Ginsenoside Rb1 prevents lipopolysaccharide-induced depressive-like behavior by inhibiting inflammation and neural dysfunction and F2 elicits a novel antidepressant-like effect: A metabolite-based network pharmacology study

Liang, Wenyi; Liu, Yue; Zhou, Kun; Jian, Ping; Zhang, Qiunan; Wu, Lingfang; Chang, Hong-Sheng; Zhang, Lanzhen

doi:10.1016/j.jep.2021.114655

Cited by 13 publications

(9 citation statements)

References 46 publications

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“…In addition, our network pharmacological analysis results showed that GRd is implicated in antidepressant activity. 30 The behavioral despair mouse model of depression is a proven depression model which places animals in irresistible adversity to breed despair. The immobility of animals after forced swimming stress is sensitive to antidepressants, making it an ideal behavioral experiment for preliminarily testing of the pharmacodynamics of antidepressants.…”

Section: Discussionmentioning

confidence: 99%

Antidepressant-Like Effect and Mechanism of Ginsenoside Rd on Rodent Models of Depression

Wang

Zhang

et al. 2022

DDDT

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Background: There is growing evidence to suggest that ginsenoside Rd (GRd) has a therapeutic effect on depression, but the specific mechanisms behind its activity require further study. Objective: This study is designed to investigate the antidepressant-like effect and underlying mechanisms of GRd. Methods: In this study, the behavioral despair mouse model of depression and chronic unpredictable mild stress (CUMS) rat model of depression were established to explore the effects of GRd on depression-like behavior and its underlying mechanisms. Behavioral tests were used to evaluate the replication of animal models and depression-like behaviors. The hypoxia-inducible factor-1α (HIF-1α) blocker 2-methoxyestradiol (2-ME) was injected to determine the role of HIF-1α in the antidepressant-like effect of GRd. In addition, molecular biology techniques were used to determine the mRNA and protein expression of HIF-1ɑ signaling pathway and synaptic plasticity-related regulators, that is synapsin 1 (SYN 1) and postsynaptic density protein 95 (PSD 95). In silico binding interaction studies of GRd with focused target proteins were performed using molecular docking to predict the affinity and optimal binding mode between ligands and receptors. Results: Our data show that GRd significantly reversed depression-like behavior and promoted mRNA and protein expression of HIF-1ɑ signaling pathway and synaptic plasticity-related regulators. However, the antidepressant-like effect of GRd disappeared upon inhibition of HIF-1α expression following administration of 2-ME. Furthermore, molecular docking results showed that GRd possessed significant binding affinity for HIF-1α, VEGF, and VEGFR-2. Conclusion: Our results show that GRd exhibits significant antidepressant-like effect and that HIF-1α signaling pathway is a promising target for the treatment of depression.

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Section: Discussionmentioning

confidence: 99%

Antidepressant-Like Effect and Mechanism of Ginsenoside Rd on Rodent Models of Depression

Wang

Zhang

et al. 2022

DDDT

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“…In addition, oral administration of ginsenoside Rg3 (30 mg/kg) reduced the expression of iNOS and cyclooxygenase-2 (COX-2) in brain tissue (Park et al 2012 ). Ginsenoside Rb1 (GRb1), a major constituent of ginseng, is known to inhibit the inflammatory cascade and alleviate depressive-like behavior (Zhang et al 2021 ; Liang et al 2022 ). Studies have shown that oral administration of GRb1 alleviates depressive-like behavior in CRS model mice, which may be due to the reduction of hippocampus protein expression of IL-1β, TNF-α and ionized calcium-binding adapter molecule 1 by increasing the brain-derived neurotrophic factor and phosphorylated protein kinase B/protein kinase B (p-AKT/AKT) protein expression and reducing the serum IL-1β and TNF-α levels (Guo et al 2021 ).…”

