CN115838653A - Lactobacillus plantarum GM11 for improving bad mood and application thereof - Google Patents
Lactobacillus plantarum GM11 for improving bad mood and application thereof Download PDFInfo
- Publication number
- CN115838653A CN115838653A CN202210810812.7A CN202210810812A CN115838653A CN 115838653 A CN115838653 A CN 115838653A CN 202210810812 A CN202210810812 A CN 202210810812A CN 115838653 A CN115838653 A CN 115838653A
- Authority
- CN
- China
- Prior art keywords
- medicament
- lactobacillus plantarum
- level
- depression
- hippocampus
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 240000006024 Lactobacillus plantarum Species 0.000 title claims abstract description 43
- 235000013965 Lactobacillus plantarum Nutrition 0.000 title claims abstract description 43
- 229940072205 lactobacillus plantarum Drugs 0.000 title claims abstract description 43
- 206010027940 Mood altered Diseases 0.000 title abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 41
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 34
- 230000036506 anxiety Effects 0.000 claims abstract description 32
- 235000013376 functional food Nutrition 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 238000004321 preservation Methods 0.000 claims abstract description 6
- 238000009629 microbiological culture Methods 0.000 claims abstract description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 60
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 claims description 46
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 claims description 46
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 claims description 46
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims description 42
- 210000001320 hippocampus Anatomy 0.000 claims description 23
- 210000002966 serum Anatomy 0.000 claims description 23
- 229960000890 hydrocortisone Drugs 0.000 claims description 21
- 102000005636 Cyclic AMP Response Element-Binding Protein Human genes 0.000 claims description 18
- 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 claims description 18
- 230000014509 gene expression Effects 0.000 claims description 15
- 102000003777 Interleukin-1 beta Human genes 0.000 claims description 14
- 108090000193 Interleukin-1 beta Proteins 0.000 claims description 14
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims description 11
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 11
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 11
- 230000000638 stimulation Effects 0.000 claims description 11
- 239000002068 microbial inoculum Substances 0.000 claims description 9
- 230000001580 bacterial effect Effects 0.000 claims description 6
- 208000020401 Depressive disease Diseases 0.000 claims description 5
- 235000021107 fermented food Nutrition 0.000 claims description 5
- 239000000275 Adrenocorticotropic Hormone Substances 0.000 claims description 4
- 101800000414 Corticotropin Proteins 0.000 claims description 4
- 102100027467 Pro-opiomelanocortin Human genes 0.000 claims description 4
- 239000003470 adrenal cortex hormone Substances 0.000 claims description 4
- 229960000258 corticotropin Drugs 0.000 claims description 4
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 claims description 4
- RKHQGWMMUURILY-UHRZLXHJSA-N cortivazol Chemical compound C([C@H]1[C@@H]2C[C@H]([C@]([C@@]2(C)C[C@H](O)[C@@H]1[C@@]1(C)C2)(O)C(=O)COC(C)=O)C)=C(C)C1=CC1=C2C=NN1C1=CC=CC=C1 RKHQGWMMUURILY-UHRZLXHJSA-N 0.000 claims description 4
- 239000003488 releasing hormone Substances 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims description 2
- 210000004907 gland Anatomy 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 238000000855 fermentation Methods 0.000 claims 1
- 230000004151 fermentation Effects 0.000 claims 1
- 239000006041 probiotic Substances 0.000 abstract description 13
- 235000018291 probiotics Nutrition 0.000 abstract description 13
- 230000036651 mood Effects 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 6
- 230000036541 health Effects 0.000 abstract description 6
- 230000003340 mental effect Effects 0.000 abstract description 6
- 244000005700 microbiome Species 0.000 abstract description 6
- 230000002411 adverse Effects 0.000 abstract description 4
- 230000008451 emotion Effects 0.000 abstract description 4
- 239000000654 additive Substances 0.000 abstract description 2
- 230000000996 additive effect Effects 0.000 abstract description 2
- 241000700159 Rattus Species 0.000 description 36
- 238000002474 experimental method Methods 0.000 description 22
- 230000000694 effects Effects 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 230000000971 hippocampal effect Effects 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 12
- 230000004179 hypothalamic–pituitary–adrenal axis Effects 0.000 description 11
- 230000002757 inflammatory effect Effects 0.000 description 10
- 230000006870 function Effects 0.000 description 7
- 230000003542 behavioural effect Effects 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 239000002858 neurotransmitter agent Substances 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 230000009182 swimming Effects 0.000 description 5
- 238000010171 animal model Methods 0.000 description 4
- 230000006399 behavior Effects 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000008506 pathogenesis Effects 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 108020004465 16S ribosomal RNA Proteins 0.000 description 3
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000000529 probiotic effect Effects 0.000 description 3
- 208000020016 psychiatric disease Diseases 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 2
- 244000046052 Phaseolus vulgaris Species 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 235000013365 dairy product Nutrition 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000007267 depressive like behavior Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 244000005709 gut microbiome Species 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000000877 morphologic effect Effects 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000003956 synaptic plasticity Effects 0.000 description 2
- 238000012549 training Methods 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 235000020926 24-h fasting Nutrition 0.000 description 1
- PLXMOAALOJOTIY-FPTXNFDTSA-N Aesculin Natural products OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)[C@H]1Oc2cc3C=CC(=O)Oc3cc2O PLXMOAALOJOTIY-FPTXNFDTSA-N 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000007415 Anhedonia Diseases 0.000 description 1
- 206010002869 Anxiety symptoms Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102000016938 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- WNBCMONIPIJTSB-BGNCJLHMSA-N Cichoriin Natural products O([C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1)c1c(O)cc2c(OC(=O)C=C2)c1 WNBCMONIPIJTSB-BGNCJLHMSA-N 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-CUHNMECISA-N D-Cellobiose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-CUHNMECISA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 101000831205 Danio rerio Dynein axonemal assembly factor 11 Proteins 0.000 description 1
