• The Journal of Korean Medicine
• /
• v.44 no.2
• /
• pp.119-131
• /
• 2023

Objectives: Betula Platyphylla(BP) has been used as a analgesic, anti-microbial, anti-oxidant drug in Eastern Asia. However, it is still unknown whether BP ethanol extract could exhibit the inhibitory activities against ultraviolet B(UVB)-induced skin injury on human keratinocytes, HaCaT cells. This study was aimed to investigate the protective activity of BP ethanol extract on UVB-irradiated skin injury in HaCaT cells. Methods: The skin injury model of HaCaT cells was established under UVB stimulation. HaCaT keratinocyte cells were pre-treated with BP ethanol extract for 1 h, and then stimulated with UVB. Then, the cells were harvested to measure the cell viability, production of reactive oxygen species(ROS), pro-inflammatory cytokines such as interleukin(IL) 1-beta, IL-6, and tumor necrosis factor(TNF)-𝛼, hyaluronidase, type 1 collagen, matrix metalloproteinase(MMP)s. In addition, we examined the mitogen activated protein kinases(MAPKs) and inhibitory kappa B alpha(I𝜅;-B𝛼) as inhibitory mechanisms of BP ethanol extract. Results: The treatment of BP ethanol extract inhibited the UVBinduced cell death and ROS production in HaCaT cells. BP ethanol extract treatment inhibited the UVB-induced increase of IL-1beta, IL-6, and TNF-𝛼. BP ethanol extract treatment inhibited the increase of hyaluronidase, MMP and decrease of collagen. BP ethanol extract treatment inhibited the activation of MAPKs and the degradation of I𝜅-B𝛼. Conclusions: Our result suggest that treatment of BP ethanol extract could inhibit the UVB-induced skin injury via deactivation of MAPKs and nuclear factor kappa B(NF-𝜅B) in HaCaT cells. This study could suggest that BP ethanol extract could be a beneficial agent to prevent skin damage or inflammation.

• Journal of Veterinary Science
• /
• v.23 no.1
• /
• pp.8.1-8.15
• /
• 2022

Background: Brucella infection induces brucellosis, a zoonotic disease. The intracellular circulation process and virulence of Brucella mainly depend on its type IV secretion system (T4SS) expressing secretory effectors. Secreted protein BspJ is a nucleomodulin of Brucella that invades the host cell nucleus. BspJ mediates host energy synthesis and apoptosis through interaction with proteins. However, the mechanism of BspJ as it affects the intracellular survival of Brucella remains to be clarified. Objectives: To verify the functions of nucleomodulin BspJ in Brucella's intracellular infection cycles. Methods: Constructed Brucella abortus BspJ gene deletion strain (B. abortus ∆BspJ) and complement strain (B. abortus pBspJ) and studied their roles in the proliferation of Brucella both in vivo and in vitro. Results: BspJ gene deletion reduced the survival and intracellular proliferation of Brucella at the replicating Brucella-containing vacuoles (rBCV) stage. Compared with the parent strain, the colonization ability of the bacteria in mice was significantly reduced, causing less inflammatory infiltration and pathological damage. We also found that the knockout of BspJ altered the secretion of cytokines (interleukin [IL]-6, IL-1β, IL-10, tumor necrosis factor-α, interferon-γ) in host cells and in mice to affect the intracellular survival of Brucella. Conclusions: BspJ is extremely important for the circulatory proliferation of Brucella in the host, and it may be involved in a previously unknown mechanism of Brucella's intracellular survival.

• Journal of Ginseng Research
• /
• v.47 no.4
• /
• pp.515-523
• /
• 2023

Background: 20(S)-protopanaxadiol (PPD), one of the main components of ginseng, has anti-inflammatory, anti-estrogenic, and anti-tumor activities. It is known that activated hepatic stellate cells (HSCs) are the primary producers of extracellular matrix (ECM) in the liver, and the Wnt/β-catenin pathway participates in the activation of HSCs. We aimed to explore whether PPD inhibits liver fibrosis is associated with the Wnt/β-catenin pathway inactivation. Methods: The anti-fibrotic roles of PPD were examined both in vitro and in vivo. We also examined the levels of Wnt inhibitory factor 1 (WIF1), DNA methyltransferase 1 (DNMT1) and WIF1 methylation. Results: PPD obviously ameliorated liver fibrosis in carbon tetrachloride (CCl₄)-treated mice and reduced collagen deposition. PPD also suppressed the activation and proliferation of primary HSCs. Notably, PPD inhibited the Wnt/β-catenin pathway, reduced TCF activity, and increased P-β-catenin and GSK-3β levels. Interestingly, WIF1 was found to mediate the inactivation of the Wnt/β-catenin pathway in PPD-treated HSCs. WIF1 silencing suppressed the inhibitory effects of PPD on HSC activation and also restored α-SMA and type I collagen levels. The downregulation of WIF1 expression was associated with the methylation of its promoter. PPD induced WIF1 demethylation and restored WIF1 expression. Further experiments confirmed that DNMT1 overexpression blocked the effects of PPD on WIF1 expression and demethylation and enhanced HSC activation. Conclusion: PPD up-regulates WIF1 levels and impairs Wnt/β-catenin pathway activation via the downregulation of DNMT1-mediated WIF1 methylation, leading to HSC inactivation. Therefore, PPD may be a promising therapeutic drug for patients with liver fibrosis.

