Antidepressant-like effects of standardized gypenosides: involvement of brain-derived neurotrophic factor signaling in hippocampus

Mu, Rong-Hao; Fang, Xiaoyan; Wang, Shuangshuang; Li, Cheng-Fu; Chen, Shao-Mei; Chen, Xuemei; Liu, Qing; Li, Yucheng; Yi, Long

doi:10.1007/s00213-016-4357-z

Cited by 37 publications

(17 citation statements)

References 44 publications

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“…Treating CUMS-induced rats with Flx 10 mg/kg or CA (400 and 800 mg/kg) reversed the locomotor deficits, which is evident by the increased number of lines crossed. Previous studies have shown that treatment with fluoxetine a selective serotonin reuptake inhibitor reversed depression-related behaviors in CUMS-induced rats 35,50 , which is consistent with the current work. While CA at the doses of 400 and 800 mg/kg have similar effects like fluoxetine at 10 mg/kg, suggesting anxiolytic effects of CA on CUMSinduced rats.…”

Section: Discussionsupporting

confidence: 93%

Centella asiatica prevents chronic unpredictable mild stress-induced behavioral changes in rats

et al. 2019

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Background: Depression is a psychological disorder which is associated with mood swings and cognitive deficits, and is ranked third among the leading causes of global health care burden. Chronic unpredictable mild stress (CUMS) has been shown to induce depression-like behaviors in rodents, which exhibit similarities to the human form of depression. Centella asiatica (CA) is an ancient medicinal plant which has neuroprotective potential. This work aimed to assess the protective role of CA on CUMS-induced rats. Methods: Thirty six rats randomly divided into six groups were used for the evaluation. The groups were as follows: 1, Unstressed + normal saline (control); 2, CUMS + normal saline (model); 3, CUMS + fluoxetine (10 mg/kg) standard antidepressant; 4-6, CUMS + CA (200, 400 & 800 mg/kg). Nine different stressors (S) (S1: 24-h food deprivation, S2: 24- h water deprivation, S3: 5-min cold swimming (at 5◦C), S4: 12-h change of cage mate, S5: 1-min tail pinch (1 cm from the tip of the tail), S6: 12-h cage tilt (at 45◦), S7: 12-h overcrowding of cage, S8: 12-h wet bedding with 200 mL of water, and S9: 4-h physical restraint) were administered to the stressed groups with at least 2 stressors per day. The treatments lasted for 8 weeks, and the rats were evaluated through open field test (OFT) and elevated plus maze (EPM) for anxiety-like behavior, forced swimming test (FST) for depression-like behaviour, and T-maze spontaneous alternation for learning and memory. Furthermore, serum cortisol levels were also evaluated. Results: CUMS-induced rats showed anxiety-like behaviors in OFT and EPM tests, depression-like behavior in FST and cognitive deficits in T-maze test, as well as increased serum cortisol levels. Conversely, administration of CA (at 400 and 800 mg/kg doses) and fluoxetine (at 10 mg/kg dose) prevented the aberrant behavioral changes and also the changes in the serum cortisol levels. No significant differences of behaviors were observed between the groups of rats administered with CA (400 and 800 mg/kg) and those administered with fluoxetine (10 mg/kg), suggesting that the therapeutic potential of CA is comparable to that of fluoxetine. Conclusion: The data obtained showed that CA, at doses of 400 and 800 mg/kg, effectively reversed the anxiety and depression-like behaviors, amnesic behaviors, as well as serum cortisol levels in a CUMS-induced rat model of depression. This suggests that CA is a potential candidate for the development of future anti-depressants.

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Section: Discussionsupporting

confidence: 93%

Centella asiatica prevents chronic unpredictable mild stress-induced behavioral changes in rats

et al. 2019

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“…They are used extensively as a traditional Chinese medicine for a long time. GPS is a bioactive component with various pharmacological properties and beneficial clinical effects on conditions including hyperlipoproteinemia, 1 cancer, [2][3][4] hepatitis, 5 and cardiovascular disease. 6 However, like other saponins, GPS are easily degraded due to their sensitivity to environmental factors, such as heat, light, and oxygen and are limited in their bioavailability and clinical applications owing to their poor lipid and water solubilities and hemolytic properties.…”

Section: Introductionmentioning

confidence: 99%

<p>Formulation design, characterization, and in vitro and in vivo evaluation of nanostructured lipid carriers containing a bile salt for oral delivery of gypenosides</p>

