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Bio-guided isolation of the cytotoxic terpenoids from the roots of Euphorbia kansui against human normal cell lines L-O2 and GES-1.

Zhang L, Gao L, Li Z, Yan X, Yang Y, Tang Y, Cao Y, Ding A - Int J Mol Sci (2012)

Bottom Line: The 95% ethanol extract showed a significant inhibition of cell proliferation against human normal cell lines L-O2 and GES-1.Bioassay-guided separation of the 95% ethanol extract from the roots of E. kansui led to the isolation of 12 diverse terpenoids whose structures were identified by (1)H, (13)C NMR spectroscopy and ESI-MS as kansuinine A (1), kansuinine B (2), kansuinine C (3), kansuiphorin C (4), 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol (5), 3-O-(2'E,4'Edecadienoyl)-20-O-acetylingenol (6), 3-O-(2'E,4'Z-decadienoyl)-20-deoxyingenol (7), 3-O-benzoyl-20-deoxyingenol (8), 5-O-benzoyl-20-deoxyingenol (9), kansenone (10), epi-kansenone (11), euphol (12).These results will be significantly helpful to reveal the mechanism of toxicity of kansui and to effectively guide safer clinical application of this herb.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210046, China; E-Mails: zhangli@njutcm.edu.cn (L.Z.); gaolan1000@126.com (L.G.); lizhengjun404@126.com (Z.L.); yanxiaojing963@163.com (X.Y.); candy-jing@qq.com (Y.Y.); raindc@163.com (Y.C.).

ABSTRACT
The dried roots of Euphorbia kansui (kansui) have been used for centuries in China as a herbal medicine for edema, ascites, and asthma. The 95% ethanol extract showed a significant inhibition of cell proliferation against human normal cell lines L-O2 and GES-1. Bioassay-guided separation of the 95% ethanol extract from the roots of E. kansui led to the isolation of 12 diverse terpenoids whose structures were identified by (1)H, (13)C NMR spectroscopy and ESI-MS as kansuinine A (1), kansuinine B (2), kansuinine C (3), kansuiphorin C (4), 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol (5), 3-O-(2'E,4'Edecadienoyl)-20-O-acetylingenol (6), 3-O-(2'E,4'Z-decadienoyl)-20-deoxyingenol (7), 3-O-benzoyl-20-deoxyingenol (8), 5-O-benzoyl-20-deoxyingenol (9), kansenone (10), epi-kansenone (11), euphol (12). All these 12 terpernoids were evaluated in vitro for cytotoxicity on L-O2 and GES-1 cell lines. Most ingenane-type diterpenoids and 8-ene-7-one triterpenoids (5-11) exhibited a relatively lower IC(50) value; therefore, these compounds had stronger cytotoxicity against human normal cell lines L-O2 and GES-1 with dose-dependent relationships. These results will be significantly helpful to reveal the mechanism of toxicity of kansui and to effectively guide safer clinical application of this herb.

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The cytotoxicity and dose-dependent relationship of compounds 5–11 on human normal cell lines L-O2.
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f3-ijms-13-11247: The cytotoxicity and dose-dependent relationship of compounds 5–11 on human normal cell lines L-O2.

Mentions: Compared with the control group, compounds 5, 7, 8 and 10 in the concentration range of 0.78–12.5 μg/mL, compounds 6 and 11 in the concentration range of 0.39–6.25 μg/mL, and compound 9 in the concentration range of 1.56–25 μg/mL, showed significant inhibition activity on GES-1 cell lines growth with a dose-dependent relationship (Figure 2). And compounds 5, 6, 7, 10 and 11 in the concentration range of 0.78–12.5 μg/mL, compound 9 in the concentration range of 1.56–25 μg/mL, and compound 8 in the concentration range of 3.125–50 μg/mL, had significant inhibition activity on L-O2 cell lines growth with a dose-dependent relationship (Figure 3). Whereas, other compounds did not show the obvious cytotoxicity activity in the concentration range of 3.125–50 μg/mL. Considering their structure, the results indicated that ingenane-type diterpenoids (5–9) except compound 4 and 8-ene-7-one triterpenoids (10 and 11) in kansui possessed stronger gastrointestinal toxicity and hepatotoxicity than other compounds. More interestingly, the IC50 values of 5–11 and the kansui extracts on GES-1 cell lines were less than those on L-O2 cell lines, which suggested that the gastrointestinal toxicity of kansui is stronger than its hepatotoxicity. This result coincided with the clinical toxic performance of kansui [14–16].


