OBJECTIVETo observe the effect of natural borneol on the permeability of blood tumor barrier (BTB) model and the expression and activation of mitogen-activated protein kinase (MAPKs) signal transduction pathway related protein kinase in vitro.

METHODSC6 rat glioma cells and human umbilical vein endothelial cells (HUVECs) were co-cultured to establish BTB model. Then 4 groups were set up, the blank control group, low, middle, and high dose borneol groups (25, 50, 100 µg/mL), 3 samples collected at 7 time points (0, 10, 30, 60, 120, 180, 240 min, respectively). Blank culture medium was exchanged in the blank control group while medication. Different doses of natural borneol were administered to the 3 borneol groups. Cells were collected at different time points. BTB permeability was determined using horseradish peroxidase (HRP). Expression levels of extracellular signal regulated protein kinase (ERK), phosphorylation extracellular signal regulated protein kinase (P-ERK), P38MAPK, phosphor-P38MAPK, c-Jun N-terminal kinase (JNK), and phosphorylation c-Jun N-terminal kinase (P-JNK) were detected using Western blot.

RESULTSCompared with the same group at min 0, the permeation rate obviously increased (P < 0.01) in the 3 borneol groups at the rest time points. P-ERK expression was elevated first, reached the peak at 30 min, and gradually recovered to the initial level (P > 0.05). Compared with the blank control group, HRP permeation rate increased from 10 min to 240 min (P < 0.01), and expression of P-ERK protein increased at 30 min and 60 min (P < 0.05) in the low dose borneol group; expression of P-JNK protein decreased in the 3 borneol groups at 180 min and 240 min (P < 0.05). Compared with the low dose borneol group, expression of P-ERK protein increased from 10 min to 180 min (P < 0.05), HRP permeation rate increased from 30 min to 180 min (P < 0.05), expression of P-JNK protein decreased at 180 and 240 min (P < 0.05) in the middle dose borneol group. Compared with the middle dose borneol group, HRP permeation rate increased from 10 min to 180 min (P < 0.05), expression of P-ERK protein increased from 10 min to 180 min (P < 0.05), expression of P-JNK protein increased at 180 min and decreased at 240 min (both P < 0.05) in the high dose borneol group.

CONCLUSIONNatural borneol arrived at the effect of regulating reversible BTB patency possibly through activating phosphorylation of ERK in MAPKs signal transduction pathway, and further reversibly down-regulating expression of associated proteins.