Tag Nrho Glycosides Los Ntawm Stems Of Cistanche Tubulosa Alleviate Depression-zoo li Cwj Pwm

Hu rau:joanna.jia@wecistanche.com/ WhatsApp: 008618081934791

Li Fan, Ying Peng, Jingwen Wang, Ping Ma, Lijuan Zhao, Xiaobo Li *

TSAB NTAWV

Keeb kwm:Raws li feem ntau sivraum-yang detoxifying tshuaj ntsuabHauv cov tshuaj suav tshuaj, qhuav succulent stems ntawm Cistanche tubulosa (Schenk) Wight (CT) tau pom tias muaj txiaj ntsig zoo hauv kev kho kev nyuaj siab. Txawm li cas los xij, cov tshuaj tiv thaiv kev ntxhov siab thiab lawv cov txheej txheem hauv qab tseem tsis meej.

Lub hom phiaj:Txhawm rau tshawb xyuas cov khoom nquag ntawm CT tiv thaiv kev nyuaj siab, nrog rau cov txheej txheem muaj peev xwm. Txoj kev tshawb no tsim thiab cov txheej txheem: Kev ntsuam xyuas tus cwj pwm poob siab tau siv los ntsuas cov tshuaj tiv thaiv kev ua haujlwm ntawm polysaccharides, oligosaccharides, thiab sib txawv glycoside-enriched fractions cais los ntawm CT, nrog rau cov plab hnyuv microbiota metabolites suav nrog 3-hydroxyphenylpropionic acid ({{2 }}HPP) thiab hydroxytyrosol (HT). Tsis tas li ntawd, cov teebmeem ntawm bioactive fractions thiab metabolites ntawm cov qauv tsis muaj kev ntxhov siab me me (CUMS) tau tshawb pom nrog ntau yam tshuaj pharmacodynamics thiab biochemical tsom xam. Cov kev hloov pauv hauv colonic histology thiab cov kab mob plab hnyuv tau pom los ntawm staining thiab immunohistochemical tsom xam. Lub plab microbial nta thiab tryptophan-kynurenine metabolism tau tshawb fawb siv 16S rRNA sequencing thiab western-blotting, feem.

Cov txiaj ntsig:Tag nrho cov glycosides (TG) ua rau txo qis kev nyuaj siab zoo li tus cwj pwm piv rau cov feem sib txawv sib txawv, qhia txog kev sib koom ua ke ntawm phenylethanoid thiab iridoid glycosides ntawm hyperactivation ntawm hypothalamic-pituitary-adrenal (HPA) axis, mob hnyav neuro-, thiab peripheral mob. thiab qhov tsis txaus hauv 5-hydroxytryptamine (5-HT) thiab lub hlwb-derived neurotrophic yam hauv hippocampus. Tsis tas li ntawd, TG txo qis qis qis hauv cov hnyuv thiab plab hnyuv teeb meem cuam tshuam, thiab kev nplua nuj ntawm ntau cov kab mob muaj feem cuam tshuam nrog HPA axis thiab o hauv CUMS nas. Raws li qhov tshwm sim, qhov kev qhia ntawm indoleamine 2, 3-dioxygenase 1 (IDO1) hauv txoj hnyuv tau txo qis tom qab kev tswj hwm TG, nrog rau kev tawm tsam ntawm tryptophan-kynurenine metabolism. Ntawm qhov tod tes, HT kuj tau ua kom muaj cov tshuaj tiv thaiv kev nyuaj siab los ntawm kev ua kom HPA axis muaj nuj nqi, pro-inflammatory cytokine tso tawm, thiab tryptophan-kynurenine metabolism, thaum nws tsis tuaj yeem kho cov kab mob plab microbiota zoo ib yam li TG. Kuj ceeb tias, zoo dua rau fluoxetine, TG thiab HT tuaj yeem txhim kho kev ua haujlwm tsis zoo ntawm hypothalamic-pituitary-gonadal axis thiab txawv txav cyclic nucleotide metabolism.

cistanche salsa cov txiaj ntsigtuaj yeem ntxivtxhim kho kev ua haujlwm tsis zoo.

Taw qhia

Kev nyuaj siab yog ib qho mob ntev, rov muaj dua, thiab muaj feem cuam tshuam txog kev puas siab puas ntsws uas cuam tshuam txog li 20 feem pua ​​​​ntawm cov pej xeem thoob ntiaj teb (Nabavi li al., 2017). Tam sim no, txawm hais tias ntau cov tshuaj tiv thaiv kev ntxhov siab tau pom zoo, cov kev mob tshwm sim muaj txog. Qhov tseem ceeb, kev kho mob mus sij hawm ntev nrog kev xaiv serotonin reuptake inhibitors (SSRIs) xws li fluoxetine, tus kws tshuaj loj rau kev nyuaj siab, ua rau muaj teeb meem hnyav xws li kev sib deev tsis zoo (Bijlsma et al., 2014); qhov no tau ua rau muaj kev xav ntau ntxiv rau kev tshawb pom cov tshuaj tiv thaiv kev ntxhov siab tshiab los ntawm cov tshuaj ntsuab (Wang li al., 2019). Hauv cov tshuaj suav tshuaj suav tshuaj (TCM) txoj kev xav, lub raum-yang tsis muaj peev xwm ua rau muaj kev ua haujlwm zoo ib yam li cov tsos mob ntawm kev nyuaj siab xws li kev xav hauv cov pob tawb, tsis txaus siab, thiab kev xav (Yang li al., 2020), txhawb kev xav. txhawm rau txo cov kev nyuaj siab zoo li tus cwj pwm los ntawm tonifying raum-yang. Coincidentally, ntau lub raum-yang tonifying tshuaj ntsuab muaj qhov zoo ntawm kev txhim kho kev sib deev (Wu li al., 2015). Cov kev tshawb fawb no ua rau peb ua tib zoo mloog rau cov ntawv thov uas muaj peev xwm ntawm Cistanches Herba, uas yog siv ntau tshaj plaws hauv lub raum-yang tonifying tshuaj ntsuab hauv TCM thiab muaj txiaj ntsig zoo hauv kev kho txiv neej kev ua haujlwm tsis zoo (Wang li al., 2020), hais txog kev txhim kho antidepressant. Cistanches Herba, tau sau tseg raws li cov txiv hmab txiv ntoo qhuav ntawm Cistanche tubulosa (Schrenk) Wight (CT) thiab Cistanche deserticola (YC Ma) hauv Suav Pharmacopoeia (Wang li al., 2017), tau siv hauv Suav teb thiab lwm lub tebchaws Esxias sab hnub tuaj. txij li thaum xyoo pua 15th los kho tej yam mob xws li raum-yang deficiency, impotence, thiab poj niam infertility. Cov kev tshawb fawb tshuaj niaj hnub no qhia tias Cistanches Herba muaj ntau yam bioactivities, xws li kev tiv thaiv kab mob, kev tiv thaiv kab mob, tshuaj tiv thaiv kab mob, tiv thaiv kev laus, thiab tshuaj tiv thaiv kab mob (Wang li al., 2017). Cov khoom tiv thaiv neuroprotective ntawm Cistanches Herba qhia nws cov peev xwm kho mob hauv kev paub txog kev mob nkeeg xws li mob stroke, kev nyuaj siab, thiab Alzheimer's kab mob (Wang li al., 2020). Hauv peb txoj kev tshawb fawb yav dhau los, peb pom tias CT extract alleviated cov kev nyuaj siab zoo li tus cwj pwm ntawm cov kab mob me me uas tsis muaj kev ntxhov siab (CUMS) nas (Li et al., 2018). Txog rau tam sim no, tshuaj ntsuam xyuas ntawm CT tau pom tias nws lub ntsiab tseem ceeb suav nrog phenylethanoid glycosides, iridoid glycosides, polysaccharides, thiab oligosaccharides (Jiang thiab Tu, 2009), txawm li cas los xij, hom kev sib xyaw uas ua lub luag haujlwm tseem ceeb hauv nws cov tshuaj tiv thaiv kev ntxhov siab tseem tsis paub meej.

