Citrus Essential Oils nyob rau hauv Aromatherapy: Therapeutic Effects and Mechanisms

5. Aromatherapy Siv Citrus EOs rau kev noj qab haus huv thiab kho cov kab mob

5.1. Oxidative Stress

Nyem qhov no kom tau txais Cistanche rau kev tiv thaiv kev laus

Dawb radicals, xws lireactive oxygen hom(ROS), ibd reactive nitrogen hom(RNS) yog tsim thaum lub sij hawm cellular aerobic respiration nyob rau hauv mitochondria (endogenous). ROS tseem muajtsim thaum daim tawv nqaij raug ultraviolet(UV) lub teeb (UV-A; 320–400 nm, thiab UV-B; 290–320 nm) thiab qhov no yog lub npe hu ua exogenous keeb kwm ntawm dawb radicals. Ntxiv rau ROS, superoxide anion radical (*O2 •– ), hydrogen peroxide (H2O2), hydroxyl radical (*OH), singlet oxygen (*O2), lipid peroxides (LOOH), thiab lawv cov radicals (LOO*) kuj tsim uas koom nrog cov txheej txheem ntawm daim tawv nqaij laus, phototoxicity, induction ntawm o, thiab o ntawm cov qog nqaij hlav malignant [115–119]. Cov dawb radicals tawm tsam thiab degenerate cov qauv molecules, xws li collagen; thiab ua haujlwm biomolecules, xws li RNA thiab DNA, fatty acids, proteins, thiab lwm yam tseem ceeb molecules. Qhov no ua rau muaj ntau yam teeb meem uas ua rau kev laus, mob, mob qog noj ntshav,Alzheimer tus kab mob, Parkinson's disease, ntshav qab zib, atherosclerosis, kab mob siab, thiab lwm yam Oxidative kev nyuaj siab yog ib qho ntawm cov laj thawj tseem ceeb tom qab ua xua thiab o ntawm daim tawv nqaij, xws li atopic dermatitis, urticaria, thiab psoriasis. Tsis tas li ntawd, kab mob microbial, piv txwv li, uas yog tshwm sim los ntawmS. aureus, tej zaum yuav ua rau cov tawv nqaij puas thiab lesioned los ntawm kev tsim ROS [120]. Kev ua pa aerobic ntawm qib cellular tshwm sim hauv mitochondria. Cov tom kawg yog ob-phab ntsa organelle (hauv eukaryotic hlwb) uas ua rau aerobic ua pa thiab tsim adenosine triphosphate (ATP). ATP yog daim ntawv siv tau ntawm cov tshuaj siv hluav taws xob uas siv los ntawm lub xov tooj ntawm tes hauv nws cov haujlwm ntau yam.

Hauv cov kab mob, xws liAlzheimer tus kab mob, dementia, lossis kev laus, lub mitochondria tau dhau los ua haujlwm tsis zoo thaum lub sijhawm oxidizing dawb radicals yog tsim nyob rau hauv ntau ntau uas nws thiaj li ua rau oxidative kev nyuaj siab thiab oxidative puas tsuaj rau cov molecules tseem ceeb hauv cell thiab thaum kawg pathological txawv txav. Beta-amyloid (A ) yog ib qho pib ntawm hom reactive oxygen (ROS) thiab reactive nitrogen hom (RNS). Cov dawb radicals tawm tsam thiab ua rau cov molecules tseem ceeb tam sim no nyob rau hauv lub cell nrog rau daim nyias nyias lipids, thiab cellular organelles thiab tsim mitochondrial co toxins, xws li hydroxynonenal (HNE) thiab malondialdehyde. Thaum lub membrane-bound ion xaiv ATPase puas vim yog oxidative kev nyuaj siab, nws nkoos NMDA receptors, membrane nres complex (MAC), thiab ion-specific A. pore tsim. Raws li qhov tshwm sim, kev nkag mus ntawm calcium ions nce thiab yog li cytosolic thiab mitochondrial calcium load. Nyob rau theem tom ntej, cellular amyloid lub hom phiaj tseem ceeb enzymes, uas yog cytochrome-C oxidase, -ketoglutarate dehydrogenase, pyruvate dehydrogenase, thiab manganese superoxide dismutase (MnSOD). Qhov no ua rau kev puas tsuaj rau mitochondrial DNA thiab thaum kawg fragmentation ntawm cov qauv. A txhawb kev ntxhov siab vim muaj protein ntau kinases-p38, c-jun N-terminal kinase (JNK), thiab qog nqaij hlav protein (P53) ua rau apoptosis lossis cellular puas.

Nyob rau hauv tej yam ntuj tso thiab noj qab nyob zoo physiological tej yam kev mob, cov dawb radicals generated yog neutralized rau non-radical cov ntaub ntawv nyob rau hauv qhov kev txiav txim ntawm tej enzymes, xws li catalase (CAT) thiab hydroxy peroxidase. Hauv cov mob hnyav thiab mob ntev lossis kev tiv thaiv qis, kev tsim tawm ntawm cov dawb radicals ua radically siab. Txhawm rau nthuav dav rau qhov no, cov khoom ntawm lipid peroxidation txhawb nqa phosphorylation thiab sib sau ua ke ntawm tau cov protein. Lub tom kawg inhibits complex-I nyob rau hauv ib tug cell nyob rau hauv oxidative kev nyuaj siab, thiab ntau ntau ntawm ROS thiab RNS yog tsim nyob rau hauv complexes I thiab III. Nyob rau theem kawg, mitochondrial membrane muaj peev xwm (MMP) poob, thiab permeability-transition pores (ψm) qhib. Qhov kawg tshwm sim hauv kev ua kom cov caspases thiab cellular puas. Thaum kawg, hom reactive (ROS thiab RNS) tau pib oxidative degradation ntawm somatic thiab hlwb hlwb (neural, microglial, thiab cerebrovascular hlwb). Hauv cov xwm txheej zoo li no, kev tswj hwm ntxiv ntawm cov dawb radical scavengers raug pom zoo [58,121].

