Won-Yung Lee1, Soon-Woo Jang1, Jin-Seok Lee2, Yun-Hee Kim3, Hyeong-Geug Kim2, Jong-Min Han2, Dong-Woon Kim4, Min-Hee Yi4, Min-Kyung Choi2, Chang-Gue Son5. 1. Korean Medical College of Daejeon University, 22-5 Yongwoon-dong, Dong-gu, Daejeon 301-724, Republic of Korea. 2. Liver and Immunology Research Center, Korean Medical College of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, Republic of Korea. 3. KM-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, 461-24, Jeonmin-dong, Yuseong-gu, Deajeon 350-811, Republic of Korea. 4. Department of Anatomy, Chungnam National University, Daejeon 301-040, Republic of Korea. 5. Liver and Immunology Research Center, Korean Medical College of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon 301-724, Republic of Korea. Electronic address: ckson@dju.ac.kr.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Uwhangchungsimwon (UCW) is a representative traditional herbal medicine for central nervous system disorders in East Asia countries over thousand years. To evaluate the pharmacological effects of UCW against oxidative brain injury in a chronic restraint stress mice model. METHODS AND MATERIALS: C57BL/6 male mice underwent daily oral administration of distilled water, UCW or ascorbic acid 1h before induction of restraint stress (5h of immobilization daily for 14 days). Nitric oxide (NO), total reactive oxygen species (ROS) levels, malondialdehyde, protein carbonyl contents, and activities of antioxidant enzymes, and concentrations of corticosterone, adrenaline, noradrenaline, and dopamine, were measured in brain tissues or sera. RESULTS: Restraint stress notably increased NO and ROS levels, malondialdehyde and protein carbonyl contents in brain tissues, but decreased activities of catalase, glutathione reductase and glutathione peroxidase. These alterations were significantly ameliorated by UCW. UCW significantly attenuated the elevated serum concentrations of corticosterone, adrenaline and noradrenaline. UCW also significantly normalized the gene expressions in brain tissues altered by restraint stress; up-regulation of phenylethanolamine N-methyltransferase (PNMT) and N-methyl-d-aspartate type 1 receptor (NMDAR1), and down-regulation of gamma-Aminobutyric acid type A receptor (GABAAR), glutamate decarboxylase 1 (GAD 67), and glutamate decarboxylase 2 (GAD 65), respectively. Moreover, UCW considerably restored neurogenesis in the hippocampal regions which was disturbed by chronic restraint stress. CONCLUSIONS: These results evidenced that UCW has pharmacological properties for brain protection and neurogenesis in status of stress-associated oxidative damage, and the underlying mechanisms involve the regulation of HPA axis in stress responses.
ETHNOPHARMACOLOGICAL RELEVANCE: Uwhangchungsimwon (UCW) is a representative traditional herbal medicine for central nervous system disorders in East Asia countries over thousand years. To evaluate the pharmacological effects of UCW against oxidative brain injury in a chronic restraint stress mice model. METHODS AND MATERIALS: C57BL/6 male mice underwent daily oral administration of distilled water, UCW or ascorbic acid 1h before induction of restraint stress (5h of immobilization daily for 14 days). Nitric oxide (NO), total reactive oxygen species (ROS) levels, malondialdehyde, protein carbonyl contents, and activities of antioxidant enzymes, and concentrations of corticosterone, adrenaline, noradrenaline, and dopamine, were measured in brain tissues or sera. RESULTS: Restraint stress notably increased NO and ROS levels, malondialdehyde and protein carbonyl contents in brain tissues, but decreased activities of catalase, glutathione reductase and glutathione peroxidase. These alterations were significantly ameliorated by UCW. UCW significantly attenuated the elevated serum concentrations of corticosterone, adrenaline and noradrenaline. UCW also significantly normalized the gene expressions in brain tissues altered by restraint stress; up-regulation of phenylethanolamine N-methyltransferase (PNMT) and N-methyl-d-aspartate type 1 receptor (NMDAR1), and down-regulation of gamma-Aminobutyric acid type A receptor (GABAAR), glutamate decarboxylase 1 (GAD 67), and glutamate decarboxylase 2 (GAD 65), respectively. Moreover, UCW considerably restored neurogenesis in the hippocampal regions which was disturbed by chronic restraint stress. CONCLUSIONS: These results evidenced that UCW has pharmacological properties for brain protection and neurogenesis in status of stress-associated oxidative damage, and the underlying mechanisms involve the regulation of HPA axis in stress responses.