Original Article

Effects of various principles from Chinese herbal medicine on rhodamine123 accumulation in brain capillary endothelial cells.

Authors: Ling HE, Guo-Qing LIU


AIM: To search for novel effective P-glycoprotein (P-gp) reversal agents in the
blood-brain barrier (BBB).
METHODS: Using rhodamine123 (Rh123) to examine the functional activity of P-gp in
cultured bovine brain capillary endothelial cells (BCEC) and screen various
principles on P-gp modulation in BBB.
RESULTS: All of tested compounds (1-10 micromol/L) increased the intracellular
accumulation of Rh123 in a concentration-dependent manner. The rank order of
these agents in increasing Rh123 accumulation in BCEC was: cyclosporin A (CsA) >
tetrandrine (Tet) > vincrinstine (VCR) approximate, equals flunarizine (Flu) >
dl-tetrahydropalmatine (dl-THP) > dauricine (DRC) > azithromycin (Azi) >
verapamil (Ver) approximate, equals berbamine (BBM) > daurisoline (DRS) >
berberine (BBR) approximate, equals doxorubicin (Dox) > l-tetrahydropalmatine
(l-THP) > tetramethylpyrazine (TMP). These agents at concentration of 10
micromol/L increased Rh123 accumulation by 346 %, 203 %, 136 %, 129 %, 115 %, 103
%, 92 %, 87 %, 81 %, 75 %, 67 %, 67 %, 63 %, and 54 %, respectively. The effects
of CsA, Tet, Ver, Flu, Azi, and dl-THP on cellular accumulation of Rh123 in BCEC
were reversible. When CsA, Tet, Ver, Flu, Azi, or dl-THP-pretreated BCEC were
examined at 48, 36, 24, 36, 36, or 12 h, respectively, after removing the agent,
the amount of cellular Rh123 accumulation in BCEC returned to control levels (no
drug treatment).
CONCLUSION: The functional activity of P-gp on the blood-brain barrier could be
modulated by various MDR-reversing agents and some principles with low toxicity
extracted from medicinal herbs, such as some isoquinoline alkaloids without
permanent modifying effects on the intrinsic level of P-gp function.

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