• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2019년도 추계학술대회
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• pp.75-75
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• 2019

The aim of the study was to determine the anti-inflammatory activities of the plants with origin of China. The Fissistigma poilanei, which is a species of plant in the family Annonaceae and Rubus laxus Focke, which is a species of plant in the family Rosaceae from China were tested for anti-inflammatory activities. Samples were prepared using 95% ethanol using nitric oxide (NO) assay for assessing the anti-inflammatory activity. NO assay experiment showed that extracts of the Fissistigma poilanei give 28.3% increases in anti-inflammatory activity and extracts of Rubus laxus Focke give 57.1% decreases in anti-inflammatory activity, compared to control. To determine the cell toxicity, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used. MTT assay experiment showed that Fissistigma poilanei and Rubus laxus Focke might have less toxicity of 60.5% and 62.3%, respectively, compared to control. Taken together, these experiments showed that Fissistigma poilanei extracts might have significantly higher anti-inflammatory activities and relatively lower toxicity, compared to control. This implies that this study might give a tool to develop a new potential anti-inflammatory therapeutic candidate.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2019년도 추계학술대회
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• pp.68-68
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• 2019

In this study, we evaluated the effect of Rodgersia podophylla leave extracts (RPL) on ${\beta}$-catenin level in human cancer cells. RPL dose-dependently inhibited cell proliferation in SW480, A549, MDA-MB-231, PC-3 and AsPC-1 cells. RPL dramatically decreased ${\beta}$-catenin protein level in all cancer cells. However, decreased level of ${\beta}$-catenin mRNA expression was observed in A549 and AsPC-1 cells. In addition, RPL dramatically attenuated cyclin D1 mRNA expression in all cancer cells. MG132 decreased the downregulation of ${\beta}$-catenin protein level induced by RPL in all cancer cells, while RPL-induced downregulation of ${\beta}$-catenin was inhibited by the inhibition of $GSK-3{\beta}$ by LiCl in MDA-MB-231 cells. RPL phosphorylated ${\beta}$-catenin and $GSK-3{\beta}$. In addition, the inhibition of $GSK-3{\beta}$ by LiCl attenuated RPL-induced ${\beta}$-catenin phosphorylation. Based on these findings, RPL may be a potential candidate for the development of chemopreventive or therapeutic agents for human cancer.

• Natural Product Sciences
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• 제27권2호
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• pp.115-121
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• 2021

Lentinus edodes contains functional metabolites such as polysaccharopeptides, lectins, and secondary metabolites. Fermented soybean paste is representative fermented materials in Korea, and is gradually increasing due to various biological activities. In the present study, ethanol extracts of fermented products with/without L. edodes were designated as SPL and SP, and prepared to develop safer and therapeutic functional foods with antioxidant and anti-inflammatory activities for treatment of inflammatory disorders. SP and SPL extracts exhibited antioxidant effects via inhibiting radical activities. Inflammatory mediators, nitric oxide (NO), prostaglandin E₂ (PGE₂), interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) production and nuclear factor-kappa B (NF-κB) activation were down-regulated by two extracts. SPL extract more strongly enhanced the antioxidant and anti-inflammatory activities than SP extract. Its' activities shown more longer fermentation period and more strong inhibitory effects. Taken together, our results suggested that fermented product with medicinal plant has synergic effect and SPL can be a potential candidate for treatment of inflammatory bowel diseases.

• Natural Product Sciences
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• 제27권1호
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• pp.28-35
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• 2021

The aim of this study was to anatomize the therapeutic potential of alaternin (=7-hydroxyemodin) against inflammation, advanced glycation end products (AGEs) formation, tyrosinase, and two cyclin-dependent kinases (CDKs), CDK2 and CDK4, and compare its potency with emodin. Alaternin showed lower cytotoxicity and higher dose-dependent inhibition against lipopolysaccharide (LPS) induced nitric oxide (NO) production with half maximal inhibitory concentration (IC50) of 18.68 µM. Similarly, alaternin efficaciously inhibited biotransformation of fluorescent AGEs and amyloid cross-β structure on the bovine serum albumin (BSA)-glucose-fructose system, five times more than emodin. Interestingly, alaternin also showed selective activity against CDK4 at 170 µM, whereas emodin inhibited both CDK2 and CDK4 at a concentration of 17 and 380 µM respectively. In addition, alaternin showed dose-dependent inhibitory activity against mushroom tyrosinase with inhibition percentage of 35.84 % at 400 µM. Altogether, alaternin with pronounced inhibition against inflammatory mediator (NO), glycated products formation, and targeted inhibition towards CDK4 receptor can be taken as an important candidate to target multiple diseases.

