I-Ergothioneine, ihhashi elimnyama emhlabeni ophikisana nokuguga 

I-Ergothioneine (EGT) yaqala ukuhlukaniswa nesikhunta se-ergot ngusosayensi uCharles Tanret ngo-1909, yingakho igama layo. Kuvela ngokwemvelo kokuphuma kwe-amino acid esatshalaliswa kabanzi kusikhunta, kwezinye izitshalo, nasezilwaneni. Ekudleni kwabantu, amakhowe, okusanhlamvu, nezilwane ezithile zasolwandle ziyimithombo yako eyinhloko. Ngokucwaninga okujulile kwesayensi yesimanje, imiphumela emangalisayo ye-ergothioneine iye yavela kancane kancane.

Izimiso zokulwa nokuguga kanye nezindlela zokwenza

Imiphumela emibi ye-antioxidant

Ukuthungathwa okuqondile kwama-radicals wamahhala: I-EGT ingakwazi ukunqanda ngokushesha izinhlobo ze-oxygen esebenzayo (ROS) nezinhlobo ze-nitrogen esebenzayo (RNS), okuhlanganisa i-superoxide anion (O₂⁻), i-hydrogen peroxide (H₂O₂), i-hydroxyl radicals (·OH), ne-singlett oxygen (¹O₂). Lo mphumela wokulahla uqinisekiswe ngokugcwele ekuhlolweni kwe-in vitro.

Izinzuzo zokuqhathanisa

Ukulawulwa kwesistimu yokuzivikela ye-antioxidant: I-EGT ilawula ukuvezwa kwezakhi zofuzo ze-antioxidant ezingezansi (ezifana ne-HO-1, NQO1, SOD, ne-CAT) ngokwenza kusebenze indlela yokusayina ye-KEAP1-NRF2. Ukudluliselwa kwe-nuclear kwe-NRF2 kulawulwa izindlela zokusayina ze-PI3K/AKT ne-PKC, futhi i-EGT ingase ikhuthaze ukukhululwa nokudluliselwa kwe-nuclear kwe-NRF2 ngokumodela inzwa ye-thiol ye-KEAP1.

Iqhaza Lokuvikela ekuzinzeni kweGenome

Ukunciphisa Ukulimala Kwe-DNA: I-EGT ivimbela ngempumelelo i-ROS- kanye ne-RNS-induced DNA umonakalo, ikakhulukazi ku-mitochondrial DNA (mtDNA). Ucwaningo lukhombisile ukuthi amaseli antula izithuthi ze-EGT akhombisa amazinga aphezulu omonakalo we-DNA.

Ukukhuthaza Ukulungiswa Kwe-DNA: I-EGT ayimumbi nje kuphela imisebe ye-ultraviolet (UV) kodwa futhi ikhuthaza ukulungiswa kwe-DNA ngemva kokushiswa kwemisebe ye-UV, ivikela amaseli esikhumba ekulimaleni kwezithombe.

Ukulawulwa Kwezinguquko ze-Epigenetic

Ithinta I-Synthesis ye-Methyl Donor SAM: I-EGT ithinta ngokungaqondile ukutholakala kwe-S-adenosylmethionine (SAM) ngokulawula amazinga e-glutathione (GSH), ngaleyo ndlela ilawula umsebenzi we-DNA methyltransferases (DNMTs) kanye ne-histone methyltransferases (HMTs).

Ukugcina I-Iron Ion Homeostasis Yamahhala: I-EGT igcina i-iron ion homeostasis yamahhala ngokukhipha i-ROS, ngaleyo ndlela iqinisekise umsebenzi we-demethylases (njenge-TETs ne-JmjC).

Ukusebenzisana nendlela yokusayina ye-Sirtuin:

Ukulungiswa kwenkulumo ye-SIRT1/SIRT6: I-EGT ibambezeleka endothelial cell senescence futhi idala i-necrotizing apoptosis kumaseli omdlavuza we-colorectal ngokulawula ukubonakaliswa kwe-SIRT1 ne-SIRT6.

Ukugcina amazinga e-NAD⁺: I-EGT ithuthukisa umsebenzi we-Sirtuin ngokulawula isimo se-redox yeselula nokugcina isilinganiso se-NAD⁺/NADH.

Ukulungiselela Mindlela

Indlela Yokukhipha Yemvelo:

I-EGT itholakala emikhiqizweni yemvelo efana nesikhunta esidliwayo, i-ergot, okusanhlamvu, nezicubu zezilwane. Isikhunta esidliwayo sinokuqukethwe okuphezulu kwe-EGT futhi siwumthombo obalulekile we-EGT.

