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Loganin Exerts Sedative and Hypnotic Effects via Modulation of the Serotonergic System and GABAergic Neurons.

Rui Shi, Yan Han, Yu Yan, Hao-Yi Qiao, Jun He et al.
Other Frontiers in pharmacology 2019 52 उद्धरण
PubMed DOI PDF
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Study Design





            

                

                    

                        
                        

                            
अध्ययन प्रकार

                            
In Vitro

                        

                        
                        
                        
                        
                    

                    

                        
                        

                            
हस्तक्षेप

                            
Loganin Exerts Sedative and Hypnotic Effects via Modulation of the Serotonergic System and GABAergic Neurons. 20-50 mg/kg (sedative effect in mice); 35 mg/kg (EEG/EMG in rats)

                        

                        
                        
                        

                            
तुलनित्र

                            
Placebo

                        

                        
                        
                        

                            
प्रभाव की दिशा

                            

                                
                                    Positive
                                
                            

                        

                        
                        

                            
पूर्वाग्रह का जोखिम

                            
Unclear

                        

                        
                    

                

            

        

        

        
        
        

            

  
Abstract





            

                
Corni fructus, the fruit of Cornus officinalis Sieb. et Zucc., has been used as a tonic for the kidney in China for thousands of years. Loganin is one of the major constituents derived from Corni fructus. In this study, we revealed the sedative and hypnotic activity of loganin and investigated its mechanisms for the first time. Pentobarbital-induced sleep test and insomnia mice models [induced by caffeine and p-chlorophenylalanine (PCPA)] were used for the assessment of sedative and hypnotic effects of loganin. It was found that loganin (20-50 mg/kg) exerted sedative effect in normal mice. Loganin exhibited hypnotic effect by increasing sleep onset and sleep duration in pentobarbital-treated mice, recovering PCPA-induced insomnia and exerting synergistic hypnosis effect with 5-HTP. In addition, electroencephalograph (EEG) and electromyography (EMG) recordings of rats showed that loganin (35 mg/kg) prolonged the ratio of non-rapid eye movement (NREM) sleep and shortened wakefulness significantly, further immunohistochemistry showed that loganin (35 mg/kg) increased c-Fos expression in GABAergic neurons of rats in the ventrolateral preoptic nucleus (VLPO). The levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and its metabolite were measured in the hippocampus, prefrontal cortex and striatum of mice, 1 h after loganin (35 mg/kg) treatment. 5-HT, 5-HIAA/5-HT, DA, and DOPAC were decreased significantly in the prefrontal cortex. In conclusion, these results indicated that loganin produced beneficial sedative and hypnotic activity, which might be mainly mediated by modification of the serotonergic system and GABAergic neurons.

            

        

        

        
        

        
        
        

            

  
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Figures





            

                
                
                    
                    

                        Experimental design for testing loganin's sedative and hypnotic effects in mice models, including pentobarbital-induced sleep and insomnia paradigms.
                    

                    
                    

                        
FIGURE 1

                        
                        
Experimental design for testing loganin's sedative and hypnotic effects in mice models, including pentobarbital-induced sleep and insomnia paradigms.

                        
                        
                        diagram
                        
                    

                
                
                
                    
                    

                        Pentobarbital-induced sleep test results demonstrate that loganin administration significantly altered sleep onset latency and total sleep duration in mice.
                    

                    
                    

                        
FIGURE 2

                        
                        
Pentobarbital-induced sleep test results demonstrate that loganin administration significantly altered sleep onset latency and total sleep duration in mice.

                        
                        
                        chart
                        
                    

                
                
                
                    
                    

                        Dose-response analysis of loganin's hypnotic effects in the pentobarbital sleep model reveals concentration-dependent changes in sleep parameters.
                    

                    
                    

                        
FIGURE 3

                        
                        
Dose-response analysis of loganin's hypnotic effects in the pentobarbital sleep model reveals concentration-dependent changes in sleep parameters.

                        
                        
                        chart
                        
                    

                
                
                
                    
                    

                        Loganin's effects on serotonergic system markers, including 5-HT levels and receptor expression in the brain, are quantified in treated versus control mice.
                    

                    
                    

                        
FIGURE 4

                        
                        
Loganin's effects on serotonergic system markers, including 5-HT levels and receptor expression in the brain, are quantified in treated versus control mice.

                        
                        
                        chart
                        
                    

                
                
                
                    
                    

                        GABAergic neuron activity measurements show that loganin modulates GABA receptor signaling, contributing to its observed sedative properties.
                    

