Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway

WANG Zhe; CHENG Ya-ting; LU Ye; SUN Guo-qiang; PEI Lin

doi:10.1007/s11655-022-3590-z

Your Location：

Home >

Browse articles >

Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway

Original Article | Updated：2023-04-27

- Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway
- Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway
- 中国结合医学杂志（英文版） 2023年29卷第5期页码：405-412
- Affiliations：
  
  1.School of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang (050200), China
  2.Hebei Province Academy of Chinese Medicine Sciences, Shijiazhuang (050031), China
- Author bio：
  
  Dr. PEI Lin, E-mail: peilin13831190309@126.com
- Funds：
  
  the National Key Research and Development Program(2017YFC1701701);the Postgraduate Innovation Funding Project of Hebei University of Chinese Medicine(XCXZZBS2020005)
- DOI：10.1007/s11655-022-3590-z
  中图分类号：
- 纸质出版日期：2023-05，
  
  网络出版日期：2023-01-06，
  
  录用日期：2022-07-01
Scan for full text
Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway[J]. 中国结合医学杂志（英文版）, 2023,29(5):405-412.

WANG Zhe, CHENG Ya-ting, LU Ye, et al. Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway[J]. Chinese Journal of Integrative Medicine, 2023,29(5):405-412.
Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway[J]. 中国结合医学杂志（英文版）, 2023,29(5):405-412. DOI： 10.1007/s11655-022-3590-z.

WANG Zhe, CHENG Ya-ting, LU Ye, et al. Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway[J]. Chinese Journal of Integrative Medicine, 2023,29(5):405-412. DOI： 10.1007/s11655-022-3590-z.

摘要

Abstract

Objective:

To investigate the role of hippocampal neurodevelopment in the antidepressant effect of baicalin.

Methods:

Forty male Institute of Cancer Research mice were divided into control

corticosterone (CORT

40 mg/kg)

CORT+baicalin-L (25 mg/kg)

CORT+baicalin-H (50 mg/kg)

and CORT+fluoxetine (10 mg/kg) groups according to a random number table. An animal model of depression was established by chronic CORT exposure. Behavioral tests were used to assess the reliability of depression model and the antidepressant effect of baicalin. In addition

Nissl staining and immunofluorescence were used to evaluate the effect of baicalin on hippocampal neurodevelopment in mice. The protein and mRNA expression levels of neurodevelopment-related factors were detected by Western blot analysis and real-time polymerase chain reaction

respectively.

Results:

Baicalin significantly ameliorated the depressive-like behavior of mice resulting from CORT exposure and promoted the development of dentate gyrus in hippocampus

thereby reversing the depressive-like pathological changes in hippocampal neurons caused by CORT neurotoxicity. Moreover

baicalin significantly decreased the protein and mRNA expression levels of glycogen synthase kinase 3β (GSK3β)

and upregulated the expression levels of cell cycle protein D1

p-mammalian target of rapamycin (mTOR)

doublecortin

and brain-derived neurotrophic factor (all

0.01). There were no significant differences between baicalin and fluoxetine groups (

0.05).

Conclusion:

Baicalin can promote the development of hippocampal neurons via mTOR/GSK3β signaling pathway

thus protect mice against CORT-induced neurotoxicity and play an antidepressant role.

关键词

Keywords

baicalindepressionneurodevelopmenthippocampal neuronalmammalian target of rapamycin/glycogen synthase kinase 3β pathway

references

König H, König HH, Konnopka A. The excess costs of depression: a systematic review and meta-analysis. Epidemiol Psychiatr Sci 2019;29:e30.

GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018;392:1789-1858.

Jiang B, Wu RM, Li HD, Li K, Li H, Dang WZ, et al. Yixin Ningshen Tablet alleviates comorbidity of myocardial infarction and depression by enhancing myocardial energy metabolism and increasing availability of monoamine neurotransmitter. Chin J Integr Med 2022;28:586-593.

Sun KH, Jin Y, Mei ZG, Feng ZT, Liu JR, Cao MQ, et al. Antidepressant-like effects of Chaihu Shugan Powder on rats exposed to chronic unpredictable mild stress through inhibition of endoplasmic reticulum stress-induced apoptosis. Chin J Integr Med 2021;27:353-360.