Kodwa-ke, okuqukethwe kwe-EGT kwemikhiqizo yemvelo ngokuvamile kuphansi kakhulu, kudinga inani elikhulu lezinto ezingavuthiwe ukuze kukhishwe, okuholela ezindlekweni eziphezulu zokukhipha. Ngaphezu kwalokho, izindaba ezifana namazinga aphezulu okungcola kanye nezinsalela zezidakamizwa ezintweni ezingavuthiwe zikhawulela ukusetshenziswa kwezimboni kwezindlela zokukhipha umkhiqizo wemvelo.

I-Chemical Synthesis Method: Ukwenziwa kwamakhemikhali omdabu we-EGT kusebenzisa i-histidine njengento yokuqala, ihlanganisa i-EGT kusisombululo esinamanzi ngezinyathelo eziningi ezihlanganisa i-thiolation, i-thioprotection, i-methylation, kanye nokuvikela. Le ndlela inomzila omude wokwenziwa kanye nesivuno esincane. Eminyakeni yamuva nje, izifundo zilingise izindlela ze-biosynthetic zokuthuthukisa ukuhlanganiswa kwamakhemikhali e-EGT. Isibonelo, u-Erdelmeier et al. isebenzise i-histidine betaine, i-cysteine, ne-mercaptopropionic acid njengezinto zokuqala zokwakha i-EGT isebenzisa ukusabela okwenziwe lula kwebhodwe elilodwa, igwema ukwethulwa kwamaqembu e-thioprotective, ukufinyeza umzila wokwenziwa, kanye nokuthuthukisa isivuno.

Ukuhlanganiswa kwamakhemikhali nakho kunezinselele ezithile. Isibonelo, i-chirality ye-α-carbon eqenjini le-carboxyl iholela kalula ku-racemization ngaphansi kwezimo ezine-acidic noma ze-alkaline, okwenza kube nzima ukuthola i-high-optical-purity EGT. Ngaphezu kwalokho, izinto zokusetshenziswa ezidingekayo ukuze kuhlanganiswe amakhemikhali ziyabiza, i-2-mercaptoimidazole yokuqala kunzima ukuyilungisa, kanti ukucutshungulwa komkhiqizo nakho kuyinselele. Ngakho-ke, abacwaningi badinga ukwandisa futhi bathuthukise izindlela zokuhlanganisa amakhemikhali ukuze bahlangabezane nezidingo zokukhiqizwa kwezimboni ezinkulu.

Ukuvutshelwa kwe-Microbial: Ukuthola i-EGT nge-biosynthesis kunezinzuzo ezifana nezinto zokusetshenziswa ezitholakala kalula kanye nezindleko eziphansi uma kuqhathaniswa, futhi sekuyindlela eyinhloko yokulungiselela i-EGT eminyakeni yamuva. Ngokwemvelo, i-EGT ikhona ngezindlela ezimbili: i-aerobic biosynthesis kanye ne-anaerobic biosynthesis.

I-Aerobic Biosynthesis ye-EGT

Ucwaningo oluningi luye lwacacisa inqubo ye-biosynthetic ye-EGT. Ngokuyisisekelo, indlela ye-aerobic biosynthetic ye-EGT ingahlukaniswa ngezindlela zamagciwane kanye nesikhunta. Seebeck et al. yacacisa futhi yakha kabusha indlela ye-aerobic biosynthetic ye-EGT in vitro ku-Mycobacterium smegmatis, ihlonza izakhi zofuzo ezinhlanu ezihilelekile endleleni: i-EgtA, i-EgtB, i-EgtC, i-EgtD, ne-EgtE. Lezi zakhi zofuzo zihlanganisa i-glutamylcysteine ​​​​synthase (EgtA), Fe2+-dependent oxidase (EgtB), gamma-glutamyl transferase (EgtC), S-adenosyl methionine (SAM) -encike ku-histidine methyltransferase (EgtD), kanye ne-pyridoxantgly-Esependent-Esependent phosphate. Kule nqubo, i-EgtA igqugquzela ukufiphala kwe-glutamate kanye ne-cysteine ​​​​ukukhiqiza i-γ-glutamylcysteine; I-EgtB igqugquzela ukuhlangana kwe-oxidative lapho kukhona umoya-mpilo kanye ne-ferrous sulfate, yengeza iqembu le-thiol elisuka ku-γ-glutamylcysteine ​​​​kuya kuchungechunge oluseceleni lwe-histidine betaine (ekhiqizwe ku-histidine ne-SAM ecushwe yi-EgtD); I-EgtC bese igqugquzela ukwakheka okuqhubekayo kwe-histidine betaine cysteine ​​​​sulfoxide; ekugcineni, i-EgtE igqugquzela ukukhishwa kwe-pyruvate ne-ammonia ukuze kukhiqizwe i-EGT.