• BMB Reports
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• 제54권11호
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• pp.545-550
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• 2021

Anisomycin is known to inhibit eukaryotic protein synthesis and has been established as an antibiotic and anticancer drug. However, the molecular targets of anisomycin and its mechanism of action have not been explained in macrophages. Here, we demonstrated the anti-inflammatory effects of anisomycin both in vivo and in vitro. We found that anisomycin decreased the mortality rate of macrophages in cecal ligation and puncture (CLP)- and lipopolysaccharide (LPS)-induced acute sepsis. It also declined the gene expression of proinflammatory mediators such as inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-1β as well as the nitric oxide and proinflammatory cytokines production in macrophages subjected to LPS-induced acute sepsis. Furthermore, anisomycin attenuated nuclear factor (NF)-κB activation in LPS-induced macrophages, which correlated with the inhibition of phosphorylation of NF-κB-inducing kinase and IκB kinase, phosphorylation and IκBα proteolytic degradation, and NF-κB p65 subunit nuclear translocation. These results suggest that anisomycin prevented acute inflammation by inhibiting NF-κB-related inflammatory gene expression and could be a potential therapeutic candidate for sepsis.

• Journal of Microbiology and Biotechnology
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• 제32권6호
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• pp.718-729
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• 2022

Esophageal squamous cell carcinoma (ESCC) is the most common primary esophageal malignancy with poor prognosis. Here, due to the necessity for exploring potential therapies against ESCC, we obtained the gene expression data on ESCC from the TCGA and GEO databases. Venn diagram analysis was applied to identify common targets. The protein-protein interaction network was constructed by Cytoscape software, and the hub targets were extracted from the network via cytoHubba. The potential hub nodes as drug targets were found by pharmacophore-based virtual screening and molecular modeling, and the antitumor activity was evaluated through in vitro studies. A total of 364 differentially expressed genes (DEGs) in ESCC were identified. Pathway enrichment analyses suggested that most DEGs were mainly involved in the cell cycle. Three hub targets were retrieved, including CENPF, CCNA2 (cyclin A), and CCNB1 (cyclin B1), which were highly expressed in esophageal cancer and associated with prognosis. Moreover, amentoflavone, a promising drug candidate found by pharmacophore-based virtual screening, showed antiproliferative and proapoptotic effects and induced G1 in esophageal squamous carcinoma cells. Taken together, our findings suggested that amentoflavone could be a potential cell cycle inhibitor targeting cyclin B1, and is therefore expected to serve as a great therapeutic agent for treating esophageal squamous cell carcinoma.

• The Korean Journal of Physiology and Pharmacology
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• 제25권5호
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• pp.467-478
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• 2021

In this study, we aimed to synthesize PAMAMG3 derivatives (PAMAMG3-KRRR and PAMAMG3-HKRRR), using KRRR peptides as a nuclear localization signal and introduced histidine residues into the KRRR-grafted PAMAMG3 for delivering a therapeutic, carcinoma cell-selective apoptosis gene, apoptin into human primary glioma (GBL-14) cells and human dermal fibroblasts. We examined their cytotoxicity and gene expression using luciferase activity and enhanced green fluorescent protein PAMAMG3 derivatives in both cell lines. We treated cells with PAMAMG3 derivative/apoptin complexes and investigated their intracellular distribution using confocal microscopy. The PAMAMG3-KRRR and PAMAMG3-HKRRR dendrimers were found to escape from endolysosomes into the cytosol. The JC-1 assay, glutathione levels, and Annexin V staining results showed that apoptin triggered cell death in GBL-14 cells. Overall, these findings indicated that the PAMAMG3-HKRRR/apoptin complex is a potential candidate for an effective nonviral gene delivery system for brain tumor therapy in vitro.

