Jiawen Huang1, Xiangyu Wang2, Liyuan Xie3, Mingan Wu4, Wei Zhao5, Yongbin Zhang6, Qi Wang7, Limei Yao8, Weirong Li9. 1. Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou, 510405, China. Electronic address: 20171112689@stu.gzucm.edu.cn. 2. Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou, 510405, China. Electronic address: 20151112616@stu.gzucm.edu.cn. 3. Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou, 510405, China. Electronic address: 20181112655@stu.gzucm.edu.cn. 4. Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou, 510405, China. Electronic address: 20191112284@stu.gzucm.edu.cn. 5. Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou, 510405, China. Electronic address: athenaty@gzucm.edu.cn. 6. Laboratory Animal Center, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou, 510405, China. Electronic address: yongbinzhang@gzucm.edu.cn. 7. Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou, 510405, China. Electronic address: wangqi@gzucm.edu.cn. 8. School of Traditional Chinese Medicine Healthcare, Guangdong Food and Drug Vocational College, 321 Longdong North Road, Tianhe District, Guangzhou, 510520, China. 9. Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou, 510405, China. Electronic address: liwr@gzucm.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine formula Danggui-Shaoyao-San (DSS) has been reported to show therapeutic effect on alleviating the symptoms of Alzheimer's disease (AD). AIM OF THE STUDY: The present study aims to investigate the relation between DSS treatment of AD and DHA metabolism and evaluates its neuroprotective effect on cognitive in APP/PS1 mice. MATERIAL AND METHODS: DSS (1.6, 3.2, 6.4 g/kg/day) or Aricept (3 mg/kg/day) was orally administered (i.g.) to APP/PS1 mice, and saline was orally administered to Wild-type (WT) male mice as control group. Then, the Morris water maze (MWM) test, Y-maze spontaneous alternation test, open filed test and fear conditioning test were conducted for evaluation of learning and memory abilities. The DHA content was assessed by HPLC-MS/MS. Physiological indices were determined, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), ROS level, activity of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), PEG2, TXB2 and LTB4. The expressions of COX-1, COX-2, cPLA2, iPLA2, 15-LOX, and were assessed by Western blot. RESULTS: APP/PS1 mice showed serious cognitive impairment in behavioral tests. However, treatment of DSS extract significantly ameliorated the cognitive deficits of APP/PS1 mice. Biochemical measurements showed the increases in TG, TC, LDL-c and the decrease in HDL-c in APP/PS1 mice compared with WT mice, and DSS extract significantly retarded these changes. Low content of DHA, low expression of iPLA2 and 15-LOX were observed both in hippocampus and cortex of APP/PS1 mice, while DSS extract significantly restored these changes. Additionally, the abnormal activity of SOD and ROS level, the decreased levels of MDA and GSH were observed in APP/PS1 mice, while DSS extract prominently lessened these changes. Moreover, DSS extract decreased the level of PEG2, TXB2 and LTB4 and also attenuated the expression of cPLA2, COX-1 and COX-2 in hippocampus as well as cortex of APP/PS1 mice. CONCLUSIONS: Based on these results, we suggest that DSS play a positive effective role in increasing DHA content by up-regulating iPLA2 and 15-LOX, resulting in ameliorating oxidative stress and inflammation and finally ameliorating cognition deficits in APP/PS1 mice.
ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine formula Danggui-Shaoyao-San (DSS) has been reported to show therapeutic effect on alleviating the symptoms of Alzheimer's disease (AD). AIM OF THE STUDY: The present study aims to investigate the relation between DSS treatment of AD and DHA metabolism and evaluates its neuroprotective effect on cognitive in APP/PS1mice. MATERIAL AND METHODS: DSS (1.6, 3.2, 6.4 g/kg/day) or Aricept (3 mg/kg/day) was orally administered (i.g.) to APP/PS1mice, and saline was orally administered to Wild-type (WT) male mice as control group. Then, the Morris water maze (MWM) test, Y-maze spontaneous alternation test, open filed test and fear conditioning test were conducted for evaluation of learning and memory abilities. The DHA content was assessed by HPLC-MS/MS. Physiological indices were determined, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), ROS level, activity of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), PEG2, TXB2 and LTB4. The expressions of COX-1, COX-2, cPLA2, iPLA2, 15-LOX, and were assessed by Western blot. RESULTS:APP/PS1mice showed serious cognitive impairment in behavioral tests. However, treatment of DSS extract significantly ameliorated the cognitive deficits of APP/PS1mice. Biochemical measurements showed the increases in TG, TC, LDL-c and the decrease in HDL-c in APP/PS1mice compared with WT mice, and DSS extract significantly retarded these changes. Low content of DHA, low expression of iPLA2 and 15-LOX were observed both in hippocampus and cortex of APP/PS1mice, while DSS extract significantly restored these changes. Additionally, the abnormal activity of SOD and ROS level, the decreased levels of MDA and GSH were observed in APP/PS1mice, while DSS extract prominently lessened these changes. Moreover, DSS extract decreased the level of PEG2, TXB2 and LTB4 and also attenuated the expression of cPLA2, COX-1 and COX-2 in hippocampus as well as cortex of APP/PS1mice. CONCLUSIONS: Based on these results, we suggest that DSS play a positive effective role in increasing DHA content by up-regulating iPLA2 and 15-LOX, resulting in ameliorating oxidative stress and inflammation and finally ameliorating cognition deficits in APP/PS1mice.
Authors: Jinfei Yang; Chenrui Li; Yan Liu; Yachun Han; Hao Zhao; Shilu Luo; Chanyue Zhao; Na Jiang; Ming Yang; Lin Sun Journal: Front Pharmacol Date: 2022-08-19 Impact factor: 5.988