Cov citrus EOs muaj cov khoom tiv thaiv oxidative vim muaj peev xwm ntawm cov khoom molecules los pub hydrogen atom, los yog ib qho hluav taws xob rau cov dawb radicals uas tuaj yeem de-localize lub unpaired electrons (hauv conjugated / aromatic qauv), yog li neutralizing cov dawb radicals thiab tiv thaiv. cov roj ntsha molecules los ntawm kev puas tsuaj los ntawm oxidation los yog oxidative kev nyuaj siab. Cov khoom EO tseem cuam tshuam nrog lipid metabolism hauv cov ntaub so ntswg tsiaj los ntawm kev tswj hwm cov haujlwm ntawm cov tshuaj tiv thaiv oxidative, xws li superoxide dismutase, catalase, thiab glutathione peroxidase. Qhov no ua rau inhibition ntawm kev tsim cov reactive oxygen hom thiab oxidation ntawm polyunsaturated fatty acids uas ua rau kom tawm-flavors nyob rau hauv cov khoom noj [122,123]. Kev nqus pa ntawm Citrus EOs tuaj yeem ua rau GSH nce ntxiv thiab ua rau txo qis lipid peroxidation hauv lub hlwb, thiab nws pab tiv thaiv DNA cleavage thiab cell apoptosis los ntawm kev tshem tawm cov dawb radicals (ROS) ntawm cov teebmeem antioxidant. Kev nqus pa ntawm EOs nce qib ntawm cov enzymes antioxidant koom nrog hauv lub cev tiv thaiv kab mob, xws li superoxide dismutase (SOD), glutathione peroxidase, thiab catalase (CAT). Nws tau pom tias terpenes tam sim no nyob rau hauv citrus EOs tuaj yeem txo cov tsos mob tshwm sim los ntawm kev txo qis / txwv kev tso tawm ntawm cov cytokines pro-inflammatory, xws li NF-κB (nuclear transcription factor-kappa B), IL-1 (interleukin{ {8}} ), thiab TNF- (cov qog necrosis factor-alpha) [124].

Ntxiv nrog rau monoterpene hydrocarbons, limonene kuj tseem tuaj yeem tiv thaiv kev tsim cov cytokines pro-inflammatory cytokines hauv lipopolysaccharide (LPS)-induced o cov tsos mob, thiab zus tau tej cov ROS nyob rau hauv H2O2-induced oxidative kev nyuaj siab thiab lub qhov txhab kho. EOs tau los ntawm bergamot thiab txiv kab ntxwv qab zib tau pom los kho pob txuv vulgaris tshwm sim los ntawm kev tso tawm ntau dhau ntawm androgen los ntawm kev txo qis kev loj hlob thiab kev tso tawm los ntawm, qog sebaceous. Qhov no activates inhibition ntawm triglyceride (TG) tsub zuj zuj thiab tso tawm ntawm inflammatory cytokines nyob rau hauv cov qog sebaceous. Qhov no ua rau apoptosis hauv qog sebaceous ua rau txo qis T / E2 piv. Cov EOs ua kom txo qis IL-1 qib hauv cov qog sebaceous uas pab txhim kho pob txuv los ntawm kev txo cov kab mob inflammatory [121,125,126]. Lwm txoj kev tshawb nrhiav limonene cov tshuaj tiv thaiv kab mob rau tib neeg eosinophilic leukemia HL-60 clone 15 hlwb tau nthuav tawm cov txiaj ntsig zoo. Hirota et al. [127] tau tshaj tawm tias qhov qis qis ntawm limonene (7.34 mmol / L) tuaj yeem inhibit ROS tsim rau eotaxin-stimulated HL-60 clone 15 hlwb.

Qhov siab dua limonene concentration ntawm 14.68 mmol / L tau pom tias txo qis cov pa roj carbon monoxide (DEP)-induced MCP-1 ntau lawm, qhia tau hais tias cov tshuaj tiv thaiv antioxidant ntawm limonene tuaj yeem pab txwv tsis pub monocyte infiltration rau hauv lub ntsws thiab tiv thaiv kev tsiv teb tsaws ntawm eosinophil. - tiv thaiv lub ntsws asthmatic thiab tiv thaiv kev puas tsuaj los ntawm DEPs hauv lub ntsws. Tsis tas li ntawd, kev tsim NF-κB kuj tau txo qis thaum ntxiv ntawm proteasome inhibitor MG132. Cov limonene tuaj yeem inhibit DEP induced p38 MAPK signaling pathway thiab inhibit eotaxin-induced chemotaxis los ntawm eosinophils [127]. Citrus EO Cheebtsam nthuav tawm cov haujlwm tiv thaiv oxidative tiv thaiv oxidation ntawm linoleic acid. Tsis tas li ntawd, kev ua haujlwm antioxidant kuj tau tshaj tawm tawm tsam hauv vitro oxidation ntawm tib neeg cov lipoprotein tsawg-density induced los ntawm Cu2 ntxiv , thiab 2, 20 -azobis (2-amino propane) hydrochloride [128]. Cov khoom antioxidant ntawm citrus EOs yog vim muaj cov phenolic tebchaw hauv lawv cov muaj pes tsawg leeg. Monoterpene hydrocarbons (limonene, thujene), thiab oxygenated monoterpenes (monoterpenes nrog ntau pawg ua haujlwm, xws li phenols, alcohols, aldehydes, ethers, esters, thiab ketones) ua rau muaj txiaj ntsig zoo rau cov khoom antioxidant ntawm citrus EOs [129]. Cov xwm txheej thiab qhov tshwm sim ntawm oxidative kev nyuaj siab nyob rau hauv lub somatic thiab paj hlwb, thiab cov kev kho mob ntawm citrus EO aromatherapy yog tso tawm nyob rau hauv daim duab 7-9.

Thujene, ib qho monoterpene, tau tshaj tawm tias muaj kev ua haujlwm zoo antioxidant vim nws lub peev xwm los tua singlet oxygen zoo [130]. Cov tshuaj cawv, xws li carveol thiab perillyl cawv; ketones, xws li carvone thiab aldehydes, perillyl aldehyde; esters, piv txwv li, citronellyl acetate, geranyl acetate, neryl acetate nthuav tawm cov haujlwm zoo antioxidant. Ntawm cov tebchaw, -terpinene, geranial, R-(ntxiv) limonene, thiab -pinene tau tshaj tawm tias muaj peev xwm ua kom muaj zog antioxidant ntau tshaj [131-133].