• Journal of Nutrition and Health
• /
• v.56 no.6
• /
• pp.615-628
• /
• 2023

Purpose: Increasing levels of domestic fine dust (DFD) have emerged as a serious problem that threatens public health by causing chronic respiratory diseases and skin aging. The present study was performed to investigate the inhibitory effects of Gryllus bimaculatus (the two-spotted cricket), which has recently attracted attention as an edible insect in South Korea, on DFD-induced aging and inflammation. Methods: To verify that DFD causes skin aging and investigate the anti-aging effect of an aqueous ethanolic-Gryllus bimaculatus extract (AE-GBE), human diploid fibroblasts (HDF) were treated with 100 ㎍/mL of European reference material (ERM)-CZ100 dust for 24 hrs in the presence or absence of 100 ㎍/ml AE-GBE. Aging and cellular toxicities were assessed by measuring reactive oxygen species (ROS) levels, DNA fragmentation, and β-galactosidase activity. The protein levels of cyclooxygenase (COX) 2, matrix metalloproteinase (MMP)-1, and collagen were measured by western blot, and the mRNA expressions of inflammation-related genes were assayed by quantitative reverse transcriptase polymerase chain reaction. Results: Treatment with ERM-CZ100 induced an aged phenotype in HDF cells, as evidenced by increased ROS levels, DNA fragmentation, and senescence-associated β-galactosidase activity, but cotreatment with AE-GBE significantly reduced these inductions. The mRNA expressions of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, induced by ERM-CZ100 were also reduced by AE-GBE cotreatment, which also reduced COX2 expression. Moreover, ERM-CZ100-induced MMP-1 expression and reduced collagen type I expression were recovered by AE-GBE treatment. Conclusion: These results suggest that AE-GBE is a potential treatment for domestic fine dust-induced skin inflammation and inflammaging.

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2020.08a
• /
• pp.82-82
• /
• 2020

염증 (Inflammation)은 물리적인 상처나 세균감염이 되었을 때 손상된 조직을 재생하고 신체를 방어하기 위해 일어나는 선천성 면역반응으로 알려져 있다. 주로 선천면역을 담당하는 대식세포는 lipopolysaccharide, reactive oxygen species와 cytokine 등에 의해 활성화되어 tumor necrosis factor-α. interleukin-1β, interleukin-6 등 염증인자들의 생성에 관여한다. 특히, 산화질소는 superoxide 음이온과 쉽게 반응하고 peroxynitrite와 같은 독성이 강한 산화제를 생성하여 단백질 및 지질의 과산화를 유도하고 세포독성을 일으키는 것으로 보고되고 있다. 따라서 본 연구에서는 항산화 및 항염증 소재를 탐색하기 위해 오미자 (Schisandra chinensis), 꾸지뽕 (Cudrania tricuspidata)을 이용하여 항산화 활성을 평가하고자 하였으며, 세포주를 활용한 세포독성 및 항염증 활성을 확인하고자 하였다. 본 연구는 전북 순창군에서 재배된 오미자, 꾸지뽕을 열 건조(60℃) 통해 건조한 후 분말화하였다. 최적 추출 조건 선정을 위해 다양한 용매 (열수, 증류수, 주정 20, 40, 60%), 온도 (25, 40, 60, 80℃) 및 시간 (1, 2, 3, 4, 5 h) 조건에서 추출된 추출물의 총 폴리페놀 함량을 비교함으로써 최적 조건을 선정하였다. 오미자와 꾸지뽕의 DPPH 및 ABTS radical 소거 활성, 총 플라보노이드 함량을 확인하여 항산화능 및 기능성 성분 함량을 평가하였다. 또한 대식세포주인 Raw 264.7을 활용하여 MTT assay, 산화질소 생성 억제 활성을 확인하여 세포독성 및 항염증 활성을 평가하였다. 실험 결과, 오미자 및 꾸지뽕은 각각 주정 40%, 60℃ 그리고 증류수, 60℃에서 추출 시 가장 높은 총 폴리페놀 함량 (약 98.3 mg GAE/g 및 88.2 mg GAE/g)을 함유하며, DPPH 라디칼 소거 활성은 약 44.6% 및 24.4%, ABTS 라디칼 소거 활성은 약 30.3% 및 40.8%로 확인되었다. 총 플라보노이드 함량은 약 21.80 mg QE/g 및 35.68 mg QE/g으로 확인되었다. 또한 오미자 및 꾸지뽕 기능성 추출물을 100 ug/mL 처리 시 세포 독성이 나타나지 않는 것으로 확인되었으며, NO 생성량을 약 56.3% 및 21.7% 저감시켜 항염증 효능을 나타내는 것으로 확인되었다.

