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논문 기본 정보

자료유형
학위논문
저자정보

Yejin Ahn (고려대학교, 고려대학교 대학원)

지도교수
서형주
발행연도
2022
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고려대학교 논문은 저작권에 의해 보호받습니다.

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이 논문의 연구 히스토리 (3)

2022

Antidepressant Effects of Ethanol and Ethyl Acetate Extracts from Cannabis sativa L. (Hemp) Seeds in Invertebrate and Vertebrate Models
Yejin Ahn ,  Hyung Joo Suh ,  Sung Hee Han 한국원예학회 학술발표요지 2022.05 학술대회자료
Antidepressant Effects of Ethanol and Ethyl Acetate Extracts from Cannabis sativa Seeds in Invertebrate and Vertebrate Models
Yejin Ahn 의생명융합과학과 2022.01 학위논문

2021

Ethyl Acetate Fraction from Hemp (Cannabis sativa L.) Seed Ameliorate Depression-like Behavior in Unpredictable Chronic Mild Stress-induced Mice by Regulation BDNF Signaling
Yejin Ahn ,  Ki-Bae Hong ,  Hyung Joo Suh 외 2명 한국식품영양과학회 학술대회발표집 2021.10 학술대회자료

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Depression is a serious social disease in which a feeling of helplessness and depressed mood persists, affecting physical activity and mental function, leading to deterioration of daily functions. Various antidepressants have been developed for the treatment of depression over the past few decades, most of which act by inhibiting the reuptake of neurotransmitters. However, antidepressants are ineffective in some patients and have side effects that cause central nervous system and gastrointestinal disturbances. Accordingly, there is an increasing demand for natural products that have a low risk of side effects and have antidepressant effects. Hemp seeds are rich in protein and fat, are easily digestible, and help improve blood circulation, anti-inflammatory and constipation. In addition, hemp seeds contain cannabinoids that have anti-inflammatory, anxiety-reducing, stress-reducing, and analgesic effects, so it can be used as a non-pharmacological treatment for depression.
Three experiments in this study were designed to evaluate the antidepressant effects of hemp seeds ethanol extract (HE) and ethyl acetate fraction (EA) in invertebrate and vertebrate models. In an invertebrate model, the antidepressant effect of HE was confirmed in a Drosophila model with chlorpromazine (CPZ)-induced depression. Administration of HE significantly reversed the CPZ-induced reductions of daytime activity and nighttime sleep. In addition, HE significantly increased the mRNA expression levels of dopaminergic and serotonergic receptors and antioxidant enzymes, and significantly increased the levels of depression-related neurotransmitters compared to control group.
In a vertebrate model, the antidepressant effects of HE and EA were evaluated in unpredictable chronic mild stress (UCMS)-induced depressed mice. Administration of HE and EA significantly improved behavioral factors related to depression, such as decreased sucrose preference and increased immobility time in tail suspension test and forced swimming test, compared with control group. In addition, the UCMS-induced changes in the levels of stress hormones and neurotransmitters were significantly reversed by administration of HE and EA. EA relieves depressive symptoms more effectively than HE, and shows antidepressant effects through upregulation of brain-derived neurotrophic factor signaling.
Finally, the effects of HE and EA on changes in the gut microbiota were investigated in a UCMS-induced mouse model. UCMS reduced species diversity and richness and caused intestinal microbiota dysbiosis in the intestinal microbiota. Administration of EA significantly increased species diversity and the concentration of short chain fatty acids, a major metabolite of microorganisms, compared to the control group. Furthermore, the major microbial changes associated with depression were improved with the administration of EA. In particular, EA decreased the relative abundance of Deferribacteraceae and significantly increased the relative abundance of Lactobacillaceae compared to the control group.
In conclusion, HE and EA alleviate depressive symptoms by increasing dopaminergic and serotonergic signaling, upregulating BDNF pathway, a major signaling pathway in depression, and improving the dysbiosis of gut microbiome
#depression #hemp seeds #cannabinoids #Drosophila melanogaster #unpredictable chronic mild stress #gut microbiome