                    
                    

                        
FIGURE 5

                        
                        
GABAergic neuron activity measurements show that loganin modulates GABA receptor signaling, contributing to its observed sedative properties.

                        
                        
                        chart
                        
                    

                
                
                
                    
                    

                        Immunohistochemical or western blot analysis of c-Fos expression in sleep-promoting brain regions following loganin treatment indicates enhanced neuronal activation.
                    

                    
                    

                        
FIGURE 6

                        
                        
Immunohistochemical or western blot analysis of c-Fos expression in sleep-promoting brain regions following loganin treatment indicates enhanced neuronal activation.

                        
                        
                        chart
                        
                    

                
                
                
                    
                    

                        Neurotransmitter level quantification in key brain regions demonstrates that loganin treatment alters the balance of serotonin and GABA pathways associated with sleep regulation.
                    

                    
                    

                        
FIGURE 7

                        
                        
Neurotransmitter level quantification in key brain regions demonstrates that loganin treatment alters the balance of serotonin and GABA pathways associated with sleep regulation.

                        
                        
                        chart
                        
                    

                
                
                
                    
                    

                        Behavioral analysis in insomnia mouse models shows that loganin reverses sleep disturbances induced by p-chlorophenylalanine, suggesting serotonergic involvement.
                    

                    
                    

                        
FIGURE 8

                        
                        
Behavioral analysis in insomnia mouse models shows that loganin reverses sleep disturbances induced by p-chlorophenylalanine, suggesting serotonergic involvement.

                        
                        
                        chart
                        
                    

                
                
                
                    
                    

                        Proposed mechanism of action diagram illustrates how loganin from Corni fructus exerts sedative and hypnotic effects through dual modulation of the serotonergic system and GABAergic neurons.
                    

                    
                    

                        
FIGURE 9

                        
                        
Proposed mechanism of action diagram illustrates how loganin from Corni fructus exerts sedative and hypnotic effects through dual modulation of the serotonergic system and GABAergic neurons.

                        
                        
                        diagram
                        
                    

                
                
            

        

        

        
        
        

            

  
Tables





            

                
                

                    

                        
Table 1

                        
                    

                    

                        
GroupsDosage (mg/kg, i.g.)No. of falling asleep/totalSleep onset (%)
Vehicle–1/254.0
Estazolam0.1525/25100.0∗
Loganin59/2536.0∗
2015/2560.0∗
5015/2560.0∗

                    

                

                
                

                    

                        
Table 2

                        
                    

                    

                        
GroupsDosage (mg/kg)No. of falling asleep/totalSleep onset (%)
Vehicle–0/120.0
5-HTP2.5 (i.p.)2/1216.7∗
Loganin5 (i.g.)2/1216.7∗
5-HTP + Loganin2.5 (i.p.) +5 (i.g.)12/1291.67∗∗

                    

                

                
                

                    

                        
Table 3

                        
                    

                    

                        
GroupNE (ng/g)5-HT (ng/g)5-HIAA (ng/g)DA (ng/g)DOPAC (ng/g)5-HIAA/5-HTDOPAC/DA
PFCControl673.5 ± 119.11115 ± 151.4337.5 ± 49.211031 ± 698.4417.3 ± 145.40.29 ± 0.020.58 ± 0.18
Loganin469.5 ± 72.33687.7 ± 91.16∗241.3 ± 40.44223.8 ± 56.61∗∗124.7 ± 8.557∗∗0.35 ± 0.05∗0.63 ± 0.071
STRControl263 ± 64.29466.8 ± 99.63322.1 ± 73.2116052 ± 36931088 ± 190.40.78 ± 0.140.09 ± 0.005
Loganin265.6 ± 26.61723 ± 80.8605.2 ± 92.07∗15287 ± 16451284 ± 125.50.80 ± 0.070.09 ± 0.003
HIPControl478.4 ± 78.22445.6 ± 61.47346.8 ± 84.6666.42 ± 16.19ND0.60 ± 0.10ND
Loganin515.9 ± 68.09499.3 ± 62.03382.7 ± 98.1675.44 ± 29.22ND0.59 ± 0.11ND

                    

                

                
            

        

        

        
        
        

            

  
References





            
    
                
                
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Used In Evidence Reviews





            

                
                
                    

                        B

                        
                            GABA के लिए नींद शुरू होने में कठिनाई
                        
                    

                    
                
                
                
                    

                        B

                        
                            5-HTP के लिए अनिद्रा
                        
                    

                    
                
                
            

        

        

        
        
        

            

  
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