- 102100024282 Dynein axonemal assembly factor 11 Human genes 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241001559542 Hippocampus hippocampus Species 0.000 description 1
- 101000831210 Homo sapiens Dynein axonemal assembly factor 11 Proteins 0.000 description 1
- 241000218588 Lactobacillus rhamnosus Species 0.000 description 1
- 241000194035 Lactococcus lactis Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000736262 Microbiota Species 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 206010027951 Mood swings Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 206010029216 Nervousness Diseases 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 208000012545 Psychophysiologic disease Diseases 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 235000014897 Streptococcus lactis Nutrition 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 230000007529 anxiety like behavior Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000008918 emotional behaviour Effects 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 230000006397 emotional response Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- XHCADAYNFIFUHF-TVKJYDDYSA-N esculin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC(C(=C1)O)=CC2=C1OC(=O)C=C2 XHCADAYNFIFUHF-TVKJYDDYSA-N 0.000 description 1
- 229940093496 esculin Drugs 0.000 description 1
- AWRMZKLXZLNBBK-UHFFFAOYSA-N esculin Natural products OC1OC(COc2cc3C=CC(=O)Oc3cc2O)C(O)C(O)C1O AWRMZKLXZLNBBK-UHFFFAOYSA-N 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000012048 forced swim test Methods 0.000 description 1
- 235000012055 fruits and vegetables Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000007149 gut brain axis pathway Effects 0.000 description 1
- 230000008821 health effect Effects 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000021056 liquid food Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000007472 neurodevelopment Effects 0.000 description 1
- 230000004766 neurogenesis Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000004031 neuronal differentiation Effects 0.000 description 1
- 230000007514 neuronal growth Effects 0.000 description 1
- 230000006576 neuronal survival Effects 0.000 description 1
- 210000000607 neurosecretory system Anatomy 0.000 description 1
- 239000003900 neurotrophic factor Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000004796 pathophysiological change Effects 0.000 description 1
- 230000008289 pathophysiological mechanism Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 235000021110 pickles Nutrition 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000001671 psychotherapy Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000007363 regulatory process Effects 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000021055 solid food Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Images
Landscapes
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention belongs to the field of microorganisms and biomedicines, and particularly relates to lactobacillus plantarum GM11 for improving adverse emotion and application thereof. The invention provides lactobacillus plantarum (named as GM 11), which is a strain preserved by the China general microbiological culture Collection center (CGMCC) with the preservation number of CGMCC No. 25063. The strain has the potential of being developed into the mental probiotics for improving the bad moods such as anxiety, depression and the like. GM11 can be independently formed into a preparation, can also be added into other medicines, health products or functional foods as an additive for improving the unfavorable mood of anxiety, depression and the like, and has very wide application prospect.
Description
Technical Field
The invention belongs to the field of microorganisms and biomedicines, and particularly relates to lactobacillus plantarum GM11 for improving adverse emotion and application thereof.
Background
Depression and anxiety disorders are two types of mental disorders or bad mood which are relatively common in people, and the prevalence rate shows a rising trend, which seriously affects the life quality of patients. Anxiety and depression, although two different mental disorders, are closely related and may be present in combination. Survey shows that 33-95% of depression patients are simultaneously associated with anxiety symptoms. Depression is a complex, multifactorial mental disorder with severe medical complications and high disability affecting approximately 20% of the global population.
Depression (Depression) is a common mood disorder, characterized primarily by marked and persistent mood swings, a psychosomatic disorder with behavioral changes, changes in the nervous system, and other pathophysiological changes. The pathogenesis of the traditional Chinese medicine is complex, the symptoms are various, and the life quality and the social function of a patient are seriously influenced. In addition to the high relevance to suicide mortality, depression is also often associated with many other chronic diseases, and the world health organization reports that depression will be the greatest health challenge by 2030.
Anxiety (Anxiety) and depression are often associated, both of which are commonly referred to as "Anxiety-depression syndrome". Anxiety refers to the state of restlessness, hands rubbing and feet shaking, mental stress of the patient in the absence of corresponding objective factors. It is a normal emotional response, but excessive anxiety can lead to emotional or physiological disorders, which not only result in impaired patient function and reduced quality of life, but also increase the risk of death.
Despite favorable performance in drug development, most treated individuals do not achieve adequate symptomatic relief and functional recovery. At present, the treatment rate of depression and anxiety is low, the treatment effect is poor, the recurrence rate is high, and huge medical expense is caused, so that the treatment method becomes a heavy burden for society and families. The prevention and treatment of depression and anxiety have become a worldwide problem. Furthermore, a significant proportion of patients are unable to tolerate the adverse effects of current drug therapies. At present, common relief measures for unfavorable moods such as depression and anxiety also comprise psychotherapy, health education, relaxation training, family intervention and the like, but all have certain defects in application. Therefore, it is important to develop and search better solutions or alternative measures to relieve the bad mood such as depression and anxiety, and the solution is a research topic to be solved urgently.
