Considerations of the chemical biology of microbial natural products provide an effective drug discovery strategy

( Hyukjae Choi ),( Dong Chan Oh ) 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-

Conventional approaches to natural product drug discovery rely mainly on random searches for bioactive compounds using bioassays. These traditional approaches do not incorporate a chemical biology per-spective. Searching for bioactive molecules using a chemical and biological rationale constitutes a powerful search paradigm. Here, the authors review recent examples of the discovery of bioactive natural products based on chemical and biological interactions between hosts and symbionts, and propose this method provides a more effective means of exploring natural chemical diversity and eventually of discovering new druge.

Cyanopeptoline CB071: A Cyclic Depsipeptide Isolated from the Freshwater Cyanobacterium <i>Aphanocapsa</i> sp.

Choi, Hyukjae,Oh, Sun Kwan,Yih, Wonho,Chin, Jungwook,Kang, Heonjoong,Rho, Jung-Rae The Pharmaceutical Society of Japan 2008 Chemical & pharmaceutical bulletin Vol.56 No.8

<P>Cyanopeptolin CB071 (1), a trypsin inhibitor, was isolated from the freshwater cyanobacterium <I>Aphanocapsa</I> sp. Its complete structure was determined by detailed NMR spectroscopy and MS analyses, along with chemical reactions. The compound showed inhibition of trypsin at a concentration of IC<SUB>50</SUB>=2.5 μ<SMALL>M</SMALL>.</P>

Chrysin attenuates atopic dermatitis by suppressing inflammation of keratinocytes

Choi, Jin Kyeong,Jang, Yong Hyun,Lee, Soyoung,Lee, Sang-Rae,Choi, Young-Ae,Jin, Meiling,Choi, Jung Ho,Park, Jee Hun,Park, Pil-Hoon,Choi, Hyukjae,Kwon, Taeg Kyu,Khang, Dongwoo,Kim, Sang-Hyun Elsevier 2017 Food and chemical toxicology Vol.110 No.-

<P><B>Abstract</B></P> <P>We previously reported the inhibitory effect of chrysin, a natural flavonoid plentifully contained in propolis, vegetables and fruits, on the mast cell-mediated allergic reaction. In this study, we evaluated the effect of chrysin on atopic dermatitis (AD) and defined underlying mechanisms of action. We used an AD model in BALB/c mice by the repeated local exposure of 2,4-dinitrochlorobenzene (DNCB) and house dust mite (<I>Dermatophagoides farinae</I> extract, DFE) to the ears. Repeated alternative treatment of DNCB/DFE caused AD-like skin lesions. Oral administration of chrysin diminished AD symptoms such as ear thickness and histopathological analysis, in addition to serum IgE and IgG2a levels. Chrysin decreased infiltration of mast cells, and reduced serum histamine level. Chrysin also suppressed AD by inhibiting the inflammatory responses of Th1, Th2, and Th17 cells in mouse lymph node and ear. Interestingly, chrysin significantly inhibited the production of cytokines, Th2 chemokines, CCL17 and CCL22 by the down-regulation of p38 MAPK, NF-κB, and STAT1 in tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated human keratinocytes (HaCaT). Chrysin also inhibited TNF-α/IFN-γ-stimulated IL-33 expression in HaCaT cells and mouse primary keratinocytes. Taken together, the results indicate that chrysin suppressed AD symptoms, suggesting that chrysin might be a candidate for the treatment of AD and skin allergic diseases.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Chrysin suppresses AD symptoms by inhibiting T helper cell immune reaction. </LI> <LI> Chrysin downregulates CCL17 and CCL22 expression via p38 MAPK, STAT1, and NF-κB in human keratinocytes. </LI> <LI> Chrysin and tacrolimus have overlapping effects in inhibiting AD immune responses. </LI> <LI> Chrysin might be a candidate for the treatment of skin allergic diseases. </LI> </UL> </P>

Mabikibacter ruber gen. nov., sp. nov., a bacterium isolated from marine sediment, and proposal of Mabikibacteraceae fam. nov. in the class Alphaproteobacteria

Choi, Grace,Gao, Ming,Lee, Dae-Sung,Choi, Hyukjae Microbiology Society 2017 International journal of systematic and evolutiona Vol.67 No.9

Inhibitory Effect of Three Diketopiperazines from Marine-derived Bacteria on Secretory Group IIA Phospholipase A2

Choi, Hyukjae,Ku, Sae-Kwang,Bae, Jong-Sup NATURAL PRODUCT COMMUNICATIONS 2016 Natural product communications Vol.11 No.9