목차

ABSTRACT I
CONTENTS III
LIST OF TABLES VI
LIST OF FIGURES VII
LIST OF ABBREVIATIONS X
Backgrounds 1
Chapter 1. Antidepressant effect of ethanol extract from Cannabis sativa seeds in chlorpromazine-induced Drosophila melanogaster model 12
1-1. Introduction 14
1-2. Materials and Methods 18
1-2-1. Materials 18
1-2-2. Extraction of HE 18
1-2-3. Cannabinoids analysis 18
1-2-4. Drosophila stocks 19
1-2-5. Locomotor activity assay 19
1-2-6. Behavioral tests 20
1-2-7. Quantitative real time polymerase chain reaction (qRT-PCR) 21
1-2-8. Depression-related neurotransmitters analysis 22
1-2-9. Statistical analysis 22
1-3. Results 23
1-3-1. Cannabinoids contents in HE 23
1-3-2. Chlorpromazine (CPZ)-induced depression Drosophila model 27
1-3-3. Effect of hemp seeds on locomotor activity in Drosophila 29
1-3-4. Effect of hemp seeds on locomotor activity in CPZ-induced Drosophila model 31
1-3-5. Effect of HE on locomotor activity in Drosophila model 33
1-3-6. Effect of HE on locomotor activity in CPZ-induced Drosophila model 35
1-3-7. Effect of HE on behavioral patterns in CPZ-induced Drosophila model 38
1-3-8. Effect of HE on climbing activity in CPZ-induced Drosophila model 40
1-3-9. Effect of HE on the mRNA expression of depression-related receptors in CPZ-induced Drosophila model 42
1-3-10. Effect of HE on the mRNA expression associated with antioxidant in CPZ-induced Drosophila model 44
1-3-11. Effect of HE on the neurotransmitter contents in CPZ-induced Drosophila model 46
1-4. Discussion 48
1-5. Conclusion 53
Chapter 2. Antidepressant effects of cannabinoids-rich ethyl acetate fraction from hemp seeds in unpredictable mild chronic stress-induced BALB/c mice model 54
2-1. Introduction 56
2-2. Materials and Methods 58
2-2-1. Sample preparation 58
2-2-2. Cannabinoid analysis 58
2-2-3. Polyphenol and flavonoid content and radical scavenging activity 58
2-2-4. Animals 59
2-2-5. UCMS procedure 60
2-2-6. Sucrose preference test (SPT) 60
2-2-7. Behavioral tests 62
2-2-8. Determination of stress hormone levels 62
2-2-9. Neurotransmitter analysis 63
2-2-10. Western blotting 63
2-2-11. Statistical analysis 64
2-3. Results 64
2-3-1. Cannabinoid contents in HE and EA 64
2-3-2. Polyphenol and flavonoid content and radical scavenging activity of HE and EA 67
2-3-3. Polyphenol contents of HE and EA 69
2-3-4. Effects of EA and HE on body weight in UCMS-induced mice 71
2-3-5. Effects of EA and HE on sucrose preference in UCMS-induced mice 73
2-3-6. Effects of EA and HE on depressive-like behaviors in UCMS-induced mice 75
2-3-7. Effects of EA and HE on stress-related hormone levels in UCMS-induced mice 78
2-3-8. Effects of EA and HE on neurotransmitter levels in UCMS-induced mice brains 80
2-3-9. Effects of EA and HE on the protein expressions of BDNF pathway in UCMS-induced mice brains 82
2-3-10. Effects of EA and HE on the protein expressions of synaptophysin, Cox-2, and iNOS in UCMS-induced mice 84
2-4. Discussion 87
2-5. Conclusion 91
Chapter 3. Effects of ethanol extract and ethyl aceatate fraction from hemp seeds on gut microbiome in UCMS-induced mice 92
3-1. Introduction 94
3-2. Materials and methods 97
3-2-1. Animal experiments 97
3-2-2. Short chain fatty acid (SCFA) analysis in cecal feces 97
3-2-3. Microbial analysis in fecal microorganisms 98
3-2-4. Statistical analysis 98
3-3. Results 99
3-3-1. Effects of EA and HE on SCFA concentrations in UCMS-induced mice 99
3-3-2. Effects of EA and HE on α-diversity and β-diversity in UCMS-induced mice 101
3-3-3. Effects of EA and HE on the gut microbiota composition in UCMS-induced mice 104
3-3-4. Correlation analysis between depression-related parameters and gut microbiota 115
3-3-5. LDA score analysis 117
3-4. Discussion 121
3-5. Conclusion 125
CONCLUSION 126
ABSTRACT IN KOREAN 128
REFERENCES 131

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