Pretreatment with Ginseng Fruit Saponins Affects Serotonin Expression in an Experimental Comorbidity Model of Myocardial Infarction and Depression
Liu Mei-Yan1,*, Ren Yan-Ping2, Zhang Li-Jun3, Ding Jamie Y.4
1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China 2Department of Geriatric-Cardiovascular Diseases, the First Hospital of Xi’an Jiaotong University, Xi'an, Shaanxi 710061, China 3Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100029, China 4Wayne State University School of Medicine, Detroit, Michigan 48201, USA
We previously demonstrated that serotonin (5-HT) and 5-HT2A receptor (5-HT2AR) levels in platelets were up- or down-regulated after myocardial infarction (MI) associated with depression. In this study, we further evaluated the effects of pretreatment with ginseng fruit saponins (GFS) on the expression of 5-HT and 5-HT2AR in MI with or without depression. Eighty Sprague-Dawley (SD) rats were treated with saline and GFS (n=40 per group). The animals were then randomly divided into four subgroups: sham, MI, depression, and MI + depression (n=10 per subgroup). Protein levels of 5-HT and 5-HT2AR in the serum, platelets and brain tissues were determined with ELISA. The results demonstrated that serum 5-HT levels was significantly increased by GFS pretreatment in all subgroups (except the sham subgroup) when compared with saline-treated counterparts (p<0.01). In platelets, GFS pretreatment significantly increased 5-HT levels in all subgroups when compared with their respective saline-treated counterparts (p<0.01). Brain 5-HT levels also declined with GFS pretreatment in the MI-only and depression-only subgroups (p<0.05 vs. saline pretreatment). With respect to 5-HT2AR levels, platelet 5-HT2AR was decreased in GFS pretreated MI, depression and MI + depression subgroups (p<0.01 vs. saline pretreatment). Similarly, brain 5-HT2AR levels decreased in all four subgroups pretreated with GFS (p<0.01 vs. saline pretreatment). We conclude that GFS plays a clear role in modulating 5-HT and 5-HT2AR expressions after MI and depression. Although the effects of GFS on brain 5-HT remain to be elucidated, its therapeutic potential for comorbidities of acute cardiovascular events and depression appears to hold much promise.
Liu Mei-Yan,Ren Yan-Ping,Zhang Li-Jun, et al. Pretreatment with Ginseng Fruit Saponins Affects Serotonin Expression in an Experimental Comorbidity Model of Myocardial Infarction and Depression[J]. Aging and disease,
2016, 7(6): 680-686.
Figure 1. Animals were first randomly divided into two groups: saline and GFS (n=40 per group). The rats were pretreated with GFS (20 mg/kg) or with an equivalent volume of saline once daily via oral gavage for a period of 4 weeks. Rats were then equally divided randomly into four subgroups (n=10 per subgroup) and the appropriate surgeries and tests were performed: Sham, MI, Depression, MI + Depression. After 3 days, animals were sacrificed and 5-HT levels measured in the serum, platelets, and brain tissues using an ELISA kit. Data are presented as mean ± SD. A) Quantification of 5-HT level in serum. As compared with saline-treated animals, GFS pretreatment increased 5-HT levels in the sham group although it did not achieve significance (p=0.184). However, there was a significant increase in 5-HT levels in the GFS-pretreated MI, depression, and MI + depression subgroups. *p<0.01, n=10 per subgroup. B) Quantification of 5-HT level in platelets. GFS pretreatment significantly increased 5-HT levels when compared with saline pretreatment for all subgroups: sham, MI, depression, and MI + depression. *p<0.01, n=10 per subgroup. C) Quantification of 5-HT level in the brain. With GFS pretreatment, 5-HT levels declined for all four animal subgroups. The declines for the MI-only (*p=0.025) and depression-only (*p=0.044) subgroups were significant, while the decreases did not achieve significance for the sham (p=0.060) and MI + depression subgroups (p=0.663).
Figure 2. 5- HT2AR levels were measured in the platelets and brain tissues using an ELISA kit. Data are presented as mean ± SD. A) Platelet 5-HT2AR quantification. There was no significant difference in 5-HT2AR levels between the saline- and GFS-pretreated groups in the sham subgroup (p=0.838). GFS pretreatment induced significant decreases in the MI, depression and MI + depression subgroups. *p<0.01 vs. saline, n=10 per subgroup. B) Brain 5-HT2AR quantification. All four subgroups demonstrated significant decreases in 5-HT2AR levels after GFS pretreatment. *p<0.01 vs. saline, n=10 per subgroup.
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