• Journal of Microbiology and Biotechnology
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• 제16권12호
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• pp.1904-1911
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• 2006

The cell-free extracts of 250 yeasts were screened for their in vitro anti-angiogenic activity, to develop a new cancer metastasis inhibitor. Saccharomyces cerevisiae K-7 was selected as the producer of the anti-angiogenic agent, because it had the highest anti-angiogenic activity. The anti-angiogenic agent was produced maximally from hydrolysates of Saccharomyces cerevisiae K-7, when the yeast was cultured in yeast extract-peptone-dextrose medium at 30$^{\circ}C$ for 24 h, and cell-free extracts were than digested with pepsin for 4 h at 37$^{\circ}C$. The anti-angiogenic agent was further purified by ultrafiltration, Sephadex G-25 gel permeation chromatography and reverse-phase HPLC, and the anti-angiogenic activity of the final purified preparation was 72.7% at 10 $\mu$M/egg. The purified anti-angiogenic agent was found to originate from the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) molecule of Saccharomyces cerevisiae K-7, and its peptide sequence was Val-Ser-Trp-Tyr-Asp-Asn-Glu-Tyr-Gly-Tyr-Ser-Thr-Arg-Val-Val-Asp. In the MTT assay, the shape of the HT-l 080 cell was clearly changed to a circular type at 0.2 mM purified anti-angiogenic agent. This result indicated that the growth of the HT-I080 cell was significantly inhibited at 0.2 mM of the purified anti-angiogenic agent. The MMP activity of the treated HT-l080 cells was not affected, evidenced by the gelatin zymography, indicating that the anti-angiogenic mechanism of the purified anti-angiogenic agent is not mediated through MMP activity.

• 생약학회지
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• 제37권4호
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• pp.253-257
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• 2006

We examined anti-angiogenic effects of water extracts from 32 plant materials (20 Korean medicinal plants and 12 western herbs) using cell-based anti-angiogenic assay, HUVEC tube formation assay, and then we found that 7 plant extracts inhibited HUVEC tube formation strongly. The plant materials which showed anti-angiogenic effects are Cinnamomi Ramulus, Atractylodis Rhizoma alba, Polygalae Radix, Myristicae Semen, Artemisiae Iwayomogii Herba, leaves of Rosmarinus officinalis, and leaves of Melissa officinalis. We also investigated inhibitory effects of these anti-angiogenic herbal extracts on MMP (matrix metalloproteinase) activity which has important roles in angiogenesis. Among extracts tested in this study, water extract of Melissa officinalis showed the most potent anti-angiogenic and MMP inhibitory activity.

• Biomolecules & Therapeutics
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• 제21권1호
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• pp.72-78
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• 2013

This work aimed to assess some pharmacological activities of P. leptostachya var. asiatica Hara. The dried roots of P. leptostachya var. asiatica Hara were extracted with 70% ethanol to generate the powdered extract, named PLE. Anti-angiogenic activity was detected using chick chorioallantoic membrane (CAM) assay. In vitro anti-inflammatory activity was evaluated via analyzing nitric oxide (NO) content, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Antioxidant activity was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and reactive oxygen species (ROS) level in the stimulated macrophage cells. Matrix metalloproteinase-9 (MMP-9) and -2 (MMP-2) activities in the culture media were detected using zymography. PLE exhibits an anti-angiogenic activity in the CAM assay, and displays an inhibitory action on the generation of NO in the LPS-stimulated macrophage cells. In the stimulated macrophage cells, it is able to diminish the enhanced ROS level. It can potently scavenge the stable DPPH free radical. It suppresses the induction of iNOS and COX-2 and the enhanced MMP-9 activity in the stimulated macrophage cells. Both monooxygenase and oxidase activities of tyrosinase were strongly inhibited by PLE. Taken together, the dried roots of P. leptostachya var. asiatica Hara possess anti-angiogenic, anti-inflammatory, antioxidant and skin whitening activities, which might partly provide its therapeutic efficacy in traditional medicine.

• Journal of Microbiology and Biotechnology
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• 제11권4호
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• pp.656-662
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• 2001

Angiogenesis is known as a crucial process in the growth and spreading of tumor cells. Accordingly, the effective inhibition of this process would appear to be a promising way to cure angiogenesis-related diseases, including cancer. This study demonstrates that acalycixenolide E (AX-E) from the marine organism Acalycigorgia inermis exhibits a potent anti-angiogenic activity both in vitro and in vivo. AX-E inhibits the bFGF-induced proliferation of HUVECs in a dose dependent manner, along with the bFGF-induced migration, invasion, and tube formation of HUVECs. Moreover, AX-E potently inhibits the in vivo neovascularization of the chorioallantoic membranes (CAMs) of growing chick embryos. interestingly, AX-E suppresses the expression of metalloproteases 2 and 9, yet shows no effect on their activities. The novel chemical structure and potent anti-angiogenic activity of AX-E will be of great value in elucidating the molecular mechanism of angiogenesis as well as in the development of a novel anti-angiogenic drug.

