A new lignan from Euscaphis konishii / 中国中药杂志

The chemical constituents from the extract of the twigs of Euscaphis konishii with anti-hepatoma activity were investigated, twelve compounds by repeated chromatography with silica gel, Sephadex LH-20 and preparative-HPLC. The structures of the chemical components were elucidated by spectroscopy methods, as konilignan(1),(7R, 8S)-dihydrodehydrodico-niferylalcohol-9-O-β-D-glucopyranoside(2),illiciumlignan B(3),threo-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-panediol(4),erythro-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-panediol(5), matairesinol(6), wikstromol(7), isolariciresinol(8),(+)-lyoniresinol(9), 4-ketopinoresinol(10), syringaresin(11), and vladinol D(12). Among them, compound 1 is a new lignan. Compounds 10 and 12 had moderate inhibitory activity on HepG2 cells, with IC_(50) values of 107.12 μmol·L~(-1) and 183.56 μmol·L~(-1), respectively.

Spectrum-effect Relationship of Anti-hepatoma Activity from 3 Kinds of Genus Paris Based on Cluster Analysis and Grey Relational Analysis / 中国实验方剂学杂志

Objective::To study the spectrum-effect relationship between HPLC fingerprints and anti-hepatoma activity of Paris polyphylla var. yunnanensis, P. forrestii and P. vietnamensis, and to elucidate its effective substance. Method::HPLC was used to establish the fingerprint of three extracts from the plant. The mobile phase was consisted of acetonitrile (A)-water (B) for gradient elution (0-10 min, 20%A; 10-20 min, 20%-25%A; 20-30 min, 25%-30%A; 30-40 min, 30%-35%A; 40-50 min, 35%-40%A; 50-60 min, 40%A; 60-75 min, 40%-45%A; 75-80 min, 45%-60%A), and the flow rate was 0.9 mL·min-1. The UV detection wavelength was 203 nm. Thiazolyl blue tetrazolium bromide (MTT) array was used to detect the inhibitory effects of three extracts on the proliferation of HepG2 cells, and the half inhibitory concentration (IC50) was calculated. Cluster analysis and grey relational analysis were used to analyze the data of spectrum and efficacy, and to find out the components that contributed a lot to the anti-liver cancer effect. Result::A total of 11 common peaks were identified as common peaks among HPLC fingerprints of three kinds of Paris. After treated 72 h, P. forrestii has the highest inhibitory effect on the HepG2 cells, the IC50 of P. forrestii, P. polyphylla var. yunnanensis and P. vietnamensis were 148.33, 178.87, 208.09 mg·L-1, respectively. According to the grey relational analysis, the common peaks 1-10 from P. polyphylla var. yunnanensis had great correlation to anti-tumor effect, and the common peaks 1-7 for P. forrestii, the common peaks 1-4, 6-10, N1 for P. vietnamensis, all the correlation degrees with IC50 were >0.7.Cluster analysis of variables in each Paris showed that peaks with correlation degree >0.7 could cluster with IC50. Conclusion::The established HPLC fingerprint method is reliable with good reproducibility. The peaks 1-4, 6 and 7 from three kinds of Paris have the greatest contribution to the anti-hepatoma effect.

Study on Spectrum-effect Relationship of Anti-hepatoma Effect of C Ⅱ-3 Extract from Periplaneta americana / 中国药房

