Effect of tetramethylpyrazine on learning memory ability and antioxidative status in mice

• Main Authors: Chien-Cheng Liang, 梁健成
• Other Authors: Keh-Feng Huang
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/c3zc4t

博士 === 靜宜大學 === 應用化學研究所 === 97 === Tetramethylpyrazine (TMP), an active ingredient originally isolated from Ligusticum wallichii Franchat. in 1957, has been widely used in China for the treatment of cardiovascular and cerebrovascular disease. It is known to pass blood-brain barrier and increase the cerebral blood flow. The purpose of this study were to examine the effect of TMP on learning and memory ability, antioxidative status in mice. On the 1st experiment, the six healthy three-month-old male and female SAMR1 mice were undertaken the acute oral LD50 of TMP. The LD50 of TMP was 1329 mg/kg from the acute oral toxicity study. On the 2nd experiment, the SAMR1 mice were divided into the pathological control, the blank control, the TMP-treated group (400 mg/kg, p.o.) and the EGb761-treated group (200 mg/kg, p.o.), once a day for 2 weeks. The scopolamine (1.0 mg/kg, i.p.) was combined with the TMP-treated group or EGb761 treated group at 30 minutes before the training trial on the 14th day. The step-through latency (STL) time in the light compartment was recorded at 24 hrs after the training trial. The results indicated that both TMP-treated group and the EGb761-treated group could attenuate the scopolamine-induced amnesia SAMR1 mice on learning and memory. On the 3rd experiment, the ICR mice were treated with TMP (80 mg/kg, 400 mg/kg, p.o.) once a day for 2 weeks. The training trial was taken place at 1hr after the administration of TMP on the 14th day. The combination with scopolamine (1.0 mg/kg, i.p.) at 0.5 hr before the training trial on the 14th day. The pathological control group was treated with scopolamine (1.0 mg/kg, i.p.) only, and the blank control group was treated with saline. Physostigmine or neostigmine (acetylcholinesterase inhibitor, 0.02 mg/kg, i.p.) was administrated at 20 minutes before the training trial. N-methylscopolamine bromide (peripheral acetylcholinesterase inhibitor, 0.5 mg/kg, i.p.) was administrated at 30 minutes before the training trial. The step-through latency (STL) time in the light compartment was recorded at 24 hrs after the training trial. The results showed that TMP (400 mg/kg, p.o.) could attenuate the scopolamine-induced amnesia ICR mice on learning and memory. Besides, its mechanism was not the acetylcholinesterase inhibitor pathway. On the 4th experiment, seven-month-old male SAMP8 were divided into the control, 10 mg/kg, 20 mg/kg, 40 mg/kg of TMP, EGb761 (100 mg/kg, p.o.) and EGb761 (100 mg/kg, p.o.) combination with TMP (40 mg/kg, i.p.), while SAMR1 mice was used to be the control. Seven-month-old female SAMP8 were divided into the control, 10 mg/kg, 20 mg/kg, 40 mg/kg of TMP, while SAMR1 mice was used to be the control.The administration of TMP was once a day for one week. Aging score, open field activity test, single-trial passive avoidance and active shuttle avoidance test were performed in the experiment. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (GPx), glutathione reductase (GR), cholinesterase (ChE), malondialdehyde (MDA) in liver, heart or brain tissues were analyzed after sacrifice. Explored the effect of TMP on beta-amyloid in brain section. The results indicated that TMP could ameliorate SAMP8 mice on learning and memory and promote antioxidative status including the SOD activity in brain and heart, GPx and CAT activities in liver. The MDA concentrations in liver, heart and brain were significantly lower than the control group. After the immunostaining and image analysis of brain beta-amyloid deposits, we compared the brain section-treated TMP with the control brain section and found that in the brain of TMP-treated SAMP8 mice could significantly reduce the beta-amyloid deposits.