During the last decade, a number of studies have demonstrated that the gut flora, gut-brain axis, plays an important role in the regulation of the central nervous system, such as emotional behavior, cognitive function, etc. Evidence from animal experiments and clinical studies reveals the potential role of intestinal flora in adverse mood pathogenesis, such as depression, anxiety, etc. The core of the intestinal flora-gut-brain axis is the intestinal microflora, which involves neurotransmitters and neuropeptides, and low-level immune activation of changes in neural functions and behaviors, such as hypothalamic-pituitary-adrenal-adrenocortical (HPA) axis activity and neurogenesis.
The role of the gut microbiota in health and disease has been of increasing concern, and over the last decade, studies evaluating gut commensal microbiota have shown that they are involved in important physiological processes, and that Probiotics (Probiotics) not only affect and shape the host immune system and affect its metabolism, but also the function of the gut and central nervous system. Accordingly, the function of probiotics in preventing and treating unfavorable moods such as depression and anxiety also arouses high attention of scholars at home and abroad, and a new idea and a new direction are possibly provided for improving depression and anxiety. Probiotics refer to a class of living microorganisms that, when ingested in sufficient quantities, exert a beneficial health effect on the host. Probiotics that are capable of modulating central nervous function and behavior are also defined as "mental probiotics". The novel mental probiotics and the composition thereof which can relieve the unfavorable emotions such as depression and anxiety and the like are screened, and the method has great scientific and practical significance for improving and assisting in treating depression and other intestinal-cerebral axis related unfavorable emotions.
However, the number and variety of microorganisms in nature are large, and even microorganisms of the same species may have a large difference in their beneficial effects in the organism. Therefore, screening for new probiotic bacteria remains a very challenging topic.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides lactobacillus plantarum for improving depression, anxiety and other undesirable moods and application thereof, and aims to provide novel lactobacillus plantarum for improving depression, anxiety and other undesirable moods.
Lactobacillus plantarum (GM 11) is a strain with the preservation number of CGMCC No.25063 and is preserved by the China general microbiological culture Collection center of China Committee for culture Collection of microorganisms.
The invention also provides a microbial inoculum prepared from the lactobacillus plantarum, wherein the viable count of the lactobacillus plantarum is more than or equal to 2 multiplied by 10 9 CFU/mL。
The invention also provides application of the lactobacillus plantarum or the microbial inoculum in preparing a medicament for treating depression and/or anxiety.
Preferably, the medicament is used for increasing the level of at least one of 5-hydroxytryptamine and brain-derived neurotrophic factor in serum;
and/or the medicament is used for reducing the level of at least one of cortisol, corticoid releasing hormone and adrenocorticotropic hormone in serum;
and/or, the medicament is for reducing the level of at least one of TNF-alpha, IL-1 beta in serum;
and/or, the medicament is for increasing the level of at least one of 5-hydroxytryptamine and brain-derived neurotrophic factor in hippocampus;
and/or, the medicament is for use in reducing cortisol levels in the hippocampus;
and/or, the medicament is for reducing the level of at least one of TNF-alpha, IL-1 beta in the hippocampus;
and/or, the medicament is for up-regulating the expression level of CREB protein in the cortex and hippocampus.
Preferably, the drug is a drug that relieves the stimulation of the hypothalamic-pituitary-adrenal axis caused by stress.
The invention also provides a medicament for treating depression and/or anxiety, which is prepared by taking the lactobacillus plantarum or the microbial inoculum as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.
Preferably, the medicament is used for increasing the level of at least one of 5-hydroxytryptamine and brain-derived neurotrophic factor in serum;
and/or the medicament is used for reducing the level of at least one of cortisol, corticoid releasing hormone and adrenocorticotropic hormone in serum;
and/or, the medicament is for reducing the level of at least one of TNF-alpha, IL-1 beta in serum;
and/or, the medicament is for increasing the level of at least one of 5-hydroxytryptamine and brain-derived neurotrophic factor in hippocampus;
and/or, the medicament is for use in reducing cortisol levels in the hippocampus;
and/or, the medicament is for reducing the level of at least one of TNF-alpha, IL-1 beta in the hippocampus;
and/or, the medicament is for up-regulating the expression level of CREB protein in the cortex and hippocampus.
Preferably, the drug is a drug that relieves the stimulation of the hypothalamic-pituitary-adrenal axis caused by stress.
The invention also provides a functional food for treating depression and/or anxiety, and the preparation raw materials of the functional food comprise the lactobacillus plantarum or the microbial inoculum.
Preferably, the lactobacillus plantarum strain is fermented food prepared by inoculating the lactobacillus plantarum strain or the microbial inoculum and then fermenting.
Preferably, the fermented food comprises dairy products, bean products and fruit and vegetable foods.
Preferably, the fermented food includes solid food, liquid food, and semi-solid food.
According to the invention, the lactobacillus plantarum GM11 is found to improve anxiety and depression behaviors through model animal research for the first time, the serum and hippocampal 5-HT and BDNF levels of a rat of a depression model can be increased, and the BDNF and CREB expressions of cortex and hippocampal are up-regulated. Meanwhile, the strain can also relieve the stimulation of hypothalamus-pituitary-adrenal (HPA) axis caused by stress and inhibit the levels of serum and hippocampal inflammatory factors of a model rat. The strain has the potential of being developed into the mental probiotics for improving the bad moods such as anxiety, depression and the like. GM11 can be independently formed into a preparation, can also be added into other medicines, health products or functional foods as an additive for improving the unfavorable mood of anxiety, depression and the like, and has very wide application prospect.
