• Journal of Nutrition and Health
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• v.52 no.1
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• pp.17-25
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• 2019

Purpose: Obesity is a major health problem of global significance because it is clearly associated with an increased risk of health problems, such as nonalcoholic fatty liver disease (NAFLD), diabetes, cardiovascular diseases, and cancer. Lonicera caerulea (LC) originates from high mountains or wet areas and has been used as a traditional medicine in northern Russia, China, and Japan. LC contains a range of bioactive constituents, such as vitamins, minerals, and polyphenols. This study examined the anti-obesity effects of LC during differentiation in preadipocytes. Methods: The cell viability assay was performed after the differentiation of 3T3-L1 cells for 7 days. Oil Red O staining was used to visualize the changes in lipid droplets in 3T3-L1 cells and mouse adipose-derived stem cells (MADSCs). The mRNA expression of obesity-related genes was determined by quantitative real-time PCR. Results: According to the results of Oil Red O staining, the lipid levels and size of lipid droplets in the adipocytes were reduced and the LC extract (LCE, 0.25-1 mg/mL) markedly inhibited adipogenesis in a dose-dependent manner. The treatment of LCE also decreased the mRNA expression of peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), CCAAT/enhancer binding protein-${\alpha}$ ($C/EBP{\alpha}$), and sterol regulatory element binding protein 1 (SREBP1) in 3T3-L1 cells. Western blot analysis showed that the $PPAR{\gamma}$, $C/EBP{\alpha}$, and SREBP1 protein levels in both 3T3-L1 and MADSC were reduced in a dose-dependent manner. Conclusion: These results suggest that LCE can inhibit adipogenic differentiation through the regulation of adipogenesis-related markers.

• Korean Journal of Food Science and Technology
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• v.51 no.2
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• pp.141-146
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• 2019

Sparassis crispa is an edible mushroom that is distributed in Korea, Japan, Europe, and North America. It exerts various biological activities such as immunopotentiation, anti-diabetic, anti-cancer, and anti-inflammatory effects. Recently, we separated the health functional non-aqueous fraction from the chloroform extract of S. crispa (SCF4). In this study, we evaluated the antiangiogenic activity of SCF4 in human umbilical vein endothelial cells (HUVECs). SCF4 effectively inhibited vascular endothelial growth factor (VEGF)-induced cell growth at concentrations ($5-25{\mu}g/mL$) showing no cytotoxic effects. SCF4 inhibited VEGF-induced invasiveness and tube formation ability, which are in vitro angiogenic features of HUVECs, in a dose-dependent manner. In addition, SCF4 markedly suppressed in vivo angiogenesis of chorioallantoic membrane from growing chick embryos without cytotoxicity. Furthermore, SCF4 downregulated the phosphorylation of VEGFR2, AKT, and ERK1/2, which are major angiogenic signal mediators. These results suggest that SCF4 inhibited angiogenesis by suppressing the VEGFR2 signaling pathways without cytotoxicity.

• Journal of Life Science
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• v.32 no.1
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• pp.51-55
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• 2022

Matrix metalloproteinase (MMP) enzymes are responsible for the degradation and formation of the extracellular matrix (ECM), and overproduction of MMPs is observed in several diseases, such as cancer and asthma, that progress with metastatic characteristics. Natural products, especially phytochemicals, have been an important source of MMP inhibitors with reduced side effects. Although the majority of phytochemicals inhibit the enzymatic activity of MMPs, some suppress MMP production. In this context, the current study evaluated the potential of Corydalis heterocarpa, a halophyte with reported bioactivities, to inhibit MMP expression in PMA-stimulated HT-1080 cells. A crude C. heterocarpa extract was shown to decrease the mRNA and protein expression of MMP-2 and MMP-9 while increasing the endogenous MMP inhibitors TIMP-1 and TIMP-2 which regulate MMP expression in healthy tissues. In addition, our results show that the inhibitory effects of C. heterocarpa might occur through suppression of the phosphorylation of MAPK signaling, the upstream activator of MMP overexpression. In conclusion, C. heterocarpa is a potential source of antimetastatic compounds that might serve as lead molecules to develop novel MMP inhibitors.