• Journal of Life Science
• /
• v.34 no.4
• /
• pp.279-285
• /
• 2024

The zonula occludens (ZO) protein serves as a scaffolding protein, providing structural support at the junctions between cells and the cytoplasmic surface. It acts as a bridge between integral membrane proteins and the cytoskeleton. Besides its structural role, it also participates in regulating cell growth and proliferation. Recent studies have highlighted the involvement of ZO protein in various diseases, including cancer. Specifically, research has indicated that ZO protein influences the cancer microenvironment surrounding cancer cells, thereby facilitating their growth and development. ZO proteins exert diverse functions in the cancer microenvironment, impacting processes such as angiogenesis, inflammatory responses, the epithelial-mesenchymal transition, and interactions with mesenchymal stem cells. The specific mechanisms vary depending on the type of cancer and environmental conditions. Recent research unveiled several signaling pathways involving ZO protein, which could potentially impede cancer progression in the tumor microenvironment. Consequently, these insights open avenues for novel treatment strategies. While the numerous physiological, structural, and morphological roles of ZO protein have been observed at the cellular and in vivo levels, understanding the signaling mechanisms it operates in vivo and how these mechanisms influence the cancer microenvironment remains a challenge. In this review, we delineate the characteristics and regulatory mechanisms of ZO protein in the context of the cancer microenvironment. Additionally, we propose leveraging the properties of ZO protein to devise defense mechanisms within the cancer cell environment and provide an overview of its in vivo role.

• Food Science and Preservation
• /
• v.30 no.3
• /
• pp.502-513
• /
• 2023

This study aimed to evaluate the anti-adipogenic and anti-inflammation effects of extract from Maclura tricuspidata twig fermented with Ganoderma lucidum mycelium (EMFG) in 3T3-L1 preadipocytes. 3T3-L1 adipocytes were treated with 100, 200, 300 ㎍/mL of EMFG. The result showed that EMFG dose-dependently inhibited the accumulation of intracellular lipid content in differentiated 3T3-L1 adipocytes and enhanced increase of adiponectin release and inhibition of leptin release. EMFG treatment reduced expression of adipogenic transcriptional factor such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα). EMFG also decreased production of lipopolysaccharide (LPS)-induced inflammatory cytokine [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1)] and the protein expression of cyclooxygenase-2 (COX-2) and inducible NOS (iNOS) in differentiated 3T3-L1 adipocytes. The study demonstrated that EMFG inhibited adipogenesis and inflammation in a dose-dependent manner. These findings suggest that EMFG may have potential as an anti-obesity and anti-metabolic disease agent that works by inhibiting adipogenesis and inflammation.