It will be apparent that various other modifications, substitutions and alterations can be made in the present invention without departing from the basic technical concept of the invention as described above, according to the common technical knowledge and common practice in the field.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Drawings
Figure 1 effect of lactobacillus plantarum GM11 on rat behavioural experiments after 8 weeks of intervention. (A) an elevated plus maze test; (B) open field testing; (C) forced swimming test; (D) a sugar water preference test; each group contained 10 animals. # P<0.05vs Normal group (Control); ## P<0.01vs Normal group (Control); * P<0.05vs depression model group (CUMS); ** P<0.01vs depression model group (CUMS).
FIG. 2 Effect of Lactobacillus plantarum GM11 on levels of relevant indices of rat serum 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), and HPA axis 8 weeks after intervention. (a) 5-HT levels; (B) BDNF levels; (C) Cortisol (CORT) levels; each group contained 10 animals. # P<0.05vs Normal group (Control); ## P<0.01vs Normal group (Control); * P<0.05vs depression model group (CUMS); ** P<0.01vs depression model group (CUMS).
Figure 3 effect of lactobacillus plantarum GM11 on serum inflammatory factor levels in rats 8 weeks after intervention. (a) TNF- α levels; (B) IL-1 β levels; each group contained 10 animals. # P<0.05vs Normal group (Control); ## P<0.01vs Normal group (Control); * P<0.05vs depression model group (CUMS); ** P<0.01vs depression model group (CUMS).
FIG. 4 Effect of Lactobacillus plantarum GM11 on levels of relevant indices of rat hippocampal 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), and HPA axis 8 weeks after intervention. (a) 5-HT levels; (B) BDNF levels; (C) Cortisol (CORT) levels; each group contained 10 animals. # P<0.05vs Normal group (Control); ## P<0.01vs Normal group (C)ontrol)； * P<0.05vs depression model group (CUMS); ** P<0.01vs depression model group (CUMS).
Figure 5 effect of lactobacillus plantarum GM11 on rat hippocampal inflammatory factor levels after 8 weeks of intervention. (a) TNF- α levels; (B) IL-1 β levels; each group contained 10 animals. # P<0.05vs Normal group (Control); ## P<0.01vs Normal group (Control); * P<0.05vs depression model group (CUMS); ** P<0.01vs depression model group (CUMS).
Figure 6 effect of lactobacillus plantarum GM11 intervention on rat cortex and hippocampal brain-derived neurotrophic factor (BDNF) and cAMP response element binding protein (CREB) protein expression levels after 8 weeks. (a) cortical BDNF and CREB expression levels; (B) hippocampal BDNF and CREB expression levels; each group contained 10 animals. # P<0.05vs Normal group (Control); ## P<0.01vs Normal group (Control); * P<0.05vs depression model group (CUMS); ** P<0.01vs depression model group (CUMS).
Detailed Description
The reagents and materials used in the following examples and experimental examples are commercially available ones without specific reference.
EXAMPLE 1 Strain screening and preparation of bacterial solutions (inoculants)
1. Strain isolation and bacterial liquid preparation
The method comprises the steps of screening various Lactobacillus plantarum, lactobacillus rhamnosus, lactococcus lactis and the like from sources such as plateau dairy products, plateau salt lakes, sichuan special fermented foods (pickles, bean cotyledons and the like), screening Lactobacillus plantarum GM11 from strains meeting basic requirements in early detection through physicochemical analysis, category identification and partial safety index detection, and preparing a bacterial solution. The viable count of Lactobacillus plantarum in the bacterial liquid is more than or equal to 2 multiplied by 10 9 CFU/mL。
2. Identification and preservation
The GM11 strain is identified to be Lactobacillus plantarum (Lactobacillus plantarum), and is preserved in China general microbiological culture Collection center (CGMCC) in 2022, 6 months and 10 days; the preservation address is as follows: western road No.1 institute of north chen, institute of microbiology, academy of sciences of china, tokyo, japan; the preservation number is: CGMCC No.25063
The specific identification characteristics are as follows:
(1) Morphological characteristics
Gram positive, no spores. The bent rod-shaped or short rod-shaped is mostly a short rod, the two ends of the short rod are blunt and round, and the short rod-shaped or short rod-shaped is singly arranged in pairs.
(2) Physiological and biochemical characteristics
The bacterial colony is medium-sized, convex, milky white, opaque, wet and smooth in surface, neat in edge, and circular. (1) Maltose, cellobiose, mannitol, lactose, esculin, sorbitol, sucrose can be used. (2) H 2 O 2 The catalase, nitrate reduction, gelatin liquefaction and indole experiments are all negative.