Valero J, Paris I, Sierra A. Lifestyle shapes the dialogue between environment, microglia, and adult neurogenesis. ACS Chem Neurosci 2016;7:442-453.

Aguayo FI, Pacheco AA, García-Rojo GJ, Pizarro-Bauerle JA, Doberti AV, Tejos M, et al. Matrix metalloproteinase 9 displays a particular time response to acute stress: variation in its levels and activity distribution in rat hippocampus. ACS Chem Neurosci 2018;9:945-956.

Zhang CY, Zeng MJ, Zhou LP, Li YQ, Zhao F, Shang ZY, et al. Baicalin exerts neuroprotective effects via inhibiting activation of GSK3β/NF-κB/NLRP3 signal pathway in a rat model of depression. Int Immunopharmacol 2018;64:175-182.

Neis VB, Moretti M, Rosa PB, Dalsenter YO, Werle I, Platt N, et al. The involvement of PI3K/Akt/mTOR/GSK3β signaling pathways in the antidepressant-like effect of AZD6765. Pharmacol Biochem Behav 2020;198:173020.

Tye SJ, Borreggine K, Price JB, Sutor SL, Cuéllar-Barboza AB, McElroy SL, et al. Dynamic insulin-stimulated mTOR/GSK3 signaling in peripheral immune cells: preliminary evidence for an association with lithium response in bipolar disorder. Bipolar Disord 2021;24:39-47.

Walker AJ, Price JB, Borreggine K, Sutor SL, Gogos A, McGillivray JA, et al. Insulin-stimulated mTOR activation in peripheral blood mononuclear cells associated with early treatment response to lithium augmentation in rodent model of antidepressant-resistance. Transl Psychiatry 2019;9:113.

Alonso SB, Reinert JK, Marichal N, Massalini S, Berninger B, Kuner T, et al. An increase in neural stem cells and olfactory bulb adult neurogenesis improves discrimination of highly similar odorants. EMBO J 2019;38:e98791.

Jiang N, Huang H, Zhang Y, Lv J, Wang Q, He Q, et al. Ginsenoside Rb1 produces antidepressant-like effects in a chronic social defeat stress model of depression through the BDNF-Trkb signaling pathway. Front Pharmacol 2021;12:680903.

Ma ZX, Zhang RY, Rui WJ, Wang ZQ, Feng X. Quercetin alleviates chronic unpredictable mild stress-induced depressive-like behaviors by promoting adult hippocampal neurogenesis via FoxG1/CREB/BDNF signaling pathway. Behav Brain Res 2021;406:113245.

Viana GSB, Vale EMD, Araujo ARA, Coelho NC, Andrade SM, Costa ROD, et al. Rapid and long-lasting antidepressant-like effects of ketamine and their relationship with the expression of brain enzymes, BDNF, and astrocytes. Braz J Med Biol Res 2020;54:e10107.

de Carvalho RS, Duarte FS, de Lima TC. Involvement of GABAergic non-benzodiazepine sites in the anxiolytic-like and sedative effects of the flavonoid baicalein in mice. Behav Brain Res 2011;221:75-82.

Sowndhararajan K, Deepa P, Kim M, Park SJ, Kim S. Neuroprotective and cognitive enhancement potentials of baicalin: a review. Brain Sci 2018;8:104.

Jia Z, Yang J, Cao Z, Zhao J, Zhang J, Lu Y, et al. Baicalin ameliorates chronic unpredictable mild stress-induced depression through the BDNF/ERK/CREB signaling pathway. Behav Brain Res 2021;414:113463.

Xiao Z, Cao Z, Yang J, Jia Z, Du Y, Sun G, et al. Baicalin promotes hippocampal neurogenesis via the Wnt/β-catenin pathway in a chronic unpredictable mild stress-induced mouse model of depression. Biochem Pharmacol 2021;190:114594.

Zhang K, Pan X, Wang F, Ma J, Su G, Dong Y, et al. Baicalin promotes hippocampal neurogenesis via SGK1- and FKBP5-mediated glucocorticoid receptor phosphorylation in a neuroendocrine mouse model of anxiety/depression. Sci Rep 2016;6:30951.