5.2. Kev ntxhov siab ntsig txog kev puas siab puas ntsws / Kev xav tsis zoo

Kev ntxhov siab ntsig txog kev ntxhov siab lossis kev xav tsis zoo tau dhau los ua ntau yam hauv lub neej txhua hnub. Cov kev xav tsis zoo muaj xws li ntau yam kev puas siab puas ntsws uas tseem ceeb (qee zaum hnyav) cuam tshuam rau kev xav txog kev ua haujlwm ntawm tus neeg (tus neeg mob). Cov teeb meem tsis zoo no tshwm sim los ntawm kev paub tsis meej xws li kev kawm tsis zoo, tsis nco qab, thiab tsis muaj peev xwm ua kom pom tseeb / ua kom pom tseeb. Sudden, tseem ceeb, thiab pheej hloov pauv hauv kev xav lossis lub xeev ntawm lub siab, kev tu siab, kev ntxhov siab, kev nyuaj siab, kev pw tsaug zog, thiab insomnia yog cov tsos mob cuam tshuam nrog kev ntxhov siab lossis kev raug mob. Cov kev xav tsis zoo tshwm sim los ntawm lub cev nqaij daim tawv, thiab kev puas siab puas ntsws, kev puas tsuaj rau cov hlab ntsha, cov kev mob tshwm sim ntawm cov tshuaj, kev nyuaj siab, thiab lwm yam. (hloov lub qab los noj mov, xws li dhau / nyob rau hauv noj), pw tsaug zog, insomnia, melancholy, hopelessness, poob siab, detachment ntawm lub neej txhua hnub / niaj hnub ua ub no, qaug zog, thiab txawm suicidal tendencies. Kev ntxhov siab feem ntau yog tshwm sim los ntawm kev cuam tshuam ntawm lub cev thiab lub hlwb, xws li kev xav, kev coj cwj pwm, ib puag ncig, somatic, thiab kev sib raug zoo. Thaum ib qho ntawm cov ntsiab lus no ua rau cov xwm txheej tsis zoo lossis kev xav, kev ntxhov siab, phobias, kev tsis txaus siab, lossis kev ntxhov siab, tib neeg lub siab nkag mus rau qhov kev ntxhov siab lossis kev ntxhov siab. Kev ntxhov siab ntev ntev ua rau muaj theem thaum tus neeg ntsib qhov pib ntawm cov tsos mob ntxhov siab, xws li cov xwm txheej tsis txaus ntseeg uas muaj kev kub ntxhov, tawm hws, palpitation, mob hauv siab, migraine, papillary dilation, ua tsis taus pa, thiab lwm yam [134,135]. Raws li WHO tsab ntawv ceeb toom, ntau dua 260 lab tus tib neeg raug kev nyuaj siab nrog ntau theem thiab kwv yees li 800,000 cov neeg tuag los ntawm kev tua tus kheej txhua xyoo [136]. Tsis tas li ntawd, ntau tshaj 50 lab tus tib neeg tau paub tias muaj kev mob dementia / Alzheimer's tus kab mob uas tau npaj siab yuav nce mus txog 82 txog 152 lab los ntawm xyoo 2030 thiab 2050, feem. Tus neeg muaj kev ntxhov siab lossis muaj mob pom tias nws nyuaj rau ua nws lub neej txhua hnub thiab teb kwv yees li ntawm cov teeb meem, kev nyuaj, lossis cov xwm txheej tseem ceeb raws sijhawm. Tsis tas li ntawd, tus kab mob ntxiv zuj zus nrog kev nco. Hauv cov kab mob pathological, tus neeg mob tau kuaj pom los ntawm qhov pom ntawm amyloid plaques, neurofibrillary tangles, thiab poob ntawm neural kis tau tus mob hauv lub hlwb [137,138]. Cov neeg mob insomnia muaj cov tsos mob ntawm kev nyuaj siab thiab kev ntxhov siab, thiab tsis muaj ib qho tshuaj twg paub los kho tus mob no kom raug. Insomnia kuj tseem tshwm sim los ntawm kev pw tsaug zog tsis zoo. Kev ntxhov siab ntev hauv cov qauv pw tsaug zog tuaj yeem ua rau muaj ntshav siab, kab mob plawv, thiab muaj kev pheej hmoo loj ntawm kev mob hlwb [139–141].