• 운동영양학회지
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• 제24권3호
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• pp.19-24
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• 2020

[Purpose] Although physical activity is required to prevent or ameliorate osteoporosis, medicine prescription should precede it, since it may be limited in severe osteoporosis patients. Furthermore, osteoporosis has a great effect on physical activity disorders that accompany fractures and pain, and therefore, research on treatment or prevention to decrease the number of patients is required. The purpose of this study was to discover candidate substances from natural products with an effective pharmacological action and to prepare basic data to help patients. [Methods] To prepare the osteoporosis model, ovariectomy (OVX) was performed using surgical methods. The prepared prescription [Shinkiwhan (SKH), a Korean medicine] was administered orally at a dose of 210 mg/kg/day for 8 weeks. After completion of the animal experiment, the bone mineral density (BMD) was analyzed using double-energy X-ray absorptiometry. The analysis of the effect of drugs on bones was performed using histological analysis and immunostaining. [Results] SKH increased the BMD in the OVX rats. Furthermore, SKH significantly increased the expression of osteoprotegerin and downregulated receptor activator of nuclear factor kappa B ligand and phosphorylation of c-jun N-terminal kinases in the bones of the OVX model. [Conclusion] Our findings suggest a protective effect of SKH against BMD loss in the OVX model.

• Molecules and Cells
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• 제45권11호
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• pp.820-832
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• 2022

As a potential candidate to generate an everlasting cell source to treat various diseases, embryonic stem cells are regarded as a promising therapeutic tool in the regenerative medicine field. Cohesin, a multi-functional complex that controls various cellular activities, plays roles not only in organizing chromosome dynamics but also in controlling transcriptional activities related to self-renewal and differentiation of stem cells. Here, we report a novel role of the α-kleisin subunits of cohesin (RAD21 and REC8) in the maintenance of the balance between these two stem-cell processes. By knocking down REC8, RAD21, or the non-kleisin cohesin subunit SMC3 in mouse embryonic stem cells, we show that reduction in cohesin level impairs their self-renewal. Interestingly, the transcriptomic analysis revealed that knocking down each cohesin subunit enables the differentiation of embryonic stem cells into specific lineages. Specifically, embryonic stem cells in which cohesin subunit RAD21 were knocked down differentiated into cells expressing neural alongside germline lineage markers. Thus, we conclude that cohesin appears to control the fate determination of embryonic stem cells.

• Journal of Applied Biological Chemistry
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• 제65권4호
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• pp.463-469
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• 2022

Cudrania tricuspidata (C. tricuspidata), a medicinal plant widely employed throughout Asia in ethnomedicine, has various bioactive properties, including antidiabetic, antiobesity, antitumor, and anti-inflammatory activities. In addition, the C. tricuspidata root extract reportedly inhibits platelet aggregation. Therefore, we focused on the active substances present in the C. tricuspidata extract. Sanggenon N (SN) is a flavonoid found in the root bark of C. tricuspidata. In the present study, we examined the inhibitory effects of SN on platelet aggregation, phosphoproteins, thromboxane A₂ generation, and integrin αIIbβ3 activity. SN inhibited collagen-induced human platelet aggregation in a dose-dependent manner without cytotoxicity. Furthermore, SN suppressed Ca²⁺ mobilization and influx through associated signaling molecules, such as inositol 1, 4, 5-triphosphate receptor I (Ser¹⁷⁵⁶), and extracellular signal-regulated kinase. In addition, SN inhibited thromboxane A₂ generation and associated signaling molecules, including cytosolic phospholipase A₂ and mitogen-activated protein kinase p38. Finally, SN could inhibit integrin (αIIb/β₃) activity by regulating vasodilator-stimulated phosphoprotein and Akt. Collectively, SN possesses potent antiplatelet effects and is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.