• Journal of Life Science
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• v.31 no.12
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• pp.1120-1127
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• 2021

Depression has a negative impact on social functioning due to its high prevalence and increased suicide rate, and is a disease with a high economic burden. Depression is related to diverse brain-related phenomena, such as neuroinflammation, synaptic dysfunction, and cognitive deficit. As antidepressant drugs used in clinical trials have shown poor therapeutic effects, antidepressant drugs that show rapid efficacy urgently need to be developed. Although studies on various genes, proteins, and signaling pathways related to depression have been conducted, the pathogenesis of depression has not been clearly elucidated. Sirtuin 1 is a nicotinamide-adenine dinucleotide- (NAD+-) dependent histone deacetylase and is involved in cell differentiation, apoptosis, autophagy, and cancer metabolism. Recent genetic studies found that sirtuin 1 is a potential target gene for depression. In addition, preclinical studies reported that sirtuin 1 signaling affects depression-like behavior. In this review, we attempt to present up-to-date knowledge of depression and sirtuin 1. We describe the various roles of sirtuin 1 in the regulation of glial activation, circadian rhythm, neurogenesis, and cognitive function and the effects of its expression on depression. Further, we discuss the effect of sirtuin 1 on the impairment of neural plasticity, one of the key mechanisms of depression, and the associated mechanisms of sirtuin 1.

• Journal of Chest Surgery
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• v.55 no.1
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• pp.10-19
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• 2022

Background: According to the eighth TNM (tumor-node-metastasis) staging system, the presence of separate tumor nodules in the same lobe is designated as a T3 descriptor. However, it remains unclear whether adjuvant chemotherapy confers survival advantages in this setting. Methods: We retrospectively identified 142 pathologic T3N0M0 patients with additional pulmonary nodules in the same lobe from a single-institutional database from 2004 to 2019. The main outcomes were overall survival and recurrence-free survival. Multivariable Cox regression was used to identify the benefit of adjuvant chemotherapy while adjusting for other variables. Results: Sixty-one patients received adjuvant chemotherapy (adjuvant group) and 81 patients did not receive adjuvant therapy after surgery (surgery-only group). There were no demonstrable differences between the 2 groups regarding hospital mortality and postoperative complications, indicating that treatment selection had not significantly occurred. However, the use of adjuvant chemotherapy was associated with improved 5-year overall survival (70% vs. 59%, p=0.006) and disease-free survival (60% vs. 46%, p=0.040). A multivariable Cox model demonstrated that adjuvant chemotherapy was associated with a survival advantage (adjusted hazard ratio, 0.54; p<0.001). In exploratory analyses of subgroups, the effect of adjuvant chemotherapy seemed to be insufficient in those with small main tumors (<4 cm). Conclusion: Adjuvant chemotherapy was associated with better survival in T3 cancers with an additional tumor nodule in the same lobe. However, the role of adjuvant chemotherapy in patient subgroups with small tumors or those without risk factors should be determined via large studies.

• Journal of Life Science
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• v.32 no.11
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• pp.899-907
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• 2022

Quercetin is one of bio-flavonoids which are abundant in fruits and vegetables and has been reported to have various pharmacological potentials such as anti-oxidation, anti-inflammation, anti-cancer, and anti-virus effects. In the present study, the anti-inflammatory effects and its working molecular mecha- nism of quercetin were investigated in mouse macrophage RAW264.7 cells. Quercetin significantly inhibited nitric oxide (NO) production in a dose-dependent manner without affecting cell viability and decreased inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated RAW264.7 cells. In addition, quercetin decreased phosphorylation of p38, JNK, and ERK, and inhibited phosphorylation of NF-κB p65 protein and its inhibitor IκBα indicating that quercetin has the anti-inflammatory effects via regulation of MAPKs and NF-κB signaling pathway. We also detected expression changes of four kinds of pro-inflammatory cytokine genes (CSF2, IL-1β, IL-6, and TNF-α) with quantitative real-time PCR. The results showed that quercetin decreased the expression of four pro-inflammatory genes in LPS-stimulated RAW264.7 cells. Overall, our results showed that quercetin effectively suppressed inflammation responses induced by LPS in RAW264.7 cells via regulating MAPK and NF-κB pathway and down-regulating the expression of pro-inflammatory cytokine genes.

• The Korea Journal of Herbology
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• v.29 no.2
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• pp.1-6
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• 2014