Ntau cov kev tshawb fawb tau lees paub tias lub cev ua haujlwm ntawm lub plab (tshwj xeeb tshaj yog commensal microbiota) ua lub luag haujlwm tseem ceeb hauv kev txhim kho kev nyuaj siab thiab tuaj yeem tswj cov neuroendocrine, lub cev tsis muaj zog, thiab lub cev tiv thaiv kab mob (Yang li al., 2020). Ntxiv mus, kev sib raug zoo txuas nrog tryptophan metabolism, plab microbiota, thiab kev nyuaj siab tau maj mam nyiam ntau yam. Hloov cov plab hnyuv microbiota tuaj yeem qhib txoj hauv kev tryptophan-kynurenine, tom qab ntawd txo qis peripheral thiab cerebral tryptophan muaj, uas ua rau 5-HT tsis txaus (Agus et al., 2018). Peb txoj kev tshawb fawb yav dhau los tau pom tias phenylethanoid glycosides hauv CT feem ntau ua rau qis bioavailability, thiab tuaj yeem hloov pauv sai sai rau 3-hydroxy-phenyl propionic acid (3-HPP) thiab hydroxytyrosol (HT) los ntawm lub plab microbiota (Li et ib., 2016). Tsis tas li ntawd, CT extract tau tshaj tawm los kho lub plab microbiota homeostasis hauv CUMS nas (Li li al., 2018). Raws li cov kev tshawb fawb no, peb tau txiav txim siab tias kev sib cuam tshuam ntawm cov phytochemicals thiab plab microbiota tuaj yeem tswj hwm cov tshuaj tiv thaiv kev ntxhov siab ntawm cov khoom siv bioactive ntawm CT. Tshwj xeeb, cov tebchaw yuav hloov mus rau hauv cov metabolites absorbable (xws li 3-HPP thiab HT) hauv plab hnyuv los ntawm plab microbiota, thiab tom qab ntawd, siv tshuaj tiv thaiv kev nyuaj siab. Nyob rau hauv lem, bioactive tivthaiv-vim lub plab microbiota cov qauv kev hloov pauv tuaj yeem ua ib lub luag haujlwm tseem ceeb hauv kev ua haujlwm antidepressant.

Cov ntaub ntawv thiab cov txheej txheem

Khoom siv

Tag nrho cov qauv siv rau kev tshuaj xyuas tshuaj tau yuav los ntawm Durst (Sichuan, Suav). 3-HPP, HT, fluoxetine, thiab imipramine tau yuav los ntawm Aladdin (Shanghai, Suav). Cov khoom siv BCA protein ntau tau yuav los ntawm Boster (Wuhan, Suav). Nanjing Jiancheng (Nanjing, Tuam Tshoj) muab 5-HT, BDNF, qog necrosis factor-alpha (TNF- ), interleukin -1beta (IL-1 ), thiab interferon-gamma (IFN- ) Cov khoom siv enzyme-linked immunosorbent assay (ELISA). Corticosterone (CORT), adrenocorticotropic hormone (ACTH), thiab corticotrophin-releasing hormone (CRH) ELISA cov khoom siv tau yuav los ntawm Multi Sciences (Hangzhou, Suav). Cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), testosterone (T), thiab gonadotropin-tso hormone (GnRH) ELISA cov khoom siv tau yuav los ntawm Enzyme-linked Biotechnology (Shanghai, Suav). Cov khoom siv tryptophan thiab kynurenine ELISA tau txais los ntawm Me Molecule Antibodies (Bordeaux, Fabkis). Cov tshuaj tiv thaiv thawj / theem nrab suav nrog zonula occludens 1 (ZO-1), indoleamine 2, 3-dioxygenase 1 (IDO1), -actin, thiab HRP tshis tiv thaiv luav IgG (H plus L) tau muas los ntawm Proteintech (Wuhan, Suav teb). Tag nrho lwm cov reagents ntawm analytical qib lossis siab dua purity tau txais los ntawm cov chaw muag khoom lag luam.

cistanche extract ntxiv

Kev npaj cov feem sib txawv sib cais los ntawm CTE

CT tau sau thaum lub Kaum Ib Hlis 2015 hauv Hetian, Xinjiang, Tuam Tshoj, thiab tau lees paub los ntawm Prof. Xiaobo Li. Daim voucher specimen (20151108) tau muab tso rau hauv Tsev Kawm Ntawv Pharmacy ntawm Shanghai Jiao Tong University.

Cov qauv crushed tau muab rho tawm peb zaug nrog dej distilled (1:10, w / v) rau 2 h ntawm 80 ~ 90 ◦C kom tau txais CTE (cov qoob loo yog 57.1 feem pua). CTE tau yaj hauv dej distilled thiab maj mam nplawm nrog ethanol (1: 4, v / v) thiab muab tso rau ntawm 4 ◦C rau 24 teev. Tom qab ntawd, precipitate thiab supernatant tau sau los ntawm centrifugation ntawm 4000 rpm rau 20 min. Tag nrho cov polysaccharides (TP; qhov tawm los yog 5.7 feem pua) tau los ntawm kev ntxuav nrog 80 feem pua ​​​​ethanol, thiab deproteinization nrog Sevage reagent peb zaug los ntawm cov precipitate sau. Tom qab ntawd cov supernatant ntxiv tau chromatographed hla D101 microporous resin kem thiab eluted nrog dej distilled thiab 40 feem pua ​​​​ethanol. Cov dej eluted thiab 40 feem pua ​​​​ethanol feem muaj tag nrho cov oligosaccharides (TO; cov txiaj ntsig yog 35.1 feem pua) thiab tag nrho glycosides (TG; cov txiaj ntsig yog 12.1 feem pua), feem. TG tau ntxiv eluted nrog dej distilled thiab 5 feem pua, 10 feem pua, thiab 40 feem pua ​​ethanol los ntawm D101 microporous resin dua, thiab cov eluted feem ntawm 5 feem pua ​​thiab 40 feem pua ​​ethanol yog tag nrho iridoid glycosides (TG-IrG; cov yield yog 2.7 feem pua) thiab tag nrho phenylethanoid glycosides (TG-PhG; cov txiaj ntsig yog 8.7 feem pua), feem.

Tshuaj ntsuam xyuas

Ua ntej, cov ntsiab lus tshuaj tseem ceeb ntawm cov feem sib txawv sib cais los ntawm CTE yog tus cwj pwm los ntawm UPLC-QTOF-MS. Qhov thib ob, cov ntsiab lus txheeb ze ntawm tag nrho cov carbohydrates thiab glycosides tau txiav txim siab los ntawm UV-Vis txoj kev. Thib peb, cov khoom tseem ceeb (echinacoside, verbascoside, isoverbascoside, 8-epiloganic acid, thiab geniposidic acid) tau txheeb xyuas los ntawm HPLC txoj kev siv tau. Cov ncauj lus kom ntxaws parameters thiab txoj kev siv tau yog qhia hauv Cov Khoom Siv Ntxiv.

Fig. 1. Flow chart of animal trials

Table 1 Cov ncauj lus thiab qhov ntau npaum li cas rau nas lossis nas hauv txhua pab pawg.

Tsiaj sim

Cov sijhawm sim tsiaj tshwj xeeb tau qhia hauv daim duab 1. Tag nrho cov tsiaj sim tau nyob hauv tsev thiab ua kom zoo rau 1 lub lis piam ua ntej qhov kev sim hauv Laboratory Tsiaj Center ntawm Shanghai Jiao Tong University (Shanghai, Suav), nyob rau hauv kev tswj ntawm chav tsev kub (25 ± 2). ◦C; 55 ± 10 feem pua ​​​​ntawm cov av noo) nrog 12: 12 h lub voj voog tsaus nti. Qhov kev tshawb fawb no tau ua raws li Cov Lus Qhia rau Kev Saib Xyuas thiab Kev Siv Cov Tsiaj Looj ntawm SJTU. Cov chaw tsiaj thiab cov txheej txheem tau pom zoo los ntawm Pawg Saib Xyuas Kev Ncaj Ncees Tsiaj ntawm SJTU (No. A2019008).