Zhao F, Tao W, Shang Z, Zhang W, Ruan J, Zhang C, et al. Facilitating granule cell survival and maturation in dentate gyrus with baicalin for antidepressant therapeutics. Front Pharmacol 2020;11:556845.

Chuang HW, Wei IH, Lin FY, Li CT, Chen KT, Tsai MH, et al. Roles of Akt and ERK in mTOR-dependent antidepressant effects of vanillic acid. ACS Omega 2020;5:3709-3716.

Lima IVA, Almeida-Santos AF, Ferreira-Vieira TH, Aguiar DC, Ribeiro FM, Campos AC, et al. Antidepressant-like effect of valproic acid-possible involvement of PI3K/Akt/mTOR pathway. Behav Brain Res 2017;329:166-171.

Corrales WA, Silva JP, Parra CS, Olave FA, Aguayo FI, Román-Albasini L, et al. Sex-dependent changes of miRNA levels in the hippocampus of adrenalectomized rats following acute corticosterone administration. ACS Chem Neurosci 2021;12:2981-3001.

Ma L, Shen Q, Yang S, Xie X, Xiao Q, Yu C, et al. Effect of chronic corticosterone-induced depression on circadian rhythms and age-related phenotypes in mice. Acta Biochim Biophys Sin (Chin) 2018;50:1236-1246.

Qi X, Xu H, Wang L, Zhang Z. Comparison of therapeutic effects of TREK1 blockers and fluoxetine on chronic unpredicted mild stress sensitive rats. ACS Chem Neurosci 2018;9:2824-2831.

Li B, Xu Y, Quan Y, Cai Q, Le Y, Ma T, et al. Inhibition of RhoA/ROCK pathway in the early stage of hypoxia ameliorates depression in mice via protecting myelin sheath. ACS Chem Neurosci 2020;11:2705-2716.

Sun DC, Wang RR, Xu H, Zhu XH, Sun Y, Qiao SQ, et al. A network pharmacology-based study on antidepressant effect of Salicornia europaea L. extract with experimental support in chronic unpredictable mild stress model mice. Chin J Integr Med 2022;28:339-348.

Li YC, Wang LL, Pei YY, Shen JD, Li HB, Wang BY, et al. Baicalin decreases SGK1 expression in the hippocampus and reverses depressive-like behaviors induced by corticosterone. Neuroscience 2015;311:130-137.

Zhang K, He M, Wang F, Zhang H, Li Y, Yang J, et al. Revealing antidepressant mechanisms of baicalin in hypothalamus through systems approaches in corticosterone-induced depressed mice. Front Neurosci 2019;13:834.

Yu Z, Li D, Zhai S, Xu H, Liu H, Ao M, et al. Neuroprotective effects of macamide from maca (Lepidium meyenii Walp.) on corticosterone-induced hippocampal impairments through its anti-inflammatory, neurotrophic, and synaptic protection properties. Food Funct 2021;12:9211-9228.

Suwannakot K, Sritawan N, Prajit R, Aranarochana A, Sirichoat A, Pannangrong W, et al. Melatonin protects against the side-effects of 5-fluorouracil on hippocampal neurogenesis and ameliorates antioxidant activity in an adult rat hippocampus and prefrontal cortex. Antioxidants(Basel) 2021;10:615.

Luhach K, Kulkarni GT, Singh VP, Sharma B. Attenuation of neurobehavioural abnormalities by papaverine in prenatal valproic acid rat model of ASD. Eur J Pharmacol 2021;890:173663.

Gilchrist CP, Cumberland AL, Kondos-Devcic D, Hill RA, Khore M, Quezada S, et al. Hippocampal neurogenesis and memory in adolescence following intrauterine growth restriction. Hippocampus 2021;31:321-334.

Liu JYW, Matarin M, Reeves C, McEvoy AW, Miserocchi A, Thompson P, et al. Doublecortin-expressing cell types in temporal lobe epilepsy. Acta Neuropathol Commun 2018;6:60.

Friocourt G, Koulakoff A, Chafey P, Boucher D, Fauchereau F, Chelly J, et al. Doublecortin functions at the extremities of growing neuronal processes. Cereb Cortex 2003;13:620-626.

