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( Hyun Hwangbo ),( So Young Kim ),( Hyesook Lee ),( Shin-hyung Park ),( Su Hyun Hong ),( Cheol Park ),( Gi-young Kim ),( Sun-hee Leem ),( Jin Won Hyun ),( Jaehun Cheong ),( Yung Hyun Choi ) 한국응용약물학회 2020 Biomolecules & Therapeutics(구 응용약물학회지) Vol.28 No.5
The thioredoxin (Trx) system plays critical roles in regulating intracellular redox levels and defending organisms against oxidative stress. Recent studies indicated that Trx reductase (TrxR) was overexpressed in various types of human cancer cells indicating that the Trx-TrxR system may be a potential target for anti-cancer drug development. This study investigated the synergistic effect of auranofin, a TrxR-specific inhibitor, on sulforaphane-mediated apoptotic cell death using Hep3B cells. The results showed that sulforaphane significantly enhanced auranofin-induced apoptosis by inhibiting TrxR activity and cell proliferation compared to either single treatment. The synergistic effect of sulforaphane and auranofin on apoptosis was evidenced by an increased annexin-V-positive cells and Sub-G1 cells. The induction of apoptosis by the combined treatment caused the loss of mitochondrial membrane potential (ΔΨm) and upregulation of Bax. In addition, the proteolytic activities of caspases (-3, -8, and -9) and the degradation of poly (ADP-ribose) polymerase, a substrate protein of activated caspase-3, were also higher in the combined treatment. Moreover, combined treatment induced excessive generation of reactive oxygen species (ROS). However, treatment with N-acetyl-L-cysteine, a ROS scavenger, reduced combined treatment-induced ROS production and apoptosis. Thereby, these results deduce that ROS played a pivotal role in apoptosis induced by auranofin and sulforaphane. Furthermore, apoptosis induced by auranofin and sulforaphane was significantly increased through inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Taken together, the present study demonstrated that down-regulation of TrxR activity contributed to the synergistic effect of auranofin and sulforaphane on apoptosis through ROS production and inhibition of PI3K/Akt signaling pathway.
Effect of fermented oyster extract on growth promotion in Sprague–Dawley rats
Hyesook Lee,Hyun Hwang-Bo,Seon Yeong Ji,Min Yeong Kim,So Young Kim,우민지,Young-Sam Keum,Jeong Sook Noh,Joung-Hyun Park,Bae-Jin Lee,Gi-Young Kim,Eui Kyun Park,장영채,You-Jin Jeon,Yung Hyun Choi 한국한의학연구원 2020 Integrative Medicine Research Vol.9 No.4
Background: Oysters (Crassostrea gigas) are a popular marine product worldwide and have the advantage of nutritional benefits. This study aimed to investigate the effect of fermented oyster extract (FO) on growth promotion, including analysis of body size, bone microarchitecture, hematology and biochemistry in vivo. Methods: The amount of nutrients and gamma aminobutyric acid (GABA) were determined. Sprague–Dawley rats were randomly divided into four groups: the control group, FO 50 group (FO 50 mg/kg), and FO 100 group (FO 100 mg/kg) were administered orally once daily and the recombinant human growth hormone (rhGH) group (200 μg/kg) was intraperitoneally injected once daily for 14 days. Results: Oral administration of FO 100 significantly increased body length and had no effect on organ damage or hematological profiles. However, administration of rhGH significantly induced hypertrophy of the liver, kidney and spleen along with a marked increase in body length. Tibia length and the growth plate were increased, and bone morphometric parameters were slightly improved by FO and rhGH administration. Serum analysis showed that the levels of GH and insulin like growth factor-1 (IGF-1) were slightly upregulated by FO administration. Nevertheless, the protein expression of hepatic IGF-1 was markedly increased by FO 100 and rhGH administration. Conclusions: FO have high content of GABA, and induced positive effects on body length, tibial length, growth-plate length and hepatic IGF-1 synthesis in SD rats with no toxicity or alterations of hematological profile. Therefore, these results suggest that GABA-enriched FO could be considered a potential alternative treatment for growth stimulation.
( Hyesook Hyun ),( Sunjin Lee ),( Jong Suk Lee ),( Kyungyun Cho ) 한국미생물생명공학회(구 한국산업미생물학회) 2018 Journal of microbiology and biotechnology Vol.28 No.7
DKxanthenes are a class of yellow secondary metabolites produced by myxobacterial genera Myxococcus and Stigmatella. We identified a putative 49.5 kb DKxanthene biosynthetic gene cluster from Myxococcus stipitatus DSM 14675 by genomic sequence and mutational analyses. The cluster consisted of 15 genes (MYSTI_06004-MYSTI_06018) encoding polyketide synthases, non-ribosomal peptide synthases, and proteins with unknown functions. Disruption of the genes by plasmid insertion resulted in defects in the production of yellow pigments. Highperformance liquid chromatography and liquid chromatography-tandem mass spectrometry analyses indicated that the yellow pigments produced by M. stipitatus DSM 14675 might be novel DKxanthene derivatives. M. stipitatus did not require DKxanthenes for the formation of heat-resistant viable spores, unlike Myxococcus xanthus. Furthermore, DKxanthenes showed growth inhibitory activity against the fungi Aspergillus niger, Candida albicans, and Rhizopus stolonifer.
