• Natural Product Sciences
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• 제2권1호
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• pp.1-8
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• 1996

Flavonoids are widely distributed polyphenol compounds in plant kingdom and known to possess varieties of biological/pharmacological activities in vitro and in vivo. A search for antiinflammatory/immunoregulatory flavonoids as potential therapeutic agents has been continued, since serious side effects of currently used nonsteroidal and steroidal antiinflammatory drugs limit their long term uses for the inflammatory disorders. In this reserch, various flavonids were isolated and tested for their in vivo antiinflammatory activity and in vitro inhibitory activity of lymphocyte proliferation. Using a mouse ear edema assay, it was found that certain flavones/flavonols possess mild antiinflammatory activity and a C-2,3-double bond might be essential. Isoflavones were less active. These flavonoids inhibited in vitro lymphocyte proliferation, relatively specific for T-cell proliferation $(IC_{50}=1-10\;{\mu}M)$ and the inhibition was reversible. We have also tested several biflavonoid derivatives, since we recently found that biflavones were phospholipase $A_2$ inhibitors. It was demonstrated that biflavones such as ochnaflavone and ginkgetin inhibited lymphocyte proliferation induced by both concanavaline A and lipopolysaccharide. The inhibition was irreversible in contrast to that of flavones/flavonols. And antiinflammatory activity of biflavonoids are discussed.

• Journal of Microbiology and Biotechnology
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• 제23권7호
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• pp.953-958
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• 2013

Selaginella tamariscina is a traditional herb used in medicine. Phytochemical amentoflavone, a biflavonoid class of flavonoids, was isolated from the plant of Selaginella tamariscina. In this study, the antibacterial effects and combination effects of amentoflavone and conventional antibiotics such as ampicillin, cefotaxime, and chloramphenicol were investigated. These results showed that amentoflavone had a considerable antibacterial effect and synergistic interaction with antibiotics against various bacterial strains (fractional inhibitory concentration index ${\leq}$ 0.5), except for Streptococcus mutans. To study the mechanism(s) involved in the synergistic activities between amentoflavone and antibiotics, we detected hydroxyl radical formation using 3'-(p-hydroxyphenyl) fluorescein and measured the $NAD^+/NADH$ ratio by $NAD^+$ cycling assay. The results indicated that the formation of hydroxyl radical would be a cause of the synergistic effect and that this oxidative stress originated from a transient NADH depletion. This study suggests that amentoflavone synergizes with antibiotics and has potential as a therapeutic agent for antimicrobial chemotherapy.

• Mass Spectrometry Letters
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• 제11권4호
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• pp.113-117
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• 2020

Cytochrome P450 2J2 (CYP2J2) is a member of the cytochrome P450 superfamily, and is known to be arachidonic acid epoxygenase that mediates the formation of four bioactive regioisomers of epoxyeicosatrienoic acids (EETs). CYP2J2 is also involved in the metabolism of drugs such as albendazole, astemizole, danazol, ebastine, and terfenadine. CYP2J2 is highly expressed in the heart and cancer tissues. In this study, the inhibitory potential of ten natural products against CYP2J2 activity was evaluated using human liver microsomes and tandem mass spectrometry. Among them, bilobetin, which is a kind of biflavonoid, exhibits a strong inhibitory effect against the CYP2J2-mediated astemizole O-demethylation (IC50 = 0.73 μM) and terfenadine hydroxylation (IC50 = 0.89 μM). This result suggests that bilobetin can be used as strong CYP2J2 inhibitor in drug metabolism study.

• Biomolecules & Therapeutics
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• 제28권2호
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• pp.145-151
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• 2020

Alzheimer's disease (AD) is a devastating neurodegenerative disease and a major cause of dementia in elderly individuals worldwide. Increased deposition of insoluble amyloid β (Aβ) fibrils in the brain is thought be a key neuropathological hallmark of AD. Many recent studies show that natural products such as polyphenolic flavonoids inhibit the formation of insoluble Aβ fibrils and/or destabilize β-sheet-rich Aβ fibrils to form non-cytotoxic aggregates. In the present study, we explored the structure-activity relationship of naturally-occurring biflavonoids on Aβ amyloidogenesis utilizing an in vitro thioflavin T assay with Aβ1-42 peptide which is prone to aggregate more rapidly to fibrils than Aβ1-40 peptide. Among the biflavonoids we tested, we found amentoflavone revealed the most potent effects on inhibiting Aβ1-42 fibrillization (IC₅₀: 0.26 µM), as well as on disassembling preformed Aβ1-42 fibrils (EC₅₀: 0.59 µM). Our structure-activity relationship study suggests that the hydroxyl groups of biflavonoid compounds play an essential role in their molecular interaction with the dynamic process of Aβ1-42 fibrillization. Our atomic force microscopic imaging analysis demonstrates that amentoflavone directly disrupts the fibrillar structure of preformed Aβ1-42 fibrils, resulting in conversion of those fibrils to amorphous Aβ1-42 aggregates. These results indicate that amentoflavone affords the most potent anti-amyloidogenic effects on both inhibition of Aβ1-42 fibrillization and disaggregation of preformed mature Aβ1-42 fibrils.

