Anti-Malignant Ascites Effect of Total Diterpenoids from Euphorbiae Ebracteolatae Radix Is Attributable to Alterations of Aquaporins via Inhibiting PKC Activity in the Kidney.
This study evaluated the anti-ascites effect of total diterpenoids extracted from Euphorbiae Ebracteolatae Radix (TDEE) on malignant ascitic mice and elucidated its underlying mechanism. TDEE was extracted by dichloromethane and subjected to column chromatography. The purity of six diterpenoids isolated from TDEE was determined to be 77.18% by HPLC. TDEE (3 and 0.6 g raw herbs/kg, p.o.) reduced ascites and increased urine output. Meanwhile, analysis of tumor cell viability, cycle and apoptosis indicated that TDEE had no antitumor activity. In addition, the expression levels of aquaporins (AQPs) and the membrane translocation levels of protein kinase C (PKC) α and PKCβ in kidney and cells were measured. TDEE reduced the levels of AQP1-4, and inhibited PKCβ expression in membrane fraction. Four main diterpenoids, except compound 2, reduced AQP1 level in human kidney-2 cells. Compounds 4 and 5 inhibited AQP2-4 expression in murine inner medullary collecting duct cells. The diterpenoid-induced inhibition of AQP1-4 expression was blocked by phorbol-12-myristate-13-acetate (PMA; agonist of PKC). The diterpenoids from TDEE are the main anti-ascites components. The anti-ascites effect of diterpenoids may be associated with alterations in AQPs in the kidneys to promote diuresis. The inhibition of AQP1-4 expression by TDEE is related to the inhibition of PKCβ activation.
['Zhang|Yuanbin|Y|0000-0001-5137-9661', 'Liu|Dongfang|D|0000-0003-3010-1876', 'Xue|Fan|F|0000-0001-5766-8501', 'Yu|Hongli|H|', 'Wu|Hao|H|', 'Cui|Xiaobing|X|', 'Zhang|Xingde|X|', 'Wang|Hepeng|H|0000-0001-6044-6619']
D000818:Animals D017209:Apoptosis D020346:Aquaporins D001201:Ascites D006528:Carcinoma, Hepatocellular D049109:Cell Proliferation D004224:Diterpenes D028481:Euphorbia D005786:Gene Expression Regulation D006801:Humans D007668:Kidney D008113:Liver Neoplasms D008297:Male D051379:Mice D008813:Mice, Inbred ICR D011493:Protein Kinase C D014407:Tumor Cells, Cultured D023041:Xenograft Model Antitumor Assays
diuresis Euphorbia ebracteolata Hayata PKC inhibitor bioactive components kidney cells terpenoids