Hyesook Lee,Hyun Hwangbo,So Young Kim,Seon Yeong Ji,Min Yeong Kim,Da Hye Kim,Yung Hyun Choi 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10
Cornus officinalis Sieb. et Zucc fruit (CF) has traditionally been used as therapeutic agents for tonifying the liver and kidney, immunoregulation, neuroprotection and cardiovascular protection. Particulate matter (PM) comprises a harmful toxic mixture, which on directly contact with the eye, caused the onset of dry eye disease (DED). In present study, we evaluate the effect of CF in DED rats which was induced by topically administered onto the both eyes with 5 mg/mL PM four times daily for 14 days. During the same period, 200 mg/kg of CF was orally administered once daily. Topical exposure of PM significantly reduced tear secretion and increased corneal fluorescein staining score, whereas this alteration was markedly reversed by CF administration. In addition, CF greatly improved he detachment of corneal epithelium, goblet cells loss of conjunctiva and inflammation of lacrimal gland followed by PM exposure. Furthermore, CF markedly increased the population of ganglion cells in the retina. These results are suggestive of the potential of CF as a therapeutic agent for threating PM-induced DED.
Hyesook Lee,Cheol Park,Da Hye Kwon,Hyun Hwangbo,So Young Kim,Min Yeong Kim,Seon Yeong Ji,Da Hye Kim,Jin-Woo Jeong,Gi-Young Kim,Hye-Jin Hwang,Yung Hyun Choi 한국영양학회 2021 Nutrition Research and Practice Vol.15 No.6
BACKGROUND/OBJECTIVES: Schisandrae Fructus, the fruit of Schisandra chinensis Baill., has traditionally been used as a medicinal herb for the treatment of various diseases, and has proven its various pharmacological effects, including anti-inflammatory and antioxidant activities. In this study, we investigated the inhibitory effect of Schisandrae Fructus ethanol extract (SF) on inflammatory and oxidative stress in particulate matter 2.5 (PM2.5)-treated RAW 264.7 macrophages. MATERIALS/METHODS: To investigate the anti-inflammatory and antioxidant effects of SF in PM2.5-stimulated RAW 264.7 cells, the levels of pro-inflammatory mediator such as nitric oxide (NO) and prostaglandin E2 (PGE2), cytokines including interleukin (IL)-6 and IL-1β, and reactive oxygen species (ROS) were measured. To elucidate the mechanism underlying the effect of SF, the expression of genes involved in the generation of inflammatory factors was also investigated. We further evaluated the anti-inflammatory and antioxidant efficacy of SF against PM2.5 in the zebrafish model. RESULTS: The results indicated that SF treatment significantly inhibited the PM2.5-induced release of NO and PGE₂, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. SF also attenuated the PM2.5-induced expression of IL-6 and IL-1β, reducing their extracellular secretion. Moreover, SF suppressed the PM2.5-mediated translocation of nuclear factor-kappa B (NF-κB) from the cytosol into nuclei and the degradation of inhibitor IκB-α, indicating that SF exhibited anti-inflammatory effects by inhibiting the NF-κB signaling pathway. In addition, SF abolished PM2.5-induced generation of ROS, similar to the pretreatment of a ROS scavenger, but not by an inhibitor of NF-κB activity. Furthermore, SF showed strong protective effects against NO and ROS production in PM2.5-treated zebrafish larvae. CONCLUSIONS: Our findings suggest that SF exerts anti-inflammatory and antioxidant effects against PM2.5 through ROS-dependent down-regulating the NF-κB signaling pathway, and that SF can be a potential functional substance to prevent PM2.5-mediated inflammatory and oxidative damage.
