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Cited by 70Treatment of Major DepressionMedicinal Plant Extracts EffectsMedicinal Plants and Neuroprotection

Asiaticoside produces an antidepressant‑like effect in a chronic unpredictable mild stress model of depression in mice, involving reversion of inflammation and the PKA/pCREB/BDNF signaling pathway

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Wang, Luoqing, Guo, Ting, Guo, Yuanfang, Xu, Yujie·2020·Molecular Medicine Reports
DOI 10.3892/mmr.2020.11305PMC PMC7411460
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Abstract

Asiaticoside is one of the triterpenoid components found in Centella asiatica that has promising neuroprotective properties. The present study aimed to evaluate the antidepressant‑like properties of asiaticoside and to investigate the possible mechanisms underlying its mode of action using a mouse model of chronic unpredictable mild stress (CMS). Behavioral tests, including sucrose preference test, forced swimming test and tail suspension test, were performed to evaluate symptoms of depression. The expression levels of neurotransmitters, 5‑hydroxytryptamine (5‑HT) and norepinephrine (NE), in the hippocampus were measured by high‑performance liquid chromatography. ELISA and western blotting were used to detect protein expression. It was demonstrated that asiaticoside treatment (20 and 40 mg/kg; intragastric) significantly reversed the decrease in sucrose consumption, and reduced the immobility time in tail suspension tests and forced swimming tests in CMS mice. Furthermore, asiaticoside treatment upregulated the expression of 5‑HT and NE in the CMS mouse model. Asiaticoside administration also downregulated the levels of interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α in the hippocampus, and reduced the phosphorylation of nuclear factor (NF)‑κBp65 and the expression of nod‑like receptor protein 3 (NLRP3), thus decreasing the expression of mature caspase‑1. Furthermore, asiaticoside significantly increased the levels of cAMP and protein kinase A (PKA), and enhanced phosphorylation of the cAMP‑related specific marker vasodilator‑stimulated phosphoprotein at serine 157. Therefore, asiaticoside may activate the cAMP/PKA signaling pathway to inhibit NF‑κB‑ and NLRP3‑related inflammation. Moreover, phosphorylation of the cAMP‑responsive element‑binding protein at serine 133 and the expression of brain‑derived neurotrophic factor were increased after asiaticoside administration. Collectively, the present results suggested that asiaticoside may play a vital role as an antidepressant and anti‑inflammatory agent in the CMS mouse model by regulating the cAMP/PKA signaling pathway.

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Sorted by citations

Authors
Wang, L., Guo, T., Guo, Y., & Xu, Y.
Affiliations
  • Department of Cardiovascular Medicine, The Second People's Hospital of Lianyungang, Lianyungang, Jiangsu 222000, P.R. China
  • Xuzhou Medical College (CN)
  • Department of Respiratory Medicine, Ganyu District People's Hospital, Lianyungang, Jiangsu 222100, P.R. China
  • Department of Anesthesiology and Perioperative Medicine, Jiangsu Province Hospital, Nanjing, Jiangsu 210000, P.R. China
ORCID
Venue
Molecular Medicine Reports
Publisher
Spandidos Publications
Published
2020-07-06
Volume
22
Issue
3
Pages
2364-2372
ISSN
  • 1791-2997 (ISSN-L)
  • 1791-3004
DOI
10.3892/mmr.2020.11305
PMC
PMC7411460
OpenAlex
W3040287805
Cited by
70
References
3
Citations by year
2026: 17 · 2025: 9 · 2024: 12 · 2023: 9 · 2022: 16 · 2021: 5 · 2020: 1 · 2013: 1
FWCI
4.53
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Molecular Medicine Reports (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81870943)
  • Xuzhou Medical University
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
Keywords
asiaticoside, Centella asiatica, antidepressant-like effects, chronic unpredictable mild stress, depression, neuroinflammation, cAMP/PKA signaling, NF-κB, NLRP3 inflammasome, caspase-1, hippocampal serotonin, norepinephrine, triterpenoids
MeSH terms
Animals, Antidepressive Agents, Behavior, Animal, Disease Models, Animal, Gene Expression Regulation, Male, Norepinephrine, Phosphorylation, Serotonin, Stress, Psychological, Triterpenes, Signal Transduction, Up-Regulation, Cyclic AMP Response Element-Binding Protein, Cyclic AMP-Dependent Protein Kinases, Brain-Derived Neurotrophic Factor, Mice

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