The effects of berberine on glycated brain damages induced by D-galactose in model rats were observed Randomly grouping paralleled control study. Setting: Department of Ophthalmol., Xiamen Traditional Chinese Medicine Hospital. The experiment was conducted in the Department of Pharmacol., Pharmacy College of Jinan University from June to Oct. 2005. Ninety SD rats (6 wk old) were selected and divided into 6 groups: control group, model group, hydrochloride aminoguanidine group and high (300 mg/kg), middle (150 mg/kg) and low (75 mg/kg) doses berberine groups with 15 rats in each group. The glycated models were established by i.p. injection of D-galactose. The main drugs: berberine was from Guangzhou Wanji Drugs Limited Company; D-galactose was from Shanghai Yuanju Bioscience Technol. Limited Company. The rats in the control group were i.p. injected the normal saline for 8 wk; rats in other groups were injected 5% D-galactose (150 mg/kg) for 8 wk. From the 3rd week, the hydrochloride aminoguanidine group was infused hydrochloride aminoganidine (150 mg/kg); the three doses berberine groups were given corresponding doses berberine; the control group and model group were given distilled water for 6 wk with the volume of 10 mL/kg. At the end of the 8th week, the erythrocyte aldose reductase activity was determined by coomassie brilliant blue method; the level of plasma glycoHb was measured by thiobarbituric acid chromatometry, and the fructosamine in serum was measured by nitroblue tetrazolium colorimetry. The quantity of advanced glycation end products (AGEs) in serum, and AGEs, malondialdehyde (MDA), and activity of superoxide dismutase (SOD) in brain tissue and calcium ion in neurons were also determined Moreover, the changes of mitochondria in brain hippocampus clils were observed under electronic microscope. Main outcome measures: the AGEs, plasma glycoHb, serum fructosamine and aldose reductase activity; AGEs in brain tissues; calcium level in brain; MDA content and SOD activity in brain tissues; changes of mitochondria in hippocampus neurons. All 90 animals were involved in the result anal. After the rats were treated with D-galactose for 8 wk, the aldose reductase activity in red blood cells and the content of fructosamine in serum, glycoHb, AGEs in the model group were significantly higher than those in the normal control group (P<0.01). After treated by high and middle doses berberine for 6 wk, the activity of aldose reductase and content of fructosamine in serum (absorbance value of Hb every 10 g), glycoHb, and AGEs were obviously lower than those in the control group [(1.07±0.39), (1.22±0.47), (1.76±0.30) nkat/g, t=5.052, 5.484, P<0.01; (0.740±0.142), (0.862±0.131), (0.958±0.083) mmol/L, t=7.829, P<0.01, t=2.404, P<0.05; 58.434±12.135, 64.614±13.418, 83.747±7.990, t=4.922, 6.748, P<0.01; (3.104±0.814), (2.937±0.514), (4.156±0.860) U/mg, t=4.104, 3.440, P<0.05]. The aldose reductase activity of the low dose berberine group was lower than that of the model group (P<0.05), which had no obvious effect on glycated products. AGEs in brain tissues: the contents in the hydrochloride aminoguanidine group, high and middle doses berberine groups were lower than those in the model group [(10.52±1.22), (10.95±1.75), (11.95±2.27), (14.26±3.51) U/mg, t=-3.892, -3.263, P<0.01, t=-2.139, P<0.05], and the low dose berberine had little effect (P>0.05). Calcium level in neurons: the levels in the hydrochloride aminoguanidine group, and high dose berberine groups were lower than those in the model group [(271.52±32.71), (293.84±31.58), (337.15±58.49) nmol/L, t=-3.421, P<0.01, t=-2.275, P<0.05], and the low dose berberine group had no obvious effect (P>0.05). MDA content and SOD activity in brain tissues: MDA contents in the hydrochloride aminoguanidine group, high and middle doses berberine groups were lower than those in the model group, and the SOD activity was markedly higher than that in the model group [(2.09±0.16), (2.12±0.22), (2.41±0.12), (2.54±0.21) μmol/g, t=6.601, 5.348, P<0.01, t=2.082, P<0.05; (8.79±1.09), (8.80±1.52), (7.90±1.48), (6.48±1.34) mkat/g, t=4.571, 4.254, P<0.01, t=2.226, P<0.05]. Mitochondria structure in brain hippocampus cells: under the electronic microscope, mitochondria in brain hippocampus cells of the model group appeared obvious swelling with broken crests and disorganized structure, even obvious big vacuoles were observed In the hydrochloride aminoguanidine, and high and middle doses berberine groups, no obvious swelling was observed with vacuoles only in a few mitochondria. Nevertheless, obvious swelling appeared in mitochondria of low dose berberine group with broken crest and disorganized structure, and vacuoles were observed D-galactose-induced damage in mitochondria may be related to AGEs formation in brain tissue, maladjustment of calcium ions in neurons and oxidative stress in rat models. Berberine can inhibit glycation induced by D-galactose and protect rat brain tissues from glycated damage.