Ib puas thiab tsib caug txiv neej ICR nas (qhov hnyav 18-20 g, 6 lub lis piam) tau yuav los ntawm Shanghai Slack Biotechnology Company (Shanghai, Suav) thiab muab faib ua 10 pawg (n=15/pab). Cov kev kawm thiab koob tshuaj rau cov nas uas poob siab rau kev coj tus cwj pwm hauv txhua pab pawg tau qhia hauv Table 1. Cov koob tshuaj ntawm CTE thiab nws cov feem sib cais tau suav los ntawm cov qauv hauv qab no: ntau npaum li cas=4.55 g/kg.d.bw × tawm los, uas tau txiav txim siab raws li peb qhov sib npaug tib neeg cov koob tshuaj suav nrog raws li thaj tsam ntawm lub cev. Cov koob tshuaj ntawm cov tshuaj zoo imipramine thiab plab microbiota metabolites (3-HPP thiab HT) tau teeb tsa raws li cov kev tshawb fawb yav dhau los (Gupte li al., 2016; Pablos et al., 2019). Tom qab kev tswj hwm intragastric ib zaug ib hnub rau 7 hnub, qhov kev sim qhib qhov chaw (OFT), tail ncua kev xeem (TST), thiab yuam ua luam dej (FST) tau ua nyob rau hnub 8, 9, thiab 10th hnub, raws li. Cov txheej txheem tshwj xeeb ntawm kev ntsuas tus cwj pwm tau piav qhia hauv Cov Khoom Siv Ntxiv.

Xya caum ob tug txiv neej Sprague-Dawley nas (qhov hnyav 160–180 g, 6 lub lis piam) tau yuav los ntawm Shanghai Slack Laboratory Tsiaj Tuam Txhab (Shanghai, Suav). Ua ntej qhov kev sim, tag nrho cov nas tau raug rau qhov kev ntsuam xyuas sucrose (SPT) tom qab kev cob qhia sib raug. Cov nas tau muab faib ua 8 pawg (n=9/pab) raws li lawv qhov kev nyiam sucrose (Ntxiv Fig. S1). Cov ntsiab lus thiab koob tshuaj rau cov nas nyob rau hauv txhua pab pawg muaj nyob rau hauv Table 1. Cov koob tshuaj tau teeb tsa raws li kev hloov pauv ntawm tus nas thiab nas raws li lawv cov koob tshuaj zoo hauv cov nas uas poob siab rau tus cwj pwm. Thiab qhov koob tshuaj ntawm cov tshuaj tiv thaiv zoo fluoxetine tau ua raws li kev tshawb fawb yav dhau los (Hou li al., 2017). Tag nrho cov pab pawg tau txais cov kab mob uas tsis muaj kev ntxhov siab me me (CUMS) tshwj tsis yog rau pawg tswj hwm. Cov kev ntxhov siab tau thov tsis tu ncua thiab tsis tu ncua rau 4 lub lis piam (saib Daim Ntawv Ntxiv S1 kom paub meej). Cov zaub mov thiab dej tau muaj pub dawb rau cov nas tswj, uas tseem tsis muaj kev cuam tshuam hauv lwm chav, tshwj tsis yog rau kev kuaj tus cwj pwm. Cov kev kawm tau muab tshuaj intragastrically 1 teev ua ntej CUMS txheej txheem nyob rau hauv 4 lub lis piam. Tom qab 28 hnub ntawm kev ntxhov siab tsis tu ncua thiab kev tswj hwm tshuaj, OFT, SPT, thiab FST tau ua rau hnub 29, 31, thiab 33rd, feem. Cov txheej txheem tshwj xeeb ntawm kev sim coj tus cwj pwm yog qhia hauv Cov Khoom Siv Ntxiv.

Table 2 Cov ntsiab lus ntawm echinacoside, verbascoside, isoverbascoside, 8-epiloganic acid, thiab geniposidic acid nyob rau hauv txhua feem.

Kev sau cov qauv thiab kuaj biochemical

Tom qab kev ntsuam xyuas tus cwj pwm, cov nas yoo mov tau muab tshuaj loog nrog pentobarbital sodium, thiab tag nrho cov ntshav tau muab coj los kuaj ntshav. Tom qab lub plawv perfusion nrog saline, hippocampus, txoj hnyuv, thiab cov ntsiab lus cecal tau sau thiab khaws cia rau hauv -80 ◦C. Distal colonic ntu raug tshem tawm thiab kho hauv 4 feem pua ​​​​ntawm paraformaldehyde. Cov theem ntawm CORT, CRH, ACTH, TNF-, IL-1 , IFN- , cAMP, cGMP, T, GnRH, tryptophan, thiab kynurenine hauv cov ntshav, 5-HT, BDNF, thiab TNF- nyob rau hauv lub hippocampus, thiab TNF- thiab IFN- nyob rau hauv txoj hnyuv raug ntsuas raws li cov lus qhia muab nrog rau cov khoom siv ELISA.

Histology, immunohistochemistry thiab western-blotting assay

Hematoxylin thiab eosin (H&E) thiab Alcian xiav-periodic acid-Schiff (AB-PAS) staining tau siv los soj ntsuam cov kev hloov pauv hauv cov hnyuv. Tsis tas li ntawd, kev soj ntsuam immunohistochemistry ntawm cov ntu no tau ua los soj ntsuam ZO-1 cov protein qhia hauv cov kab mob hauv cov hlab ntsha (Ding li al., 2020). Cov ntsiab lus hais txog kev npaj ua qauv thiab kev ntsuam xyuas sab hnub poob-blotting los txiav txim siab IDO1 cov protein qhia hauv txoj hnyuv thiab hippocampus kuj tau piav qhia hauv Cov Khoom Siv Ntxiv.

Kev txheeb xyuas qhov profile ntawm plab microbiota

16S rRNA high-throughput sequencing yog ua los ntawm MajorBio Co., Ltd. (Shanghai, Tuam Tshoj), thiab cov ncauj lus kom ntxaws txoj kev thiab cov ntaub ntawv ua tau qhia nyob rau hauv cov ntaub ntawv ntxiv.

Kev txheeb cais

Cov ntaub ntawv raug nthuav tawm raws li qhov nruab nrab ± tus qauv yuam kev ntawm qhov nruab nrab (SEM). Ib txoj kev tsom xam ntawm qhov sib txawv (ANOVA) tau siv los sib piv ntau pawg los ntawm kev siv SPSS 20.0 software. Qhov sib txawv tau suav tias yog qhov tseem ceeb ntawm p <0.05. cov="" kev="" sib="" raug="" zoo="" ntawm="" cov="" plab="" hnyuv="" microbes="" thiab="" qee="" yam="" kev="" nyuaj="" siab="" ntsig="" txog="" lub="" cev="" muaj="" zog="" tau="" txheeb="" xyuas="" siv="" spearman="" correlation="" coefficient="" raws="" li="" kev="" txheeb="" xyuas="" qhov="" cua="">

Cov txiaj ntsig

Kev tshuaj ntsuam xyuas ntawm cov feem sib txawv sib cais los ntawm CTE

Cov khoom tseem ceeb tau pom zoo siv UPLC-QTOF-MS (Cov Lus Ntxiv S2 thiab Fig. S2), thiab tag nrho ntawm 21 cov neeg koom nrog tau txheeb xyuas, suav nrog 16 tus neeg sawv cev ntawm phenylethanoid glycosides, 2 tus neeg sawv cev ntawm phenolic glycosides hauv CTE, TG, thiab TG. PhG; thiab 3 cov ntsiab lus ntawm iridoid glycosides hauv CTE, TG, thiab TG-IrG. Zuag qhia tag nrho, cov ntsiab lus txheeb ze ntawm tag nrho cov carbohydrates hauv TP thiab TO yog 60.3 feem pua ​​thiab 80.8 feem pua. Cov ntsiab lus txheeb ze ntawm tag nrho glycosides hauv TG yog 87.7 feem pua. Raws li txoj cai, phenylethanoid thiab iridoid glycosides suav txog 86.7 feem pua ​​thiab 53.4 feem pua ​​ntawm TG-PhG thiab TG-IrG, feem. Cov ntsiab lus ntawm echinacoside, verbascoside, isoverbascoside, 8-epiloganic acid, thiab geniposidic acid nyob rau hauv txhua feem yog qhia nyob rau hauv Table 2, thiab HPLC chromatogram thiab cov ntaub ntawv validation yog teev nyob rau hauv Supplementary Table S3 thiab Fig. S3.