Bio-guided isolation of the cytotoxic terpenoids from the roots of Euphorbia kansui against human normal cell lines L-O2 and GES-1.

Zhang L, Gao L, Li Z, Yan X, Yang Y, Tang Y, Cao Y, Ding A - Int J Mol Sci (2012)

The cytotoxicity and dose-dependent relationship of compounds 5–11 on human normal cell lines L-O2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472742&req=5

f3-ijms-13-11247: The cytotoxicity and dose-dependent relationship of compounds 5–11 on human normal cell lines L-O2.
Mentions: Compared with the control group, compounds 5, 7, 8 and 10 in the concentration range of 0.78–12.5 μg/mL, compounds 6 and 11 in the concentration range of 0.39–6.25 μg/mL, and compound 9 in the concentration range of 1.56–25 μg/mL, showed significant inhibition activity on GES-1 cell lines growth with a dose-dependent relationship (Figure 2). And compounds 5, 6, 7, 10 and 11 in the concentration range of 0.78–12.5 μg/mL, compound 9 in the concentration range of 1.56–25 μg/mL, and compound 8 in the concentration range of 3.125–50 μg/mL, had significant inhibition activity on L-O2 cell lines growth with a dose-dependent relationship (Figure 3). Whereas, other compounds did not show the obvious cytotoxicity activity in the concentration range of 3.125–50 μg/mL. Considering their structure, the results indicated that ingenane-type diterpenoids (5–9) except compound 4 and 8-ene-7-one triterpenoids (10 and 11) in kansui possessed stronger gastrointestinal toxicity and hepatotoxicity than other compounds. More interestingly, the IC50 values of 5–11 and the kansui extracts on GES-1 cell lines were less than those on L-O2 cell lines, which suggested that the gastrointestinal toxicity of kansui is stronger than its hepatotoxicity. This result coincided with the clinical toxic performance of kansui [14–16].

Bottom Line: The 95% ethanol extract showed a significant inhibition of cell proliferation against human normal cell lines L-O2 and GES-1.Bioassay-guided separation of the 95% ethanol extract from the roots of E. kansui led to the isolation of 12 diverse terpenoids whose structures were identified by (1)H, (13)C NMR spectroscopy and ESI-MS as kansuinine A (1), kansuinine B (2), kansuinine C (3), kansuiphorin C (4), 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol (5), 3-O-(2'E,4'Edecadienoyl)-20-O-acetylingenol (6), 3-O-(2'E,4'Z-decadienoyl)-20-deoxyingenol (7), 3-O-benzoyl-20-deoxyingenol (8), 5-O-benzoyl-20-deoxyingenol (9), kansenone (10), epi-kansenone (11), euphol (12).These results will be significantly helpful to reveal the mechanism of toxicity of kansui and to effectively guide safer clinical application of this herb.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210046, China; E-Mails: zhangli@njutcm.edu.cn (L.Z.); gaolan1000@126.com (L.G.); lizhengjun404@126.com (Z.L.); yanxiaojing963@163.com (X.Y.); candy-jing@qq.com (Y.Y.); raindc@163.com (Y.C.).

ABSTRACT
The dried roots of Euphorbia kansui (kansui) have been used for centuries in China as a herbal medicine for edema, ascites, and asthma. The 95% ethanol extract showed a significant inhibition of cell proliferation against human normal cell lines L-O2 and GES-1. Bioassay-guided separation of the 95% ethanol extract from the roots of E. kansui led to the isolation of 12 diverse terpenoids whose structures were identified by (1)H, (13)C NMR spectroscopy and ESI-MS as kansuinine A (1), kansuinine B (2), kansuinine C (3), kansuiphorin C (4), 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol (5), 3-O-(2'E,4'Edecadienoyl)-20-O-acetylingenol (6), 3-O-(2'E,4'Z-decadienoyl)-20-deoxyingenol (7), 3-O-benzoyl-20-deoxyingenol (8), 5-O-benzoyl-20-deoxyingenol (9), kansenone (10), epi-kansenone (11), euphol (12). All these 12 terpernoids were evaluated in vitro for cytotoxicity on L-O2 and GES-1 cell lines. Most ingenane-type diterpenoids and 8-ene-7-one triterpenoids (5-11) exhibited a relatively lower IC(50) value; therefore, these compounds had stronger cytotoxicity against human normal cell lines L-O2 and GES-1 with dose-dependent relationships. These results will be significantly helpful to reveal the mechanism of toxicity of kansui and to effectively guide safer clinical application of this herb.

Show MeSH
Related in: MedlinePlus