erythro-Austrobailignan-6

Phytomedicine . 2015 Feb 15;22(2):256-261.

Inhibitory effects of Saururus chinensis and its components on stomach cancer cells[Pubmed: 25765830]

Saururus chinensis (SC) Baill. (Saururaceae), a perennial herb commonly called Chinese lizard's tail or Sam-baekcho in Korea, has been used in the treatment of edema, gonorrhea, jaundice, and inflammatory diseases. Recently, several reports have been commissioned to examine the anti-cancer activities of this plant. In this study, we evaluated the inhibitory activity and mechanism of action on SC and its components against stomach cancer cells. SC extracts displayed cytotoxic effects on AGS cells in a dose-dependent manner. Moreover, SC increased the number of annexin V-positive apoptotic bodies and phosphorylated JNK and p38 in AGS cells. SC also down-regulated anti-apoptotic (Bcl-2) genes and up-regulated apoptotic (Bax) genes in AGS cells. We further confirmed that caspase activation plays an important role in SC-induced apoptosis in AGS cells. Furthermore, we examined erythro-Austrobailignan-6 and meso-dihydroguaiaretic acid, major active constituents of SC, which induced apoptosis in both the AGS and NCI-N87 stomach cancer cell lines. Taken together, our data provide the evidence that SC and its components induce apoptosis in stomach cancer cells, making it a potential candidate as a chemotherapeutic drug.

Planta Med . 2001 Nov;67(8):700-704.

Antiproliferative, anti-aromatase, anti-17beta-HSD and antioxidant activities of lignans isolated from Myristica argentea[Pubmed: 11731908]

Four lignans were isolated from the petrol extract of Myristica argentea mace (Myristicaceae) and their structures were elucidated by means of NMR and mass spectrometry. Although they have been previously described, NMR data are only available for threo-austrobailignan-5, which has been isolated only once, and is incomplete. Three of them, erythro-Austrobailignan-6, meso-dihydroguaiaretic acid and nectandrin-B, exert an antiproliferative effect on MCF-7 cells as well as antioxidant activity on the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, but not the threo-austrobailignan-5. Nectandrin-B also possesses anti-17beta-hydroxysteroid dehydrogenase and anti-aromatase activities.

Pest Manag Sci . 2007 Sep;63(9):935-940.

Isolation and antifungal activity of lignans from Myristica fragrans against various plant pathogenic fungi[Pubmed: 17659535]

Background: In a search for plant extracts with potent in vivo antifungal activity against various plant diseases, we found that treatment with a methanol extract of Myristica fragrans Houttyn (nutmeg) seeds reduced the development of various plant diseases. The objectives of the present study were to isolate and determine antifungal substances from My. fragrans and to evaluate their antifungal activities. Results: Three antifungal lignans were isolated from the methanol extract of My. fragrans seeds and identified as erythro-Austrobailignan-6 (EA6), meso-dihydroguaiaretic acid (MDA) and nectandrin-B (NB). In vitro antimicrobial activity of the three lignans varied according to compound and target species. Alternaria alternata, Colletotrichum coccodes, C. gloeosporioides, Magnaporthe grisea, Agrobacterium tumefaciens, Acidovorax konjaci and Burkholderia glumae were relatively sensitive to the three lignans. In vivo, all three compounds effectively suppressed the development of rice blast and wheat leaf rust. In addition, EA6 and NB were highly active against the development of barley powdery mildew and tomato late blight, respectively. Both MDA and NB also moderately inhibited the development of rice sheath blight. Conclusion: This is the first study to demonstrate the in vitro and in vivo antifungal activities of the three lignans from My. fragrans against plant pathogenic fungi.

Biol Pharm Bull . 2004 Jul;27(7):1147-1150.

Lignans from the bark of Machilus thunbergii and their DNA topoisomerases I and II inhibition and cytotoxicity[Pubmed: 15256759]

Activity-guided fractionation based on topoisomerase I inhibitory activity lead to the isolation of ten lignans (1-10) from the methylene chloride extract of the bark of Machilus thunbergii SIEB. et ZUCC. (Lauraceae). These were identified as machilin A (1), erythro-Austrobailignan-6 (2), meso-monomethyl dihydroguaiaretic acid (3), meso-dihydroguaiaretic acid (4), galbacin (5), machilin F (6), nectandrin A (7) nectandrin B (8), (-)-acuminatin (9) and (7S,8S)-7-(4-hydroxy-3-methoxyphenyl)-1'-formyl-3'-methoxy-8-methyldihydrobenzofuran (10) by spectral evidence. In DNA topoisomerase I and II assays in vitro at a concentration of 100 microM, 4 showed the most potent inhibitory activity, 93.6 and 82.1% inhibition, respectively, and 8 showed 79.1 and 34.3% inhibition, respectively. All of these compounds exhibited weak or no cytotoxicities against either the human colon carcinoma cell line (HT-29) or the human breast carcinoma cell line (MCF-7).