• 한국버섯학회지
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• 제1권1호
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• pp.44-47
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• 2003

버섯으로부터 새로운 암전이 억제물질을 개발하기 위하여 먼저 7종 52균주의 자실체 (또는 균사체)에 대한 다양한 추출물들을 제조한 후 이들의 암전이 억제에 관련된 혈관신생 억제활성을 수정란을 이용하여 Choriollantoic membrane (CAM) assay로 조사하였다. 7종 52균주의 버섯에 대한 물, 에탄올, 메탄올 추출물 중에서 장수버섯(Fomitella fraxinea) ASI 17003과 17009의 물 추출물과 비늘버섯(Pholiota sp.) ASI 24008과 잎새버섯(Grifola frondosa) ASI 9017의 에탄올 추출물 그리고 차가버섯(Inonotus obliquus) ASI 74012의 메탄올 추출물에서 $10{\mu}g/egg$농도일 때 62.5%~68.8%의 높은 혈관신생 억제활성을 보였다. 그러나 추출 수율과 안전성 등을 고려하여 비늘버섯 ASI 24008을 혈관신생 억제효과 우수버섯으로 최종 선정하여 현재 이들의 암전이 억제 기작 규명을 위한 정제 실험을 실시하고 있다.

• 약학회지
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• 제50권5호
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• pp.338-344
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• 2006

A novel series of 4-senecioyloxymethyl-6,7-dimethoxycoumarin, isolated from Crinum latifolium, was prepared by reacting 4-bromomethyl or 4-bromomethyl-6,7- dimethoxycoumarin with various carboxylic acids and examined for their anti-angiogenic activities in human umbilical vein endothelial cells (HUVECs). Among them, 4e, 4f, 4g and 4i with noncyclic moiety exhibited potent anti-angiogenic activity. However, compounds with cyclic moiety such as phenyl, pyridinyl, thiophenyl and furanyl group did not exhibit any anti-angiogenic activity. Also, compounds 4f and 4g which exhibited strong anti-angiogenic activity in a dose-dependent manner showed antitumor activity.

• Biomolecules & Therapeutics
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• 제16권2호
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• pp.132-136
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• 2008

The current study aimed to assess some novel pharmacological activities of vanillin. Vanillin inhibited the chick chorioallantoic membrane (CAM) angiogenesis. Vanillin had anti-inflammatory activity using the acetic acid-induced permeability model in mice. Anti-nociceptive activity of vanillin was shown using the acetic acid-induced writhing test in mice. Vanillin inhibited production of nitric oxide (NO) and induction of inducible nitric oxide synthase (iNOS) but not cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Vanillin decreased the level of iNOS mRNA in the LPS-activated macrophages. Taken together, these results suggest that vanillin can have anti-angiogenic, anti-inflammatory and anti-nociceptive activities in ICR Mice.

• Bulletin of the Korean Chemical Society
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• 제26권4호
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• pp.619-628
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• 2005

We attempted to replace a benzopyran ring of 4-[(N-imidazol-2-ylmethyl)-4-chloroanilino]benzopyran, previously discovered as anti-angiogenic agent with antitumor activity, with pyranopyridines. The [3,2-c]-, [3,2-b]-, [2,3-c]-, and [2,3-b]-pyranopyridines with -(imidazol-2-ylmethyl)aniline moiety at the 4-position, were synthesized respectively, and evaluated for primary anti-angiogenic properties through primary cultured HUVEC tube formation assay. From this study, we found that the pyranopyridine ring, especially [3,2-b]- and [2,3-c]-isomer, can replace the benzopyran ring of the compound 1 and can be optimized through the introduction of substituents both on the pyranopyridine ring and the aniline moiety for the identification of a novel anti-angiogenic agent.

• 동의생리병리학회지
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• 제20권1호
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• pp.15-19
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• 2006

The anti-angiogenic activity of ethanol extract of Bojungbangam-tang, a new herbal prescription composed of nine crude drugs, was evaluated in human umbilical vein endothelial cells (HUVECs). HPLC profile revealed that five major compunds such as apioliquiritin, narirutin, hesperidin, liquiritin and glycyrrhizin. Ethanol extract of Bojungbangam-tang (EBJT) did not showed any significant cytotoxicity against HUVECs up to 200 ug/ml. EBJT significantly inhibited basic fibroblast growth factor (bFGF)-induced HUVECs proliferation to 69% at 200 ${\mu}g/ml$. Migration using window scraping method and tube formation in bFGF stimulated HUVECs were also significantly suppressed by EBJT in a dose-dependent manner. Taken together, these results suggest that Bojungbangam-tang can be a potent prescription for angiogenesis related disease.

• Biomolecules & Therapeutics
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• 제16권3호
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• pp.231-236
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• 2008

The current work was designed to assess novel pharmacological activities of 4-hydroxybenzaldehyde (HD), a major phenolic constituent of various natural products of plant origin, such as Gastrodia elata Blume. HD exhibited a significant inhibition in the chick chorioallantoic membrane (CAM) angiogenesis. HD also displayed an inhibitory effect in acetic acid-induced permeability in mice. Anti-nociceptive activity of HD was convinced using the acetic acid-induced writhing test in mice. HD was able to suppress production of nitric oxide (NO) and induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-activated RAW264.7 macrophages. HD also diminished the reactive oxygen species (ROS) level elevated in the LPS-activated macrophages. In brief, HD exhibits anti-angiogenic, anti-inflammatory and anti-nociceptive activities possibly via down-regulating iNOS and/or COX-2, which may be partly responsible for pharmacological efficacies of various natural products.