Fig. 2. Cov teebmeem ntawm cov feem sib txawv sib cais los ntawm CTE thiab cov metabolites raug los ntawm plab microbiota ntawm FST, TST, OFT hauv cov nas.

Kev cuam tshuam ntawm cov feem sib txawv sib cais los ntawm CTE thiab cov metabolites raug los ntawm plab microbiota ntawm kev coj cwj pwm kev poob siab hauv cov nas.

Raws li pom hauv daim duab 2, piv nrog rau pawg tswj hwm, cov nas raug rau 7 hnub ntawm imipramine (zoo tswj) kev tswj hwm tau nthuav tawm qhov txo qis hauv lub sijhawm tsis muaj zog hauv FST thiab TST thiab tsis pom qhov cuam tshuam loj rau tag nrho cov kev mus ncig hauv OFT. . Cov kev hloov pauv zoo sib xws kuj tau pom nyob rau hauv CTE, TG, thiab HT pawg, qhia tias CTE, TG, thiab HT tau siv cov tshuaj tiv thaiv kev ntxhov siab thiab cov teebmeem tsis cuam tshuam rau kev ua kom muaj zog. Yog li, TG thiab HT yog qhov tseem ceeb ntawm bioactive feem cais los ntawm CTE thiab cov metabolites los ntawm plab microbiota, feem. Qhov zoo siab, tsis muaj kev hloov pauv tseem ceeb hauv lub sijhawm tsis muaj zog hauv FST tau pom tom qab TG-PhG thiab TG-IrG kev tswj hwm piv nrog cov kev tswj hwm, lossis hauv TST tom qab TG-PhG tswj hwm, qhia tias muaj phenylethanoid thiab iridoid glycosides. yog qhov tseem ceeb hauv kev ua haujlwm antidepressant ntawm CTE.

Table 3 Cov teebmeem ntawm qhov sib txawv glycoside-enriched feem thiab HT ntawm FST, SPT, thiab OFT hauv CUMS nas.

Pharmacodynamic teebmeem thiab biochemical hloov pauv ntawm qhov sib txawv glycoside-enriched fractions thiab HT ntawm CUMS nas

Raws li pom nyob rau hauv Table 3, nas raug rau 28 hnub ntawm CUMS paradigm pom kev txo qis (p < 0.001)="" hauv="" sucrose="" nyiam="" hauv="" spt,="" tag="" nrho="" cov="" kev="" mus="" ncig,="" thiab="" tus="" lej="" txhawb="" nqa="" hauv="" oft,="" nrog="" rau="" kev="" nce="" ntxiv="" (p="">< 0.01)="" hauv="" tag="" nrho="" lub="" sijhawm="" tsis="" muaj="" zog="" hauv="" fst="" piv="" nrog="" cov="" tswj,="" qhia="" txog="" kev="" cuam="" tshuam="" ntawm="" kev="" nyuaj="" siab="" zoo="" li="" phenotypes="" hauv="" cums="" nas.="" cov="" kev="" nyuaj="" siab="" ua="" yeeb="" yam="" tau="" thim="" rov="" qab="" hauv="" flx="" (zoo="" tswj)="" pab="" pawg.="" ib="" yam="" li="" ntawd,="" cte,="" tg,="" tg-phg,="" tg-irg,="" thiab="" ht="" kev="" kho="" mob="" tau="" ua="" rau="" kev="" kho="" dua="" tshiab="" ntawm="" sucrose="" nyiam="" mus="" rau="" qib="" qub="" hauv="" cums="" nas,="" uas="" yog="" 102.7="" feem="" pua,="" 94.1="" feem="" pua,="" 89.8="" feem="" pua,="" 91.9="" feem="" pua,="" thiab="" 94.3="" feem="" pua.="" tswj,="" raws.="" raws="" li="" nyob="" rau="" hauv="" fst,="" cte="" thiab="" tg="" pawg="" tau="" nthuav="" tawm="" cov="" teebmeem="" pom="" tseeb="" tshaj="" plaws,="" thiab="" lub="" sijhawm="" tsis="" muaj="" zog="" mus="" txog="" 103.3="" feem="" pua="" ​​​​thiab="" 93.4="" feem="" pua="" ​​​​ntawm="" cov="" pab="" pawg="" tswj="" hwm,="" feem,="" thaum="" lub="" sijhawm="" tsis="" muaj="" zog="" ntawm="" tg-phg,="" tg-irg,="" thiab="" ht="" pawg.="" tsuas="" yog="" mus="" txog="" 62.1="" feem="" pua,="" 73.2="" feem="" pua,="" thiab="" 69.9="" feem="" pua="" ​​ntawm="" cov="" pab="" pawg="" tswj.="" kev="" nce="" ntxiv="" tseem="" ceeb="" zoo="" sib="" xws="" (p=""><0.05) tau="" pom="" nyob="" rau="" hauv="" tag="" nrho="" cov="" kev="" mus="" ncig="" thiab="" kev="" txhawb="" nqa="" tus="" lej="" hauv="" oft="" tom="" qab="" cte,="" tg,="" thiab="" ht="" kev="" tswj="" hwm,="" thiab="" tg-phg="" thiab="" tg-irg="" kev="" kho="" mob="" tau="" hloov="" mus="" rau="" kev="" kho="" tus="" lej="" txhawb="" nqa="" hauv="" cums="" nas.="" cov="" txiaj="" ntsig="" tau="" qhia="" tias="" tg="" yog="" qhov="" tseem="" ceeb="" ntawm="" bioactive="" antidepressant="" feem="" cais="" los="" ntawm="" cte,="" thiab="" phenylethanoid="" thiab="" iridoid="" glycosides="" yog="" qhov="" tseem="" ceeb="" hauv="" kev="" siv="" nws="" cov="" tshuaj="" tiv="" thaiv="" kev="" nyuaj="" siab.="" ntxiv="" mus,="" ht="" tau="" pom="" tias="" yog="" ib="" qho="" ntawm="" cov="" metabolites="" nquag="" ntawm="" tg="" hauv="">

Raws li qhov tshwm sim, kev txom nyem los ntawm CUMS tau nce qib ntawm CORT, CRF, ACTH, TNF-, IL-1 , thiab IFN- hauv cov ntshav thiab TNF- hauv hippocampus ntawm nas piv nrog cov pab pawg tswj hwm (p< 0.05),="" resulting="" in="" significant="" reductions="" (p="" <="" 0.05)="" in="" the="" levels="" of="" hippocampal="" 5-ht="" and="" bdnf="" (fig.="" 3).="" except="" for="" a="" non-significant="" difference="" in="" the="" level="" of="" hippocampal="" bdnf="" between="" flx="" and="" cums="" groups,="" the="" above-mentioned="" alterations="" in="" cums="" rats="" could="" be="" significantly="" reversed="" (p="" <="" 0.05)="" after="" administration="" of="" fluoxetine,="" cte,="" tg,="" and="" ht,="" indicating="" that="" cte,="" tg,="" and="" ht="" showed="" ameliorative="" effects="" on="" the="" hyperactivation="" of="" hpa="" axis,="" severe="" peripheral="" and="" neural="" inflammation,="" and="" deficiencies="" in="" 5-ht="" and="" bdnf.="" likewise,="" tg-irg="" and="" tgphg="" treatment="" significantly="" reduced="" the="" levels="" of="" serum="" cort,="" tnf-α,="" ifn-γ,="" and="" hippocampal="" tnf-α,="" and="" increased="" the="" level="" of="" hippocampal="" 5-ht="" in="" cums="" rats="" (p="" <="" 0.05).="" significant="" decreases="" (p="" <="" 0.05)="" in="" the="" levels="" of="" serum="" crf="" and="" acth="" were="" also="" observed="" in="" the="" tg-irg="" group="" compared="" with="" cums="" group.="" interestingly,="" the="" levels="" of="" serum="" cort,="" tnf-α,="" acth,="" and="" crf="" in="" tg-phg="" and="" tg-irg="" groups="" were="" significantly="" higher="" than="" those="" in="" the="" tg="" group="" (p="" <="" 0.05),="" and="" the="" levels="" of="" hippocampal="" 5-ht="" and="" bdnf="" exhibited="" the="" opposite="" expression="" pattern="" (p="" <="" 0.05).="" these="" results="" showed="" that="" the="" effects="" of="" tg-phg="" and="" tg-irg="" on="" the="" hyperactivity="" of="" the="" hpa="" axis,="" peripheral="" and="" neural="" inflammation="" and="" shortage="" of="" 5-ht="" were="" clearly="" inferior="" to="" tg,="" indicating="" that="" phenylethanoid="" and="" iridoid="" glycosides="" might="" exert="" synergistic="" effects="" on="" the="" above-mentioned="" multiple="">

TG thiab HT tswj HPG axis thiab cyclic nucleotide metabolism hauv CUMS nas

Cov theem ntawm T, GnRH, cAMP, thiab cGMP thiab qhov piv ntawm cAMP thiab cGMP (cAMP/cGMP) hauv cov ntshav uas raug rau CUMS tau ntsuas, thiab cov txiaj ntsig tau qhia hauv Table 4. Cov concentrations ntawm T, GnRH, cAMP, thiab cAMP/cGMP hauv cov ntshav tau txo qis, thiab qib ntawm cGMP tau nce ntxiv (p < 0.05)="" hauv="" cums="" pawg="" piv="" nrog="" cov="" tswj,="" qhia="" tias="" raug="" cums="" ua="" rau="" inhibition="" ntawm="" hpg="" axis="" thiab="" cyclic="" nucleotide="" metabolism="" tsis="" ua="" haujlwm.="" piv="" nrog="" cums="" pab="" pawg,="" tsis="" muaj="" kev="" hloov="" pauv="" tseem="" ceeb="" hauv="" flx="" pawg.="" kuj="" ceeb="" tias,="" tom="" qab="" kev="" kho="" tg="" thiab="" ht,="" kev="" nce="" ntxiv="" (p="">< 0.05)="" tau="" nthuav="" tawm="" hauv="" cov="" qib="" ntshav="" qab="" zib="" t,="" gnrh,="" camp,="" thiab="" camp="" cgmp,="" thaum="" qib="" ntawm="" cov="" ntshav="" cgmp="" tau="" txo="" qis="" (p=""><0.05). cov="" txiaj="" ntsig="" no="" tau="" qhia="" tias="" tg="" thiab="" ht="" tswj="" hwm="" hpg="" axis="" thiab="" cyclic="" nucleotide="" metabolism,="" uas="" yog="" qhov="" zoo="" tshaj="" rau="" kev="" tswj="" hwm="" zoo="">

Fig. 3. Cov teebmeem ntawm cov glycoside-enriched feem ntau thiab HT ntawm cov theem ntawm CORT, ACTH, CRF, TNF-, IL-1 , IFN- hauv cov ntshav thiab 5-HT, BDNF, TNF- hauv hippocampus ntawm CUMS nas.

TG thiab HT alleviate low-grade inflammatory in the colon and intestinal barrier interruption in CUMS nas.

H&E staining tau siv los ntsuas qhov kev puas tsuaj ntawm lub plab morphological, thiab tsis muaj qhov sib txawv tseem ceeb hauv txoj hnyuv tau pom ntawm cov pab pawg sim (Daim duab 4a). Tsis tas li ntawd, cov teebmeem ntawm TG thiab HT ntawm qhov mob ntawm txoj hnyuv thiab plab hnyuv cuam tshuam tau raug soj ntsuam (Daim duab 4b-d). Piv nrog rau cov pab pawg tswj hwm, tus naj npawb ntawm goblet hlwb thiab lub thickness ntawm cov mucus txheej raug txo nyob rau hauv CUMS pawg. Raws li qhov tshwm sim, cov protein qhia ntawm ZO-1, thiab qib IFN- thiab TNF- hauv txoj hnyuv tau txo qis (p < 0.05)="" thiab="" nce="" (p="">< {="" {13}}.="" tom="" qab="" kev="" kho="" mob="" fluoxetine,="" tg,="" thiab="" ht,="" tus="" naj="" npawb="" ntawm="" goblet="" hlwb="" thiab="" lub="" thickness="" ntawm="" cov="" mucus="" txheej="" tau="" nce,="" thiab="" theem="" ntawm="" colonic="" ifn-="" thiab="" tnf-="" tau="" txo="" qis="" (p=""><0.05). tsis="" tas="" li="" ntawd,="" tg="" thiab="" ht="" tau="" nce="" ntxiv="" (p=""><0.05) cov="" protein="" qhia="" ntawm="" zo-1="" mus="" rau="" qib="" zoo="" ib="" yam="" li="" pawg="" tswj="" hwm.="" cov="" txiaj="" ntsig="" no="" tau="" pom="" tias="" tg="" thiab="" ht="" tuaj="" yeem="" txo="" qis="" qis="" qis="" hauv="" cov="" hnyuv="" thiab="" plab="" hnyuv="" cuam="" tshuam="" hauv="" cums="">

Table 4 Cov teebmeem ntawm TG, HT, lossis fluoxetine ntawm HPG axis-txog cov tshuaj hormones thiab nucleotide metabolism-txog indexes hauv cov ntshav ntawm CUMS nas.

Cov teebmeem ntawm TG thiab HT ntawm lub plab microbiota muaj pes tsawg leeg

Tom qab tshem tawm cov kev ua tsis tiav, tag nrho ntawm 1,874,721 nyeem tau zoo. Kev sib txawv ntawm alpha (Fig. 5a) thiab beta diversity (Fig. 5b) tau pom tias txawm hais tias kev nplua nuj (Chao) thiab ntau haiv neeg (Shannon) ntawm lub plab microbiota hauv cov ntsiab lus cecal tsis txawv, tag nrho cov qauv ntawm lub plab microbiota hauv qhov kev tsom xam ntawm tus thawj tswj hwm kev tswj hwm (PCoA) cov phiaj xwm qhia txog qhov sib txawv ntawm kev tswj hwm thiab CUMS pawg. Tsis tas li ntawd, kev kho TG thiab HT tau nce cov kab mob nplua nuj ntawm CUMS nas thiab ua rau muaj qhov sib txawv ntawm PCoA cov phiaj xwm piv nrog cov nas ntawm CUMS, qhia meej qhov zoo sib xws nrog kev tswj hwm, tshwj xeeb tshaj yog thaum TG tau soj ntsuam.

Cov kev hloov pauv hauv microbiota ntxiv tau lees paub tias TG ua rau muaj kev tswj hwm zoo ntawm cov plab hnyuv microbiota. Tom qab kev tswj hwm TG, kev nplua nuj ntawm feem ntau ntawm kev hloov pauv se hauv CUMS nas tau hloov mus rau qib zoo ib yam li cov pab pawg tswj hwm. Qhov tseem ceeb txo (14.2 feem pua, p < 0.05)="" thiab="" enrichment="" (53.6="" feem="" pua,="">< 0.05)="" in="" the="" abundances="" of="" the="" phylum="" firmicutes="" and="" bacteroidetes="" were="" observed="" in="" the="" tg="" group="" compared="" with="" cums="" group="" (fig.="" 5c),="" respectively.="" consistently,="" at="" the="" family="" level="" (supplementary="" table="" s4),="" tg="" decreased="" the="" abundances="" of="" ruminococcaceae="" (phylum="" firmicutes)="" and="" peptococcaceae="" (phylum="" firmicutes)="" by="" 33.9%="" and="" 82.9%,="" respectively,="" compared="" with="" cums="" group="" (p="" <="" 0.05).="" conversely,="" significant="" enrichments="" in="" the="" abundances="" of="" family="" erysipelotrichaceae="" (phylum="" firmicutes,="" 78.4%,="" p="" <="" 0.05)="" and="" muribaculaceae="" (phylum="" bacteroidetes,="" 77.3%,="" p="" <="" 0.05)="" existed="" in="" tg="" group.="" consistently="" at="" the="" genus="" level="" (fig.="" 5d),="" the="" abundances="" of="" anaerotruncus,="" harryflintia,="" ruminiclostridium_9,="" unclassified_f_ruminococcaceae="" (members="" of="" the="" family="" ruminococcaceae),="" and="" peptococcus="" (a="" member="" of="" the="" family="" peptococcaceae)="" were="" significantly="" decreased="" while="" norank_f_erysipelotrichaceae,="" allobaculum,="" dubosiella="" (members="" of="" the="" family="" erysipelotrichaceae)="" and="" norank_f_muribaculaceae="" (a="" member="" of="" the="" family="" muribaculaceae)="" displayed="" higher="" abundances="" in="" tg="" group="" than="" those="" of="" cums="" group="" (p="">< 0.05).="" in="" addition,="" tg="" decreased="" the="" abundances="" of="" tyzzerella_3,="" acetatifactor,="" and="" norank_f_lachnospiraceae="" assigned="" to="" the="" family="" lachnospiraceae="" (p="" <="" 0.05),="" although="" the="" abundance="" of="" the="" family="" lachnospiraceae="" was="" similar="" across="" all="" experimental="" groups.="" unlike="" tg,="" ht="" decreased="" the="" abundances="" of="" partially="" altered="" taxa="" induced="" by="" cums,="" including="" the="" family="" ruminococcaceae,="" 3="" genera="" (anaerotruncus,="" harryflintia,="" and="" ruminiclostridium_9)="" assigned="" to="" the="" family="" ruminococcaceae="" and="" 2="" genera="" (tyzzerella_3,="" acetatifactor)="" assigned="" to="" the="" family="" lachnospiraceae.="" additionally,="" converse="" variations="" were="" observed="" in="" the="" abundances="" of="" ruminococcaceae_ucg_013="" and="" streptococcus="" in="" the="" ht="" group.="" these="" results="" indicated="" that="" tg="" and="" ht="" exerted="" clear="" differences="" in="" the="" regulation="" of="" gut="" microbiota="" composition,="" and="" the="" effect="" of="" tg="" was="" superior="" to="" that="" of="" tg="" especially="" in="" altering="" the="" genera="" assigned="" to="" the="" family="" erysipelotrichaceae,="" peptococcaceae,="" and="">

Fig. 4. Cov teebmeem ntawm TG, HT, los yog fluoxetine ntawm cov kev hloov morphologic, ZO-1 protein qhia, IFN- , thiab TNF- concentrations nyob rau hauv txoj hnyuv ntawm CUMS nas.

Kev txheeb xyuas kev sib raug zoo ntawm kev hloov pauv microbial genera cuam tshuam los ntawm TG thiab HT, HPA axis-related hormones, pro-inflammatory cytokines, 5-HT thiab BDNF

Txhawm rau txheeb xyuas cov kev sib raug zoo ntawm cov kev hloov hauv plab microbiota muaj pes tsawg leeg cuam tshuam los ntawm TG thiab HT, thiab cov xwm txheej cuam tshuam txog kev nyuaj siab, Spearman qhov kev txheeb xyuas kev sib raug zoo tau ua. Raws li pom nyob rau hauv daim duab 6, cov theem ntawm 5-HT thiab BDNF nyob rau hauv lub hippocampus tsuas yog muaj kev sib raug zoo nrog norank_f_Muribaculaceae. Txwv tsis pub, kev sib raug zoo meej tuaj yeem raug txheeb xyuas ntawm cov hloov pauv microbial genera thiab HPA axis ntsig txog cov tshuaj hormones. Tshwj xeeb, Dubosiella, norank_f_Muribaculaceae, norank_f_ Erysipelotrichacea, thiab Peptococcus tau cuam tshuam nrog HPA axis muaj nuj nqi. Serum CORT, CRF, thiab ACTH muaj kev cuam tshuam tsis zoo nrog Dubosiella, norank_f_Muribaculaceae, thiab norank_f_Erysipelotrichacea, thiab kev koom tes zoo nrog Peptococcus. Tsis tas li ntawd, Dubosiella thiab norank_f_ Erysipelotrichacea tau nthuav tawm cov koom haum tsis zoo nrog colonic IFN- thiab hippocampal TNF-, thaum muaj kev sib raug zoo zoo sib xws hauv Allobaculum, Harryfinita, thiab ntshav thiab hippocampal TNF-, nrog rau tsis muaj npe. _f_Lachnospiracea, thiab ntshav IFN- thiab TNF- . Nyob rau hauv sib piv, Peptococcus tau zoo txuam nrog colonic TNF- thiab ntshav TNF-. Ib yam li ntawd, norank_f_Muribaculaceae tau muaj txiaj ntsig zoo rau cov ntshav IFN- thiab TNF- . Cov txiaj ntsig no tau qhia tias qhov hloov pauv microbial genera, tshwj xeeb tshaj yog qee cov genera uas yog tsev neeg Erysipelotrichaceae, Peptococcaceae, thiab Muribaculaceae, uas tau cuam tshuam tshwj xeeb los ntawm TG, tau pom muaj kev sib koom ua ke nrog HPA axis ntsig txog cov tshuaj hormones thiab pro-inflammatory cytokines ib txhij, qhia lub luag haujlwm tseem ceeb. ntawm plab microbiota hauv regulating HPA axis muaj nuj nqi thiab o.

cistanche propiedades

TG thiab HT inhibit tryptophan-kynurenine metabolism hauv CUMS nas

Cov teebmeem ntawm TG thiab HT ntawm cov theem ntawm tryptophan thiab kynurenine hauv cov ntshav ntawm cov nas, nrog rau kev qhia ntawm IDO1 hauv txoj hnyuv thiab hippocampus, tau txiav txim siab. Raws li pom nyob rau hauv daim duab 7 thiab daim duab 8, piv nrog rau cov pab pawg neeg tswj, theem ntawm tryptophan nyob rau hauv cov ntshav tau txo qis nyob rau hauv CUMS pab pawg neeg, nyob rau hauv sib piv nrog rau cov theem ntawm kynurenine thiab kynurenine-to-tryptophan ratio (Kyn / Trp) thiab IDO1 protein qhia nyob rau hauv txoj hnyuv thiab hippocampus. Piv nrog CUMS pab pawg, ntshav Kyn/Trp hauv FLX pawg tau txo qis (p< 0.05).="" tg="" and="" ht="" treatment="" resulted="" in="" a="" significant="" increase="" in="" the="" serum="" tryptophan="" level="" in="" cums="" rats="" (p="" <="" 0.05),="" and="" a="" decrease="" in="" the="" levels="" of="" serum="" kynurenine="" and="" kyn/trp="" (p="" <="" 0.05).="" in="" addition,="" tg="" significantly="" inhibited="" the="" expression="" of="" ido1="" protein="" in="" the="" colon="" of="" cums="" rats="" (p="" <="" 0.05),="" while="" a="" non-significant="" difference="" in="" the="" expression="" of="" ido1="" protein="" in="" the="" hippocampus="" was="" observed="" between="" cums="" and="" tg="" groups.="" however,="" the="" effect="" of="" ht="" on="" the="" expression="" of="" ido1="" protein="" in="" the="" colon="" and="" hippocampus="" was="" contrary="" to="" that="" of="" tg,="" indicating="" that="" tg="" and="" ht="" inhibited="" tryptophan-kynurenine="" metabolism="" by="" decreasing="" the="" expression="" of="" ido1="" in="" the="" colon="" and="" hippocampus="" of="" cums="" rats,="">

Fig. 5. Kev txheeb xyuas qhov sib txawv, muaj pes tsawg leeg, thiab qhov sib txawv ntawm plab microbiota hauv cov qauv cecal.

Kev sib tham

Hauv txoj kev tshawb no, ob hom tsiaj sib txawv tau siv los tshuaj xyuas cov tshuaj bioactive hauv CT uas txo cov kev nyuaj siab zoo li tus cwj pwm thawj zaug. TP thiab TO feem ntau yuav tsis muaj txiaj ntsig cov khoom xyaw hauv CTE, thaum TG nthuav tawm qhov muaj peev xwm tshaj plaws hauv kev kho kev nyuaj siab. Cov kev tshawb fawb yav dhau los ntawm CT, nrog rau cov nroj tsuag Cistanche, feem ntau tau tsom mus rau bioactivities ntawm phenylethanoid glycosides nrog cov ntsiab lus siab tshaj plaws thiab tsis saib xyuas qhov tseem ceeb ntawm iridoid glycosides thiab lwm yam khoom xyaw tsawg dua. Qhov zoo siab, peb txoj kev tshawb fawb tau pom tias phenylethanoid thiab iridoid glycosides tau pom muaj kev sib koom ua ke ntawm kev ua haujlwm siab ntawm HPA axis, mob hnyav peripheral thiab neural o, thiab qhov tsis zoo hauv hippocampal 5-HT thiab BDNF, uas tej zaum yuav yog qhov laj thawj tseem ceeb rau cov tshuaj tiv thaiv zoo. effect of TG. Cov txiaj ntsig no ntxiv qhia txog cov yam ntxwv ntawm ntau yam thiab ntau lub hom phiaj ntawm cov tshuaj ntsuab thiab ceeb toom peb tias cov khoom sib xyaw nrog cov qib qis, txawm tias cov khoom xyaw kab kuj tseem tuaj yeem ua lub luag haujlwm tseem ceeb hauv cov tshuaj pharmacological.

Kev ntxhov siab ntev ua rau muaj kev ntxhov siab ntawm HPA axis, uas txhawb kev pib ntawm kev nyuaj siab, nrog rau kev tawm tsam ntawm HPG axis los ntawm kev txo qis GnRH tso tawm thiab / lossis pituitary rhiab heev ntawm GnRH (Kirby li al., 2009). Lub caij no, cAMP thiab cGMP yog cov chaw nruab nrab tseem ceeb uas tso siab rau ntau cov neurotransmitters thiab cov tshuaj hormones kom ua rau lawv lub cev muaj zog (Siawrys li al., 2002). Cov kev tshawb fawb tsis ntev los no tau pom zoo tas li tias qhov tshwm sim ntawm lub raum-yang tsis muaj peev xwm cuam tshuam nrog kev ua haujlwm tsis zoo ntawm hypothalamus-pituitary-target caj pas caj pas (Zhang li al., 2019). Hauv lub raum-yang deficiency syndrome, cov cim txo qis hauv cov qib ntawm cov ntshav cAMP thiab cAMP / cGMP kuj tau pom. Hauv txoj kev tshawb no, peb pom tias TG tuaj yeem cuam tshuam cov qib ntawm cov ntshav CORT, CRF, thiab ACTH, thiab nce cov ntshav T thiab GnRH cov ntsiab lus hauv CUMS nas, qhia txog kev rov qab los ntawm HPA thiab HPG axis tsis ua haujlwm tom qab TG tswj hwm. Tsis tas li ntawd, TG thim rov qab qhov txo qis hauv qib ntawm cov ntshav cAMP/cGMP hauv cov nas uas raug CUMS. Yog li, lub peev xwm hauv qab txheej txheem ntawm CT hauv kev kho mob ntawm kev nyuaj siab thiab lub raum-yang deficiency tej zaum yuav zoo ib yam thiab tsim nyog yuav tsum tau tshawb nrhiav ntxiv. Tsis tas li ntawd, kev tsim cov kev xav ntawm kev sib deev thiab kev coj cwj pwm yog cov txheej txheem neural reflex. Cov tshuaj hormones kev sib deev yog qhov tseem ceeb ntawm kev sib deev hauv nruab nrab, thiab tsis muaj cov tshuaj hormones poj niam txiv neej tuaj yeem ua rau muaj kev sib deev tsawg dua lossis kev sib deev tsis zoo (Holoway thiab Wylie, 2015). Tshwj xeeb, ntau dhau 5-HT inhibits qhov tso tawm ntawm GnRH, uas yog qhov tseem ceeb rau qhov tshwm sim ntawm kev sib deev tsis zoo tom qab kev kho mob ntev nrog SSRIs (Prasad et al., 2015). Hauv peb txoj kev tshawb fawb, fluoxetine (tus neeg sawv cev ntawm SSRIs) tsis muaj txiaj ntsig hauv HPG axis tsis ua haujlwm. Txawm li cas los xij, txawm tias TG tau txhim kho qib ntawm 5-HT hauv hippocampus, qhov kev hloov pauv zoo sib xws hauv qib T thiab GnRH kuj tau pom, yog li ameliorating qhov kev tawm tsam ntawm HPG axis. Cov txiaj ntsig no qhia tau hais tias muaj txiaj ntsig zoo ntawm CT hauv kev kho mob ntawm kev nyuaj siab, thiab lub luag haujlwm tseem ceeb ntawm cov teebmeem no yuav tsum tau kawm ntxiv.

Ntau cov pov thawj tau pom tias lub plab yog lub hom phiaj rau kev kho mob ntawm cov kab mob ntev uas siv cov khoom siv ntuj tsim nrog qis bioavailability (Zhou et al., 2020). Kev tshawb fawb tsis ntev los no (Wei li al., 2019) tau qhia tias kev kho mob CUMS induces fecal microbiome alterations thiab plab hnyuv barrier defects, uas pab txhawb cov kab mob nkag mus rau hauv colonic mucosa thiab exacerbate inflammatory dab nyob rau hauv txoj hnyuv. Raws li daim ntawv tshaj tawm no, peb cov txiaj ntsig tau pom tias 4 lub lis piam ntawm CUMS raug cuam tshuam ua rau muaj kev cuam tshuam ntau ntawm goblet cell xov tooj thiab cov mucus txheej tuab nyob rau hauv cov nas nyuas nyuv, nrog rau qhov pib ntawm plab hnyuv cuam tshuam los ntawm kev nce plab permeability, uas tau txiav txim los ntawm ntsuas ZO-1 protein. Tsis tas li ntawd, kev nthuav qhia ntau ntxiv ntawm cov kab mob pro-inflammatory (xws li TNF- thiab IFN- ) tau pom nyob rau hauv txoj hnyuv. Raws li, cov kev tshawb pom no tau qhia tias txawm hais tias tsis muaj kev puas tsuaj histological raug ntxias, CUMS kev kho mob pib mob plab hnyuv thiab plab hnyuv cuam tshuam. Cov kev tshawb fawb yav dhau los tau tshaj tawm tias CT tau txhim kho kev ua tau zoo hauv kev tiv thaiv DSS-induced colitis hauv nas (Jia li al., 2014). Tsis sib haum, TG kuj tau pom tias txo qis qis qis hauv cov hnyuv thiab plab hnyuv cuam tshuam ntawm CUMS nas, uas qhia txog nws lub peev xwm rau kev kho mob rau cov kab mob colonic o.

Cov kev tshawb fawb dav dav kuj tau pom tias kev sib raug zoo ntawm kev sib txuas ntawm cov plab hnyuv microbiota, HPA axis, thiab o yog qhov nyuaj thiab ua lub luag haujlwm tseem ceeb hauv kev txhim kho kev nyuaj siab (Misiak, et al., 2020). Kev hloov pauv hauv plab microbiota muaj pes tsawg leeg tuaj yeem ua rau kev txhim kho kev tso tawm ntawm cytokines thiab kev sib txuas ntawm cov khoom siv bioactive me me (Du li al., 2020). Qee cov cytokines (xws li TNF- ) tuaj yeem dhau los ntawm cov hlab ntsha-hlwb thiab yog cov muaj zog ua kom muaj zog ntawm HPA axis (Misiak li al., 2020). Nyob rau hauv lem, lub hyperactivation ntawm HPA axis tuaj yeem ua rau lub plab microbiota dysbiosis, mob ntev hauv txoj hnyuv, thiab hloov lub plab permeability (Misiak li al., 2020). Raws li cov kev tshawb fawb ua ntej, TG-kev hloov kho ntawm lub plab microbiota yuav muaj feem cuam tshuam rau nws cov txiaj ntsig zoo rau kev nyuaj siab. Peb tau pom tias TG thim rov qab qhov ntau ntawm microbial taxa ntawm ntau qib hauv cov nas raug rau CUMS mus rau qib zoo ib yam li cov kev tswj hwm. Hauv particular, lub ntsiab hloov pauv ntawm tsev neeg Peptococcaceae, Erysipelotrichaceae, thiab Muribaculaceae tau pom tias muaj kev sib raug zoo nrog HPA axis thiab mob. Raws li peb cov txiaj ntsig, tsev neeg Peptococcaceae, Erysipelotrichaceae, thiab Muribaculaceae tau raug tshaj tawm los ua lub luag haujlwm tseem ceeb hauv kev tswj cov mucosal barrier kev ncaj ncees thiab tshwm sim ntawm qhov mob (Kankoush, 2015; Borton et al., 2017; Zhang et al., 2020). Yog li ntawd, peb tau pom tias TG tuaj yeem txo qis qhov kev nplua nuj ntawm qee cov genera uas tau muab rau tsev neeg Erysipelotrichacea, Peptococcaceae, thiab Muribaculaceae, tom qab ntawd txo qis qis qis hauv txoj hnyuv, hyperactivity ntawm HPA axis, thiab cuam tshuam ntawm mucosal barrier integrity. Interestingly, nyob rau hauv peb txoj kev tshawb no, tsuas yog ib tug genus hu ua los yog ank_f_Muribaculaceae tau correlated nrog 5-HT thiab BDNF nyob rau hauv lub hippocampus. Cov txheej txheem tshwj xeeb ntawm kev sib raug zoo tseem tsis meej thiab yuav tsum tau tshuaj xyuas ntxiv. Txwv tsis pub, qhov kev tshawb pom kuj qhia tias nws nyuaj heev rau feem ntau ntawm cov kab mob hloov pauv los ntawm TG los cuam tshuam ncaj qha rau theem ntawm 5-HT hauv hippocampus. Los piav qhia txog yuav ua li cas hloov pauv hauv plab microbiota muaj pes tsawg leeg cuam tshuam rau qib ntawm hippocampal 5-HT tom qab kev kho TG, kev sib raug zoo sib txuas nrog tryptophan metabolism, HPA axis, inflammatory cytokines, thiab 5-HT tau txais peb lub siab. Tryptophan yog ib qho tseem ceeb amino acid rau tib neeg thiab tsawg tshaj li 1 feem pua ​​yog siv nyob rau hauv protein synthesis, nrog rau feem ntau (tshaj li 90 feem pua) tau hloov los ntawm IDO1 thiab tryptophan 2,3-dioxygenase 2 (TDO2) rau hauv kynurenines, thiab kwv yees li. 5 feem pua ​​yog tsav los ntawm tryptophan hydroxylase los ntawm txoj kev serotonin (Duan, li al. 2018). Qib ntawm 5-HT nyob rau hauv lub hlwb feem ntau yog nyob ntawm peripheral tryptophan muaj, muab tias tryptophan raug thauj mus rau hauv lub hlwb ntawm nruab nrab amino acid transporters (Duan li al., 2018). IDO1, tus nqi-txheej enzyme nyob rau hauv thawj kauj ruam ntawm txoj kev kynurenine, feem ntau yog induced los ntawm IFN-, thiab lwm yam pro-inflammatory cytokines, xws li IL-1 thiab TNF- (Kennedy li al., 2017), uas tau pom tias cuam tshuam nrog plab microbiota hauv peb txoj kev tshawb fawb. Raws li tau tshaj tawm, ntau tryptophan yog metabolized los ntawm txoj kev kynurenine, yog li kev sib tw txo qis kev hloov pauv ntawm tryptophan rau 5-HT, thiab txuas mus rau qhov txo qis 5-HT feem ntau pom hauv kev nyuaj siab (O'Mahony li al., 2015). Yog li, qis qis tryptophan thiab siab dua Kyn / Trp yog qhov tshwm sim thiab ua rau muaj kev pheej hmoo siab ntawm kev nyuaj siab. Tom qab kev tswj hwm TG, qhov overexpression ntawm IDO1 nyob rau hauv txoj hnyuv tau inhibited, ua rau muaj zog cov ntshav tryptophan ntau ntau thiab txo qis hauv cov ntshav Kyn/Trp, uas qhia txog kev sib txuas ntawm plab microbiota thiab hippocampus 5-HT theem cuam tshuam los ntawm TG. Lub caij no, BDNF, ib tus neeg hauv tsev neeg neurotrophin, yog qhov tseem ceeb rau kev sib txawv ntawm tes, neuronal ciaj sia, tsim synapse, thiab cov txheej txheem neuroplasticity hauv kev nyuaj siab (Greenberg li al., 2009). Cov kev tshawb fawb tsis ntev los no tau pom tias BDNF tau pom tias muaj feem cuam tshuam nrog cov hnyuv mucosal barrier muaj nuj nqi thiab plab microbiota (Maqsood and Stone, 2016). Ib yam nkaus li, cov kev hloov hauv plab microbiota tau tshaj tawm tias muaj peev xwm nce qib ntawm BDNF qhia thiab yog li cuam tshuam rau kev loj hlob ntawm kev nyuaj siab zoo li tus cwj pwm (Du et al., 2020). Txawm li cas los xij, zoo ib yam li 5-HT variation, nws yog qhov tsis yooj yim sua rau feem ntau hloov pauv genera tshwm sim los ntawm TG hauv peb txoj kev tshawb fawb kom cuam tshuam ncaj qha rau theem ntawm BDNF hauv hippocampus, thiab qhov sib txuas ntawm cov molecular thiab cov txheej txheem xav tau kev kuaj ntxiv.

Hauv qhov sib piv, HT, lub plab microbiota metabolite ntawm TG, kuj tau nthuav tawm cov nyhuv antidepressant hauv txoj kev tshawb fawb tam sim no, uas zoo ib yam nrog nws cov txiaj ntsig zoo tiv thaiv kab mob (Hu li al., 2014). Ntawm kev txhawj xeeb, HT kuj tseem tuaj yeem ua rau nruab nrab cov cytokines, HPA thiab HPG axis-txog cov tshuaj hormones, thiab hippocampal 5-HT concentrations rau qib zoo ib yam li cov tswj hauv CUMS nas, thaum feem ntau ntawm cov kab mob microbial hloov pauv cuam tshuam. los ntawm HT muaj kev sib cuam tshuam tsis muaj zog nrog rau saum toj no physiological indexes, qhia tias lub plab microbiota tej zaum yuav tsis yog lub hom phiaj ntawm cov tshuaj tiv thaiv kev nyuaj siab ntawm HT. Tsis tas li ntawd, HT tau txwv tsis pub tshaj tawm ntawm IDO1 nyob rau hauv hippocampus tab sis tsis yog txoj hnyuv, nrog rau cov ntshav siab ntxiv tryptophan. Qhov tshwm sim ntawm qhov sib txawv ntawm TG thiab HT tuaj yeem yog vim qhov nqus tau zoo ntawm HT mus rau hauv cov hlab ntsha thiab lub peev xwm rau HT hla cov hlab ntsha hauv hlwb (Robles-Almazan li al., 2018), uas tseem qhia tau tias cov muaj zog metabolic muaj peev xwm ntawm plab microbiota yog tshwj xeeb tshaj yog tseem ceeb nyob rau hauv lub antidepressant kev ua si ntawm TG, ntxiv rau nws physiological functions. Li no, peb tau ua pov thawj ua ntej tias kev sib cuam tshuam ntawm cov phytochemicals thiab plab microbiota ua lub luag haujlwm tseem ceeb hauv kev kho kev nyuaj siab nrog kev tswj hwm TG (raws li qhia hauv daim duab 9).

Cistanche Dietary Supplementsua si alub luag haujlwm tseem ceeb hauv kev kho kev nyuaj siab.

Yog xav paub ntxiv, thov nias

Xaus

Hauv cov ntsiab lus, TG yog lub luag haujlwm tseem ceeb rau kev ua haujlwm ntawm cov tshuaj tiv thaiv kev ntxhov siab ntawm CT, xav txog kev sib koom ua ke ntawm phenylethanoid thiab iridoid glycosides ntawm kev ua haujlwm siab ntawm HPA axis, mob hnyav peripheral thiab neural o, thiab qhov tsis zoo hauv 5-HT thiab BDNF hauv lub hippocampus. Tsis tas li ntawd, lub peev xwm molecular mechanism ntawm antidepressant nyhuv ntawm TG tau ua tiav los ntawm kev sib cuam tshuam ntawm bidirectional ntawm phytochemicals thiab plab microbiota. Tsis tas li ntawd, amelioration ntawm suppressed HPG axis thiab cyclic nucleotide abnormality los ntawm TG thiab HT, uas tsis tau tswj los ntawm kev kho mob nrog SSRIs sawv cev los ntawm fluoxetine, qhia qhov txawv qhov zoo ntawm CT hauv kev kho kev nyuaj siab. Cov kev hloov pauv no sawv cev rau lub tswv yim zoo rau kev kho mob ntawm kev nyuaj siab siv CT thiab cov tshuaj tshuaj ntsuab zoo sib xws.