Bergamot roj tau pom tias txo cov ntshav siab thiab lub plawv dhia thiab pab txhawb kev pw tsaug zog thiab pab kom tsis txhob qaug zog. EOs muab rho tawm los ntawm cov txiv kab ntxwv qab zib thiab lavender EO tau pom zoo los txhim kho kev pw tsaug zog zoo thiab muab kev nplij siab los ntawm kev nkees hauv cov neeg mob hemodialysis [142]. Takeda et al. tau ua ib txoj kev tshawb fawb txog kev nqus tau cov aromatherapy rau cov neeg laus dementia los ntawm kev siv EO poob ntawm cov phuam qhwv lawv lub hauv ncoo thaum lawv pw tsaug zog. Cov kws tshawb fawb tau sau tseg qhov kev pw tsaug zog zoo dua thiab txhim kho tag nrho lub sijhawm pw tsaug zog thiab ua haujlwm ntawm kev pw tsaug zog ntawm cov neeg kho [143]. Cov tshuaj tsw qab EO molecules nkag mus rau hauv limbic system hauv lub hlwb ntawm qhov ntswg qhov ntswg thiab txhawb nqa GABA receptors hauv hypothalamus. Tag nrho cov txheej txheem induces thiab tswj kev pw tsaug zog [144]. Citrus EO (nrog 95 feem pua ​​​​citral nyob rau hauv muaj pes tsawg leeg) tau raug soj ntsuam kom induce ib tug qab ntxiag mus ob peb vas rau cov neeg txom nyem los ntawm kev tu siab [145]. Txoj hauv kev molecular koom nrog hauv pathophysiology ntawm kev nyuaj siab muaj xws li hypothalamic-pituitary-adrenal axis, sympathetic paj hlwb, monoamine neurotransmission system (xws li, serotonergic ({5}}HT), dopaminergic (DA), thiab GABAergic pathways), cyclic adenosine monophosphate (c-AMP) teb cov ntsiab lus-binding (CREB)protein signaling pathway [58,146–152]. Raws li neurotropic hypothesis, kev nyuaj siab yog txuam nrog kev tsis txaus ntawm cov teeb meem neurotrophic tshwm sim los ntawm kev cuam tshuam ntev rau kev ntxhov siab uas ua rau poob ntawm neural plasticity [153]. Brain-derived neurotrophic yam (BDNF), cov protein nyob rau hauv lub hlwb tsim los ntawm BDNF noob, thiab neurotrophins, ib chav kawm ntawm kev loj hlob yam, txhawb txoj kev loj hlob ntawm cov neurons thiab tswj kom txaus neural plasticity. Thaum muaj kev nyuaj siab, qib ntawm BDNF hauv cov ntshav qis qis. Yog li, qhov tsis txaus ntawm neurogenesis lossis kev tsim cov neurons tshiab hauv lub hlwb hippocampus yog qhov laj thawj tseem ceeb tom qab kev nyuaj siab. EO-raws li kev kho mob nrog EOs ntawm lavender, txiv qaub, thiab bergamot tau tshaj tawm los tiv thaiv cov tsos mob tsis zoo ntawm kev nyuaj siab, xws li kev tsis txaus ntawm neurogenesis, inhibited dendritic kev loj hlob ntawm cov hlwb tsis paub qab hau, thiab cov ntshav qis BDNF hauv lub hlwb hippocampus [154-157] . Hauv kev tshawb fawb soj ntsuam nrog rau cov neeg mob kuaj pom tias muaj kev ntxhov siab- thiab kev nyuaj siab txog cov tsos mob, xws li kev tsis txaus siab thiab kev ntxhov siab, plaub lub lis piam ua haujlwm EO-raws li aromatherapy tau ua rau txo qis ntawm kev ntxhov siab thiab kev nyuaj siab thiab ib txhij nce ntshav ntshav BDNF. qib hauv lub hlwb hippocampal cov ntaub so ntswg [157] Ntxiv mus, hais txog neurogenic thiab txhim kho cov teeb meem neurotrophic hauv tib neeg lub hlwb, citrus EOs kuj tau pom los koom nrog hauv kev tswj hwm ntawm cov kab mob neuroendocrine. Kev nyuaj siab thiab kev ntxhov siab ntxhov siab tso tawm cov tshuaj hormone cortisol. Aromatherapy nrog lavender EO tau pom tias txo qis kev tso tawm ntawm cov tshuaj hormones kev ntxhov siab thiab txo qis hauv cov kua qaub thiab cov ntshav cortisol tau sau tseg [48,158]. Tsis tas li ntawd, bergamot EO thiab txiv kab ntxwv noob txiv EO kuj tau tshaj tawm los ua kom txo qis cortisol hauv cov ntshav, yog li txo cov tsos mob ntsig txog kev ntxhov siab. Kuj tseem tau sau tseg tias kev txhim kho coronary khub tshaj tawm thiab txhim kho hauv kev so. Bergamot EOs tau pom tias ua rau muaj kev hloov pauv ntawm HPA axis thiab txo qis cov qib corticosterone hauv cov ntshav [159]. Lemon EOs tau raug sau tseg los tsim cov tshuaj tiv thaiv kev ntxhov siab nyob rau hauv cov nqe lus ntawm kev hloov pauv ntawm dopamine hauv lub hlwb hippocampal cheeb tsam tsim kho cov teebmeem ntawm EOs hauv kev kho cov neeg mob los ntawm kev nyuaj siab thiab cov tsos mob cuam tshuam [58].

Anshen EO, sib xyaw ntawm EOs los ntawm lavender, txiv kab ntxwv qab zib, thiab sandalwood, tau pom tias muaj kev ntxhov siab, tshuaj tiv thaiv kev ntxhov siab, sedative, thiab hypnotic teebmeem. Cov kws tshawb fawb tau ua qhov kev sim pw tsaug zog latency thiab pw tsaug zog ntev, qhov uas lawv piv diazepam - feem ntau siv los kho insomnia - nrog anshen EOs [160]. Cov lus teb nas lub paj hlwb raug tshuaj xyuas siv ELISA kuaj txhawm rau txheeb xyuas cov kev hloov pauv hauv 5-HT thiab GABA qib. Cov txiaj ntsig tau pom qhov txo qis hauv cov dej num impulsive thiab txo kev pw tsaug zog. Kev nce qib ntawm 5-HT thiab GABA tau pom nyob rau hauv nas hlwb. Cov teebmeem anxiolytic ntawm BEO (1.0, 2.5, thiab 5.0 feem pua ​​w/w) tau kawm los ntawm kev tswj hwm nws rau cov nas uas muaj kev ntxhov siab ntsig txog tus cwj pwm, qhov siab ntxiv-xws li, thiab qhov kev xeem ntawm lub qhov rooj, thiab Tom qab ntawd ntsuas cov qib kev ntxhov siab ntawm plasma corticosterone hauv kev sib piv nrog cov teebmeem ntawm diazepam. BEO (2.5 feem pua) thiab diazepam tau nthuav tawm cov teebmeem zoo li anxiolytic thiab txo qis cov lus teb corticosterone rau kev ntxhov siab [159]. Tom qab perfusion mus rau hauv lub hippocampus ntawm lub dialysis sojntsuam (muaj ib tug volumetric txaus npaum li cas ntawm 20 µL / min), BEO tsim ib koob tshuaj-dependent thiab Ca2 ntxiv - ywj siab nce ntawm extracellular aspartate, glycine, taurine, GABA, thiab glutamate [161]. Kev nqus pa ntawm txiv kab ntxwv EO rau 90 s tau pom tias yuav ua rau muaj kev txo qis hauv oxyhemoglobin concentration nyob rau hauv txoj cai prefrontal cortex ntawm lub hlwb uas ua rau kom xis nyob, so, thiab kev xav ntawm ntuj [104]. Osbeck EO los ntawm Citrus sinensis Osbeck tau pom tias siv cov tshuaj tiv thaiv kev ntxhov siab, tsim nyog los kho kev ntxhov siab me. Cov teebmeem ntawm Osbeck EO inhalation ntawm CUMS (Chronic Unpredictable Mild Stress) nas tau pom los daws kev nyuaj siab nrog rau lub cev hnyav, kev txaus siab, kev txav, thiab dyslipidemia. Limonene tsis metabolized nyob rau hauv lub hlwb tam sim ntawd tom qab nqus tau pa. Ib qho kev tshawb fawb tob tau qhia tias limonene muaj txiaj ntsig zoo li tshuaj tiv thaiv kev ntxhov siab thiab qhia txog kev kho mob hauv cov kab mob neuroendocrine, neurotrophic, thiab monoaminergic systems [17].