<P>Diketopiperazines, natural products found in bacteria, fungi, marine sponges, gorgonian and red algae, are cyclic dipeptides possessing relatively simple and rigid structures with chiral nature and various side chains. The compounds in this structure class have been known to possess diverse bioactivities including antibiotic activity, anti-cancer activity, neuroprotective activity, and anti-inflammatory activity. The expression of secretory group IIA phospholipase A2 (sPLA2-IIA) is enhanced by development of inflammatory disorders. Aim of this study is to determine the effects of diketopiperazines on the secretion and activity of sPLA2-IIA by lipopolysaccharide (LPS) in human umbilical vein endothelial cells (HUVECs). To do this, sPLA2-IIA expression was induced in the LPS-stimulated HUVECs and mice to evaluate the effect of diketopiperazines. Results showed that diketopiperazines remarkably suppressed the LPS-mediated protein expression and activity of sPLA2-IIA via inhibition of phosphorylation of cytosolic phospholipase A2 (cPLA2) and extracellular signal-regulated kinase (ERK) 1/2. These results demonstrated that diketopiperazines might play an important role in the modulation of sPLA2-IIA expression and activity in response to the inflammatory diseases.</P>

Inhibitory effects of collismycin C and pyrisulfoxin A on particulate matter-induced pulmonary injury

Choi, Hyukjae,Lee, Wonhwa,Kim, Eonmi,Ku, Sae-Kwang,Bae, Jong-Sup Elsevier 2019 Phytomedicine Vol.62 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Inhalation of fine particulate matter (PM<SUB>2.5</SUB>) is associated with elevated pulmonary injury caused by the loss of vascular barrier integrity. Marine microbial natural products isolated from microbial culture broths were screened for pulmonary protective effects against PM<SUB>2.5</SUB>. Two 2,2′-bipyridine compounds isolated from a red alga-associated <I>Streptomyces</I> sp. MC025—collismycin C (<B>2</B>) and pyrisulfoxin A (<B>5</B>)—were found to inhibit PM<SUB>2.5</SUB>-mediated vascular barrier disruption.</P> <P><B>Purpose</B></P> <P>To confirm the inhibitory effects of collismycin C and pyrisulfoxin A on PM<SUB>2.5</SUB>-induced pulmonary injury</P> <P><B>Study design</B></P> <P>In this study, we investigated the beneficial effects of collismycin C and pyrisulfoxin A on PM-induced lung endothelial cell (EC) barrier disruption and pulmonary inflammation.</P> <P><B>Methods</B></P> <P>Permeability, leukocyte migration, proinflammatory protein activation, reactive oxygen species (ROS) generation, and histology were evaluated in PM<SUB>2.5</SUB>-treated ECs and mice.</P> <P><B>Results</B></P> <P>Collismycin C and pyrisulfoxin A significantly scavenged PM<SUB>2.5</SUB>-induced ROS and inhibited the ROS-induced activation of p38 mitogen-activated protein kinase as well as activated Akt, which helped in maintaining endothelial integrity, in purified pulmonary endothelial cells. Furthermore, collismycin C and pyrisulfoxin A reduced vascular protein leakage, leukocyte infiltration, and proinflammatory cytokine release in the bronchoalveolar lavage fluid of PM-treated mice.</P> <P><B>Conclusion</B></P> <P>These data suggested that collismycin C and pyrisulfoxin A might exert protective effects on PM-induced inflammatory lung injury and vascular hyperpermeability.</P> <P><B> <B>Graphical abstract</B> </B></P> <P>[DISPLAY OMISSION]</P>

Chemical Constituents of the Root of Angelica tenuissima and their Anti-allergic Inflammatory Activity

Choi, Hyun Gyu,Je, In-Gyu,Kim, Geum Jin,Nam, Joo-Won,Shim, Sang Hee,Kim, Sang-Hyun,Choi, Hyukjae NATURAL PRODUCT COMMUNICATIONS 2017 Natural product communications Vol.12 No.5

<P>A phthalide, levistolide A (1), and six coumarins, demethylsuberosin (2), fraxetin (3), (-)-marmesinin (4), 3'(S)-O-beta-D-glucopyranosyl-3',4'-dihydroxanthyletin (5), 3'(R)-O-beta-D-glucopyranosyl-3',4'-dihydroxanthyletin (6), and isopraeroside IV (7) were isolated from the methanolic extract of the roots of Angelica tenuissima Nakai. Their chemical structures were confirmed by comparing spectroscopic and reported data. All seven compounds were isolated for the first time from this plant source. The anti-allergic activities of compounds 1-7 were examined using human mast cells, and compounds 1-3 at 10 mu M potently suppressed IL-6 expression and inhibited histamine release from human mast cells by more than 30%.</P>

Anti-allergic inflammatory activities of compounds of amomi fructus.

