cells. Lemon balm was extracted with water (MOW100), 70% ethanol (MOE70), 50% ethanol (MOE50), and 30% ethanol (MOE30). To verify its efficacy on improving blood triglycerides, cell viability, lipid accumulation, triglyceride (TG) content, and expressions of protein kinase A (PKA), adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), perilipin, and CGI-58 proteins were evaluated. Cytotoxicity was not evident up to an extract concentration of 1 mg/mL. Lipid accumulation and TG content were decreased in a concentration-dependent manner compared to their levels in the control group. When the MOW100 extract was applied at a concentration of 0.2 mg/mL, an inhibitory effect was evident, with lipid accumulation inhibited by 21.3% and TG content reduced by 32.7%. PKA phosphorylation and ATGL HSL and CGI-58 levels were increased. The data indicate that lemon balm extract obtained using water is more efficacious than extracted with ethanol. The aqueous extract shows potential in triglyceride control through lipolysis and lowering triglyceride levels.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.73-81
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• 2023

Sirtuins (SIRTs) belong to the nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylase family. They are key regulators of cellular and physiological processes, such as cell survival, senescence, differentiation, DNA damage and stress response, cellular metabolism, and aging. SIRTs also influence carcinogenesis, making them potential targets for anticancer therapeutic strategies. In this study, we investigated the anticancer properties and underlying molecular mechanisms of a novel SIRT1 inhibitor, MHY2251, in human colorectal cancer (CRC) cells. MHY2251 reduced the viability of various human CRC cell lines, especially those with wild-type TP53. MHY2251 inhibited SIRT1 activity and SIRT1/2 protein expression, while promoting p53 acetylation, which is a target of SIRT1 in HCT116 cells. MHY2251 treatment triggered apoptosis in HCT116 cells. It increased the percentage of late apoptotic cells and the sub-G1 fraction (as detected by flow cytometric analysis) and induced DNA fragmentation. In addition, MHY2251 upregulated the expression of FasL and Fas, altered the ratio of Bax/Bcl-2, downregulated the levels of pro-caspase-8, -9, and -3 proteins, and induced subsequent poly(ADP-ribose) polymerase cleavage. The induction of apoptosis by MHY2251 was related to the activation of the caspase cascade, which was significantly attenuated by pre-treatment with Z-VAD-FMK, a pan-caspase inhibitor. Furthermore, MHY2251 stimulated the phosphorylation of c-Jun N-terminal kinase (JNK), and MHY2251-triggered apoptosis was blocked by pre-treatment with SP600125, a JNK inhibitor. This finding indicated the specific involvement of JNK in MHY2251-induced apoptosis. MHY2251 shows considerable potential as a therapeutic agent for targeting human CRC via the inhibition of SIRT1 and activation of JNK/p53 pathway.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2023.04a
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• pp.50-50
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• 2023

Prostaglandin E2(PGE2), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because PGE2 functions by signaling through PGE2 receptors (Eps), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting Eps. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibititing the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysaccharide (LPS)-enhanced cell migration and invasion through the inactivation of matrix metalloproteinases (MMP)-9 as well as the down-regulation of COX-2 expression and PGE2 production. These events were shown to be associated with the inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, the AMPK inhibitor, compound C, as well as AMPK knockdown via siRNA, attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the activation of CREB. These findings indicate that cordycepin suppresses the migration and invasion of HCT116 cells. Through modulating EP4 expression and the AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to serve as a potent anti-cancer agent in therapeutic strategies against colorectal cancer metastasis.

• Clinical and Experimental Pediatrics
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• v.45 no.6
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• pp.732-742
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• 2002

Purpose : In order to evaluate the hypoxia-ischemia(H-I) induced neurotoxicity and the protective effect of xanthine oxidase(XO) inhibitor(allopurinol), cell number, cell viability, lactate dehydrogenase(LDH), protein synthesis(PS) and protein kinase C(PKC) activity were measured in cerebral neurons and astrocytes. Methods : Cytotoxic effect was measured by in vitro assay at 12-72 hours after H-I on cerebral neurons and astrocytes derived from 7-day old neonatal rats which were subjected to unilateral common carotid artery occlusion and exposed to hypoxic condition for 3 hours. The protective effect of XO inhibitor was examined by the cell number, cell viability, LDH and PS on 14 days after H-I with allopurinol intraperitoneal injection 15 minutes prior to H-I. In addition, the effect of allopurinol on PKC activity in hypoxic conditions was examined in neurons. Results : 72 hours from H-I, the cell numbers and viability were decreased significantly in time-dependent manner on neurons and those of astrocytes also decreased slightly, compared with control. In neonatal rats treated with H-I, the cell number, cell viability, and PS in neurons were decreased, but LDH was increased significantly compared with control. In neonatal rats pretreated with allopurinol, the cell number and viability, and PS in neurons were increased and LDH was decreased significantly compared with H-I. PKC was increased remarkably after hypoxic condition. But PKC was decreased significantly against hypoxic condition after allopurinol pretreatment. Conclusion : From these results, it is suggested that H-I is more toxic in neurons than astrocytes and allopurinol is very protective with increasing of PS, and decreasing of LDH and PKC in neurons from hypoxic-ischemic condition.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.2
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• pp.199-204
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• 2006

This study was conducted to investigate the quality characteristics of noodles prepared with the addition of nanofiltered (NF) powder of sunmul. Noodles were prepared with different levels $(0\%,\;1.5\%,\;3\%\;and\;5\%,\;w/w)$ of NF powder and physico-chemical properties were examined. Results of rapid visco analyzer showed that peak, trough, final viscosity and set back decreased as the NF powder level increased. The weight and volume of cooked noodles increased with the addition of NF powder. Turbidity of soup also increased as the amount of NF powder increased, indicating higher cooking loss. The color of wet and cooked noodles became greenish yellow as the NF powder level increased. Hardness, springiness, gumminess and brittleness of cooked noodles decreased with the increasing amount of NF powder. Results of sensory evaluation showed that noodles prepared with up to $3\%$ addition of NF powder was considered to be as acceptable as noodles prepared without NF powder.