Punarnavine, an alkaloid from Boerhaavia diffusa exhibits anti-angiogenic activity via downregulation of VEGF in vitro and in vivo.
Punarnavine, a quinolizidine alkaloid isolated from Boerhaavia diffusa is known to possess analgesic, anti-inflammatory, hepato-protective, immunomodulatory and anti-proliferative properties. However, its roles in tumor angiogenesis and the involved molecular mechanism are still unknown. Therefore, we examined its anti-angiogenic effects and mechanisms in vitro and in vivo. We examined the effect of punarnavine on VEGF-A expression by RT-PCR, Western blotting and ELISA. In vivo antiangiogenic activity was determined using sponge implant angiogenesis assay and antitumor activity was evaluated against Ehrlich ascites carcinoma tumor. Punarnavine significantly inhibited endothelial cell migration and invasion and capillary structure formation of HUVECs. Punarnavine significantly at 50 μM inhibited MMP-2 and MMP-9 expression in HUVECs in vitro. Punarnavine inhibited neovascularization in sponge implant assay. Punarnavine (15 mg/kg bw/d) treatment showed dose-dependent decrease in the ascitic fluid volume by 60.94% and tumor volume by 86.40% in Ehrlich ascites model. Reduction in peritoneal angiogenesis with punarnavine treatment suggests the anti-angiogenic activity of punarnavine. The present study sheds light on the potent anti-angiogenic of the punarnavine and can be extended further to develop therapeutic protocols for treatment of cancer.
Camel Biomedical Research Unit, College of Pharmacy and Medicine, King Saud University, Riyadh, Saudi Arabia. Electronic address: saritasaraswati@gmail.com.
Sarita
S
Saraswati
Abdulqader A
AA
Alhaider
S S
SS
Agrawal
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic; D039281:Nyctaginaceae / Q000737:chemistry*; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism*
D000470:Alkaloids; D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D042461:Vascular Endothelial Growth Factor A; C526689:punarnavine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
Angiogenesis; Ehrlich ascites carcinoma; MMP-2; MMP-9; VEGF