(3) Sequence analysis of 16S rDNA
The sequence is as follows (SEQ ID NO. 1):
ATGCAGTCGAACGAACTCTGGTATTGATTGGTGCTTGCATCATGATT TACATTTGAGTGAGTGGCGAACTGGTGAGTAACACGTGGGAAACCTGC CCAGAAGCGGGGGATAACACCTGGAAACAGATGCTAATACCGCATAAC AACTTGGACCGCATGGTCCGAGCTTGAAAGATGGCTTCGGCTATCACTT TTGGATGGTCCCGCGGCGTATTAGCTAGATGGTGGGGTAACGGCTCACC ATGGCAATGATACGTAGCCGACCTGAGAGGGTAATCGGCCACATTGGG ACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTAGGGAATCTT CCACAATGGACGAAAGTCTGATGGAGCAACGCCGCGTGAGTGAAGAA GGGTTTCGGCTCGTAAAACTCTGTTGTTAAAGAAGAACATATCTGAGAG TAACTGTTCAGGTATTGACGGTATTTAACCAGAAAGCCACGGCTAACTA CGTGCCAGCAGCCGCGGTAATACGTAGGTGGCAAGCGTTGTCCGGATTT ATTGGGCGTAAAGCGAGCGCAGGCGGTTTTTTAAGTCTGATGTGAAAG CCTTCGGCTCAACCGAAGAAGTGCATCGGAAACTGGGAAACTTGAGTG CAGAAGAGGACAGTGGAACTCCATGTGTAGCGGTGAAATGCGTAGATA TATGGAAGAACACCAGTGGCGAAGGCGGCTGTCTGGTCTGTAACTGAC GCTGAGGCTCGAAAGTATGGGTAGCAAACAGGATTAGATACCCTGGTA GTCCATACCGTAAACGATGAATGCTAAGTGTTGGAGGGTTTCCGCCCTT CAGTGCTGCAGCTAACGCATTAAGCATTCCGCCTGGGGAGTACGGCCG CAAGGCTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGTGG AGCATGTGGTTTAATTCGAAGCTACGCGAAGAACCTTACCAGGTCTTGA CATACTATGCAAATCTAAGAGATTAGACGTTCCCTTCGGGGACATGGAT ACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTA AGTCCCGCAACGAGCGCAACCCTTATTATCAGTTGCCAGCATTAAGTTG GGCACTCTGGTGAGACTGCCGGTGACAAACCGGAGGAAGGTGGGGAT GACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGTGCTACA ATGGATGGTACAACGAGTTGCGAACTCGCGAGAGTAAGCTAATCTCTTA AAGCCATTCTCAGTTCGGATTGTAGGCTGCAACTCGCCTACATGAAGTC GGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCG GGCCTTGTACACACCGCCCGTCACACCATGAGAGTTTGTAACACCCAA AGTCGGTGGGGTAACCTTTTAGGAACCAGCCGCCTAA
homology comparison is carried out on the sequence in a gene bank by using a BLAST tool on an NCBI website, the result shows that the similarity of the 16S rDNA of the GM11 and the 16S rDNA sequence of the Lactobacillus plantarum (Lactobacillus plantarum) reaches more than 99.93 percent, and the strain GM11 is identified as a Lactobacillus plantarum (Lactobacillus plantarum) by combining morphological and physiological and biochemical characteristics.
The advantageous effects of the present invention will be further described below by experiments.
Experimental example 1 Effect of GM11 on improvement of anxiety and depression
1. Experimental methods
(1) Construction of animal models
Modeling an animal: male SD rats, 40, 180g-220g, provided by mastery laboratory animals ltd, laboratory production license No.: SYXK (CHUAN) 2015-010; use of license number: SYXK 2014-189.
Chronic Unpredictable Mild Stimulation (CUMS) comprises the following 11 stimuli: (1) fasting for 24h; (2) water is forbidden and the bottle is empty for 24 hours; (3) clamping tail for 3min; (4) 24h for wet padding; (5) braking and binding for 3h; (6) inclining the cage box for 24h at 45 ℃; (7) forced swimming for 10 minutes; (8) performing isolated culture for 24 hours; (9) continuously illuminating for 24h; no padding is in the red;
and (5) crowding stimulation. To avoid biorhythms, 1-2 of these were randomly applied daily (6 days of random stimulation per week), and the cumulative number of uses of each stimulation did not exceed three times throughout the duration of the experiment.
The CUMS model is an animal model simulating the disease state of depression patients and is commonly used for screening antidepressant drugs and experimental study on the pathophysiological mechanism of depression.
(2) Grouping and intervention of experimental animals
Rats were divided into a normal Control group (Control) and a depression model group (CUMS) which rats were stimulated with chronic unpredictable mild stress for 3 weeks. After 3 weeks of molding, the depression model group was further divided into a model group (CUMS) and a Lactobacillus plantarum GM11 group (GM 11). Chronic stimulation was still continued during the intervention. The behavioural assays were started 3 weeks after probiotic intervention dosing, during which time the probiotic was still gavaged daily.
(3) Behavioral indicator detection
(1) Elevated cross maze: rats were placed in the maze from the central compartment towards the open arm, immediately started timing and videotaping, and activity was recorded within 5 minutes. Open arm residence time was measured.
(2) Open field experiment: after the animals are placed in the open field center, timing and video recording are started immediately, and the video recording is stopped after 10min observation. Calculating the residence time of the rat in the central area of the open field
(3) Forced swimming: the forced swim test is a classical behavioural test to assess the characteristics of rodent depression-like behaviour. The experimental barrel is filled with clear water with the height of about 30cm, the water temperature is 24 +/-1 ℃, and each mouse is subjected to adaptive swimming training for 10 minutes 24 hours before the formal experiment. In the actual experiment, the total immobility time of each rat within the next 4min was recorded for 6 min.