OBJECTIVE：To study the spectrum-ef fect relationship of anti-hepatoma effect of C Ⅱ-3 extract from Periplaneta americana，and to preliminarily clarify the anti-hepatoma active components of it. METHODS ：Based on UHPLC fingerprints of 10 batches of C Ⅱ-3 samples，with the help of UHPL C-Q-TOF/MS，the compounds corresponding to each chromatographic peak were identified qualitatively by standard substances and related literatures. Using the IC 50 value of each batch of C Ⅱ-3 sample against human hepatoma cells HepG 2 as anti-hepatoma activity index ，the spectrum-effect relationship of fingerprint and anti-hepatoma effect was established and analyzed by the combination of grey relational analysis （GRA）and orthogonal partial least squares（OPLS）. RESULTS ：There were 25 common peaks in UHPLC fingerprints of 10 batches of C Ⅱ-3 samples，and 10 chemical compounds were identified ，which were cyclo- （Tyr-Pro）（peak 24），cyclo-（Gly-Phe）（peak 15），hypoxanthine（peak 3）， adenine（peak 7），phenylalanine（peak 10），inosine（peak 11），N-acetyldopamine（peak 16），cyclo-（Pro-Ala）（peak 13），2-hydroxy propionyl（peak 22），cyclo-（Pro-Ser）（peak 6）. The IC 50 of 10 batches of C Ⅱ-3 samples to HepG 2 cells was 70.550-200.303 μg/mL. Among 25 common peaks ，the order of GRA correlation （r）of anti-hepatoma activity was peak 20＞23＞24＞15，all of r values were greater than 0.7；the order of variable importance projection （VIP）of OPLS analysis was peak 23＞18＞15＞24＞7＞14＞6＞ 2＞20，all of VIP values were greater than 1. The standard regression coefficients of peak 7，15，20，23，24 were all greater than 0；while the standard regression coefficients of peak 2，6，14，18 were all less than 0. Conjoint analysis shows that the order of anti-hepatoma activity was peak 20＞23＞24＞15. CONCLUSIONS：unknown chemical ingredients （peak 20， ），cyclo-（Tyr-Pro）（peak 24）and cyclo- （Gly-Phe）（peak 15） in C Ⅱ-3 may be main anti-hepatoma active components.

High-throughput screening of single Chinese plant extracts on specific anti-hepatoma drugs / 中国药理学与毒理学杂志

OBJECTIVE To evaluate the effect of single traditional Chinese medicine(TCM) herb extracts on hepatoma and normal fibroblast cells using high-throughput screening in order to obtain extracts with specific anti-hepatoma effect. METHODS 242 commonly used TCM herbs were extracted by petroleum ether,ethanol and water,respectively. The total number of TCM extracts was 554. The cyto?toxicity of samples was evaluated by MTT in human hepatoma cells Bel7402 and mice normal fibroblasts NIH3T3. RESULTS 7.4%of the total extracts had an inhibitory effect greater than 50%for Bel7402,but 14.8% for fibroblasts NIH3T3 cells. Extracts with an inhibitory effect above 50% on both Bel7402 and NIH3T3 cells accounted for 4.4%of the total extracts. Our results showed that the sample DF173 had preferable cytotoxicity effect on hepatoma carcinoma cells in a good dose-effect relationship. DF173 is an ethanol extract from Stephania tetrandra,which is a commonly used herb in TCM. The cytotoxic IC50 of DF173 against Bel7402 was 8.27 mg·L-1,and 19.48 mg·L-1 on NIH3T3. CONCLUSION The components of TCM herbs are highly complicated. The combination of tumor cells with normal fibroblast cells to evaluate the cytotoxicity effect during anti-tumor drug screening will contribute much to the discovery of TCM drugs with high anti-tumor efficiency and lower toxicity.

New molecular targets and novel agents for human hepatoma / 中国药理学通报

Current anti-hepatoma agents in clinical aplication have not been proved to be satisfactory. The major obstacles are low efficacy, toxicity, and drug resistance. Identifying new drug targets and discovering new agents accordingly with high efficacies and low toxicities have become the key part of the solution. Recent studies have shown that hyper-methylation of tumor suppressor genes, interaction between hepatocyte growth factor and its receptor, vascular endothelial growth factor and its receptor, as well as cyclooxygenase-2 might be potential targets for hepatomachemotherapy. Indeed, agents acting on these targets have shown to be effective. In addition, other agents such as As 2O3 have also shown their activities against hepatoma.

New molecular targets and novel agents for human hepatoma / 中国药理学通报

Current anti-hepatoma agents in clinical aplication have not been proved to be satisfactory. The major obstacles are low efficacy, toxicity, and drug resistance. Identifying new drug targets and discovering new agents accordin gly with high efficacies and low toxicities have become the key part of the solu tion. Recent studies have shown that hyper-methylation of tumor suppressor gene s, interaction between hepatocyte growth factor and its receptor, vascular endothelial growth factor and its receptor, as well as cyclooxygenase-2 might be potential targets for hepatomachemotherapy. Indeed, agents acting on these targets have shown to be effective. In addition, other agents such as As 2O 3 have also shown th eir activities against hepatoma.