Moradi et al. [162] tau ua ib qho kev tshawb fawb ntawm cov neeg mob uas raug mob coronary angiography. Cov neeg mob tau muab faib ua ob pawg kev cuam tshuam, txhua tus muaj 40 tus neeg mob. Cov neeg mob ntawm pawg xeem tau nqus EO los ntawm Citrus aurantium rau 15-20 min txog 60 min ua ntej txheej txheem. Hauv pawg tswj hwm, cov dej distilled tau siv los hloov EO. Tom qab Citrus aurantium EO nqus tau pa, cov lus teb pom tau pom. Cov cim tseem ceeb ntawm kev ntxhov siab xws li pulse rate, systolic ntshav siab (SBP), thiab diastolic ntshav siab (DBP) tau txo qis tom qab kev cuam tshuam [162]. Li et al. [163] piv cov teebmeem ntawm cov roj tseem ceeb sib xyaw (EOM) (ib qho sib xyaw ntawm Citrus sinensis L., Mentha piperita L., Syzygium aromaticum L., thiab Rosmarinus officinalis L.), nrog peppermint EO ntawm lub cev qaug zog hauv ob pawg nas. . Tom qab ua luam dej, ob pawg nas tau khaws cia hauv ib puag ncig ntawm EOM thiab peppermint EO, raws li. Ntau lub cev tsis tau kawm tom qab peb hnub tas li ntawm nebulization. Ntshav lactic acid (BLA) thiab malondialdehyde (MDA) qib tau pom tias txo qis hauv ob pawg. Kev txhim kho lub sijhawm ntawm qaug zog thiab nce kev ua haujlwm ntawm superoxide dismutase (SOD) tau pom nyob rau hauv ob pawg. Cov txiaj ntsig tau pom hauv pawg EOM tau pom pom, xws li nce ntshav qabzib thiab txo cov ntshav urea nitrogen (BUN) thiab glutathione peroxidase (GSH-PX). Txoj kev tshawb no tau txiav txim siab tias kev tawm dag zog ua rau qaug zog tuaj yeem txo tau zoo los ntawm kev nqus pa ntawm EOs [163]. Lwm txoj kev tshawb fawb tau ua rau Swiss txiv neej nas los soj ntsuam cov neurotransmission pab ntawm nitric oxide thaum C. sinensis EO tau siv rau nws cov teebmeem anxiolytic. Txhawm rau ua qhov kev tshawb fawb no, nas tau muab tso rau hauv ib puag ncig ntawm C. sinensis rau kev nqus ntawm EOs ntawm qhov sib txawv. Nitric oxide tau siv los ua tus thawj coj los saib xyuas tus cwj pwm sib haum xeeb ntawm cov kab mob nitrergic, thiab nws tau pom tias muaj lub luag haujlwm tseem ceeb hauv cov nyhuv anxiolytic ntawm C. sinensis. Bergamot tseem ceeb roj (BEO), tau los ntawm cov txiv hmab txiv ntoo ntawm Citrus bergamia, yog siv nyob rau hauv aromatherapy raws li ib tug mob reliever, txhim kho pw tsaug zog mob, thiab txo kev ntxhov siab vim. BEO tuaj yeem ua rau muaj kev cuam tshuam neurotransmission uas cuam tshuam nrog nws cov teebmeem anxiolytic-relaxant. Cov teebmeem anxiolytic tau pom tias yog qhov tshwm sim ntawm kev sib koom tes ntawm BEO thiab cov 5-hydroxytryptamine (5-HT) 1A nrog rau kev koom tes ntawm ntau yam thiab complex mechanisms [19].

5.3. Cov mob

5.3.1. Neurogenic Inflamation

Neurogenic o yog mob nyob rau hauv neurons tshwm sim los ntawm kev tso tawm ntawm pro-inflammatory mediators, uas yog Tshuaj P, calcitonin gene-related peptide (CGRP), neurokinin A (NKA), thiab endothelin-3 (ET-3) . Kev tso tawm ntawm cov neeg kho mob pro-inflammatory hauv cov neurons yog txhawb los ntawm kev ua kom cov ion channels (transient receptor tej zaum ion channel-1 los yog TRPA-1) nyob rau hauv teb rau teeb meem / tsis kaj siab ib puag ncig stimuli. Mob neurogenic mob yog tshwm sim los ntawm kev ua kom TRPA-1 channels induced los ntawm LPS. Tom qab kev tso tawm ntawm qhov mob ua rau neuropeptides yog qhov tso tawm ntawm histamine los ntawm cov hlwb mast tam sim no nyob ib puag ncig ntawm cov neurons cuam tshuam. Lub tom kawg txhawb kev tso tawm ntawm Tshuaj P thiab calcitonin gene-related peptide, yog li tsim kom muaj kev sib txuas ntawm kev sib txuas ntawm histamine thiab neuropeptide hauv kev ua rau muaj kev mob neurogenic. Kwv yees li ntawm 25 feem pua ​​​​ntawm cov mob migraine ua rau muaj kev ua haujlwm tsis zoo ntawm lub hauv nruab nrab lub paj hlwb cuam tshuam nrog kev cuam tshuam ntawm qhov pom kev, rhiab heev rau lub teeb / suab, xeev siab, thiab / lossis ntuav [164]. Terpenes thiab terpene derivatives tau tshawb xyuas rau kev tiv thaiv kab mob bioactivities. Hauv qhov no, limonene, -pinene, -caryophyllene, thiab -myrcene tau nyiam tshaj plaws rau cov mob migraine [165]. Alpha-pinene (-pinene) tam sim no nyob rau hauv citrus EOs tau pom tias txo NF-κB/p65 nucleus ntawm LPS-stimulated THP-1 hlwb thiab nce cytoplasmic concentration ntawm Iκ-B protein. Alpha-pinene (-pinene) kuj tseem txo qis qib ntawm IL-6, TNF- , thiab TSIS TAU, nrog rau kev qhia ntawm iNOS thiab Cox-2 ntxias los ntawm LPS. Kev tshawb fawb hauv vitro ntawm d-limonene kev ua ub no tau nthuav tawm qhov nce ntawm IL-10/IL-2 piv, yog li txhim kho IL -10 qib. Cov tom kawg yog cytokine synthesis inhibitory yam thiab inhibits proinflammatory Th1 cytokine ntau lawm (IL-2) [166]. Tsis tas li ntawd, d-limonene epoxide tau raug soj ntsuam los tiv thaiv kev tso tawm ntawm cov kab mob inflammatory, inhibit vascular permeability, txo kev tsiv teb tsaws ntawm neutrophils, thiab tso saib cov kab mob thiab peripheral analgesic cuam tshuam rau lub paj hlwb opioid system (txuas nrog kev tswj qhov mob, nqi zog, thiab kev coj cwj pwm) [167]. Cov txheej txheem pathophysiological ntawm migraine induced los ntawm 5-HT thiab neuroprotective mechanisms ntawm -pinene nyob rau hauv migraine yog tso tawm nyob rau hauv daim duab 10 thiab 11, feem.