Yang

Chen

et al. 2019

IJN

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Background: Gypenosides (GPS) have been used as traditional medicine for centuries with various pharmacological effects. However, its therapeutic effects were restricted owing to the poor lipid and water solubility and low absorption. This study aimed to develop nanostructured lipid carriers (NLCs) containing a bile salt formulation (sodium glycocholate, SGC) for GPS, and to evaluate the potential of the GPS-SGC-NLCs as an oral delivery system. Methods: The preparation of GPS-SGC-NLCs was investigated using a single-factor test and a central composite design of response surface methodology. In vitro release and pharmacokinetics studies were used to evaluate the dissolution and bioavailability of GPS. Furthermore, In vivo imaging and in situ intestinal perfusion studies were performed to investigate the absorption of the preparations in the gastrointestinal tract. Results: The optimised formulation yielded nanoparticles with an approximate diameter of 146.7 nm, polydispersity of 0.137, zeta potential of −56.0 mV, entrapment efficiency of 74.22% and drug loading of 4.89%. An in vitro dissolution analysis revealed the sustained release of contents from GPS-SGC-NLCs over 48 h with 56.4% of the drug released. A pharmacokinetic analysis revealed an 8.5-fold increase of bioavailability of the GPS-SGC-NLCs compared with GPS powder. In vivo imaging and in situ intestinal perfusion studies showed that SGC-NLCs could significantly increase the absorption of GPS in intestinal tract. In vitro cytotoxicity evaluated using Caco-2 cells demonstrated that GPS-SGC-NLCs decrease the cytotoxicity of the drug. Conclusion: The SGC-NLC formulation can significantly improve the absorption of GPS, which provides an effective approach for enhancing the oral absorption of drugs.

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“…BDNF exerts its pro-survival effects by binding its high affinity receptor TrkB, to activate BDNF-TrkB signaling 14 . Behavioral responses to antidepressants have been abolished in animals in which BDNF-TrkB signaling is inhibited 15 . It is also involved in propofol-induced learning and memory impairments 16 .…”

Section: Introductionmentioning

confidence: 99%

Antidepressant-like effects and cognitive enhancement of Schisandra chinensis in chronic unpredictable mild stress mice and its related mechanism

Yan

Wan

et al. 2017

Sci Rep

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The aim of this study was to evaluate whether Schisandra chinensis extract (SCE) administration influences chronic unpredictable mild stress (CUMS)-induced depression and cognitive impairment, and explores underlying mechanisms. Sucrose preference test (SPT) and forced swimming test (FST) were used for assessing depressive symptoms, and Y-maze, Morris water maze were used for evaluating cognition processes. The results showed that CUMS (4 weeks) was effective in producing both depression and memory deficits in mice. Additionally, CUMS exposure significantly decreased brain derived neurotrophic factor (BDNF) levels in hippocampus as indicated by ELISA, immunohistochemistry and immunofluorescence assays, accompanied by down-regulated tyrosine kinase receptor B (TrkB)/cAMP-response element binding protein (CREB)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (AKT)/ glycogen synthase kinase-3β (GSK-3β) signaling pathways. Chronic administration of SCE (600 or 1200 mg/kg, i.g.) significantly prevented all these CUMS-induced behavioral and biochemical alterations. It suggested that SCE could improve the depression-like emotional status and associated cognitive deficits in CUMS mice, which might be mediated by regulation of BDNF levels in hippocampus, as well as up-regulating of TrkB/CREB/ERK and PI3K/AKT/GSK-3β pathways.

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Antidepressant-like effects of standardized gypenosides: involvement of brain-derived neurotrophic factor signaling in hippocampus

Abstract: This study demonstrates that gypenosides exhibit antidepressant-like effects in mice, which may be mediated by activation of the BDNF-ERK/Akt signaling pathway in the hippocampus.

Cited by 37 publications

References 44 publications

Centella asiatica prevents chronic unpredictable mild stress-induced behavioral changes in rats

Centella asiatica prevents chronic unpredictable mild stress-induced behavioral changes in rats

<p>Formulation design, characterization, and in vitro and in vivo evaluation of nanostructured lipid carriers containing a bile salt for oral delivery of gypenosides</p>

Antidepressant-like effects and cognitive enhancement of Schisandra chinensis in chronic unpredictable mild stress mice and its related mechanism

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