(4) Sweet water preference test: the experimental mice are subjected to sugar water adaptation for 24h before the experiment begins, and water is forbidden to be fed for 24h after the experiment is finished. In the case of the official experiment, 2 bottles of water, pre-dosed, were given simultaneously to each rat: 1 bottle of 1% sucrose water and 1 bottle of tap water, and the experiment was finished after 1 hour, and the sucrose water consumption and the pure water consumption of each rat were calculated. Calculating the sugar water preference index% = sugar water consumption/(sugar water consumption + pure water consumption) × 100% according to a formula.
(4) Blood biochemical index determination
Taking whole blood, standing, centrifuging and collecting upper serum. 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), cortisol (CORTICOST), inflammatory factors TNF-alpha and IL-1 beta were measured by Enzyme-linked immunosorbent assay (ELISA). The specific experimental procedures were performed according to the kit instructions.
(5) Biochemical index determination of sea horse
The hippocampal sample was weighed, and precooled PBS buffer was added in an amount 9 times the weight of hippocampal tissue to prepare a homogenate supernatant, which was centrifuged to be subjected to the next measurement. The ELISA method is adopted to detect the hippocampus 5-HT, BDNF, CORT, inflammatory factors TNF-alpha and IL-1 beta. The specific experimental procedures were performed according to the kit instructions.
(6) Determination of expression condition of molecule related to hippocampal BDNF-CREB signal pathway
The relative Protein expression of hippocampal brain-derived neurotrophic factor (BDNF) -cAMP Response Element Binding Protein (CREB) signaling pathway-related molecules BDNF and CREB was determined by Western blot method.
2. Results of the experiment
The pathogenesis of depression or anxiety is quite complex, with disorders of monoamine neurotransmitters being the primary direction of research. Existing studies indicate that depression or anxiety is closely related to the deficiency of monoamine neurotransmitters such as 5-hydroxytryptamine (5-HT) and the like. Depression or anxiety another possible pathogenesis that has been demonstrated by numerous studies is The hyperactivity of The hypothalamic-pituitary-adrenal axis (HPA axis). The HPA axis is an important component of the neuroendocrine system and is involved in controlling the regulatory process of stress response. The major hormone in the HPA axis is Corticosterone (CORT).
Brain-derived neurotrophic factor (BDNF) is an important member of the neurotrophic factor family, and is widely distributed in the central nervous system, particularly in the hippocampus and cortex. BNDF, by binding to its high affinity specific receptor, initiates a series of downstream signal transduction processes, exerting its biological effects on the nervous system, including promoting neuronal survival, development, growth and differentiation, and regulating synaptic plasticity and nerve regeneration. Research shows that the occurrence of depression is related to the reduction of the content of BDNF, and the expression level of BDNF in the brain of depression patients is reduced. The lack of BDNF can cause a series of physiological abnormalities such as cognitive deficits, helplessness and anhedonia.
CREB is a nuclear regulatory factor, serves as a target of multiple signal transduction pathways in cells, and plays an important role in maintaining the normal nerve functions of synthesis of neurotransmitters, neuron generation, synaptic plasticity, learning, memory and the like. On the other hand, CREB is an important transcription factor regulating BDNF and memory formation, and it has been demonstrated that the transcription factor CREB plays a key role in cognition and initiation of memory integration. Therefore, up-regulation of CREB expression to regulate BDNF levels is of great importance in the amelioration of depression or anxiety.
The effect of GM11 on rat behavioural experiments 8 weeks after intervention is shown in figure 1. As can be seen from the figure, GM11 significantly increased the time of movement of the rat in the open arm in the elevated plus maze experiment; increasing the time of movement of rats in the central area in the open field experiment. Meanwhile, the immobility time of 4 minutes after the rat in a forced swimming experiment can be obviously reduced, and the sugar water consumption proportion of the rat in a sugar water consumption experiment can be obviously increased. These phenomena indicate that GM11 is able to significantly improve the depressive-like and anxiety-like behavior in rats that are models of depression.
The effect of GM11 on levels of relevant indices of rat serum 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF) and HPA axis 8 weeks after GM11 intervention is shown in FIG. 2. The effect of GM11 on serum inflammatory factor levels in rats 8 weeks after intervention is shown in figure 3. As can be seen from the figure, GM11 has the effect of significantly increasing the serum 5-hydroxytryptamine (5-HT) level of rats in a depression model; can significantly increase the level of the serum brain-derived neurotrophic factor (BDNF). Simultaneously, the composition can also reduce the level of Cortisol (CORT) in the serum of a rat and relieve the stimulation of the hypothalamus-pituitary-adrenal (HPA) axis caused by stress. In addition, GM11 has a tendency to reduce serum levels of inflammatory factors TNF- α and IL-1 β in rats in a model of depression.
The effect of GM11 intervention on levels of relevant indices of rat hippocampal 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF) and HPA axis at 8 weeks post intervention is shown in figure 4. The effect of GM11 on rat hippocampal inflammatory factor levels 8 weeks after intervention is shown in figure 5. As can be seen from the figure, GM11 significantly increased the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in the hippocampus of rats in the depressive model. And simultaneously can obviously reduce the level of rat hippocampal Cortisol (CORT). In addition, GM11 can significantly reduce the level of inflammatory factor TNF-alpha in hippocampus of rats in depression models, and has the tendency of reducing the level of IL-1 beta in hippocampus.
The effect of GM11 on rat cortex and hippocampal BDNF and CREB protein expression levels 8 weeks after intervention is shown in figure 6. As can be seen from the figure, GM11 significantly up-regulated the protein expression levels of the CUMS rat cortex and hippocampus BDNF and CREB.
