Relation of openness of blood-brain barrier by borneol with histamine and 5-hydroxytryptamine

Weirong LI; Limei YAO; Suiqing MI; Ningsheng WANG

ABSTRACT

BACKGROUND:

Borneol can open blood-brain barrier (BBB) but the mechanisms are not very clear. Histamine and 5-hydroxtryptamine can take part in regulation of permeability of BBB. There is not report on the rela tion between the effect of opening BBB of borneol and the regulation of permeability of BBB of histamine (HA)/5-hydroxytryptamine (5-HT).

OBJECTIVE:

To study the relation between the effect of opening BBB of bornool and the regulation of permeability of BBB of histamine (HA)/5-hydroxytryptamine (5-HT).

DESIGN:

A completely randomized and controlled study.

SETTING:

Clinical Pharmacological Institute of University of Traditional Chinese Medicine of Guangzhou.MATERIALS The experiment was carried out at the Clinical Pharmacological Institute of University of Traditional Chinese Medicine of Guangzhou from September 2003 to February 2004. Totally 104 healthy male SD rats, weighting 230-27.0 g, supplied by Guangdong Medical Experimental Animal Center, were selected.

METHODS:

The rats were randomly divided into 13 groups pre-medicine group and post-medicine group (high, moderate and low dosage group and 5, 20, 45 and 60 minutes group in each dosage group) with 8 in each group. Borneol was mixed as 10% millet oil suspension. Rats were fasted before experiment for whole night, and medicine was perfused on the next morning with the high, moderate and low dosage of 0.15, 0.12 and 0.09 g/kg respectively. Hypothalami of rats was selected at various time points to make biological samples. Contents of HA and 5-HT were assayed with HPLC system electrochemical detector.MAIN OUTCOME

MEASURES:

Changes of level of histamin (HA) and 5-HT in hypothalamus of rats after administration of borneol.

RESULTS:

Data of totally 104 rats was entered the final analysis. ① Contents of HA and 5-HT in hypothalami were 2.07±0.54 μg/g and 1.45±0.14 μg/g respectively. ② The level of HA in hypothalamus of rats after different doses of borneol were higher than that of before administration. Comparing the level of HA in 20 minutes after moderate dose with before administration, the level of HA in 20 minutes was increased significantly [(3.36±0.21) μg/g, P < 0.01], the others of moderate dose, the 45 minutes after high dose, the 20 and 45 minutes after low dose were also increased significantly than before administration (P < 0.05). ③ After administration of different doses of borneol, the level of 5-HT after high dose were higher than that of before administration [5, 20, 45 and 60 minutes after medicine (1.90±0.32), (3.28 ±0.25), (2.66±0.46), (2.80±0.34) μg/g, respectively; (P < 0.05 or P < 0.01)]; the level of 5-HT after 5, 20 and 45 minutes of moderate and low dose were increased significantly too (P < 0.05 or P < 0.01).

CONCLUSION:

Borneol could open BBB by increasing levels of HA and 5-HT in hypothalamus of rats.Borneol mediates opening of BBB by increasing levels of HA and5-HT in rats.