Objectives : Reactive oxygen species (ROS) are involved in a wide spectrum of diseases including chronic inflammation and cancer. In this study, we investigated the antioxidant activities and anti-inflammatory effects of the extracts from the herbal teas such as Lonicera japonica Thunberg (L. japonica), Chrysanthemum morifolium Ramat (C. morifolium), Mentha arvensis L. (M. arvensis), and P.rhizoma. Methods : Anti-oxidant activity was evaluated using DPPH radical scavenging assay and $Fe^{2+}$ chelating assay. And DNA cleavage assay was performed to evaluate an anti-oxidative effect. Anti-inflammatory effect was performed using NO generation assay and western blot in LPS-stimulated RAW264.7 cell line. Results : L. japonica scavenged DPPH radical by 9.8% at 12.5 ${\mu}g/ml$, 24.8% at 25 ${\mu}g/ml$, 34.3% at 50 ${\mu}g/ml$, 61.1% at 100 ${\mu}g/ml$ and 75.8% at 200 ${\mu}g/ml$, respectively. In addition, C. morifolium and M. arvensis removed DPPH radical by 15.6% and 10.4% at 12.5 ${\mu}g/ml$, 34.8% and 22.8% at 25 ${\mu}g/ml$, 66.9% and 43.3% at 50 ${\mu}g/ml$, 87.4% and 69.1% at 100 ${\mu}g/ml$, and 92.1% and 73.2% at 200 ${\mu}g/ml$, respectively. However, P. rhizoma did not affect on DPPH radical scavenging. The $Fe^{2+}$ chelating activity was highest in L. japonica, but lowest in P. rhizoma among the herbal teas. In addition, the extracts from L. japonica, C. morifolium and M. arvensis inhibited oxidative DNA damage via its anti-oxidant activity. In anti-inflammatory effect, the extracts from C. morifolium inhibited NO production. In addition, it suppressed the $NF-{\kappa}B$ signaling pathway in LPS-stimulated RAW 264.7 cells. Conclusions : Together, this study indicates that L. japonica, M. arvensis and C. morifolium possess the protective effect against the oxidative DNA damage. Furthermore, C. morifolium exerts an anti-inflammatory effect.

• Journal of Life Science
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• v.32 no.6
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• pp.476-481
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• 2022

Ubiquitin signaling regulates virtually all aspects of eukaryotic biology and dynamic processes in which protein substrates are modified by ubiquitin. To regulate these processes, deubiquitinating enzymes (DUBs) cleave ubiquitin or ubiquitin-like proteins from these substrates. DUBs have been implicated in the pathogenesis of cancer, leading to the development of increasing numbers of small-molecule DUB inhibitors. On the other hand, recent studies have focused on the function of DUBs in metabolic diseases such as obesity, diabetes, and fatty liver diseases. DUBs play a positive or negative role in the progression and development of metabolic diseases. Their involvement in cell pathology and regulation of major transcription factors in metabolic syndrome has been examined in vitro and in animal and human biopsies. UCH, USP7, and USP19 were linked to adipocyte differentiation, body weight gain, and insulin resistance in genetic or diet-induced obesity. CYLD, USP4, and USP18 were found to be closely associated with fatty liver diseases. In addition, these liver diseases were accompanied by body weight change in certain cases. Collectively, in this review, we discuss the current understanding of DUBs in metabolic diseases with a particular focus on obesity. We also provide basic knowledge and regulatory mechanisms of DUBs and suggest these enzymes as therapeutic targets for metabolic diseases.

• BMB Reports
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• v.55 no.12
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• pp.609-614
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• 2022

Mutation of the gene for adenomatous polyposis coli (APC), as seen in Apc^Min/+ mice, leads to intestinal adenomas and carcinomas via stabilization of β-catenin. Transmembrane 4 L six family member 5 (TM4SF5) is involved in the development of non-alcoholic fatty liver disease, fibrosis, and cancer. However, the functional linkage between TM4SF5 and APC or β-catenin has not been investigated for pathological outcomes. After interbreeding Apc^Min/+ with TM4SF5-overexpressing transgenic (Tg^TM4SF5) mice, we explored pathological outcomes in the intestines and livers of the offspring. The intestines of 26-week-old dual-transgenic mice (Apc^Min/+:Tg^TM4SF5) had intramucosal adenocarcinomas beyond the single-crypt adenomas in Apc^Min/+ mice. Additional TM4SF5 overexpression increased the stabilization of β-catenin via reduced glycogen synthase kinase 3β (GSK3β) phosphorylation on Ser9. Additionally, the livers of the dualtransgenic mice showed distinct sinusoidal dilatation and features of hepatic portal hypertension associated with fibrosis, more than did the relatively normal livers in Apc^Min/+ mice. Interestingly, TM4SF5 overexpression in the liver was positively linked to increased GSK3β phosphorylation (opposite to that seen in the colon), β-catenin level, and extracellular matrix (ECM) protein expression, indicating fibrotic phenotypes. Consistent with these results, 78-week-old Tg^TM4SF5 mice similarly had sinusoidal dilatation, immune cell infiltration, and fibrosis. Altogether, systemic overexpression of TM4SF5 aggravates pathological abnormalities in both the colon and the liver.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.6
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• pp.521-531
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• 2023

Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (E_max) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.