The invention successfully separates the Lactobacillus plantarum GM11. Animal experiments show that GM11 can raise the levels of monoamine neurotransmitters 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF), lower the level of hormone Cortisol (CORT), and relieve HPA axis hyperexcitability. GM11 has the tendency of reducing the level of inflammatory factors, and GM11 can increase the expression level of BDNF and CREB in the cortex and hippocampus of a rat, thereby improving the behavior of the rat in depression-like and anxiety-like states. Therefore, the lactobacillus plantarum GM11 has the potential of being developed into the mental probiotics for improving the bad moods such as anxiety, depression and the like, and has a wide application prospect.
Claims (10)
1. A lactobacillus plantarum strain characterized by: it is a strain with the preservation number of CGMCC No.25063, which is preserved by the China general microbiological culture Collection center.
2. The microbial inoculum is characterized in that: it is made of the lactobacillus plantarum described in claim 1, the viable count of which is more than or equal to 2 x 10 9 CFU/mL。
3. Use of a lactobacillus plantarum as defined in claim 1 or a bacterial agent as defined in claim 2 for the preparation of a medicament for the treatment of depression and/or anxiety.
4. Use according to claim 3, characterized in that: the medicine is used for increasing the level of at least one of 5-hydroxytryptamine and brain-derived neurotrophic factor in serum;
and/or the medicament is used for reducing the level of at least one of cortisol, corticoid releasing hormone and adrenocorticotropic hormone in serum;
and/or, the medicament is for reducing the level of at least one of TNF-alpha, IL-1 beta in serum;
and/or, the medicament is for increasing the level of at least one of 5-hydroxytryptamine and brain-derived neurotrophic factor in hippocampus;
and/or, the medicament is for use in reducing cortisol levels in the hippocampus;
and/or, the medicament is for reducing the level of at least one of TNF-alpha, IL-1 beta in the hippocampus;
and/or, the medicament is for up-regulating the expression level of CREB protein in the cortex and hippocampus.
5. Use according to claim 3, characterized in that: the medicine is used for relieving the stimulation of hypothalamus-pituitary-adrenal gland axis caused by stress.
6. A medicament for the treatment of depression and/or anxiety characterized by: the lactobacillus plantarum is prepared by taking the lactobacillus plantarum of claim 1 or the microbial inoculum of claim 2 as an active ingredient, and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.
7. Use according to claim 6, characterized in that: the medicine is used for increasing the level of at least one of 5-hydroxytryptamine and brain-derived neurotrophic factor in serum;
and/or the medicament is used for reducing the level of at least one of cortisol, corticoid releasing hormone and adrenocorticotropic hormone in serum;
and/or, the medicament is for reducing the level of at least one of TNF-alpha, IL-1 beta in serum;
and/or, the medicament is for increasing the level of at least one of 5-hydroxytryptamine and brain-derived neurotrophic factor in hippocampus;
and/or, the medicament is for use in reducing cortisol levels in the hippocampus;
and/or, the medicament is for reducing the level of at least one of TNF-alpha, IL-1 beta in the hippocampus;
and/or, the medicament is used for up-regulating the expression level of CREB protein in the cortex and hippocampus.
8. Use according to claim 6, characterized in that: the medicine is used for relieving the stimulation of hypothalamus-pituitary-adrenal gland axis caused by stress.
9. A functional food for the treatment of depression and/or anxiety characterized by: the raw material for preparing the lactobacillus plantarum strain comprises the lactobacillus plantarum strain of claim 1 or the microbial inoculum of claim 2.
10. The functional food according to claim 9, characterized in that: the lactobacillus plantarum strain is a fermented food prepared by fermentation after being inoculated with the lactobacillus plantarum strain of claim 1 or the microbial inoculum of claim 2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210810812.7A CN115838653A (en) | 2022-07-11 | 2022-07-11 | Lactobacillus plantarum GM11 for improving bad mood and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210810812.7A CN115838653A (en) | 2022-07-11 | 2022-07-11 | Lactobacillus plantarum GM11 for improving bad mood and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115838653A true CN115838653A (en) | 2023-03-24 |
Family
ID=85574730
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210810812.7A Pending CN115838653A (en) | 2022-07-11 | 2022-07-11 | Lactobacillus plantarum GM11 for improving bad mood and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115838653A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116814505A (en) * | 2023-08-11 | 2023-09-29 | 顾建文 | Lactobacillus rhamnosus and application thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110066753A (en) * | 2019-05-13 | 2019-07-30 | 吉林省农业科学院 | Lactobacillus plantarum DP189 and its application |
| CN110684694A (en) * | 2019-11-05 | 2020-01-14 | 北京科拓恒通生物技术股份有限公司 | Lactobacillus plantarum for relieving mental stress and application thereof |
| CN111329884A (en) * | 2020-02-18 | 2020-06-26 | 天津科技大学 | Application of lactobacillus plantarum BC299 in medicines and foods for treating inflammatory bowel diseases and psychogenic problems |
