Kansuinine A

Ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry analysis of the impact of processing on toxic components of Kansui Radix.[Pubmed:26912002]

BMC Complement Altern Med. 2016 Feb 24;16:73.

BACKGROUND: Kansui Radix (Gansui in Chinese), the dried tuber of Euphorbia kansui, is a Chinese medicinal herb commonly used for the treatment of oedema and ascites with dyspnea. Because of its toxic nature, the herb is usually processed with vinegar to reduce the toxicity. A report has shown that the contents of toxic terpenoids in Gansui decreased after processing with vinegar. However, comprehensive comparison of the chemical profiles between vinegar-processed and raw Gansui has not yet been conducted. METHODS: An ultra-high-performance liquid chromatography in conjunction with ultra-high resolution quadrupole time-of-flight mass spectrometry (UHPLC UHD Q-TOF MS/MS) method was developed for the analysis of chemical profiles of vinegar-processed and raw Gansui in this study. RESULTS: Results showed that processing with vinegar caused conspicuous chemical changes. Among the altered components, 11 toxic terpenoids, 3-O-benzoyl-13-O- dodecanoylingenol/20-O-benzoyl-13-O-dodecanoylingenol, kansuinine D, Kansuinine A, 3-O-benzoyl-13-O-dodecanoylingenol/20-O-benzoyl-13-O-dodecanoylingenol, 3-O- benzoylingenol/20-O-benzoylingenol, 20-O-(2'E,4'Z-decadienoyl)ingenol/20-O-(2'E,4'E- decadienoyl)ingenol/3-O-(2'E,4'Z-decadienoyl)ingenol/3-O-(2'E,4'E-decadienoyl)ing enol, 3-O-(2'E,4'Z-decadienoyl)-20-deoxyingenol,3-O-(2'E,4'Z-,ecadienoyl)-5-O-acetyling enol,3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol,3-O-(2,3-dimethylbutanoyl)-13-O -dodecanoylingenol, were tentatively identified. The contents of most of these terpenoids were obviously decreased after processing with reductions of 6.66-95.25%. CONCLUSION: Our findings could help us understand the chemical basis for the toxicity reduction of Gansui afforded by processing with vinegar. Further investigations are warranted to establish the relationship between processing-induced chemical changes and the reduction of toxicity of Gansui.

Bio-guided isolation of the cytotoxic terpenoids from the roots of Euphorbia kansui against human normal cell lines L-O2 and GES-1.[Pubmed:23109850]

Int J Mol Sci. 2012;13(9):11247-59.

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.

Kansuinine A and Kansuinine B from Euphorbia kansui L. inhibit IL-6-induced Stat3 activation.[Pubmed:20379953]

Planta Med. 2010 Oct;76(14):1544-9.

The current study was performed to examine the mechanisms underlying the potential effects of E. KANSUI on IL-6-induced cellular signaling in human hepatoma cells. We found that two diterpenoids, Kansuinine A and B, from E. KANSUI have an inhibitory effect on IL-6-induced Stat3 activation by activating ERK1/2. Inhibition of MEK significantly blocked the effects of Kansuinine A and B on IL-6-induced Stat3 activation and tyrosine phosphorylation. These results suggest that blocking of IL-6-induced signal transduction is partially due to the sustained activation of ERK1/2 by Kansuinine A and B, which in turn results in an increase of Stat3 serine phosphorylation and SOCS-3 expression. Treatment with Kansuinine A and B represents a novel method to block these IL-6-induced effects.

Bioassay-guided separation of the proinflammatory constituents from the roots of Euphorbia kansui.[Pubmed:19844773]

J Nat Med. 2010 Jan;64(1):98-103.

In view of the toxic inflammatory reaction induced by Euphorbia kansui roots, a traditional Chinese medicine used for the treatment of edema, ascites, and asthma, the 95% ethanol extract was found to have a significant stimulating effect on inflammatory cells. Bioassay-guided separation of the 95% ethanol extract from the roots of E. kansui led to the isolation of five diterpenoids whose structures were identified by (1)H, (13)C NMR spectroscopy and HR-ESI-MS as kansuinine B (1), Kansuinine A (2), kansuiphorin C (3), 3-O-benzoyl-20-deoxyingenol (4), and 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol (5). The proinflammatory effect of compounds 1-5 was evaluated in vitro in models of inflammation using exoteric mice splenic lymphocytes (SPL) and rat peritoneal macrophages (PMphi). Compounds 1, 2, and 5 markedly promoted SPL proliferation and NO production by PMphi at concentrations from 0.78 to 12.50 microg/mL. Hence the three compounds are believed to be important proinflammatory components of the roots of E. kansui.