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Apocynum venetum leaf extract reverses depressive-like behaviors in chronically stressed rats by inhibiting oxidative stress and apoptosis.
Biomed Pharmacother. 2018 Apr; 100:394-406.BP

Abstract

BACKGROUND

Major depressive disorder (MDD) is a common but serious psychiatric disorder, but current treatments are inadequate for approximately half of the patients with MDD. Thus, better methods of treatment are urgently needed. This study aimed to investigate the antidepressant-like effects and potential mechanism of Apocynum venetum leaf extract (AVLE) in chronic unpredictable mild stress (CUMS) rat model of depression.

MATERIALS AND METHODS

The CUMS rat model of depression was used to investigate the antidepressant-like activity and relevant mechanism of AVLE (30, 60, and 125 mg/kg, i.g.). Behavioral tests, including sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST) were conducted to assess anhedonic, despairing, and spontaneous behaviors, respectively. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by measuring the serum adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) concentrations. The underlying mechanism was further explored by assessing oxidative stress parameters, cell apoptosis, and brain-derived neurotrophic factor (BDNF) expression in the rat hippocampus exposed to CUMS.

RESULTS

The AVLE (36, 60, 125 mg/kg) treatment exerted antidepressant-like effects in CUMS-exposed rats similar to fluoxetine (10 mg/kg). The AVLE treatment reduced the serum CORT and ACTH levels in CUMS rats. It also increased the activities and gene expression of antioxidant enzymes (SOD, CAT, and GPx) and decreased the ROS generation levels and the lipid peroxidation marker MDA in the rat hippocampus subjected to CUMS. Additionally, it suppressed the apoptosis of hippocampus cells by modulating Bcl-2/Bax pathways and improved the hippocampal BDNF expressions of CUMS rats.

CONCLUSION

Our findings suggested that AVLE exerted antidepressant-like effects in CUMS rats, which was possibly mediated by the prevention of oxidative stress, the inhibition of hippocampal neuronal apoptosis, and the upregulation of the hippocampal BDNF level.

Authors+Show Affiliations

Department of Integrative Medicine, Zhongshan Hospital, Fudan University, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai 200032, China.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai 200032, China.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai 200032, China.Department of Neurology, Shuguang Hospital, Shanghai University Traditional Chinese Medicine, Shanghai 201203, China.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai 200032, China.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai 200032, China.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai 200032, China.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai 200032, China.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: xiang.jun@mail.zs-hospital.sh.cn.Department of Integrative Medicine, Zhongshan Hospital, Fudan University, China; Institute of Neurology, Academy of Integrative Medicine, Fudan University, Shanghai 200032, China. Electronic address: dingfangcai@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29454288

Citation

Li, Xiangting, et al. "Apocynum Venetum Leaf Extract Reverses Depressive-like Behaviors in Chronically Stressed Rats By Inhibiting Oxidative Stress and Apoptosis." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 100, 2018, pp. 394-406.
Li X, Wu T, Yu Z, et al. Apocynum venetum leaf extract reverses depressive-like behaviors in chronically stressed rats by inhibiting oxidative stress and apoptosis. Biomed Pharmacother. 2018;100:394-406.
Li, X., Wu, T., Yu, Z., Li, T., Zhang, J., Zhang, Z., Cai, M., Zhang, W., Xiang, J., & Cai, D. (2018). Apocynum venetum leaf extract reverses depressive-like behaviors in chronically stressed rats by inhibiting oxidative stress and apoptosis. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 100, 394-406. https://doi.org/10.1016/j.biopha.2018.01.137
Li X, et al. Apocynum Venetum Leaf Extract Reverses Depressive-like Behaviors in Chronically Stressed Rats By Inhibiting Oxidative Stress and Apoptosis. Biomed Pharmacother. 2018;100:394-406. PubMed PMID: 29454288.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Apocynum venetum leaf extract reverses depressive-like behaviors in chronically stressed rats by inhibiting oxidative stress and apoptosis. AU - Li,Xiangting, AU - Wu,Ting, AU - Yu,Zhonghai, AU - Li,Tingting, AU - Zhang,Jingsi, AU - Zhang,Zhennian, AU - Cai,Min, AU - Zhang,Wen, AU - Xiang,Jun, AU - Cai,Dingfang, Y1 - 2018/02/16/ PY - 2017/11/05/received PY - 2018/01/07/revised PY - 2018/01/28/accepted PY - 2018/2/18/pubmed PY - 2018/9/1/medline PY - 2018/2/18/entrez KW - Apocynum venetum leaf extract KW - Apoptosis KW - Chronic unpredictable mild stress KW - Cytochrome c (CID: 439171) KW - Fluoxetine hydrochloride (CID: 62857) KW - Hydrogen peroxide (CID: 784) KW - Hyperoside (CID: 5281643) KW - Isoquercitrin (CID: 5280804) KW - Major depressive disorder KW - Malondialdehyde (CID: 10964) KW - Oxidative stress KW - Quercetin (CID: 5280343) KW - Superoxide anion radical (CID: 5359597) KW - Superoxide dismutase (CID: 72941490) SP - 394 EP - 406 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 100 N2 - BACKGROUND: Major depressive disorder (MDD) is a common but serious psychiatric disorder, but current treatments are inadequate for approximately half of the patients with MDD. Thus, better methods of treatment are urgently needed. This study aimed to investigate the antidepressant-like effects and potential mechanism of Apocynum venetum leaf extract (AVLE) in chronic unpredictable mild stress (CUMS) rat model of depression. MATERIALS AND METHODS: The CUMS rat model of depression was used to investigate the antidepressant-like activity and relevant mechanism of AVLE (30, 60, and 125 mg/kg, i.g.). Behavioral tests, including sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST) were conducted to assess anhedonic, despairing, and spontaneous behaviors, respectively. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by measuring the serum adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) concentrations. The underlying mechanism was further explored by assessing oxidative stress parameters, cell apoptosis, and brain-derived neurotrophic factor (BDNF) expression in the rat hippocampus exposed to CUMS. RESULTS: The AVLE (36, 60, 125 mg/kg) treatment exerted antidepressant-like effects in CUMS-exposed rats similar to fluoxetine (10 mg/kg). The AVLE treatment reduced the serum CORT and ACTH levels in CUMS rats. It also increased the activities and gene expression of antioxidant enzymes (SOD, CAT, and GPx) and decreased the ROS generation levels and the lipid peroxidation marker MDA in the rat hippocampus subjected to CUMS. Additionally, it suppressed the apoptosis of hippocampus cells by modulating Bcl-2/Bax pathways and improved the hippocampal BDNF expressions of CUMS rats. CONCLUSION: Our findings suggested that AVLE exerted antidepressant-like effects in CUMS rats, which was possibly mediated by the prevention of oxidative stress, the inhibition of hippocampal neuronal apoptosis, and the upregulation of the hippocampal BDNF level. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/29454288/Apocynum_venetum_leaf_extract_reverses_depressive_like_behaviors_in_chronically_stressed_rats_by_inhibiting_oxidative_stress_and_apoptosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(17)35846-8 DB - PRIME DP - Unbound Medicine ER -