Section: Effects Of Ginseng On Covid-19 Pandemic Caused Depressionmentioning

confidence: 99%

“…Liang et al demonstrated that ginsenoside Rb1 inhibits peripheral and hippocampal inflammation through MAPK/NF-κB signaling. In inflammation-mediated depression, ginsenoside Rb1 ameliorated glucocorticoid receptor damage and 5-HT 1A receptor expression (Liang et al 2022 ). In addition, ginsenoside Rb1 increases 5-HT levels and inhibits indoleamine 2,3-dioxygenase activity (Liang et al 2022 ).…”

Section: Effects Of Ginseng On Covid-19 Pandemic Caused Depressionmentioning

confidence: 99%

Therapeutic potential and possible mechanisms of ginseng for depression associated with COVID-19

Zhao,

Zhang,

Chen

et al. 2023

Inflammopharmacol

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Recently, a global outbreak of COVID-19 has rapidly spread to various national regions. As the number of COVID-19 patients has increased, some of those infected with SARS-CoV-2 have developed a variety of psychiatric symptoms, including depression, cognitive impairment, and fatigue. A distinct storm of inflammatory factors that contribute to the initial disease but also a persistent post-acute phase syndrome has been reported in patients with COVID-19. Neuropsychological symptoms including depression, cognitive impairment, and fatigue are closely related to circulating and local (brain) inflammatory factors. Natural products are currently being examined for their ability to treat numerous complications caused by COVID-19. Among them, ginseng has anti-inflammatory, immune system stimulating, neuroendocrine modulating, and other effects, which may help improve psychiatric symptoms. This review summarizes the basic mechanisms of COVID-19 pneumonia, psychiatric symptoms following coronavirus infections, effects of ginseng on depression, restlessness, and other psychiatric symptoms associated with post-COVID syn-dromes, as well as possible mechanisms underlying these effects.

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“…In a lipopolysaccharide (LPS)-induced depressive model, ginsenoside Rb1 significantly suppressed peripheral and hippocampal inflammation via MAPK/NF-κB signaling, improved impaired glucocorticoid receptor and inhibited activity of indoleamine 2,3-dioxygenase ( Liang et al, 2022 ). The authors also found that ginsenoside Rb1 increased the levels of 5-HT and expression of 5-HT 1A receptor.…”

Section: Ginsenoside Rb1 In Depressionmentioning

confidence: 99%

“…Rd, F2, compound K, Rh2, and Rg3 were identified as the metabolites of ginsenoside Rb1. Liang et al (2022) found that F2 exerted antidepressant-like effects and it showed higher activity than ginsenoside Rb1 against depression ( Table 4 ).…”

Section: Ginsenoside Rb1 In Depressionmentioning

confidence: 99%

Neuroprotective Mechanisms of Ginsenoside Rb1 in Central Nervous System Diseases

et al. 2022

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Panax ginseng and Panax notoginseng, two well-known herbs with enormous medical value in Asian countries, have a long usage history in China for the therapy of some diseases, such as stroke. Ginsenoside Rb1 is one of most important active ingredients in Panax ginseng and Panax notoginseng. In the last two decades, more attention has focused on ginsenoside Rb1 as an antioxidative, anti-apoptotic and anti-inflammatory agent that can protect the nervous system. In the review, we summarize the neuroprotective roles of ginsenoside Rb1 and its potential mechanisms in central nervous system diseases (CNSDs), including neurodegenerative diseases, cerebral ischemia injury, depression and spinal cord injury. In conclusion, ginsenoside Rb1 has a potential neuroprotection due to its inhibition of oxidative stress, apoptosis, neuroinflammation and autophagy in CNSDs and may be a promising candidate agent for clinical therapy of CNSDs in the future.

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Ginsenoside Rb1 prevents lipopolysaccharide-induced depressive-like behavior by inhibiting inflammation and neural dysfunction and F2 elicits a novel antidepressant-like effect: A metabolite-based network pharmacology study

Cited by 13 publications

References 46 publications

Antidepressant-Like Effect and Mechanism of Ginsenoside Rd on Rodent Models of Depression

Antidepressant-Like Effect and Mechanism of Ginsenoside Rd on Rodent Models of Depression

Therapeutic potential and possible mechanisms of ginseng for depression associated with COVID-19

Neuroprotective Mechanisms of Ginsenoside Rb1 in Central Nervous System Diseases

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