Jolkinolide A

Jolkinolide A and Jolkinolide B Inhibit Proliferation of A549 Cells and Activity of Human Umbilical Vein Endothelial Cells.[Pubmed: 28087861]

Medical Science Monitor, 2017, 23:223-237.

Jolkinolide A (JA) and Jolkinolide B (JB) are diterpenoids extracted from the roots of Euphorbia fischeriana Steud and have been shown to have anti-tumor activity. However, their effects on the ability of tumor cells to invade blood vessels and metastasize remain largely unknown. Investigations into the effects of JA and JB on the angiogenesis of tumor tissues may facilitate the identification of new natural drugs with anti-tumor growth and metastasis activities.
METHODS AND RESULTS:
We used different concentrations of JA and JB (20 μg/ml, 40 μg/ml, 60 μg/ml, 80 μg/ml, and 100 μg/ml) to stimulate A549 cells and then studied the effects on the growth and metastasis of lung cancers. In addition, we used conditional media from A549 cells (A549-CM) stimulated by either JA or JB in different concentrations to culture human umbilical vein endothelial cells (HUVECs). We found that both JA and JB significantly inhibited the Akt-STAT3-mTOR signaling pathway and reduced the expression of VEGF in A549 cells, but JB exhibited more significant inhibitory effects than JA. The JB-stimulated A549 cell conditional media had a greater inhibitory effect on the proliferation and migration of HUVECs than did the conditional media of JA-stimulated A549 cells. This effect gradually increased with increasing concentrations of either type of Jolkinolide.
CONCLUSIONS:
Our results suggest that JA and JB inhibited VEGF expression in A549 cells through the inhibition of the Akt-STAT3-mTOR signaling pathway, and directly inhibited the proliferation and migration of HUVECs. These findings are of great significance for the development of new plant-derived chemotherapy agents for the treatment of cancer.

Cytotoxic diterpenoids from the roots of Euphorbia ebracteolata.[Pubmed: 15856412]

Planta Medica, 2005, 71(4):349-354.

METHODS AND RESULTS:
Three new diterpenoids, yuexiandajisu D (1), E (2) and F were isolated from the roots of Euphorbia ebracteolata, along with eight known diterpenoids, jolkinolide B (4), Jolkinolide A, ent-11alpha-hydroxyabieta-8(14),13(15)-dien-16,12alpha-olide (6), ent-(13S)-hydroxyatis-16-ene-3,14-dione, ent-3beta,(13S)-dihydroxyatis-16-en-14-one, ent-3-oxokaurane-16alpha,17-diol, ent-16alpha,17-dihydroxyatisan-3-one and ent-atisane-3beta,16alpha,17-triol. The structures of all compounds were deduced using spectroscopic methods and confirmed for 1 and 2 by single-crystal X-ray diffraction. A biogenetic pathway for the formation of 1 and 2 is proposed briefly. Cytotoxic activities were evaluated against ANA-1, B 16 and Jurkat tumor cells.
CONCLUSIONS:
Jolkinolide B (4) displayed modest activity on ANA-1, B 16 and Jurkat tumor cells with IC50 values 4.46 x 10(-2), 4.48 x 10(-2), 6.47 x 10(-2) microM, and ent-11alpha-hydroxyabieta-8(14),13(15)-dien-16,12alpha-olide (6) showed significant activity against ANA-1 and Jurkat cells with IC50 values 7.12 x 10(-3) and 1.79 x 10(-2) microM. Compound 1 was found to be slightly active against ANA-1 cells with an IC50 value 2.88 x 10(-1)microM. Structure-activity relationships of isolated compounds are also discussed.

Chinese Journal of Pharmaceutical Analysis (2006) 26(9) 1204-1206.

HPLC determination of jolkinolide A and jolkinolide B in Chinese herb medicine＂ Lang- du＂[Reference: WebLink]

To establish a method for the determination of two diterpenoide lactones, Jolkinolide A and jolkinolide B in Chinese herbal medicine ＂Lang -du＂ by HPLC.
METHODS AND RESULTS:
： C18 column（4.6 mm *250 mm,5 mum） was used with acetonitrile -water（75：25 ）as the mobile phase. The flow rate was 1.0 mL· min^-1 ,and the detection wavelength was 250 nm. By using the established HPLC method, nine samples of ＂Lang - du＂ were analyzed to determine the contents of Jolkinolide A and B. It was showed that the contents of Jolkinolide A and B ranged from 0. 007% to 0. 043% and 0. 012% to 0. 204% , respectively. Among the samples, the two diterpenoids were found in most of the samples of Euphorbia fischeriana and E. ebracteolata, but Stellera chamaejasme and Alocasia macrorrhiza contained neither Jolkinolide A nor jolkinolide B.
CONCLUSIONS:
A simple, effective and feasible HPLC method with good accuracy, precision and reproducibility to determine the contents of two diterpenoids in＂ Lang - du＂ was established which could be applied for the quality control of this herb.