Autry AE, Monteggia LM. Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev 2012;64:238-258.

Abhrajeet VR, Michelle T, Bonnie KD, Mindy WS, Bryon AM, Christina SA, et al. Brain entropy and neurotrophic molecular markers accompanying clinical improvement after ketamine:preliminary evidence in adolescents with treatment-resistant depression. J Psychopharmacol 2021;35:168-177.

Jin Y, Sui HJ, Dong Y, Ding Q, Qu WH, Yu SX, et al. Atorvastatin enhances neurite outgrowth in cortical neurons in vitro via up-regulating the Akt/mTOR and Akt/GSK-3β signaling pathways. Acta Pharmacol Sin 2012;33:861-872.

Li Y, Song AM, Fu Y, Walayat A, Yang M, Jian J, et al. Perinatal nicotine exposure alters Akt/GSK-3β/mTOR/autophagy signaling, leading to development of hypoxic-ischemic-sensitive phenotype in rat neonatal brain. Am J Physiol Regul Integr Comp Physiol 2019;317:R803-R813.

Bockaert J, Marin P. mTOR in brain physiology and pathologies. Physiol Rev 2015;95:1157-1187.

Ryskalin L, Limanaqi F, Frati A, Busceti CL, Fornai F.mTOR-related brain dysfunctions in neuropsychiatric disorders. Int J Mol Sci 2018;19:2226.

Park SW, Lee JG, Seo MK, Lee CH, Cho HY, Lee BJ, et al. Differential effects of antidepressant drugs on mTOR signalling in rat hippocampal neurons. Int J Neuropsychopharmacol 2014;17:1831-1846.

Ciftci E, Karacay R, Caglayan A, Altunay S, Ates N, Altintas MO, et al. Neuroprotective effect of lithium in cold-induced traumatic brain injury in mice. Behav Brain Res 2020;392:112719.

Saundh SL, Patnaik D, Gagné S, Bishop JA, Lipsit S, Amat S, et al. Identification and mechanistic characterization of a peptide inhibitor of glycogen synthase kinase (GSK3β) derived from the disrupted in schizophrenia 1 (DISC1) protein. ACS Chem Neurosci 2020;11:4128-4138.

Liu RJ, Fuchikami M, Dwyer JM, Lepack AE, Duman RS, Aghajanian GK. GSK-3 inhibition potentiates the synaptogenic and antidepressant-like effects of subthreshold doses of ketamine. Neuropsychopharmacology 2013;38:2268-2277.

Matsuda S, Ikeda Y, Murakami M, Nakagawa Y, Tsuji A, Kitagishi Y. Roles of PI3K/AKT/GSK3 pathway involved in psychiatric illnesses. Diseases 2019;7:22.

Takahashi-Yanaga F, Yoshihara T, Jingushi K, Igawa K, Tomooka K, Watanabe Y, et al. DIF-1 inhibits tumor growth in vivo reducing phosphorylation of GSK-3β and expressions of cyclin D1 and TCF7L2 in cancer model mice. Biochem Pharmacol 2014;89:340-348.

Song HM, Park GH, Park SB, Kim HS, Son HJ, Um Y, et al.Vitex rotundifolia fruit suppresses the proliferation of human colorectal cancer cells through down-regulation of Cyclin D1 and CDK4 via proteasomal-dependent degradation and transcriptional inhibition. Am J Chin Med 2018;46:191-207.

More>

浏览量

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

工具集

关联资源

Baicalin Antagonizes Prostate Cancer Stemness via Inhibiting Notch1/NF-κB Signaling Pathway

A Randomized Controlled Trial of Mindfulness in Recovery from Colorectal Cancer

Meranzin Hydrate Improves Depression-Like Behaviors and Hypomotility via Ghrelin and Neurocircuitry

Efficacy and Safety of Jianpi Jieyu Decoction for Patients with Mild-to-Moderate Depression of Xin (Heart)-Pi (Spleen) Deficiency Syndrome: A Multi-centre Randomized Controlled Study

Yixin Ningshen Tablet Alleviates Comorbidity of Myocardial Infarction and Depression by Enhancing Myocardial Energy Metabolism and Increasing Availability of Monoamine Neurotransmitter