• Journal of Applied Biological Chemistry
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• 제58권2호
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• pp.109-112
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• 2015

Fruits of Rhus parviflora were extracted with 80% aqueous methanol (MeOH), and the concentrated extract was partitioned using ethyl acetate (EtOAc), n-butanol (n-BuOH), and $H_2O$, successively. Purification of EtOAc fraction led to isolation of fifteen polyphenols of which structures were identified by spectroscopic methods including 2D-NMR. Most compounds apart from compound 10 inhibited low density lipoproteinoxidation within $IC_{50}$ value of $10{\mu}M$. Among compounds, taxifolin (2), quercetin 3-O-${\alpha}$-L-rhamnopyranoside (13), agathisflavone (5) sulfuretin (4), and aureusidin (3) showed $IC_{50}$ values 0.9, 0.8, 5.8, 2.9, and $2.4{\mu}M$ which were of highly significant in comparison positive control butylated hydroxytoluene with $IC_{50}$ value of $2.1{\mu}M$. The results indicate fruits of R. parviflora as a source of antihypercholesterolemic compounds.

• Bulletin of the Korean Chemical Society
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• 제32권8호
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• pp.2717-2721
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• 2011

Peroxisome proliferator-activated receptors (PPARs) are a subfamily of nuclear receptors (NRs). Human peroxisome proliferator-activated receptor gamma (hPPAR${\gamma}$) has been implicated in the pathology of numerous diseases, including obesity, diabetes, and cancer. ELISA-based hPPAR${\gamma}$ activation assay showed that biapigenin increased the binding between hPPAR${\gamma}$ and steroid receptor coactivator-1 (SRC-1) by approximately 3-fold. In order to confirm that biapigenin binds to hPPAR${\gamma}$, fluorescence quenching experiment was performed. The results showed that biapigenin has higher binding affinity to hPPAR${\gamma}$ at nanomolar concentrations compared to indomethacin. Biapigenin showed anticancer activity against HeLa cells. Biapigenin was noncytotoxic against HaCa T cell. All these data implied that biapigenin may be a potent agonist of hPPAR${\gamma}$ with anticancer activity. We will further investigate its anticancer effects against human cervical cancer.

• 생명과학회지
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• 제15권2호
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• pp.231-235
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• 2005

기질 금속단백분해효소(MMP)는 기저막이나 간질성 조직 등에 있는 세포외기질 성분을 분해하여 상처 치유, 태아의 발생, 종양세포의 침윤과 전이 등을 포함하여 조직이 재구성되는 과정에서 생리학적 및 병리학적인 과정 양쪽 모두에 매우 중요한 역할을 한다. 본 연구에서는 MMP-9 유전자의 발현을 억제하는 물질을 천연물에서 탐색하였고, 탐색된 시료 중에서 높은 역가를 가진 낙우송과의 Metasequoia glyptostroboides가 선택되었다. 여러 가지 flavonoid 성분을 가지고 있는 Metasequoia glyptostroboides를 이용하여 4개의 biflavonoid와 2개의 monoflavonoid 구조의 물질을 분리하였고, 이 flavonoid들은 sciadopitysin, isoginkgetin, bilobetin, 2, 3-dihydrohino-kiflavone, luteolin, apigenin으로 정제하여 구조를 밝히고 zymography, WST-1을 이용한 세포독성시험, northern blot 등의 실험을 통하여 각 화합물의 구조적인 특성과 함께 MMP-9 유전자 발현을 억제하는 효과가 있는 것을 확인하였다.

• Natural Product Sciences
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• 제22권2호
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• pp.122-128
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• 2016

This paper reports in vitro cytotoxic, anti-inflammatory and adipocyte diffentiation with adipogenic effects of coumarins inophyllum D (1) and calanone (2), and a chromanone carboxylic acid namely isocordato-oblongic acid (3) isolated from Calophyllum symingtonianum as well as a biflavonoid morelloflavone (4) isolated from Garcinia prainiana on MCF-7 breast adenocarcinoma RAW 264.7 macrophages and 3T3-L1 preadipocytes cells, respectively. The cytotoxicity study on MCF-7 cell was conducted by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Meanwhile, the study of anti-inflammatory effects in RAW 264.7 macrophages and adipogenic effects on 3T3-L1 pre-adipocytes were conducted through nitrite determination assay and induction of adipocyte differentiation, respectively. In the cytotoxicity study, inophyllum D (1) was the only compounds that exhibited significant cytotoxic effect against MCF-7 cell with $IC_{50}$ of $84{\mu}g/mL$. Further, all by inhibiting the compounds have shown anti-inflammatory effects in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages of nitrite concentration with production. In addition, the compounds also exhibited adipogenic effects on 3T3-L1 pre-adipocytes by stimulating lipid formation. Thus, this study may provide significant input in discovery of the potential effects cytotoxic, anti-inflammatory and adipogenic agents.