Olanzapine, an atypical antipsychotic medication, has been associated with weight gain and metabolic toxicity, especially in long term usage. Carnosic acid (CA), a major constituent of rosemary extract, has been shown to improve metabolic abnormalities. In this experiment, the effect of CA on olanzapine-induced obesity and metabolic toxicity has been evaluated. Female Wistar rats were divided into six groups. (1) control; (2) olanzapine (5 mg/kg/day, IP); (3, 4 and 5) olanzapine (5 mg/kg/day, IP) plus CA (5, 10 and 20 mg/kg/day, gavage) and (6) CA (20 mg/kg/day, gavage). Bodyweight and food intake were measured during the study. After 14 days, mean systolic blood pressure (MSBP), glycemia, serum lipid profile, the serum concentration of leptin, insulin, AMPK, P-AMPK, and P-ACC liver protein levels were evaluated. The mean weight in the group received olanzapine increased by 4.8 g at the end of the study. The average food intake was increased by olanzapine. Olanzapine increased triglyceride, fasting blood glucose (FBG), and leptin levels. It increased MSBP and down-regulated P-AMPK/AMPK ratio and P-ACC protein levels. CA (three doses) decreased body weight gain and reduced average food intake at 10 and 20 mg/kg. CA especially at the highest dose decreased the changes in lipid profile, FBG, leptin level, and MSBP. P-AMPK/AMPK and P-ACC protein levels were increased by carnosic acid. In conclusion, the activation of AMPK by CA can be proposed as a key mechanism against olanzapine-induced metabolic toxicity where the activation of AMPK increases fat consumption and regulates glucose hemostasis in the liver.

奥氮平是一种非典型的抗精神病药物，与体重增加和代谢毒性有关，尤其是长期服用。鼠尾草酸（CA）是迷迭香提取物的主要成分，已显示可改善代谢异常。在该实验中，已经评估了CA对奥氮平诱导的肥胖症和代谢毒性的影响。将雌性Wistar大鼠分成六组。（1）控制；（2）奥氮平（5 mg / kg /天，IP）；（3、4和5）奥氮平（5 mg / kg /天，腹膜内）加上CA（5、10和20 mg / kg /天，管饲）和（6）CA（20 mg / kg /天，管饲）。在研究期间测量体重和食物摄入量。14天后，评估平均收缩压（MSBP），血糖，血清脂质谱，瘦素，胰岛素，AMPK，P-AMPK和P-ACC肝蛋白的血清浓度。在研究结束时，接受奥氮平治疗的组的平均体重增加了4.8 g。奥氮平增加了平均食物摄入量。奥氮平可增加甘油三酸酯，空腹血糖（FBG）和瘦素水平。它增加了MSBP，并下调了P-AMPK / AMPK比值和P-ACC蛋白水平。CA（三剂）可降低体重增加，并减少10和20 mg / kg的平均食物摄入量。尤其是在最高剂量下，CA降低了脂质分布，FBG，瘦素水平和MSBP的变化。肌酸使P-AMPK / AMPK和P-ACC蛋白水平升高。总之，CA激活AMPK可以被认为是对抗奥氮平诱导的代谢毒性的关键机制，其中AMPK的激活增加了脂肪的消耗并调节了肝脏的葡萄糖止血。研究结束时8克。奥氮平增加了平均食物摄入量。奥氮平可增加甘油三酸酯，空腹血糖（FBG）和瘦素水平。它增加了MSBP，并下调了P-AMPK / AMPK比值和P-ACC蛋白水平。CA（三剂）可降低体重增加，并减少10和20 mg / kg的平均食物摄入量。尤其是在最高剂量下，CA降低了脂质分布，FBG，瘦素水平和MSBP的变化。肌酸使P-AMPK / AMPK和P-ACC蛋白水平升高。总之，CA激活AMPK可以被认为是对抗奥氮平诱导的代谢毒性的关键机制，其中AMPK的激活增加了脂肪的消耗并调节了肝脏的葡萄糖止血。研究结束时8克。奥氮平增加了平均食物摄入量。奥氮平可增加甘油三酸酯，空腹血糖（FBG）和瘦素水平。它增加了MSBP，并下调了P-AMPK / AMPK比值和P-ACC蛋白水平。CA（三剂）可降低体重增加，并减少10和20 mg / kg的平均食物摄入量。尤其是在最高剂量下，CA降低了脂质分布，FBG，瘦素水平和MSBP的变化。肌酸使P-AMPK / AMPK和P-ACC蛋白水平升高。总之，CA激活AMPK可以被认为是对抗奥氮平诱导的代谢毒性的关键机制，其中AMPK的激活增加了脂肪的消耗并调节了肝脏的葡萄糖止血。空腹血糖（FBG）和瘦素水平。它增加了MSBP，并下调了P-AMPK / AMPK比值和P-ACC蛋白水平。CA（三剂）可降低体重增加，并减少10和20 mg / kg的平均食物摄入量。尤其是在最高剂量下，CA降低了脂质分布，FBG，瘦素水平和MSBP的变化。肌酸使P-AMPK / AMPK和P-ACC蛋白水平升高。总之，CA激活AMPK可以被认为是抗奥氮平诱导的代谢毒性的关键机制，其中AMPK的激活增加了脂肪的消耗并调节了肝脏的葡萄糖止血。空腹血糖（FBG）和瘦素水平。它增加了MSBP，并下调了P-AMPK / AMPK比值和P-ACC蛋白水平。CA（三剂）可降低体重增加，并减少10和20 mg / kg的平均食物摄入量。尤其是在最高剂量下，CA降低了脂质分布，FBG，瘦素水平和MSBP的变化。肌酸使P-AMPK / AMPK和P-ACC蛋白水平升高。总之，CA激活AMPK可以被认为是对抗奥氮平诱导的代谢毒性的关键机制，其中AMPK的激活增加了脂肪的消耗并调节了肝脏的葡萄糖止血。尤其是在最高剂量下，CA降低了脂质分布，FBG，瘦素水平和MSBP的变化。肌酸使P-AMPK / AMPK和P-ACC蛋白水平升高。总之，CA激活AMPK可以被认为是对抗奥氮平诱导的代谢毒性的关键机制，其中AMPK的激活增加了脂肪的消耗并调节了肝脏的葡萄糖止血。尤其是在最高剂量下，CA降低了脂质分布，FBG，瘦素水平和MSBP的变化。肌酸使P-AMPK / AMPK和P-ACC蛋白水平升高。总之，CA激活AMPK可以被认为是对抗奥氮平诱导的代谢毒性的关键机制，其中AMPK的激活增加了脂肪的消耗并调节了肝脏的葡萄糖止血。