• Biomolecules & Therapeutics
• /
• v.32 no.1
• /
• pp.154-161
• /
• 2024

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder that causes progressive paralysis. L-Citrulline is a nonessential neutral amino acid produced by L-arginine via nitric oxide synthase (NOS). According to previous studies, the pathogenesis of ALS entails glutamate toxicity, oxidative stress, protein misfolding, and neurofilament disruption. In addition, L-citrulline prevents neuronal cell death in brain ischemia; therefore, we investigated the change in the transport of L-citrulline under various pathological conditions in a cell line model of ALS. We examined the uptake of [¹⁴C]L-citrulline in wild-type (hSOD1wt/WT) and mutant NSC-34/ SOD1^G93A (MT) cell lines. The cell viability was determined via MTT assay. A transport study was performed to determine the uptake of [¹⁴C]L-citrulline. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to determine the expression levels of rat large neutral amino acid transported 1 (rLAT1) in ALS cell lines. Nitric oxide (NO) assay was performed using Griess reagent. L-Citrulline had a restorative effect on glutamate induced cell death, and increased [¹⁴C]L-citrulline uptake and mRNA levels of the large neutral amino acid transporter (LAT1) in the glutamate-treated ALS disease model (MT). NO levels increased significantly when MT cells were pretreated with glutamate for 24 h and restored by co-treatment with L-citrulline. Co-treatment of MT cells with L-arginine, an NO donor, increased NO levels. NSC-34 cells exposed to high glucose conditions showed a significant increase in [¹⁴C]L-citrulline uptake and LAT1 mRNA expression levels, which were restored to normal levels upon co-treatment with unlabeled L-citrulline. In contrast, exposure of the MT cell line to tumor necrosis factor alpha, lipopolysaccharides, and hypertonic condition decreased the uptake significantly which was restored to the normal level by co-treating with unlabeled L-citrulline. L-Citrulline can restore NO levels and cellular uptake in ALS-affected cells with glutamate cytotoxicity, pro-inflammatory cytokines, or other pathological states, suggesting that L-citrulline supplementation in ALS may play a key role in providing neuroprotection.

• Journal of Life Science
• /
• v.34 no.8
• /
• pp.548-557
• /
• 2024

Curcumin, the primary active compound in Curcumae Radix of the ginger family, exhibits a range of therapeutic effects, including blood sugar regulation, immunoregulation, antioxidant, antibacterial, and antitumor activities. However, its poor water solubility and chemical instability result in suboptimal pharmacokinetics with low oral absorption (0.18%) and bioavailability, thus limiting its efficacy. To overcome these limitations, this study aimed to enhance the oral absorption and bioavailability of curcumin by incorporating lysine and β-cyclodextrin. Following oral administration of solubilized cur- cumin, blood samples were collected to assess the oral absorption rate. Solubilized curcumin showed an approximately 1.55-fold increase in absorption at 120 min compared to its non-solubilized form. Furthermore, intravenous administration followed by blood analysis showed a 25-fold increase in bio- availability at 61 min for the solubilized curcumin compared to the non-solubilized variant. In conclusion, employing lysine for dispersion and stabilization, combined with β-cyclodextrin to enhance solubility, significantly improves curcumin's oral absorption and bioavailability. The results of this experiment are expected to lead to the development of herbal medicines and pharmaceuticals that amplify curcumin's anti-inflammatory, anti-tumor, and blood-sugar-regulation effects.

• Nutrition Research and Practice
• /
• v.18 no.5
• /
• pp.633-646
• /
• 2024

BACKGROUND/OBJECTIVES: Cladophora glomerata extract (CGE), rich in polyphenols, was reported to exhibit antidiabetic and renoprotective effects by modulating the functions of protein kinases-mediated organic anion transporter 1 (Oat1) and 3 (Oat3) in rats with type 2 diabetes mellitus (T2DM). Nevertheless, the antioxidant effects of CGE on such renoprotection have not been investigated. This study examined the mechanisms involved in the antioxidant effects of CGE on renal organic anion transport function in an in vivo study. MATERIALS/METHODS: Diabetes was induced in the rats through a high-fat diet combined with a single dose of 40 mg/kg body weight (BW) streptozotocin. Subsequently, normal-diet rats were supplemented with a vehicle or 1,000 mg/kg BW of CGE, while T2DM rats were supplemented with a vehicle, CGE, or 200 mg/kg BW of vitamin C for 12 weeks. The study evaluated the general characteristics of T2DM and renal oxidative stress markers. The renal organic transport function was assessed by measuring the para-aminohippurate (PAH) uptake using renal cortical slices and renal inflammatory cytokine expression in the normal diet (ND) and ND + CGE treated groups. RESULTS: CGE supplementation significantly reduced hyperglycemia, hypertriglyceridemia, insulin resistance, and renal lipid peroxidation in T2DM rats. This was accompanied by the normalization of high expressions of renal glutathione peroxidase and nuclear factor kappa B by CGE and vitamin C. The renal anti-inflammation of CGE was evidenced by the reduction of tumor necrosis factor-1α and interleukin-1β. CGE directly blunted sodium nitroprusside-induced renal oxidative/nitrosative stresses and mediated the PAH uptake in the normally treated CGE in rats was particularly noteworthy. These data also correlated with reduced nitric oxide production, highlighting the potential of CGE as a therapeutic agent for managing T2DM-related renal complications. CONCLUSION: These findings suggest that CGE has antidiabetic effects and directly prevents diabetic nephropathy through oxidative/nitrosative stress pathways.