Hyesook Lee,Jung-Hwa Han,Kangbin An,Yun Jeong Kang,Hyun Hwangbo,Ji Hye Heo,Byung Hyun Choi,Jae-Joon Kim,Seo Rin Kim,Soo Yong Lee,Jin Hur 생화학분자생물학회 2023 BMB Reports Vol.56 No.6
KAI1/CD82, a membrane tetraspanin protein, can prevent variouscancers and retinal disorders through its anti-angiogenicand anti-metastatic capacity. However, little is known about itsanti-inflammatory effect and molecular mechanism. Therefore,the present study aimed to inLPSvestigate effect of a recombinantprotein of the large extracellular domain of human KAI1(Gly 111-Leu 228, rhKAI1) on lipopolysaccharides (LPS)-stimulatedRAW264.7 macrophage-like cells and mouse bone marrow-derived macrophages (BMDM) and to identify its underlyingmechanism. Our data showed that rhKAI1 suppressedexpression levels of classically macrophages (M1) phenotyperelatedsurface markers F4/80+CD86+ in LPS-stimulated BMDMand RAW264.7 cells. In addition, LPS markedly increased mRNAexpression and release levels of pro-inflammatory cytokinesand mediators such as interleukin (IL)-1β, IL-6, tumor necrosisfactor-α, cyclooxygenase-2, nitric oxide and prostaglandin E2,whereas these increases were substantially down-regulated byrhKAI1. Furthermore, LPS strongly increased expression of NF-κBp65 in the nuclei and phosphorylation of ERK, JNK, and p38MAPK. However, nuclear translocation of NF-κB p65 and phosphorylationof JNK were greatly reversed in the presence ofrhKAI1. Especially, rhKAI1 markedly suppressed expression oftoll-like receptor (TLR4) and prevented binding of LPS withTLR4 through molecular docking predict analysis. Importantly,Glu 214 of rhKAI1 residue strongly interacted with Lys 360 ofTLR4 residue, with a binding distance of 2.9 Å. Taken together,these findings suggest that rhKAI1 has an anti-inflammatoryeffect on LPS-polarized macrophages by interacting withTLR4 and down-regulating the JNK/NF-κB signaling pathway.
Screening of Myxobacteria Carrying Tubulysin Biosynthetic Genes
( Hyesook Hyun ),( Juo Choi ),( Daun Kang ),( Yungpil Kim ),( Pilgoo Lee ),( Gregory J. Y. Chung ),( Kyungyun Cho ) 한국미생물생명공학회(구 한국산업미생물학회) 2021 한국미생물·생명공학회지 Vol.49 No.1
Tubulysins are a group of secondary metabolites produced by myxobacteria that inhibit the function of the eukayotic cytoskeleton. We developed a pair of PCR primers that specifically amplified tubulysin biosynthetic genes. Using these primers, eight out of the eighty-one strains of myxobacteria belonging to the Cystobacteraceae family that harbored putative tubulysin biosynthetic genes were screened through PCR analysis. The selected strains included two Archangium gephyra, two Stigmatella sp., two Vitiosangium cumulatum, and two unidentified myxobacteria. LC-MS analysis of the culture extracts from the selected strains revealed that A. gephyra KYC4066 produced putative tubulysin A and B.
Hwangbo Hyun,Kim Min Yeong,Ji Seon Yeong,Park Beom Su,Kim TaeHee,Yoon Seonhye,Kim Hyunjin,Kim Sung Yeon,Jung Haeun,Kim Taeiung,Lee Hyesook,Kim Gi-Young,Choi Yung Hyun 한국영양학회 2023 Nutrition Research and Practice Vol.17 No.1
BACKGROUND/OBJECTIVES: Benign prostatic hyperplasia (BPH) characterized by an enlarged prostate gland is common in elderly men. Corni Fructus (CF) and Schisandrae Fructus (SF) are known to have various pharmacological effects, including antioxidant and anti-inflammatory activities. In this study, we evaluated the inhibitory efficacy of CF, SF, and their mixture (MIX) on the development of BPH using an in vivo model of testosterone-induced BPH. MATERIALS/METHODS: Six-week-old male Sprague-Dawley rats were randomly divided into seven groups. To induce BPH, testosterone propionate (TP) was injected to rats except for those in the control group. Finasteride, saw palmetto (SP), CF, SF, and MIX were orally administered along with TP injection. At the end of treatment, histological changes in the prostate and the level of various biomarkers related to BPH were evaluated. RESULTS: Our results showed that BPH induced by TP led to prostate weight and histological changes. Treatment with MIX effectively improved TP-induced BPH by reducing prostate index, lumen area, epithelial thickness, and expression of BPH biomarkers such as 5α-reductase type 2, prostate-specific antigen, androgen receptor, and proliferating cell nuclear antigen compared to treatment with CF or SF alone. Moreover, MIX further reduced levels of elevated serum testosterone, dihydrotestosterone, and prostate-specific antigen in BPH compared to the SP, a positive control. BPH was also improved more by MIX than by CF or SF alone. CONCLUSIONS: Based on the results, MIX is a potential natural therapeutic candidate for BPH by regulating 5α-reductase and AR signaling pathway.