| CN111728111A (en) * | 2020-06-28 | 2020-10-02 | 武汉康复得生物科技股份有限公司 | Probiotic composition for relieving anxiety or depression and application thereof |
| CN112930392A (en) * | 2018-09-03 | 2021-06-08 | 临床营养国际(马来西亚)私人有限公司 | Probiotic bacteria for upper respiratory infections, stress, anxiety, memory and cognitive dysfunction and aging |
| CN113512514A (en) * | 2021-07-01 | 2021-10-19 | 杭州娃哈哈科技有限公司 | Lactococcus lactis with depression improving effect and application thereof |
-
2022
- 2022-07-11 CN CN202210810812.7A patent/CN115838653A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112930392A (en) * | 2018-09-03 | 2021-06-08 | 临床营养国际(马来西亚)私人有限公司 | Probiotic bacteria for upper respiratory infections, stress, anxiety, memory and cognitive dysfunction and aging |
| CN110066753A (en) * | 2019-05-13 | 2019-07-30 | 吉林省农业科学院 | Lactobacillus plantarum DP189 and its application |
| CN110684694A (en) * | 2019-11-05 | 2020-01-14 | 北京科拓恒通生物技术股份有限公司 | Lactobacillus plantarum for relieving mental stress and application thereof |
| CN111329884A (en) * | 2020-02-18 | 2020-06-26 | 天津科技大学 | Application of lactobacillus plantarum BC299 in medicines and foods for treating inflammatory bowel diseases and psychogenic problems |
| CN111728111A (en) * | 2020-06-28 | 2020-10-02 | 武汉康复得生物科技股份有限公司 | Probiotic composition for relieving anxiety or depression and application thereof |
| CN113512514A (en) * | 2021-07-01 | 2021-10-19 | 杭州娃哈哈科技有限公司 | Lactococcus lactis with depression improving effect and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| YEN-WENN LIU等: "Psychotropic effects of Lactobacillus plantarum PS128 in early life-stressed and naïve adult mice", 《BRAIN RESEARCH》 * |
| YU-TING HO等: "Effects of Lactobacillus plantarum PS128 on Depressive Symptoms and Sleep Quality in Self-Reported Insomniacs：A Randomized，Double-Blind，Placebo-Controlled Pilot Trial", 《NUTRIENTS》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116814505A (en) * | 2023-08-11 | 2023-09-29 | 顾建文 | Lactobacillus rhamnosus and application thereof |
| CN116814505B (en) * | 2023-08-11 | 2024-04-19 | 顾建文 | Lactobacillus rhamnosus and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111728111B (en) | Probiotic composition for relieving anxiety or depression and application thereof | |
| Nishida et al. | Daily administration of paraprobiotic Lactobacillus gasseri CP2305 ameliorates chronic stress-associated symptoms in Japanese medical students | |
| CN110066753B (en) | Lactobacillus plantarum DP189 and application thereof | |
| CN110964650B (en) | Bacterial strain for preventing and treating metabolic diseases and application thereof | |
| Yang et al. | Lactobacillus plantarum CCFM1143 alleviates chronic diarrhea via inflammation regulation and gut microbiota modulation: a double-blind, randomized, placebo-controlled study | |
| US11253556B2 (en) | Lactobacillus fermentum GKF3, composition comprising the strain and method for improving psychataxia using the same | |
| CN108367033A (en) | The method and composition of depressive symptom is treated or prevented using bifidobacterium longum | |
| CN110835616A (en) | Active substance of lactobacillus paracasei GKS6, composition containing active substance and application of active substance to promotion of longevity | |
| JPWO2009131208A1 (en) | Novel lactic acid bacteria having antiallergic action, antiallergic agent, food and pharmaceutical composition containing the lactic acid bacteria, and method for producing the antiallergic agent | |
| Rocks et al. | Possible use of fermented foods in rehabilitation of anorexia nervosa: the gut microbiota as a modulator | |
| CN112972502A (en) | Application of bifidobacterium breve CCFM1025 in relieving Alzheimer's disease | |
| CN115838653A (en) | Lactobacillus plantarum GM11 for improving bad mood and application thereof | |
| CN110833565A (en) | Active substance of lactobacillus plantarum GKM3, composition containing same and application of active substance to longevity promotion | |
| Tang et al. | Queen bee larva consumption improves sleep disorder and regulates gut microbiota in mice with PCPA-induced insomnia | |
| CN106472670B (en) | Sports nutritional fermented milk and preparation method thereof | |
| WO2023236739A1 (en) | Use of nucleotide mixture in preparation of formulation for preventing and treating alzheimer's disease | |
| Zhao et al. | Study on Lactiplantibacillus plantarum R6-3 from Sayram Ketteki to prevent chronic unpredictable mild stress-induced depression in mice through the microbiota–gut–brain axis | |
| Meguid et al. | Molecular characterization of probiotics and their influence on children with autism Spectrum disorder | |
| CN112915108B (en) | Application of bacillus coagulans JA845 in preparation of medicines for preventing and/or treating Alzheimer disease | |
| CN116814505B (en) | Lactobacillus rhamnosus and application thereof | |
| Zhao et al. | Research progress of naturally fermented yogurt with lactic acid bacteria in Xinjiang: a review of anti-constipation probiotics | |
| Park et al. | Effects of exercise and microbiota transplant on the memory of obesity-induced mice | |
| Lourdes et al. | Evaluation regarding the efficacy and safety of a probiotic mixture in healthy volunteers with evacuation disorders | |
| Sant’Anna et al. | Can intestinal constipation be modulated by prebiotics, probiotics and symbiotics? | |
| Baenas et al. | Probiotic and prebiotic interventions in eating disorders: A narrative review |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |