Part 1 Marine Natural Products: Kev cog lus rau cov neeg sib tw hauv qhov kev hloov kho ntawm lub plab-hlwb axis mus rau Neuroprotection
Mar 20, 2022
Hu rau: Audrey Hu Whatsapp / hp: 0086 13880143964 Email:audrey.hu@wecistanche.com
Abstract
Nyob rau hauv xyoo tsis ntev los no, ob pebneuroprotectivecov neeg sawv cev tau muab rau hauv kev sib ntaus sib tua neuronal dysfunctions; Txawm li cas los xij, tsis muaj kev kho mob tau pom zoo rau kev tshem tawm tag nrho cov kab mob neurodegenerative. Los ntawm txoj kev xav ntawm pathophysiological, cov kev tshawb fawb loj hlob tau qhia txog kev sib raug zoo ntawm lub plab thiab lub hlwb hu ua lub plab-hlwb axis hauv cov ntsiab lus ntawm kev noj qab haus huv / kab mob. Tshaj tawm lub plab-hlwb axis tau dim txoj kev cia siab tshiab hauv kev tiv thaiv, kev tswj hwm, thiab kev kho mob ntawm cov kab mob neurodegenerative. Yog li ntawd, kev qhia tshiab lwm txoj kev kho mob hauv kev tswj lub plab-hlwb axis zoo li yog ib lub tswv yim tshiab los ua txoj hauv kev hauv kev sib ntaus cov kab mob neurodegenerative. Cov kev tshawb fawb loj hlob tau tsim cov khoom lag luam marine-derived natural raws li kev cia siab cov neeg sib tw nyob rau hauv ib txhij lub hom phiaj ntawm plab-hlwb hlwb dysregulated mediators rau neuroprotection. Ntawm marine natural khoom, carotenoids (piv txwv li, fucoxanthin, thiab astaxanthin), phytosterols (piv txwv li, fucosterol), polysaccharides (piv txwv li, fucoidan, chitosan, alginate, thiab laminarin), macro acts (piv txwv li, prolactin A), diterpenes (xws li, lobocrasol. , excavatolide B, thiab crassumol E) thiab sesquiterpenes (piv txwv li, tswj) tau pom tias yog cov neeg sib tw muaj txiaj ntsig hauv kev hloov kho lub plab-hlwb axis. Cov khoom lag luam marine tau hais los saum no yog cov neeg tswj hwm ntawm inflammatory, apoptotic, thiab oxidative kev nyuaj siab mediators rau ib qho kev cai bidirectional ntawm lub plab-hlwb axis, Txoj kev tshawb no aims ntawm piav txog lub plab-hlwb axis, qhov tseem ceeb ntawm plab microbiota nyob rau hauv cov kab mob neurological, xws li zoo li lub luag haujlwm modulatory ntawm marine natural khoom ntawm neuroprotection.
Keywords: marine natural khoom; plab-hlwb axis; neuroprotection; teeb liab txoj kev; kho lub hom phiaj; kws tshuaj
Sajad Fakhri 1, Akram Yarmohammadi, Mostafa Yarmohammadi, Mohammad Hosein Farzaei, thiab Javier Echeverria
1 Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran; sajad.fakhri@kums.ac.ir
2 Pawg Neeg Tshawb Fawb Kev Tshawb Fawb, Kws Qhia Ntawv ntawm Pharmacy, Kermanshah University of Medical Sciences, Kermanshah 6714415153, Iran
3 Medical Technology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran
4Departamento de Ciencias del Ambiente, Facultad de Química thiab Biología, Universidad de Santiago de Chile, Santiago 9170022, Chile
1 Kev Taw Qhia
Txoj kev ua neej niaj hnub nrog kev noj cov zaub mov tiav, nqaij, thiab nplej tau hloov pauv cov nroj tsuag ntawm lub plab zom mov (GIT) [1]. Cov kev tshawb fawb tsis ntev los no tau ua rau lub tswv yim ntawm kev nthuav tawm kev sib raug zoo ntawm plab hnyuv thiab hauv nruab nrab lub paj hlwb (CNS) cov kab mob xws li Parkinson's disease (PD), Alzheimer's disease (AD), ntau yam sclerosis (MS), amyotrophic lateral sclerosis (ALS), autism spectrum disorders. (ASD), thiab kev puas siab puas ntsws xws li kev ntxhov siab thiab kev nyuaj siab [2]. Cov pov thawj loj hlob tau ua pov thawj ntawm kev sib txuas lus bidirectional ntawm GIT thiab CNS lub npe hu ua lub hlwb axis. Txoj cai ntawm lub plab-hlwb tib neeg lub cev physiology yuav cuam tshuam los ntawm ntau lab tus kab mob uas nyob hauv lub cev. GIT yog qhov chaw tseem ceeb uas ua rau feem ntau ntawm cov nroj tsuag no thiab cov neeg nyob hauv hu ua plab microbial (GM) [3]. Lub plab homeostasis tuaj yeem cuam tshuam los ntawm ntau yam, suav nrog kev siv tshuaj tua kab mob, kev noj zaub mov, thiab kev kis kab mob thiab qhov kev hloov pauv ntawm GM muaj feem cuam tshuam rau hauv cov kab mob plab-hlwb-hluav taws xob cuam tshuam [4]. Lub plab-hlwb axis yog lub ntsiab anatomical txoj hauv kev uas lub plab thiab lub hlwb tuav lawv txoj kev sib raug zoo thiab tuaj yeem sib txuas lus nrog ib leeg hauv kev noj qab haus huv thiab kab mob. Cov kev tshawb fawb tau pom qhov cuam tshuam ntawm GM ntawm lub hlwb evolution, mus ob peb vas, thiab lub cev tsis muaj zog [3]. GM sib txuas lus nrog plab epithelium los txhim kho lub cev hemostasis thiab tiv thaiv kab mob. Cov pov thawj muaj zog tshaj plaws rau lub luag haujlwm ntawm GM ntawm lub hlwb kev loj hlob tau los ntawm kev tshawb fawb ntawm cov kab mob tsis muaj kab mob (GF) nas [2]. Nyob rau hauv tas li ntawd, lub dysregulated muaj pes tsawg leeg ntawm plab kab mob plays lub luag hauj lwm tseem ceeb nyob rau hauv lub pathogenesis ntawm lub plab-hlwb hlwb mob [5]. Qhov no qhia tau hais tias kev sib raug zoo bidirectional los ntawm kev cuam tshuam hauv GM tuaj yeem cuam tshuam rau cov tsos mob ntawm lub paj hlwb thiab rov ua dua [2]. Hauv lwm lo lus, nrog rau lub tswv yim ntawm lub plab-hlwb axis tau muab tso rau pem hauv ntej, muaj kev ntseeg ntau ntxiv tias qhov kev sib txuas lus no ua rau ob sab los ntawm qhov uas GM cuam tshuam CNS, thiab CNS cuam tshuam rau GM. Cov kev tshawb fawb loj hlob qhia tias GM cuam tshuam rau txoj kev loj hlob, kev ua haujlwm, thiab kev tsis sib haum xeeb ntawm lub hauv paus paj hlwb los ntawm kev tswj hwm ntawm cov receptors cuam tshuam thiab cov teeb meem sib tham [6]. Cov kab mob neuroimmune thiab neuroendocrine yog ob qhov tseem ceeb ntawm lub plab-hlwb axis [7]. Tshaj tawm cov ncauj lus kom ntxaws microbiota ua haujlwm kho kom haum los ntawm txoj hauv kev tseem ceeb dysregulated yog qhov tseem ceeb rau peb qhov kev tshawb pom ntawm lub plab-hlwb axis yuav cuam tshuam cov txiaj ntsig neuronal [8]. Tsis tas li ntawd, dysregulation ntawm plab hnyuv permeability thiab plab integrity cuam tshuam rau plab-bacteria-derived metabolites thiab lwm yam kev taw qhia txoj kev, mus rau kev loj hlob / kev loj hlob ntawm cov kab mob sib txawv [9]. Yog li, GM pab rov qab ua haujlwm zoo ntawm lub paj hlwb thiab lub plab-hlwb signaling. Ob peb molecular mechanisms tom qab lub plab-hlwb bidirectional kev sib raug zoo. Hais txog kev nthuav tawm cov kev nkag siab ntawm molecular rau hauv kev cuam tshuam ntawm GM ntawm CNS, nws tau pom tias plab-microbiota sib txuas lus CNS los ntawm kev tsim ntau yam metabolites / neurotransmitters nrog cov khoom neuromodulatory. Ntawm cov no, o, apoptosis, thiab oxidative kev nyuaj siab, nrog rau kev cuam tshuam cov kev taw qhia / tus neeg nruab nrab ua lub luag haujlwm tseem ceeb hauv kev txhawb kev sib raug zoo ntawm plab thiab lub hlwb. Raws li, gamma-aminobutyric acid (GABA), glutamine, 5-hydroxytryptamine (5-HT), histamine, glial cell function, synaptic pruning, ntshav-hlwb barrier function (BBB), thiab myelination yog cov tseem ceeb players. [6, 10]. Xav txog lub plab-hlwb axis, kev tsiv teb tsaws ntawm cov tshuaj lom neeg los ntawm lub plab mus rau lub hlwb tuaj yeem ua rau astrocyte activation ntawm phosphoinositide 3-kinase (PI3K) / protein kinase B (Akt) / mammalian lub hom phiaj ntawm rapamycin (mTOR) txoj kev [11] . Hloov chaw, thaum lub sij hawm pathological, cov kab lus hais saum toj no / cov neeg nruab nrab yuav koom nrog ntau qhov xwm txheej puas hlwb.
Tseem muaj ntau yam pathophysiological mechanisms tom qab neurodegeneration, nrog rau oxidative kev nyuaj siab, neuroinflammation, apoptosis, imbalances ntawm calcium ions, malfunction ntawm mitochondria, impairment ntawm teeb liab thauj los ntawm axons, DNA puas, thiab abnormalities nyob rau hauv RNA ua [12,13]. Raws li, kev hloov pauv ntawm cov xwm txheej no zoo li ua txoj hauv kev hauv kev tiv thaiv / kev kho mob ntawm cov kab mob neuronal. Yog tsis muaj kev paub txog cov txheej txheem meej thiab etiology dag tom qab cov teeb meem no, lawv muaj qee qhov xwm txheej tshwm sim xws li kev ua haujlwm tsis zoo ntawm mitochondria, protein misfolding, thiab kev tshem tawm tsis txaus, uas ua rau lawv nyuaj rau kev daws teeb meem. Txoj hauv kev yooj yim pathological ntawm cov kab mob neurodegenerative kom paub meej tias yuav tsum tau siv cov molecules ntuj nrog ntau cov tshuaj pharmacological [14]. Los ntawm muaj 70 feem pua ntawm cov nroj tsuag npog lub ntiaj teb, thiab muaj ntau yam kab mob nyob, thaj chaw marine yog qhov tseem ceeb tshaj plaws rau cov khoom ntuj tsim. Kev nplua nuj lom neeg thiab noob caj noob ces muaj nuj nqis rau qhov hnyav ib puag ncig ntawm dej hiav txwv. Ib qho ntawm cov kev nyiam ntawm cov tshuaj ntuj tshaj hluavtaws yog nws txoj kev ua siab ntev. Nws kuj tau pom tias cov khoom lag luam hauv hiav txwv muaj cov tshuaj tiv thaiv oxidative, immunomodulatory, thiab tiv thaiv kab mob [15].
Marine tej yam ntuj tso khoom xws li carotenoids, polysaccharides, phytosterols, terpenoids, macro ua, thiab alkaloids siv tej yam antioxidant thiab scavenging yam ntxwv hauv modulating lub plab-hlwb axis. Cov ntawv ceeb toom tsis ntev los no tau qhia txog kev koom tes ntawm GM thiab cov kab mob neurodegenerative [2,11,16] los ntawm cov kab mob inflammatory / apoptotic / oxidative kev nyuaj siab. Rau qhov zoo tshaj plaws ntawm peb txoj kev paub, qhov no yog thawj qhov kev tshuaj xyuas qhia txog lub peev xwm ntawm cov khoom lag luam marine-derived ntuj hauv kev hloov kho lub plab-hlwb axis ntawm neuroprotection. Hauv kev ua haujlwm no, lub luag haujlwm tseem ceeb ntawm cov khoom lag luam marine-derived ntuj tau raug tshuaj xyuas ntawm lub plab-hlwb axis nrog rau cov kab mob neurodegenerative. Tsis tas li ntawd, kev koom tes ntawm plab hnyuv microbial muaj pes tsawg leeg thiab CNS hauv lub cev thiab cov kab mob pathological tau piav qhia. Tsis tas li ntawd, cov laj thawj tsim nyog rau kev siv cov khoom lag luam marine-derived hauv kev kho thiab tswj cov kab mob neurodegenerative tau raug tshuaj xyuas. Cov khoom lag luam hauv hiav txwv tuaj yeem raug qhia ua lwm tus neeg sib tw hauv kev hloov kho ntawm lub plab-hlwb axis ntawm neuroprotection.
2. Gut Microbiome thiab Gut-Brain Axis nyob rau hauv cov kab mob
Kev tswj hwm ntawm tib neeg lub cev yuav raug cuam tshuam los ntawm ntau lab tus kab mob uas nyob hauv lub cev. Nws tau kwv yees tias muaj 1011 kab mob ib gram ntawm cov hnyuv loj [17,18]. Lawv tsis yog tib neeg nyob hauv lub ecosystem, thiab cov kab mob, protozoa, archaea, thiab fungi kuj tseem muaj [19]; Txawm li cas los xij, microbiota zoo li yog tus huab tais ntawm GIT. GIT yog qhov chaw tseem ceeb uas ua rau feem ntau ntawm cov nroj tsuag no thiab cov neeg nyob hauv hu ua GM. Plaub pawg loj thiab ob pawg me ntawm GM yog Bacteroidetes, Firmicutes, Proteobacteria, Actinobacteria, nrog rau Verrucomicrobia, Fusobacteria, feem [20].
Kev tshawb nrhiav ntxov txog kev sib cuam tshuam ntawm GIT thiab lub hlwb tau tsom mus rau kev zom zaub mov thiab satiety [21]. Homeostasis ntawm lub plab yog tswj hwm los ntawm kev sib cuam tshuam ntawm cov kab mob no nrog rau ib leeg thiab nrog cov txheej txheem epithelium ntawm lub plab thiab qhov homeostasis no ua rau kev txhim kho kev tiv thaiv tus tswv [22,23]. Cov muaj pes tsawg leeg ntawm GM raug cuam tshuam los ntawm ntau yam thiab cov xwm txheej tau ua lub luag haujlwm tseem ceeb ntawm cov neeg nyob hauv. Lwm yam muaj xws li caj ces, hnub nyoog, kev ua si ntawm lub cev, ib puag ncig, kev kis kab mob, raug tshuaj tua kab mob [24], hloov cov mucus secretion-induced stress [25], thiab khoom noj khoom haus [5,26]. Nyob rau hauv xyoo tsis ntev los no, khoom noj khoom haus thiab zaub mov tau txais kev saib xyuas tshwj xeeb rau kev hloov kho GM.
Lub xub ntiag ntawm GM muaj ob lub luag haujlwm hauv kev noj qab haus huv thiab kab mob hauv xeev, txhim kho kev tiv thaiv kab mob thiab kev loj hlob / kev tawm tsam ntawm cov kab mob, suav nrog neurodegeneration [22,23], xws li lub plab-hlwb axis. Lub plab-hlwb axis yog lub ntsiab anatomical txoj hauv kev hauv plab thiab lub hlwb tuav lawv txoj kev sib raug zoo thiab tuaj yeem sib txuas lus nrog ib leeg hauv kev noj qab haus huv thiab kab mob [27]. Qhov nyuaj ntawm kev sib raug zoo ntawm GM thiab CNS tau nthuav tawm hauv cov kev tshawb fawb cuam tshuam. Txawm li cas los xij, qhov tseeb mechanism ntawm bidirectional plab-hlwb kev sib raug zoo tsis paub. Cov kev tshawb fawb pom tias GF nas tsis tuaj yeem txhim kho txoj hnyuv noj qab haus huv hauv kev sib piv rau cov kab mob tsis muaj kab mob (SPF) thiab GF-cov kab mob ib txwm muaj, lees paub qhov kev xav no uas GM muaj lub luag haujlwm tseem ceeb hauv kev txhim kho lub paj hlwb (ENS) [ 6,28], CNS, thiab hypothalamic-pituitary-adrenal (HPA) axis [29] nyob rau theem pib ntawm lub neej postnatal.
Hauv kab no, kev hloov pauv tau zoo ntawm GM los ntawm kev siv tshuaj tua kab mob hauv cov nas SPF tau ua rau kom muaj kev vam meej ntawm lub hlwb-derived neurotrophic factor (BDNF) hauv hippocampus thiab depleted qhia hauv amygdala [30]. Lub plab-hlwb axis muaj CNS (lub hlwb), ENS, thiab lub plab zom mov [24]. Intrinsic innervation ntawm lub plab yog ua tiav los ntawm kev sib txuas ntawm ENS neurons, suav nrog ob lub network, myenteric thiab submucosal tes hauj lwm, uas hloov cov plab hnyuv ua haujlwm xws li peristalsis, secretion, thiab absorption [31]. Nws koom nrog hauv peristalsis, hormone / acid secretion, bicarbonate, thiab mucus ntau lawm [24]. Cov paj hlwb vagus yog qhov chaw loj tshaj plaws los xa cov cim visceral rau hauv CNS kom ua rau lub siab thiab lub siab / lub siab hloov pauv thiab lub hlwb cov cim rau lub plab rau kev hloov kho ntawm plab lub cev thiab kev ua haujlwm [6,27].
Lub autonomic paj hlwb (ANS) nyob rau hauv kev koom tes nrog neuronal thiab neurohormonal signaling, tswj ntau lub physiological functions xws li ua pa, plawv dhia, digestion, peristalsis, bile secretion, permeability, carbohydrate theem, mucosa xeev, homeostasis ntawm mucosal kua, thiab osmolality, mucus ntau lawm thiab mucosal lub cev muaj zog [27,32]. ANS synapses yog qhov chaw uas nkag siab cov microbial metabolites raws li cov cuab yeej ntawm kev sib txuas lus ntawm microbiota nrog ib leeg [33]. ANS ncaj qha qhia lub plab ntawm CNS ua rau muaj kev hloov pauv hauv nws lub cev. Lub luag haujlwm ntawm lub plab epithelium hauv kev ua kom lub cev tiv thaiv kab mob tuaj yeem hloov kho los ntawm ANS hauv ob qho tib si ncaj qha thiab tsis ncaj. Hauv txoj kev ncaj nraim, nws hloov kho cov lus teb ntawm lub plab lub cev tiv thaiv kab mob rau cov kab mob microbes, thiab hauv txoj kev tsis ncaj, nws hloov cov microbes [34].
Lub microbiota-gut-brain (MGB) axis ua rau muaj kev sib raug zoo ntawm microbiota thiab lub hlwb [27], los ntawm kev cuam tshuam hauv ib qho ntawm lawv txoj haujlwm, xws li cov kab mob plab microbial, yuav cuam tshuam rau lwm tus [2]. Ib qho kev cuam tshuam hauv plab-hlwb crosstalk tuaj yeem ua rau muaj kev loj hlob ntawm kev paub thiab cov kab mob neural [35,36]. MGB axis yog ib feem ntawm lub cev muaj zog loj, suav nrog endocrine (HPA axis), lub cev tiv thaiv kab mob (kev kho los ntawm cytokines thiab chemokines), ANS, thiab ENS. Gut microbiota exerts nws cov nyhuv ntawm HPA axis thiab vagus paj hlwb los ntawm metabolites uas ua los ntawm cov metabolism hauv tryptophan [24]. Hauv kab no, ntau lub microbial molecules koom nrog hauv MGB-txoj kev taw qhia thiab kev sib txuas lus [37,38]. Nws tau raug tshaj tawm tias Clostridium sporogenes decarboxylase tuaj yeem tig tryptophan mus rau tryptamine, ib qho neurotransmitter uas ua rau serotonin thiab dopamine tso tawm los ntawm neurons [39]. Tsis tas li ntawd, ib qho tseem ceeb inhibitory neurotransmitters zoo li GABA yog tsim los ntawm Lactobacillus spp. thiab Bifidobacteria spp. los ntawm glutamate [40] Cov hlwb uas koom nrog cov kev taw qhia no hauv kev koom tes nrog cov kab mob sib kis yog cov kab mob enteroendocrine (EECs), enterochromaffin cells (ECCs), thiab cov kab mob mucosal. Stimulated EEC hlwb ua rau kev tsim cov neuropeptides zoo li peptide YY, neuropeptide Y (NPY), thiab cov tshuaj P uas cuam tshuam rau ENS [41]. Txhawm rau muab qhov tseeb molecular yam ntxwv ntawm cov teebmeem ntawm GM ntawm CNS, nws tau pom tias GM sib txuas lus CNS directionally los ntawm kev tsim ntau yam neurotransmitters / metabolites nrog neuromodulatory zog. Ntawm cov kws kho mob / txoj hauv kev, glutamine, histamine, synaptic pruning, glial cell function, ntshav-hlwb barrier BBB muaj nuj nqi, thiab myelination yog cov tseem ceeb players [6,10]. Ntxiv rau cov txheej txheem kev sib txuas lus saum toj no, microbiota tuaj yeem ncaj qha rau cov neeg sib tham hauv neuroactive xws li GABA [42], 5-HT, norepinephrine, thiab dopamine [43]. Xav txog lub plab-hlwb axis, kev tsiv teb tsaws ntawm cov tshuaj lom neeg ntawm lub plab mus rau lub hlwb tuaj yeem ua rau cov cell tsiv teb tsaws hauv astrocytes los ntawm kev ua haujlwm ntawm PI3K / Akt / mTOR txoj hauv kev [11]. Yog li ntawd, cov kws kho mob tau hais tseg saum toj no muaj lub luag haujlwm tseem ceeb hauv ntau cov txheej txheem hauv lub cev, suav nrog apoptosis, o, oxidative kev nyuaj siab, nrog rau cov cell tsiv teb tsaws thiab kev loj hlob ntawm homeostasis thiab txawm tias cov xwm txheej ntawm cov kabmob sib txawv.
Cov dej ntws tawm xws li kev loj hlob receptors, G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), thiab cytokines ua lub luag haujlwm tseem ceeb hauv kev txo qis ntawm Janus kinase (JAK) / signal transducer thiab activator of transcription (STAT). Tsis tas li ntawd, Akt phosphorylates glycogen synthase kinase 3 (GSK-3 ) nrog lub luag haujlwm tseem ceeb hauv ntau yam kab mob tshwj xeeb tshaj yog cov kab mob neurodegenerative. Akt kuj cuam tshuam rau txoj hauv kev apoptotic (piv txwv li, Bax/Bcl-2, caspases), inflammatory mediators (Ils, COX, NF-κB), thiab oxidative yam (piv txwv li, SOD, ROS, Nrf2, HO-1 , CAT) hauv kev sib ntaus cov kab mob/neurodegenerative mob [44]. Hauv kab no, kev kho mob nrog probiotics txo qis tus cwj pwm zoo li kev nyuaj siab los ntawm kev nce Bcl -2 thiab p-Akt, thaum txo qis malondialdehyde (MDA), cleaved caspase -3, thiab Bax hauv cov ntshav [8].
Raws li tau hais tseg, GM tau hais los saum toj no ua lub luag haujlwm tseem ceeb hauv kev ua kom cov metabolism hauv ntuj tsim rau kev ua haujlwm lom neeg thiab cov txiaj ntsig kev noj qab haus huv, tshwj xeeb tshaj yog cov kab mob neurodegenerative. Nyob rau hauv cov kab no, nquag tsim cov tebchaw tuaj yeem txo cov teeb meem kev sib tham nrog cov neurodegeneration. Txawm li cas los xij, qee qhov ntawm cov metabolites hla lub plab hnyuv thiab mus txog BBB ntawm cov hlab ntsha [38,45].
3. Gut-Brain Axis nyob rau hauv Neurodegenerative Disease
Niaj hnub no, cov kab mob neurodegenerative tau suav tias yog kev txhawj xeeb thoob ntiaj teb thiab ntau cov kev tshawb fawb tau tsom mus rau thaj chaw ntawm kev tshawb fawb no kom txo qis cov teeb meem cuam tshuam [46]. Cov kab mob neural xws li PD thiab AD muaj cov kab mob uas 1 feem pua thiab 8 feem pua ntawm cov pej xeem raug kev txom nyem los ntawm CNS thiab peripheral paj hlwb (PNS) deteriorations, feem [47]. Cov kev tshawb fawb tsis ntev los no tau pom tias kev hloov pauv ib txwm muaj GM muaj lub luag haujlwm tseem ceeb hauv cov kab mob neurodegenerative xws li PD, AD, ALS, thiab kev nyuaj siab; txawm li cas los xij, qhov tseeb mechanism
Hauv qab no tshwm sim yuav tsum tau soj ntsuam ntau dua [48]. Ib txoj kev tshawb fawb tsis ntev los no tau lees paub qhov kev sib raug zoo ntawm microbiota dysbiosis (piv txwv li, hloov pauv ntawm GM) thiab AD pathology [49], txo qis ntawm cov kab mob gram-negative thiab nce plab hnyuv permeability kuj tau sau tseg [48]. Hauv AD, qhov txo qis ntawm GM biodiversity los ntawm kev noj tshuaj tua kab mob ua rau muaj kev hloov pauv ntawm neuroinflammatory thiab amyloidosis uas tau lees paub lub luag haujlwm ntawm GM hauv pathology ntawm AD [50]. Ib qho ntawm cov tseem ceeb contributors rau lub pathogenesis ntawm AD yog microbiota ntau haiv neeg. Piv txwv li, nws tau pom tias nyob rau hauv cov teb chaws tsim muaj kev tu cev zoo, kev sib txawv ntawm GM qis dua yog cuam tshuam nrog AD tshwm sim [16]. Thaum lub sijhawm AD, qee qhov kev hloov pauv tau pom hauv GM, suav nrog Bacteroides vulgatus, Bacteroides fragilis, Eggerthella lenta, Odoribacter splanchnicus, Butyrivibrio hungatei, Butyrivibrio proteoclasticus, Eubacterium eligens, Eubacterium hallii splanchnicus, Eubacterium Bacterium, thiab Eubacterium. Faecalibacterium prausnitzii yog cov kab mob. Qhov no ua rau muaj kev nce ntxiv ntawm cerebral amyloid (A ) / neuroinflammation, nce cov kab mob lipopolysaccharides (LPS), nrog rau siab interleukin (IL) -1 beta, NLR tsev neeg pyrin domain muaj 3 (NLRP3), thiab chemokine (CXC). motif) ligand 2 (CXCL2). Dysregulated theem ntawm tus xov tooj zoo li receptors (TLRs), nuclear factor κB (NF-κB), IL-1 , IL-18, A , thiab caspase -1 kuj tshwm sim los ntawm bidirectional dysregulation ntawm lub plab-hlwb axis hauv AD [51–54].
Lub luag haujlwm ntawm tib neeg microbiota yog tshawb nrhiav ntau dua los ntawm kev siv thev naus laus zis hauv ob xyoo dhau los hauv ob qho tib si physiological thiab pathological xeev. Txog niaj hnub txoj kev ntawm GF tsiaj qauv, tshuaj tua kab mob pab microbiota manipulation thiab fecal microbial transplantation tau siv nyob rau hauv kev tshawb nrhiav [12]. Piv txwv li, hauv kev tshawb nrhiav kom pom lub luag haujlwm ntawm GM hauv kev nthuav dav ntawm AD hauv cov neeg mob laus, lawv tau muab piv rau cov neeg mob AD nrog cov laus noj qab nyob zoo. Lawv pom tias qhov qis dua ntawm cov kab mob butyrate tsim nrog rau ntau dua ntawm cov kab mob taxa tuaj yeem siv los ua tus kwv yees ntawm AD [51]. Qee hom kab mob xws li Firmicutes, Bacteroidetes, thiab Proteobacteria tau koom nrog hauv cov kab mob ntawm cov kab mob ua rau mob ntev los ntawm kev tsim cov amyloids suav nrog IL- 17A thiab IL-22 cytokines [55]. Lub luag haujlwm ntawm GM hauv kev tsim cov vitamin B12, uas muaj lub luag haujlwm tseem ceeb hauv kev txawj ntse, yog lwm qhov piv txwv uas qhia txog nws qhov tseem ceeb [56]. Hauv kev tshawb nrhiav kom pom lub luag haujlwm ntawm GM hauv kev nthuav dav ntawm AD hauv cov neeg laus laus, cov kws tshawb fawb tau muab piv rau cov qauv fecal ntawm AD cov neeg mob nrog cov laus noj qab nyob zoo. Lawv pom tias qis dua ntawm cov kab mob butyrate uas tsim cov kab mob ntau dua ntawm cov kab mob taxa tuaj yeem siv los ua tus kwv yees ntawm AD [51].
Ib qho ntawm cov teeb meem tseem ceeb rau kev kho GM yog hnub nyoog thiab cov kab mob cuam tshuam. Raws li lub hnub nyoog ntawm tus neeg mob nce mus, kev kho dua tshiab yuav muaj kev cuam tshuam ntau dua. Hauv cov neeg mob PD, kev hloov pauv ntawm GM thiab kev kis tus kab mob H. pylori tau pom [2]. Hauv PD, dysregulated theem ntawm GM, Enterobacteriaceae, Prevotellaceae, Verrucomicrobiaceae, Lactobacillus, Porphyromonas, Parabacteroides, Mucispirillum, thiab Bacteroides fragilis ua rau nce tus nqi ntawm TLR4, IL{{2} 3} , {4}}, IL-6, IL-13, IL-18, qog necrosis factor- (TNF-), thiab interferon (IFN)- [3]. PD metagenome suav nrog ntau qib ntawm cov noob koom nrog hauv LPS biosynthesis thiab hom 3 cov kab mob zais zis uas qhia tias muaj peev xwm ua rau mob ntau dua los ntawm microbial metabolites [57]. Cov kev tshawb fawb no txhawb nqa lub luag haujlwm ntawm cov khoom siv inflammatory hauv periphery CNS o uas nthuav tawm hauv PD [50]. Toxic alpha-synuclein (-Syn) aggregates yog cov cim ntawm Lewy lub cev uas paub zoo tias yog tus cim ntawm PD substantia nigra pars compacta neurons [58]. Hauv kev tshawb fawb, nws tau pom tias thawj qhov chaw ntawm -Syn deposition yog submucosal txheej ntawm txoj hnyuv [59]. Hauv kev soj ntsuam ua tiav ntawm cov qauv fecal ntawm cov neeg mob PD, ntau dua ntawm Enterobacteriaceae, thiab qis dua ntawm Prevotellaceae tau pom tseeb hauv kev sib piv rau pawg tswj hwm nrog tib lub hnub nyoog. Kev nce qib ntawm Enterobacteriaceae, nrog rau cov nqi ntawm Prevotellaceae depleted, qhia txog kev sib raug zoo nrog kev tsis taus thiab kev taug kev. Cov nyhuv ntawm Prevotellaceae yog vim nws muaj peev xwm tsim cov roj ntsha luv luv (SCFAs), thiamine, thiab folate raws li cov khoom lag luam los tsim kom muaj kev noj qab haus huv ib puag ncig [60].
Probiotics txhais tau tias yog cov kab mob muaj sia nyob, uas muaj txiaj ntsig zoo rau cov neeg siv khoom noj qab haus huv thaum muaj cov khoom noj txaus ntawm lawv tau zom. Lawv cov kev siv tau nce hauv kev kho mob thiab chaw kho mob nrog kev hloov pauv ntawm lwm yam CNS cuam tshuam, suav nrog kev ntxhov siab thiab kev nyuaj siab [61,62]. Lawv cov txiaj ntsig ntawm GM proliferation tau raug pov thawj [24]. Hauv cov neeg mob uas muaj kev ntxhov siab / kev nyuaj siab Bifidobacterium, Alistipes, Prevotella, Parabacteroides, Lachnospiraceae, Anaerostipes, Oscillibacter, Faecalibacterium, Ruminococcus, Clostridium, Mega monas, Streptococcus, Klebsiella, thiab Phascolarctoamine yog hloov mus rau cov kab mob hu ua AC (Doclarcto-acidosis), 3}}HT, BDNF qhia, thiab circulatory IL-10 thaum nce ntshav plasma stress hormone [63,64]. Tsis tas li ntawd, dysregulated qib ntawm GABA, dopamine, 5-HT thiab IL-10 kuj tau tshwm sim hauv kev ntxhov siab / kev nyuaj siab cuam tshuam nrog lub plab-hlwb axis [63–65]. Kev ntxhov siab txog kev puas siab puas ntsws xws li kev ntxhov siab thiab chim siab plob tsis so tswj (IBS) muaj feem cuam tshuam. Qhov kev sib raug zoo no ua rau lub tswv yim ntawm kev tshawb fawb plab-hlwb axis. Ntau tshaj 50 feem pua ntawm cov neeg mob uas raug mob los ntawm IBS muaj comorbidities ntawm kev ntxhov siab vim thiab kev nyuaj siab [66]. Hauv kev tshawb fawb los ntawm Sudo et al., nws tau pom tias tsis muaj kev cuam tshuam GM muaj pes tsawg leeg nyob rau theem pib ntawm lub neej muaj kev cuam tshuam loj rau kev tswj hwm kev ntxhov siab rau neeg laus [29]. Cov kev tshawb fawb tom qab tau pom tias qhov teeb meem no yuav cuam tshuam rau cov tshuaj neurochemical xws li cortical thiab hippocampal hlwb-derived neurotrophic factor [29,67], hippocampal 5-HT receptor 1A magnitude [67], striatal monoamine turnover [68], thiab gene qhia ntawm synaptic plasticity [68] uas qhia txog lub zog ntawm GM ntawm CNS phenotype. Ntxiv mus, lwm yam teebmeem ntawm GM yog kev ntxhov siab [67,68] thiab kev nyuaj siab [69], mob teb [70], noj, saj, thiab cov metabolism hauv cheeb tsam [71].
Ntxiv rau AD, PD, kev ntxhov siab / kev nyuaj siab, thiab kev laus, muaj lwm yam kev puas siab puas ntsws (xws li, ALS) uas feem ntau cuam tshuam nrog kev hloov pauv GM thiab txo qis biodiversity ntawm lub plab flora qhia txog kev sib cuam tshuam ntawm cov yam ntxwv no. Neuroimmune activation yuav ua tiav los ntawm kev nce qib ntawm butyrate-ua hom [48]. Tsis tas li ntawd, hauv cov quav hauv cov neeg mob ALS, cov qib siab dua ntawm inflammatory Ruminococcaceae, Enterobacteria, thiab Escherichia coli tau kuaj pom nyob rau hauv kev sib piv rau pawg tswj hwm [72]. Cov txiaj ntsig ua ntej kev kho mob pom tau tias muaj cov plab hnyuv permeability ntau ntxiv, cov qauv kev sib tshuam nruj, thiab muaj ntau tus lej ntawm Paneth hlwb txawv txav, ib hom ntawm tes ua lub luag haujlwm rau kev tiv thaiv kab mob hauv cov tsiaj ua qauv ntawm ALS. Tsis tas li ntawd, GM tau qhia txog kev hloov pauv cov txheeb ze ntawm cov kab mob microbial nrog rau kev txo qis hauv butyrate-ua Butyrivibrio fibrisolvens [73]. Cov pov thawj kho mob kuj tau lees paub tias muaj txiaj ntsig nce hauv Bacterioidetes thiab, yog li ntawd, txo qis Firmicutes rau Bacteroidetes qib, nrog rau kev txo qis hauv cov txiaj ntsig Anaerostipes, Lachnospiraceae, thiab Oscillobacter hauv GM ntawm ALS cov neeg mob. Cov kev hloov pauv ua haujlwm tau hais tseg hauv ALS cov neeg mob tau xaus lus tias muaj feem cuam tshuam nrog cov qib dysregulated nitric oxide (NO), GABA, LPS, AMPA / N-methyl-D-aspartate (NMDA), thiab oxidative txoj kev [74–76].
Kev sib txuas lus ntawm plab thiab lub hlwb yog kho los ntawm qee cov khoom siv kab mob ntawm cov kab mob neurological. Hauv MS tus kab mob, kev tshawb fawb los ntawm Farrokhi thiab cov neeg ua haujlwm sib koom ua ke tau pom tias txo qis qib lipid 654 raws li cov metabolite ntawm Bacteroides spp. Hauv kev sib piv rau pawg tswj hwm [77]. Hauv lwm txoj kev tshawb fawb, nws tau pom tias Clostridium perfringens co toxins B thiab D [78] tuaj yeem ua rau MS zoo li cov tsos mob, suav nrog qhov muag tsis pom kev thiab lub cev muaj zog ua haujlwm tsis taus [56]. Toxins-induced visual defects nyob rau hauv MS cov neeg mob yog vim retina o tshwm sim los ntawm tsim tsis xws luag nyob rau hauv lub barrier veins thiab khi rau vascular receptors [79]. Cov neeg mob nrog MS tau paub txog kev hloov pauv ntawm Acinetobacteria, Bacteroidetes, Desulfovibrionaceae, Firmicutes, Proteobacteria, Verrucomicrobia, thiab txuam nrog genus [77,80]. Qhov no tau pom zoo nrog GABA dysregulated, txo qib ntawm 5-HT thiab dopamine, thaum nce IFN- , monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP)-1 , MIP -1 , thiab IL{15}} hauv MS cov neeg mob [77,80–82].
Raws li lwm cov kab mob hauv lub paj hlwb uas muaj kev sib cuam tshuam nrog GM, ASD muaj ntau qhov kev hloov pauv hauv cov kab mob hauv plab, suav nrog Bifidobacteraceae, Veillonellaceae, Lactobacillaceae, Bifidobacterium, Megasphaera, Mitsuokella, Rumnicoccus, Lachnoclostridium, Clostridium, Suttercilla, Devia, thiab lwm yam. 83] ib. Cov kev hloov no yog concomitant nrog pathophysiological hloov nyob rau hauv signaling mediators, nrog rau upregulation ntawm mTOR, TNF-, IL-4, IL-5, IL-6, IL-8 thaum down- regulating IL-10, transforming growth factor-beta (TGF- ), and 5-HT in ASD [11,81,84–87].
Los ntawm kev xav txog kev siv tshuab, tom qab lub plab-hlwb lub koom haum, oxidative kev nyuaj siab thiab o zoo li ua lub luag haujlwm tseem ceeb. Oxidative kev nyuaj siab yog ib qho tseem ceeb ntawm kev koom tes hauv mitochondrial tsis ua haujlwm uas tau pom hauv cov kab mob neurodegenerative. Nws yog qhov tshwm sim ntawm qhov tsis sib xws ntawm cov tshuaj tiv thaiv cov pa oxygen (ROS) thiab cov tshuaj tiv thaiv antioxidant arsenal. Lub hom phiaj lom neeg rau ROS molecules yog lipids, proteins, thiab nucleic acids uas ua rau lawv puas tsuaj thiab degradation [88]. Nws tau pom tias kev sib txuas lus ntawm microbiota nrog cov tswv tsev tuaj yeem ua tiav los ntawm kev sib koom ua ke nrog cov haujlwm mitochondrial. Muaj peev xwm, kev sib cuam tshuam ntawm microbiota-gut-hlwb axis nrog CNS oxidative kev nyuaj siab yuav tshwm sim. Nyob rau hauv cov kab no, ntau npaum li cas ntawm ROS yog txuam nrog dysbiosis ntawm microbiota ua rau o ntawm CNS. Ntawm qhov tod tes, malfunction ntawm CNS tshwm sim los ntawm lub hlwb lesions tuaj yeem ua rau muaj kev hloov pauv hauv GM muaj pes tsawg leeg. Kev sib raug zoo ntawm oxidative stress-mitochondria-microbiota thiab neurodegenerative kab mob accents qhov tseem ceeb ntawm lub plab-hlwb axis [18]. Nws tau pom tias kev ntxhov siab muaj feem cuam tshuam rau postprandial gastrointestinal motility thiab induces ib ntus txo cov plab hnyuv ntxwm hauv dev [25]. Kev ntxhov siab siv nws cov txiaj ntsig los ntawm cov neeg kho kev ntxhov siab, ua rau lub cev tiv thaiv kab mob hauv zos los ntawm kev hloov ntawm txoj hnyuv permeability [89] thiab tuaj yeem ua rau muaj kev hloov pauv hauv cov kab mob sib xyaw [90].
Ntau qhov kev tshawb fawb kuj tau qhia txog qhov cuam tshuam ntawm GM ntawm CNS thiab kev tiv thaiv kab mob. Txawm li cas los xij leaky plab syndrome (LGS), uas yog permeation ntawm cov nroj tsuag ib txwm mus rau sab nraud ntawm txoj hnyuv lumen thiab thiaj li nce qib ntawm cov metabolites neuroactive ua rau cov lus teb neuroinflammatory hauv lub hlwb suav nrog cerebellum thiab hippocampus tsis ua haujlwm [91,92]. Nws tau raug pov thawj tias LGS feem ntau tshwm sim hauv cov neeg mob uas muaj ntau yam mob CNS [93] thiab cov metabolites xau rau hauv cov ntshav cuam tshuam CNS [94]. Mob mob me me ua rau tso tawm cytokines rau hauv cov ntshav thiab cuam tshuam rau lub cev. Kev mob tshwm sim los ntawm microbiota yog kho los ntawm cov molecules xws li LPS thiab peptidoglycans. Kev lees paub ntawm LPS yog ua los ntawm TLR4 uas monocytes, macrophages, thiab lub hlwb microglia yog nplua nuj nyob rau hauv lawv [24]. Cov kev tshawb fawb pom tias muaj TLR4 kho cov lus teb rau cov neeg mob IBS nyuaj siab [95,96]. Cov ntshav ntawm pro-inflammatory thiab anti-inflammatory chemokines tuaj yeem hloov kho tsis ncaj los ntawm microbiota thiab probiotics uas muaj kev cuam tshuam ncaj qha rau lub hlwb ua haujlwm [24]. Los ntawm kev qhia E. coli rau GF nas, macrophage activation thiab infiltration hauv cov ntaub so ntswg adipose coj mus rau qib siab ntawm pro-inflammatory cytokine thiab IFN qhia [97].
Los ntawm lwm qhov kev xav ntawm kev xav, GM tau pom tias hloov pauv hloov pauv, kev ua ub no, thiab qhov txawv txav ntawm CNS thiab ENS los ntawm kev khi thiab txhawb cov qauv kev lees paub (PRRs) xws li TLR2 thiab TLR4 [6,98]. Kev tsis sib haum xeeb ntawm GM zej zog, kev tsis sib haum xeeb ntawm lub plab, thiab permeability ua rau nce qib ntawm cov khoom siv microbial thiab microbes-associated molecular patterns (MAMPs) hauv cov ntaub so ntswg mesenteric lymphoid uas ua rau muaj qhov sib txawv ntawm cov kab mob neurological [2,9]. Kev sib piv ntawm cov tsiaj txhu GF nrog cov nas tswj cov lus pom zoo tau lees paub tias cov tshuaj hormone signaling, BDNF qhia, neurotransmission, thiab amino acid metabolism, yog impaired hauv GF qauv [99]. Cov kev hloov hauv microbiota muaj pes tsawg leeg vim noj tshuaj tua kab mob, cuam tshuam rau kev ncaj ncees thiab kev ua ub no ntawm ENS, neurochemistry, thiab txo tus naj npawb ntawm ganglia nyob enteric glial hlwb hauv vivo [100].
Qhov sib xyaw ua ke ntawm GM thoob plaws hauv lub neej yuav raug cuam tshuam hauv cov xwm txheej xws li mob, raug tshuaj tua kab mob, thiab hloov kev noj haus lossis kev ua neej [2]. Nyob ntawm qhov hnyav ntawm qhov xwm txheej uas tus neeg ntsib, cov nroj tsuag rov qab mus rau qhov qub qub flora sai sai los yog ncua sij hawm. Tab sis qee zaus, nws yeej tsis rov qab mus thiab tig mus rau qhov teeb meem ntev.
Ua ke, GM thiab cov kab mob neurodegenerative yog nyob rau hauv kev sib raug zoo bidirectional, thiab kev hloov kho txhua qhov ntawm cov kab lus hais saum toj no tuaj yeem cuam tshuam rau lwm tus. Table 1 qhia txog kev hloov pauv hauv GM thaum qee cov kab mob neurodegenerative thiab cov txiaj ntsig ntawm pathophysiological.
4. Marine-Derived Natural Products thiab Associated Sources
Los ntawm npog 70 feem pua ntawm lub ntiaj teb ntiaj teb thiab khaws cia muaj ntau hom kab mob sib txawv, qhov chaw nyob hauv hiav txwv tau ua qhov zoo tshaj plaws ntawm cov khoom ntuj tsim [88]. Kev sib koom ua ke ntawm kev sib txawv ntawm cov noob caj noob ces thiab cov kev ua ub no ntawm cov khoom xyaw marine active yog tshuav rau qhov hnyav ib puag ncig ntawm dej hiav txwv, nyob rau hauv cov xwm txheej ntawm kev kub siab, txias txias, thaj chaw tsaus, thiab hloov mus rau kev ntxhov siab [101]. Qhov hnyav molecular ntawm marine-derived natural products ranges ntawm 100 mus rau 1000 Da thiab yog tshwj xeeb rau ib tug neeg taxonomic classification [102]. Kev ciaj sia ntawm GIT microorganisms, uas sib tw nrog lwm cov kab mob, yog nyob ntawm ntau yam ntawm cov khoom tsim los yog kev tswj hwm los ntawm cov khoom lag luam marine-derived natural. Lawv koom nrog hauv kev nyiam, kev rov ua dua, thiab txawm tias tua lwm tus neeg sib tw. Ob leeg eukaryotic thiab prokaryotic kab mob tuaj yeem tsim cov metabolites thib ob. Piv txwv li, Bacillus spp., Pseudomonas spp., eukaryotic fungi (piv txwv li, Penicillium spp., Aspergillus spp.), filamentous actinomyces (piv txwv li, Streptomyces spp.), thiab cov nroj tsuag hauv av tau pom tias tsim cov metabolites theem nrab lossis cuam tshuam cov metabolites.
Tsis ntev los no los ntawm kev tshawb pom cov metabolites tshiab thib ob uas muaj kev ua haujlwm lom neeg, ib lub hom phiaj ntawm kev lag luam tshuaj thiab agrochemical yog tsim los ntawm cov nplai loj. Raws li kev sib txawv ntawm cov qauv ntawm cov metabolites theem nrab, lawv muaj peev xwm siv tau los tiv thaiv ntau hom kab mob [103]. Ib qho ntawm cov yam ntxwv ntawm marine natural sources yog tias lawv tuaj yeem ua raws li qhov chaw txuas ntxiv ntawm bioactive molecules [88]. Ob qhov chaw tseem ceeb ntawm cov khoom lag luam marine-derived yog cov kab mob hauv hiav txwv thiab cov fungi [104]. Kev tshawb fawb pom tau tias kev tsim cov metabolites no tsis yog qhov tshwm sim tshwm sim thiab cuam tshuam nrog ecological niche [105]. Raws li qhov tseeb no, chemists uas ua hauj lwm ntawm marine natural khoom, tab tom nrhiav nrhiav tshiab hom uas tsim cov metabolites [104] los ntawm cov cim metabolic thiab genetic pathways [88]. Yog li, cov kab mob hauv hiav txwv thiab cov fungi tau txais kev mloog ntau [106].
Txog rau tam sim no, ntau tshaj 100 metabolites tuaj yeem pom uas yog tsim los ntawm marine fungi [106]. Ntau cov khoom lag luam marine-derived tej yam ntuj tso tau pom los ua kom muaj ntau yam ntawm bioactivities thiab, yog li ntawd, txuas ntxiv ua qhov muaj txiaj ntsig zoo rau kev tsim cov tshuaj tshiab lossis tshuaj yeeb tshuaj. Peb ntseeg hais tias qhov kev tshawb pom ntawm cov chaw nyob tshiab thiab huab cua yuav ua rau kev tshawb pom tshiab ntawm macro- thiab cov kab mob microorganisms thiab, yog li, tej zaum yuav ua rau kev tshawb nrhiav thiab kev cais tawm ntawm cov khoom tshiab marine-associated natural products [107]. Ntawm cov kab mob microorganisms ntawm marine-derived natural products, Eubacteria yog cov loj, xws li Actinobacteria, Cyanobacteria, thiab lwm yam kab mob. Tsis tas li ntawd, Archaebacteria, Euglenoids (Euglenozoa, Euglenoidea, Protozoa), Dinoflagellates, (Dinozoa, Dinofllagellatea, Protozoa), Ciliates (Protozoa, Ciliophora), Chrysophytes (phaeophyta, Chrysophyceaetom), Chromaista (Chromaophora), Chrysophytes (phaeophyta, Chrysophyceaetom), Chromaista (Chromaista, Chrysophyceaetom), Phaeophyta, Eustigmatophyceae, Chromista, Raphidophytes (Chromista, Raphidophyta), Prymnesiophytes (Prymnesiophyta, Chromista), Cryptophytes (Chromista, Cryptophyceae, Cryptophyta), Prasinophytes los yog nyom-ntsuab Planega (Prasephytes) (Prasephytes ntsuab), , Liab microalgae (Rhodophyta, Plantae), thiab Fungi (Eumycota) [108]. Tshwj xeeb, marine fungi tseem underestimated tab sis cov nplua nuj qhov chaw rau cov tshiab theem nrab metabolites, txawm hais tias lawv faib thiab ecological luag hauj lwm feem ntau tseem tsis tshua muaj. Marine fungi yog qhov chaw ntawm biologically active molecules nrog lub paub anticancer,neuroprotectiveanti-angiogenesis, tshuaj tua kab mob,tshuaj tiv thaiv kab mob, antioxidative thiabanti-inflammatorykev ua si [109].
5. Marine-Derived Natural Products tiv thaiv kab mob: Txoj hauv kev mus rau lub plab-Brain Axis
Raws li tau muab, cov khoom lag luam hauv hiav txwv tuaj yeem muab rho tawm los ntawm ntau qhov chaw, tshwj xeeb tshaj yog cov kab mob, fungi, microalgae. Algae nrog ib lub npe ntawm seaweed yog ib qho ntawm cov khoom tseem ceeb ntawm marine-based compounds uas tau siv dav hauv kev lag luam [110]. Qee qhov tseem ceeb tshaj plaws marine metabolites yog carotenoids, polysaccharides, phytosterols, terpenoids, phenolic compounds, thiab alkaloids [111]. Raws li lawv cov tshuaj tiv thaiv kab mob, tshuaj tiv thaiv kab mob, thiab kev tiv thaiv kab mob, cov lus hais saum toj no tau pom tias muaj txiaj ntsig zoo hauv kev tswj cov neeg mob ntshav qab zib, rog rog, hlwb raug mob, ischemic stroke, thiab lwm yam kab mob neurodegenerative [112]. Cov kab mob neurodegenerative yog qhov tshwm sim ntawm kev hloov pauv ntawm lub cev thiab kev hloov pauv xws li ischemic strokes thiab lub hlwb raug mob uas ua rau poob ntawm qee cov neurons hauv qee thaj tsam ntawm lub hlwb [113]. Yog tsis muaj kev paub txog cov txheej txheem meej thiab etiology dag tom qab cov teeb meem no, lawv txhua tus muaj cov yam ntxwv xws li oxidative kev nyuaj siab, neuroinflammation, malfunction ntawm mitochondria, protein misfolding, thiab tsis txaus clearance, uas ua rau lawv nyuaj rau deal nrog [114]. Ib qho ntawm cov kev nyiam ntawm cov tshuaj ntuj tshaj hluavtaws yog nws txoj kev ua siab ntev. Nws tau raug pom tias cov khoom lag luam hauv hiav txwv muaj cov tshuaj tiv thaiv oxidative, immunomodulatory, thiab tiv thaiv kab mob [115]. Txoj kev nyuaj pathological ntawm cov kab mob neurodegenerative, xyuas kom meej tias qhov kev xav tau ntawm kev siv marine natural molecules nrog ntau cov tshuaj pharmacological [116].
5.1. Carotenoids: Fucoxanthin, Astaxanthin, thiab Lycopene
Raws li marine-derived compounds, carotenoids yog fat-soluble pigments nyob rau hauv cov nroj tsuag, algae, fungi, thiab photosynthetic kab mob. Cov pigments no tsim cov xim daj, liab, thiab txiv kab ntxwv hauv cov nroj tsuag, zaub, thiab txiv hmab txiv ntoo. Muaj ntau tshaj 600 ntau hom carotenoids nrog cov teebmeem antioxidant [117]. Lawv txoj kev sib raug zoo nrog photosynthesis yog muab faib ua ob chav kawm, ib pab pawg ncaj qha koom nrog hauv photosynthesis thiab lwm pab pawg tiv thaiv kab mob los ntawm photooxidation [118]. Cov carotenoids loj uas tsim los ntawm cov kab mob marine muaj xws li astaxanthin, fucoxanthin, lycopene, salinixanthin, saproxanthin, zeaxanthin, siphonaxanthin, canthaxanthin, -cryptoxanthin, diadinoxanthin, dinoxanthin, luteinxanthin, echinaxanthin 3.
Cov tshuaj tau los ntawm marine algae muaj peev xwm tiv thaiv oxidative. Xanthones yog cov khoom lag luam hauv hiav txwv uas muaj cov qauv tricyclic symmetric tau los ntawm dibenzo- -pirone [119]. Nyob ib ncig ntawm 200 xanthone molecules tau lees paub tias yog qhov chaw ntawm cov nroj tsuag, lichens, kab mob, thiab fungi [120]. Lawv cov kev ua ub no muaj xws li ntau hom tshuaj tiv thaiv oxidative [121], antiproliferative [122], antimicrobial [123], antitumoral kev ua ub no [124], thiab ntau haiv neeg no yog vim lawv kev cuam tshuam nrog ntau lub hom phiaj molecular [125].
Ib qho tseem ceeb tshaj plaws xanthones yog fucoxanthin nrog cov txiaj ntsig zoo. Fucoxanthin yog carotenoid nrog ntau yam kev ua haujlwm lom neeg thiab cov txiaj ntsig kev noj qab haus huv los ntawm kev siv tshuaj tiv thaiv kab mob hauv vitro thiab hauv vivo [126,127]. Nws kuj tau pom tias fucoxanthin suppressed lub voj voog ntawm tes thiab induced apoptosis nyob rau hauv combating cancer [128]. Cov tshuaj hepatoprotective, cardioprotective, thiab tiv thaiv kev mob ntshav qab zib ntawm fucoxanthin, nrog rau nws cov txiaj ntsig ntawm metabolic syndrome [129], kuj tau qhia hauv cov kev tshawb fawb sib koom ua ke [130]. Fucoxanthin yog ib yam khoom ntawm Sargassum siliquastrum (xim av algae) thiab tiv thaiv DNA ntawm oxidation [16]. Brown algae, raws li lub hauv paus chiv keeb ntawm fucoxanthin, pom antioxidant thiab anti-inflammatory teebmeem nyob rau hauv glial hlwb [131]. Txawm li cas los xij, ob peb lwm cov xim av algae yog marine qhov chaw rau fucoxanthin, suav nrog Sargassum siliquastrum, Hijikia fusiformis, Undaria pinnatifid, Laminaria japonica, Alaria crassifolia, thiab Cladosiphon okamuranus [117]. Cov txiaj ntsig ntawm kev tshawb fawb pom zoo siv algal metabolites, tshwj xeeb tshaj yog fucoxanthin hauv CNS kab mob [132,133]. Fucoxanthin depleted tiam ntawm A 1-42 fibril thiab A 1-42 oligomers, thaum co-incubated nrog A 1-42 monomers thiab pom qhov inhibitory nyhuv ntawm A aggregation [134]. Tsis tas li ntawd, fucoxanthin tiv thaiv kev puas tsuaj ntawm DNA ntawm H2O2 uas yog nrog los ntawm kev nce qib ntawm glutathione (GSH) thiab superoxide dismutase (SOD) [135]. Nws kuj tseem tiv thaiv LPS-activated BV-2 microglia ntawm nuclear factor erythroid 2-txog yam 2 (Nrf2)/heme oxygenase (HO)-1 txoj hauv kev thiab txhawb txoj kev ciaj sia ntawm cov cell los ntawm cAMP- dependent protein kinase (PKA)/cAMP teb lub caij-binding (CREB) txoj kev thiab nce BDNF secretion [136]. Fucoxanthin kuj tiv thaiv A 42- induced BV2 hlwb los ntawm o los ntawm kev txo cov pro-inflammatory mediators xws li TNF-, IL-6, IL-1, thiab prostaglandin (PG)E2. Kev nthuav qhia ntawm inducible nitric oxide synthase (iNOS) thiab cyclooxygenase-2 (COX-2) thiab phosphorylation ntawm mitogen-activated protein kinase (MAPK) txoj kev raug txo qis los ntawm fucoxanthin [135]. Txo kev qhia ntawm iNOS thiab COX-2 thiab tso tawm ntawm cov kab mob inflammatory xws li TNF- , IL-6, PGE2, thiab TSIS tau koom nrog inhibition ntawm Akt/NF-κB thiab MAPKs/stimulating protein{{49 }} (AP-1) txoj hauv kev, hauv LPS-activated BV-2 microglia, tau pom raws li kev tiv thaiv kev ua haujlwm ntawm fucoxanthin [135]. Ib qho ntawm cov neeg txhawb nqa loj rau cov txheej txheem pathologic ntawm AD yog qhov tso tawm ntawm A [137,138].
Oligomers ntawm A yog qhov tsis zoo rau lawv cov neurotoxicity thiab yog ib qho ntawm cov ntsiab lus tseem ceeb uas koom nrog hauv neurodegeneration ntawm AD. Nws kuj tseem pom tau tias fucoxanthin nrog nws cov tshuaj tiv thaiv oxidative thiab anti-apoptotic tuaj yeem ua lub luag haujlwm tiv thaiv oligomers ntawm A hauv SH-SY5Y hlwb. PI3K / Akt cascade raws li kev tiv thaiv kev tiv thaiv yuav raug cuam tshuam los ntawm oligomers ntawm A thiab kev puas tsuaj ntawm cov tshuaj tiv thaiv tswj hwm los ntawm cov kab hluav taws xob extracellular-regulated kinase (ERK) txoj kev yuav qhib. Nws kuj tau pom tias inhibition ntawm GSK-3 thiab mitogen-activated protein kinase (MEK) ua ke tuaj yeem nres qhov kev puas tsuaj ntawm A . Yog li, nws tuaj yeem xaus lus tias PI3K / Akt thiab ERK txoj hauv kev tuaj yeem ua rau A oligomer-stimulated neurotoxicity. Cov teebmeem ntawm A ntawm PI3K / Akt thiab ERK txoj hauv kev tuaj yeem nres los ntawm kev siv fucoxanthin. Ntxiv mus, ob PI3K inhibitor agents, LY294002 thiab wortmannin, thaum siv, tuaj yeem nres cov teebmeem ntawm fucoxanthin. Qhov txiaj ntsig no tau qhia txog cov txheej txheem los ntawm qhov uas fucoxanthin ua rau nws cov teebmeem neuroprotective tuaj yeem ua rau PI3K / Akt cascade ib txhij nrog nres ERK txoj hauv kev. Akt activation los ntawm fucoxanthin kuj tseem tuaj yeem hloov kho NF-κB txog kev txo oxidative kev nyuaj siab [139]. Nws kuj tseem txo qis apoptosis thiab oxidative kev nyuaj siab hauv SH-SY5Y hlwb los ntawm kev ua kom muaj sia nyob PI3K / Akt txoj hauv kev thiab tiv thaiv txoj hauv kev pro-apoptotic ERK thiab tiv thaiv H2O2 stimulated apoptosis [140].
Scopolamine [141], thiab A oligomer [141] tuaj yeem pab txhawb kev paub tsis meej hauv nas. Fucoxanthin, los ntawm inhibiting acetylcholinesterase (AChE), kev tswj hwm ntawm choline acetyltransferase (ChAT) kev ua, thiab nce BDNF qhia muaj lub luag haujlwm tiv thaiv hauv cov kab mob no. Nrf2/ARE thiab Nrf2-autophagy pathways-dependent neuroprotective mechanism yog koom nrog hauv fucoxanthin mediated traumatic hlwb raug mob amelioration [142]. Fucoxanthin kuj tau pom cov txiaj ntsig tau zoo tiv thaiv tib neeg cov kab mob ntsig txog mob los ntawm kev ua haujlwm PI3K / Akt / CREB / peroxisome proliferator-activated receptor gamma coactivator , thiab Nrf2 / ARE txoj hauv kev [127,130]. Hauv kev tshawb fawb tsis ntev los no los ntawm Sun et al., fucoxanthin inhibited inflammatory-related Lachnospiraceae thiab Erysipelotrichaceae thaum nce Lactobacillus / Lactococcus, Bifidobacterium, thiab qee cov kab mob butyrate-producing [143]. Guo et al. pom lub luag haujlwm tseem ceeb ntawm fucoxanthin hauv kev hloov pauv qhov piv ntawm Firmicutes / Bacteroidetes thiab kev nplua nuj ntawm Akkermansia, yog li, nws tuaj yeem yog cov khoom noj muaj txiaj ntsig microbiota-targeted functional food [144]. Nws kuj tau pom tias muaj kev cuam tshuam nrog txoj hnyuv Escherichia coli thiab lactobacilli rau kev loj hlob inhibition ntawm cov kab mob pathogenic [145]. Yog li, fucoxanthin txhim kho GM thiab hloov kho cov kab mob neuronal inflammatory / oxidative / apoptotic txoj hauv kev, yog li ua rau lub plab-hlwb axis ntawm cov lus teb neuroprotective.
Feem ntau paub carotenoids tsim los ntawm marine fungi yog cov lag luam muaj astaxanthin thiab -carotene [117], uas yav tas los yog xanthophyll carotenoid nrog cov muaj zog tshaj plaws antioxidant [146]. Extraction ntawm astaxanthin yog ua tiav vim nws lipophilic xwm los ntawm cov kuab tshuaj, acids, microwave ua ke, thiab enzyme pab txoj kev [147]. Hauv cov poov xab liab basidiomycetous hu ua Phaffifiia rhodozyma, astaxanthin tau muab rho tawm los ntawm cytoplasmic membrane [88]. Cardinal microorganisms nrog lub peev xwm los tsim astaxanthin yog microalgae Chlorella zofifingiensis, Chlorococcum spp., liab poov xab Phaffifia rhodozyma, thiab marine Agrobacterium aurantiacum [148]. Yog li ntawd, algae, poov xab, thiab crustacean tsim astaxanthin raws li ib tug byproduct. Lub hlwb muaj kev cuam tshuam ntau dua rau oxidative kev nyuaj siab yog vim nws cov metabolism ntau dhau, muaj cov oxidized molecules xws li catecholamine neurotransmitters, thiab polyunsaturated fatty acids uas nyob hauv cov qauv ntawm cov cell membrane. Kev tshawb nrhiav ntxiv tau nthuav tawm lwm cov dej num lom neeg thiab cov txiaj ntsig kev noj qab haus huv tuaj yeem tau txais los ntawm qhov sib xyaw no [149,150]. Cov tshuaj tiv thaiv kab mob [151], tiv thaiv rog / triglyceride / cholesterol, cardioprotective, [152,153], hepatoprotective [154], thiab tshuaj tiv thaiv ntshav qab zib [155] cov teebmeem ntawm astaxanthin kuj tau tshaj tawm [149].
Mus nyeem ntawv....