Daim duab 10. Lub pathophysiological mechanism ntawm migraine induced los ntawm 5-HT. (1) Platelet aggregation ua rau kev tso tawm ntawm 5-HT thiab ADP hauv cov ntshav plasma.(2) Higevel ntawm plasma 5-HI ua rau thim rov qab vasoconstriction tom qab hloov pauv ntawm 5-HI rau nws cov metabolite { {7}}HAA. Cov tom kawg yog tawm hauv cov zis. (3) Qib qis ntshav plasma 5-H1 txhawb nqa perivascular neurons tso tawm neuropeptides NO,PC. SP NKA, CCR ua rau vasodilation ntawm cerebra leeg. Tom qab ntawd ua rau cov tsos mob migraine.

Daim duab 11. Neuroprotective mechanisms ntawm a-pinene hauv migraine (168. Cov a-pinene tuaj yeem txo LPSinduced o hauv macrophages. a-pinene tuaj yeem thaiv cov phosphorylation ntawm MAPKs (ERK/INKin macrophages thiab txo cov qib ntawm active (soluble lKK). Qhov no tuaj yeem tiv thaiv kev degradation ntawm NF-kB / IkB complex. Tsis tas li ntawd, a-pinene tuaj yeem cuam tshuam NF-kB phosphorylation thiab tsim ntawm P65 / p50 / NF-kB complex uas ua rau nws txoj kev hloov pauv nuclear thiab induction ntawm cov noob caj noob ces tsim. cytokines. Abbreviations; TNF-a (tumor necrosis factor-alpha), IL-1B (Interleukin-1B)IL-6 (Interleukin), Cox-2 (Cyclooxygenase{ {17}}), Inos (Inducible nitric oxide synthase).

Neurogenic o ntxiv ua rau muaj mob rau cov kab mob ntawm ntau lwm yam kab mob neurogenic, uas yog ntau yam sclerosis, migraine, psoriasis, hawb pob, vasomotor rhinitis, thiab lwm yam. Hauv migraine, qhov stimulation ntawm cov hlab ntsha trigeminal yuav siv qhov chaw uas tso tawm cov neuropeptides, xws li Tshuaj P, nitric oxide, 5-HT, vasoactive plab hnyuv polypeptide neurokinin A, thiab CGRP uas nws thiaj li ua rau "sterile neurogenic mob". Kev tso tawm ntawm Cov Tshuaj P txhawb kev tsim tawm ntawm ntau lwm cov pro-inflammatory cytokines uas yog interleukins (IL-1, IL-6), thiab TNF-alpha (INF-a). Migraine yog tus cwj pwm los ntawm kev mob taub hau muaj zog nrog xeev siab, ntuav, thiab rhiab heev rau lub teeb uas yuav nyob ntev txog 72 teev lossis ntev dua. Cov theem hauv migraine tuaj yeem piav qhia txog qhov tshwm sim hauv plaub theem.viz, (a) prodrome: theem no txuas ntxiv rau ob peb teev mus rau ob peb hnub thiab yog tus cwj pwm los ntawm kev chim siab, kev nyuaj siab, yawning, xeev siab, qaug zog, mob leeg, nyuaj hauv concentration thiab pw tsaug zog; (b) aura: qhov no txuas ntxiv mus rau 5 txog 60 min thiab yog tus cwj pwm los ntawm kev cuam tshuam ntawm qhov muag, tsis pom kev ib ntus, loog ntawm tes thiab taw, thiab tingling hauv lub cev!(c) mob taub hau; qhov no txuas ntxiv mus rau 4 mus rau 72 h thiab yog tus cwj pwm los ntawm qhov mob throbbing, rhiab heev rau lub teeb, suab nrov, tsw, xeev siab, ntuav, giddiness, insomnia, caj dab thiab lub cev mob thiab txhav thiab kub hnyiab; thiab (d) postdrome: qhov no yog tus cwj pwm los ntawm qhov tsis muaj peev xwm mloog tau, qaug zog thiab tsis nkag siab.

5.3.2. Dementia, Alzheimer's Disease (AD), thiab Parkinson's Disease (PD)

Alzheimer's tus kab mob yog ib tug muaj hnub nyoog-hais txog neurodegenerative teeb meem tshwm sim los ntawm maj mam poob thiab dementia. Nws kuj qhia txog kev paub tsis meej thiab kev coj tus cwj pwm tsis zoo. Nyob rau theem ntawm lub cev-tshuaj lom neeg, nws raug kuaj pom los ntawm qhov tsis txaus hauv cholinergic neurotransmission nyob rau hauv lub paj hlwb (lub hlwb) cov hlab ntsha, kev paub tsis meej, kev coj tus cwj pwm turbulence, maj mam poob, tsub zuj zuj ntawm amyloid plaques (amyloid-, A) thiab neurofibrillary tangles lub hlwb tshwj xeeb, txo glutathione (GSH) cov ntsiab lus hauv hippocampus, mitochondrial tsis ua haujlwm hauv cov hlwb, thiab ntau dhau ntawm cov dawb radicals ua rau oxidative stress [169]. Cov cholinesterase (ChEs) enzyme hydrolyses acetylcholine (Ach) rau hauv choline thiab acetate thiab cov concentration ntawm Ach neurotransmitter molecules hauv lub hlwb poob ua rau kev txiav tawm ntawm neurotransmission. Acetylcholine koom nrog hauv kev ua haujlwm tseem ceeb ntawm kev kawm thiab kev nco. Tsis tas li ntawd, monoamines, viz., dopamine thiab serotonin (5HT), tso tawm hauv lub hlwb kuj raug ntaus nqi rau kev kawm thiab kev nco. Kev txo qis ntawm cov dopamine hauv lub hlwb, thiab yog li ntawd, kev ua haujlwm tsis zoo ntawm dopamine receptors tau raug txheeb xyuas tias yog ib qho ua rau Parkinson's disease thiab Alzheimer's disease [170]. Rau kev tswj cov tsos mob ntawm AD, inhibitors ntawm acetylcholinesterase (AChE) thiab butyrylcholinesterase (BChE) enzymes lub luag haujlwm rau kev degradation ntawm qhov tseem ceeb neurotransmitter acetylcholine (ACh) raug txiav txim siab rau kev txhim kho cov tshuaj tiv thaiv AD. Cov choline esterase inhibitors reversibly khi rau qhov chaw nquag ntawm acetylcholinesterase (AChE) / butyrylcholinesterase (BChE) enzymes. Yog li ntawd, hydrolytic degradation ntawm ACh neurotransmitter molecules rau hauv choline thiab acetate yog inhibited. Yog li ntawd, qhov concentration ntawm ACh nce ntawm qhov sib txawv synaptic hauv cholinergic neurons hauv hippocampus cerebral cortex thiab qee qhov ntawm cov striatum tshiab. Lwm cov kab mob neurodegenerative pathological hauv cov neeg mob uas raug kev txom nyem los ntawm AD suav nrog kev nce hauv monoamine oxidase (MAO) kev ua haujlwm thiab lipid oxidation induced los ntawm Fe2 ntxiv rau ions. Qhov nce ntawm MAO deactivates neuroactive amines, xws li serotonin, dopamine, thiab norepinephrine, thiab txhim kho kev tsim cov dawb radicals (los yog ROS) hauv tus neeg mob lub hlwb [171]. Fe2 ntxiv rau ions muaj peev xwm hla cov ntshav-hlwb teeb meem uas induces lipid oxidation ntawm Fenton cov tshuaj tiv thaiv. Qhov no ua rau muaj ntau ntawm polyunsaturated fatty acids nyob rau hauv cov ntaub so ntswg ntawm lub paj hlwb thiab ua rau muaj kev cuam tshuam rau dawb radical tawm tsam. Qhov kawg ua rau tsim cov hom radical, piv txwv li, MDA uas koom nrog hauv neurodegeneration. Raws li kev kho mob, yog tias cov tshuaj tiv thaiv antioxidant nres lossis inhibits cov khoom lipid peroxidation (MDA), nws muaj peev xwm ua kom cov concentration ntawm dawb Fe2 ntxiv rau ions hauv cytosol. Yog li ntawd, qib ntawm oxidative kev nyuaj siab txo qis hauv lub hlwb nrog rau tag nrho lub cev [172–177].

Feem ntau ntawm cov tshuaj uas siv rau hauv kev kho mob rau AD yog synthesized chemically thiab tau soj ntsuam ua rau muaj kev phiv, xws li xeev siab los yog ntuav, hepatotoxicity, dyspepsia, myalgia, kiv taub hau, anorexia, thiab hais txog. EOs tau pom muaj kev cuam tshuam nrog ntau yam ntawm cov kab mob neurotransmitter, uas yog noradrenergic (txog rau norepinephrine), 5-HTergic (txog serotonin), GABAergic (txog -aminobutyric acid), DAergic lossis dopaminergic (txog rau dopamine) , thiab lwm yam. Tsis tas li ntawd, cov ntsiab lus tshwj xeeb tam sim no hauv EOs koom nrog cov txheej txheem tshwj xeeb, piv txwv li, benzyl benzoate activates 5-HTergic thiab dopaminergic txoj hauv kev thiab thiaj li ua rau muaj kev ntxhov siab thiab tiv thaiv kev nyuaj siab [178]. Linalool thiab -pinene cuam tshuam nrog GABAergic txoj hauv kev los tsim cov teebmeem zoo sib xws. Nyob rau hauv cov kev taw qhia no, lwm yam EO Cheebtsam, uas yog limonene benzyl cawv kuj tau pom los tsim anxiolytic thiab anti-depressant teebmeem. EOs tuaj yeem cuam tshuam cov enzymes txuas nrog hydrolysis ntawm neurotransmitters, xws li monoamine oxidase (MAO). Tsis tas li ntawd, EOs muaj cov khoom tiv thaiv oxidative thiab tuaj yeem nkag mus rau cov ntshav-hlwb barrier. Hauv cov lus qhia no, Ademosun et al. nqa tawm inhibition kev soj ntsuam ntawm AChE thiab BChE, MAO, thiab lipid peroxidation [173]. Cov hom phiaj pathophysiological hauv cov kab mob ntawm dementia, Alzheimer's, thiab Parkinson's tau sau tseg hauv daim duab 12. Cov txheej txheem ntawm kev ua ntawm citrus EOs inhibit acetylcholinesterase (AChE), yog li nce qib thiab lub sijhawm ntawm acetylcholine hauv lub hlwb thiab pab nrog kev paub thiab kev txawj ntse ( nco nco) yog qhia nyob rau hauv daim duab 13. Cov syntheses ntawm txawv neurotransmitter molecules nyob rau hauv lub hlwb, namely GABA, dopamine, thiab serotonin, thiab lub mechanism ntawm neurotrans lub hom phiaj yog qhia nyob rau hauv daim duab 14. Cov neurotransmission pathways nyob rau hauv GABAergic, DAergic (dopaminergic), thiab 5-HTergic (serotoninergic) neurons thiab citrus EO Cheebtsam uas qhib neurotransmission thiab nthuav tawm los tiv thaiv kev loj hlob ntawm tib neeg neuroblastoma cell loj hlob yog qhia hauv daim duab 15.

Daim duab 13.Mechanism ntawm kev ua ntawm citrus EOs inhibit acetylcholinesterase (AChE), yog li nce qib thiab ncua sij hawm ntawm acetylcholine hauv lub hlwb thiab pab nrog kev paub txog kev kawm thiab kev nco qab) Abbreviao; ACh-acetylcholine: AChE-acetylcholinesterase: nACh-nicotinic acetylcholine receptorsEOsCitrus tseem ceeb roj Cheebtsam.

Daim duab 14. Syntheses ntawm neurotransmitter molecules, viz, GABA (Y- Aminobutyric acid), dopamine, thiab serotonin kuj hu ua 5-HI) thiab cov txheej txheem ntawm neurotransmission.AADC tseem hu ua DDC. Cov ntawv luv luv; GAD (glutamate decarboxylase), TH tyrosine hydroxylase, AADC aromatic amino acid decarboxylase, DDC (DOPA decarboxylase), TPH2 (s tryptophan hydroxylase 2).

EO tau raug soj ntsuam kom txwv tsis pub AChE, BChE, thiab MAO nyob rau hauv koob tshuaj. Txawm li cas los xij, EOs tau muab rho tawm los ntawm tev tawm pom qhov cuam tshuam ntau dua rau AChE piv nrog EOs muab rho tawm los ntawm cov noob. Ntawm qhov tod tes, EOs los ntawm cov noob tau nthuav tawm ntau dua inhibition ntawm MAO kev ua piv nrog cov tev EOs. Tsis tas li ntawd, EOs kuj tau nthuav tawm qhov txo qis ntawm malondialdehyde (MDA) ntau lawm uas muaj nyob rau hauv lub hlwb homogenates. MAO kev ua haujlwm yog qhov tseem ceeb hauv kev ua kom tsis muaj zog ntawm cov neurotransmitters, xws li serotonin, thiab dopamine hauv hlwb hlwb. Qhov no cuam tshuam rau tag nrho tus cwj pwm thiab kev xav ntawm cov neeg mob uas muaj tus kab mob Alzheimer. Zhou et al. [179] tau ua qhov kev xeem dhau kev zam dhau (PA) thiab qhib fifield habituation test (OFT) siv cov txiv qaub EO Cheebtsam, viz., s-limonene thiab nws cov derivatives-perillyl cawv los tshawb xyuas cov txiaj ntsig ntawm EOs ntawm kev nco hauv nas. Cov nas tau noj nrog s-limonene (100 mg / kg), s-perillyl cawv (50 mg / kg) hauv lawv cov zaub mov thiab scopolamine (1 mg / kg) tau txhaj tshuaj subcutaneously 30 feeb ua ntej qhov kev xeem [179]. Cov txiv qaub EO Cheebtsam tau pom tias muaj peev xwm txhim kho kev kawm thiab kev nco tsis zoo los ntawm scopolamine hauv nas. BEO tau raug tshaj tawm los nthuav tawm cov kev ua ub no tiv thaiv kev tiv thaiv kev tiv thaiv kev ciaj sia thiab kev loj hlob ntawm SH-SY5Y neuroblastoma hlwb los ntawm kev ua kom muaj ntau txoj hauv kev ua rau necrosis thiab apoptotic cell tuag [69,180,181]. Cov ntsiab lus ntawm cov kev tshawb fawb ntawm kev siv citrus EOs hauv aromatherapy yog nthuav tawm hauv Table 1.

6. Cov ntsiab lus

Citrus EOs yog kev lag luam, eco-friendly, thiab lwm yam ntuj tsim rau cov khoom siv hluavtaws siv hauv aromatherapy. Citrus-based EOs feem ntau tau txais los ntawm nplooj, paj, thiab cov txiv hmab txiv ntoo ntawm cov tub ntxhais hluas thiab cov txiv hmab txiv ntoo siav, qhia ncaj qha rau kev tswj cov khib nyiab kom txuag tau ib puag ncig los ntawm cov pa phem thiab tiv thaiv kom tsis txhob muaj kab mob ntawm cov dej hauv av. Citrus EOs los ntawm cov khib nyiab pov tseg siv hauv aromatherapy pab daws kev ntxhov siab thiab kev ntxhov siab cuam tshuam / kab mob. Cov khoom tseem ceeb tshwm sim nyob rau hauv citrus EOs thiab lawv cov teebmeem kev kho mob hauv aromatherapy tau raug sau tseg pictorially raws li hauv qab no (Daim duab 16).

Daim duab 16. Kev kho mob ntawm cov tshuaj feem ntau tshwm sim hauv cov roj citrus tseem ceeb [202,208–211]

Cov ntaub ntawv ntxiv: Cov ntaub ntawv txhawb nqa hauv qab no tuaj yeem rub tawm ntawm, Daim duab S1: Kev nyab xeeb kev ruaj ntseg thiab kev tsim cov txiv hmab txiv ntoo txhua xyoo hauv thaj chaw sib txawv thoob plaws ntiaj teb; Daim duab S2: Kev lag luam segmentation ntawm citrus tseem ceeb roj; Daim duab S3: (a) Lub ntiaj teb citrus roj lag luam los ntawm daim ntawv thov, los ntawm xyoo 2018, (b) Citrus yam tseem ceeb roj kev lag luam tus nqi kwv yees (Citrus Oil Market los ntawm Hom Khoom, 2022); Daim duab S4: Cov qauv molecular ntawm cov khoom tsis hloov pauv thiab tsis hloov pauv tam sim no hauv Citrus EOs; Daim duab S5: Kev sib xyaw ntawm EOs hauv ntau hom Citrus; Table S1: Txoj Kev/Techniques extracting Citrus tseem ceeb roj; Table S2: Cov txheej txheem / cov txheej txheem ntawm tus cwj pwm / kev lees paub ntawm Citrus tseem ceeb roj. Cov ntaub ntawv pov thawj [3,4,14,21,22,24,25,34–37,42,170,212–219] raug suav rau hauv Cov Khoom Siv Ntxiv.

Sau Kev Pabcuam: PA: conceptualization, sau thawj tsab ntawv; ZS: tsim cov duab kos duab thiab tsim cov duab; MK: conceptualization, sau thawj tsab ntawv; AD: sau cov ntawv qub; AS: sau ntawv- tshuaj xyuas thiab kho; KKS: maps thiab graphical content; MS: sau ntawv- tshuaj xyuas; NM: sau cov ntsiab lus, rov tsim cov ntawv thiab cov duab, thiab kho; AKM: tshuaj xyuas thiab kho thiab cov peev txheej; K.-HB: tshuaj xyuas, kho, thiab saib xyuas. Txhua tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau. Cov Nyiaj Txiag: Qhov kev tshawb fawb no tau txais nyiaj los ntawm Lub Tsev Haujlwm Saib Xyuas Kev Txhim Kho Hauv Nroog, Republic of Kauslim, tus lej nyiaj PJ0157260.

Kev lees paub: Txoj haujlwm no tau txais kev txhawb nqa los ntawm Kev Tshawb Fawb Kev Sib Koom Tes rau Kev Tshawb Fawb Txog Kev Ua Liaj Ua Teb thiab Kev Tshawb Fawb Technology (qhov project no. PJ015726), Republic of Kauslim. Kev tsis sib haum xeeb ntawm kev txaus siab: Cov neeg sau ntawv tshaj tawm tias tsis muaj kev tsis sib haum xeeb ntawm kev txaus siab.

Cov ntaub ntawv

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Nug ntxiv:

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