Phytomedicine . 2017 Jan 15;24:24-30.

Erythro-austrobailignan-6 down-regulates HER2/EGFR/integrinβ3 expression via p38 activation in breast cancer[Pubmed: 28160858]

Background: Despite the benefits from different options of therapy for breast cancer, resistance of the disease to these therapies is rising and a novel agent is needed. erythro-Austrobailignan-6 (EA6) exhibits anti-cancer activity. However, the detailed anti-tumor mechanisms by which EA6 inhibits 4T-1 and MCF-7 cell growth have not been well studied. Purpose: In this study, we investigated the anti-proliferative and anti-tumor properties of EA6 on breast carcinoma and its accompanying mechanisms. Methods: The cytotoxic and apoptotic effect of EA6 were measured in breast cancer cell lines of 4T-1 and MCF-7. The role of EA6 on cell proliferation and migration was examined by immunoblotting. The anti-tumor activity of EA6 was assessed in mice inoculated with 4T-1 breast cancer cells. Results: EA6 increased the number of Annexin V-positive apoptotic bodies and cleaved form of caspase-3 in a dose-dependent manner and phosphorylated JNK and p38 in both cells. Moreover, EA6 down-regulated cell cycle dependent proteins of CDK-4 and cyclin D1, and increased G0/G1 population in both cells. EA6-induced apoptosis is mediated by p38 MAPK and caspase-3 activation in both cells. EA6 significantly reduced HER2/EGFR/integrin β3 expression and Src phosphorylation, which was dependent on p38 MAPK activation in 4T-1 and MCF-7 cells. Furthermore, we confirmed the down-regulation of topoisomerases by EA6 treatment, but the overall effects of EA6 on topoisomerase isotype were cell type specific. Finally, EA6 (20mg/kg/day) significantly reduced mammary tumor volume in 4T-1 bearing mice by down-regulating HER2/EGFR/integrin β3 expression in tumor tissues. Conclusions: Our results offer a novel insight into the mechanism of EA6-induced apoptosis in breast cancer cells. We propose that EA6 treatment resulted in the activation of p38 MAPK and caspase-3, which eventually participated in regulating apoptosis in 4T-1 and MCF-7 cells.

Pest Manag Sci . 2007 Sep;63(9):935-940.

Isolation and antifungal activity of lignans from Myristica fragrans against various plant pathogenic fungi[Pubmed: 17659535]

Background: In a search for plant extracts with potent in vivo antifungal activity against various plant diseases, we found that treatment with a methanol extract of Myristica fragrans Houttyn (nutmeg) seeds reduced the development of various plant diseases. The objectives of the present study were to isolate and determine antifungal substances from My. fragrans and to evaluate their antifungal activities. Results: Three antifungal lignans were isolated from the methanol extract of My. fragrans seeds and identified as erythro-Austrobailignan-6 (EA6), meso-dihydroguaiaretic acid (MDA) and nectandrin-B (NB). In vitro antimicrobial activity of the three lignans varied according to compound and target species. Alternaria alternata, Colletotrichum coccodes, C. gloeosporioides, Magnaporthe grisea, Agrobacterium tumefaciens, Acidovorax konjaci and Burkholderia glumae were relatively sensitive to the three lignans. In vivo, all three compounds effectively suppressed the development of rice blast and wheat leaf rust. In addition, EA6 and NB were highly active against the development of barley powdery mildew and tomato late blight, respectively. Both MDA and NB also moderately inhibited the development of rice sheath blight. Conclusion: This is the first study to demonstrate the in vitro and in vivo antifungal activities of the three lignans from My. fragrans against plant pathogenic fungi.

Biol Pharm Bull . 2004 Jul;27(7):1147-1150.

Lignans from the bark of Machilus thunbergii and their DNA topoisomerases I and II inhibition and cytotoxicity[Pubmed: 15256759]

Activity-guided fractionation based on topoisomerase I inhibitory activity lead to the isolation of ten lignans (1-10) from the methylene chloride extract of the bark of Machilus thunbergii SIEB. et ZUCC. (Lauraceae). These were identified as machilin A (1), erythro-Austrobailignan-6 (2), meso-monomethyl dihydroguaiaretic acid (3), meso-dihydroguaiaretic acid (4), galbacin (5), machilin F (6), nectandrin A (7) nectandrin B (8), (-)-acuminatin (9) and (7S,8S)-7-(4-hydroxy-3-methoxyphenyl)-1'-formyl-3'-methoxy-8-methyldihydrobenzofuran (10) by spectral evidence. In DNA topoisomerase I and II assays in vitro at a concentration of 100 microM, 4 showed the most potent inhibitory activity, 93.6 and 82.1% inhibition, respectively, and 8 showed 79.1 and 34.3% inhibition, respectively. All of these compounds exhibited weak or no cytotoxicities against either the human colon carcinoma cell line (HT-29) or the human breast carcinoma cell line (MCF-7).