Choi, Hyun Gyu,Je, In-Gyu,Kim, Geum Jin,Choi, Hyukjae,Kim, Sang Hyun,Kim, Jeong Ah,Lee, Kim Seung Ho Natural Product Communications 2015 Natural product communications Vol.10 No.4

<P>Activity-guided isolation of compounds from the fruits of Amomum xanthioides resulted in the purification of fourteen phenolic compounds, 4-hydroxy-benzaldehyde (1), 3,4-dihydroxybenzaldehyde (2), 3,5-dimethoxy-4-methylbenzaldehyde (3), syringic aldehyde (4), benzoic acid (5), 3,4-dihydroxy benzoic acid (6), vanillic acid (7), 3-hydroxy-2-methoxybenzoic acid (8), o-vanillic acid (9), phenylacetic acid (10), tyrosol (11), pyrocatechol (12), 1,2,4,5-tetramethoxybenzene (13), and 3,3',5,5'-tetramethoxybiphenyl-4,4'-diol (14). To evaluate the anti-allergic inflammatory activities of these compounds, we examined the inhibitory effects of the isolates (1-14) on histamine release and on the expressions of tumor necrosis factor (TNF)-ca and interleukin (IL)-6 genes by using human mast cells. Of the tested compounds, 9, 11, and 13 suppressed histamine release from mast cells, and all isolates attenuated the expressions of the pro-inflammatory cytokines, TNF-α and IL-6 genes in human mast cells.</P>

Anti-Inflammatory and Anti-Fibrotic Activities of Nocardiopsis sp. 13G027 in Lipopolysaccharides-Induced RAW 264.7 Macrophages and Transforming Growth Factor Beta-1-Stimulated Nasal Polyp-Derived Fibroblasts

( Grace Choi ),( Geum Jin Kim ),( Hyukjae Choi ),( Il-whan Choi ),( Dae-sung Lee ) 한국미생물 · 생명공학회 2021 한국미생물·생명공학회지 Vol.49 No.4

Nocardiopsis species produce bioactive compounds, such as antimicrobial and anti-cancer agents and toxins. However, no reports have described their anti-inflammatory and anti-fibrotic effects during nasal polyp (NP) formation. In this study, we investigated whether marine-derived bacterial Nocardiopsis sp. 13G027 exerts anti-inflammatory and anti-fibrotic effects on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and transforming growth factor (TGF)-β1-induced NP-derived fibroblasts (NPDFs). Nitric oxide (NO) and prostaglandin E₂ (PGE₂) levels were analyzed. Extract from Nocardiopsis sp. 13G027 significantly inhibited the upregulation of NO and PGE₂ in LPS-activated RAW 264.7 macrophages. The expression of mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt/PKB) in LPS-induced RAW 264.7 macrophages was evaluated; smooth muscle alpha-actin (α-SMA), collagen type I (Col-1), and fibronectin also phosphorylated small mothers against decapentaplegic (SMAD) 2 and 3 in TGF-β1-stimulated NPDFs. The Nocardiopsis sp. 13G027 extract suppressed the phosphorylation of MAPKs and Akt and the DNA-binding activity of activator protein 1 (AP-1). The expression of pro-fibrotic components such as α-SMA, Col-1, fibronectin, and SMAD2/3 was inhibited in TGF-β1-exposed NPDFs. These findings suggest that Nocardiopsis sp. 13G027 has the potential to treat inflammatory disorders, such as NP formation.

부동산간접 투자자의 특성과 투자유형 분석

최혁재(Choi, Hyukjae),장희순(Jang, Heesoon) 한국주거환경학회 2021 주거환경(한국주거환경학회논문집) Vol.19 No.4

이 연구는 부동산간접투자에 투자하는 위험과 기대수익 선호도가 다른 투자자의 투자 특성과 그에 부합하는 수익증권 및 주식발행 조건을 파악하는 데 초점을 맞추고, 투자자가 취하고자 하는 위험 정도를 파악해 투자자가 요구하는 투자 유형에 대하여 확인하였다. 간접부동산투자는 기업과 개인이 부동산투자회사(리츠)와 부동산집단투자단체(펀드)를 이용해 임대수익이나 매매차익을 받는 투자 방식으로. 부동산펀드는 소액펀드를 활용해 임대수익이나 배당수익을 누리는 일종의 도관체가 되고, 부동산펀드는 대출자금, 임대자금, 개발자금 등으로 나뉜다. 이를 위해 투자자별 부동산펀드와 리츠의 특성 비교분석에 적합한 교차분석을 이용하여 통계적으로 검증하고, 부동산 간접투자상품을 통해 부동산시장 상황에 적합하면서도 안정적으로 부동산개발에 필요한 자금을 지속적, 반복적으로 공급하기 위하여는 부동산펀드 및 리츠 투자자들의 특성을 파악하여 이들의 요구에 부응하는 증권의 발행과 이러한 금융상품에 투자하는 투자자 특성을 파악하는 것이다. Indirect real estate investment has an investment method in which companies and individuals receive rental income or gains from sale using real estate investment companies (Ritz) and real estate collective investment organizations (funds). REITs serve as a kind of conduit for investing in real estate products using small funds to enjoy rental income or dividend income, and real estate funds are divided into loan funds, rental funds, and development funds.The study focused on identifying beneficiary securities and stock issuance conditions that meet investor characteristics by investors with different risk-expected return preferences, and attempted to prepare protection policies required by investors by identifying the degree of risk they want to take. To this end, it was statistically verified using cross-analysis suitable for comparative analysis of the characteristics of real estate funds and REITs by investor.The purpose of the study is to identify investors demands for securities issued by real estate funds and REITs to protect the people indirectly participating in the real estate market through the real estate indirect investment market and develop the national economy.