Endleleni ye-fungal biosynthetic, i-EGT ihilela ikakhulukazi izakhi zofuzo ezimbili ze-synthase, i-Egt1 ne-Egt2. Bello et al. ikhombe i-synthase ethile, i-NcEgt1, kokuthi *Neurospora crassa*, equkethe izizinda ezifanayo nalezo eziku-*Mycobacterium smegmatis*’s EgtB kanye ne-EgtD. I-Egt1 ibamba iqhaza ekuphenduleni okunamandla okuyizinyathelo ezimbili: okokuqala, ikhuthaza ukuguqulwa kwe-histidine ibe yi-histidine betaine, bese ikhuthaza inhlanganisela ye-histidine betaine ne-cysteine ​​​​ukwakha i-histidine betaine cysteine ​​​​sulfoxide. Ngokufana ne-EgtE, i-Egt2 igqugquzela ukwakheka kwe-EGT kusuka ku-histidine, i-betaine, ne-cysteine ​​​​sulfoxide. Njengoba kukhonjisiwe emfanekisweni, ngenxa yokuthi kuhileleke ama-enzyme amabili kuphela, indlela ye-biosynthetic ye-EGT kusikhunta ilula kakhulu kunaleyo ekubhaktheriya.

I-Anaerobic Biosynthesis ye-EGT

I-anaerobic biosynthesis ye-EGT ibikwe kubhaktheriya yodaka lwe-anaerobic (i-Chlorobium limicola), lapho i-EGT biosynthesis ifezwa ngokusabela okuyizinyathelo ezimbili ngaphandle komoyampilo. Burn et al. kuhlonzwe i-methyltransferase (EanA) kanye ne-sulfotransferase (EanB) kule bacterium yodaka lwe-anaerobic. Njengoba kuboniswe esithombeni, i-EanA igqugquzela ukuguqulwa kwe-histidine ibe i-histidine betaine, bese i-EanB, ngaphansi kwezimo ze-anaerobic, idlulisela i-athomu yesibabule kuyindandatho ye-imidazole ye-histidine betaine ukuze ikhiqize i-EGT. Nakuba indlela ye-anaerobic biosynthesis ilula, amanani e-catalytic e-EanA ne-EanB aphansi kakhulu kunalawo e-EgtD ne-EgtB endleleni ye-aerobic biosynthesis. Ngakho-ke, indlela ye-aerobic biosynthesis ihlala iyindlela ebusayo ye-EGT biosynthesis.

Amathemba ohlelo lokusebenza

I-Ergothioneine inezakhiwo ezinamandla ze-antioxidant ne-anti-aging, futhi inamathemba abanzi wokusetshenziswa kokudla, izimonyo, ukudla okusebenzayo, kanye nezimboni ze-biopharmaceutical. Ukusetshenziswa kwayo emkhakheni wobuhle ne-skincare kugqame ikakhulukazi, okwenza kube isithako esibalulekile emikhiqizweni elwa nokuguga.

Izinzuzo zayo eziyinhloko zihlanganisa:

1. I-Antioxidant kanye Ne-Anti-Aging: Umthamo onamandla we-antioxidant we-Ergothioneine ulwa ngokuphumelelayo nama-radicals mahhala, unciphisa ukulimala kwe-oxidative kumangqamuzana esikhumba, ubambezele ukuguga kwesikhumba, futhi unciphisa imibimbi nokuwohloka.
2. Ukuba mhlophe Nokuncishiswa Kwebala: Ivimbela ukukhiqizwa nokumiswa kwe-melanin, ithuthukisa umbala nokuba buthuntu, futhi ikhanyise ithoni yesikhumba.
3. I-Anti-inflammatory and Soothing: Yehlisa ukuvuvukala kwesikhumba, ikhulule ngokuphumelelayo ububomvu nokuluma, iqinise umgoqo wokuzivikela wesikhumba, futhi ithuthukise ukumelana kwaso.
4. I-Moisturizing and Repairing: Ithuthukisa ngempumelelo umsebenzi wokuvimbela isikhumba, ithuthukise ukugeleza kwesikhumba, futhi ikhuthaze ukulungiswa nokuvuselelwa kabusha kwesikhumba esonakele.
5. Ukuvikelwa Kwezithombe Nokuvikelwa Ekulimaleni Kwe-UV: Imisebe ye-Ultraviolet ingenye yezimbangela eziyinhloko zokuguga kwesikhumba. I-Ergothioneine inganciphisa ukulimala kwesikhumba okubangelwa imisebe ye-ultraviolet, ivikele isikhumba ezithombeni, futhi inikeze isivikelo esisebenzayo elangeni.

Fingqa

I-Ergothioneine, ene-antioxidant eyingqayizivele kanye nezinhlobonhlobo zezinhlelo zokusebenza, ilungisa kabusha imboni yokulwa nokuguga. Ngokuthuthuka kwebhayoloji yokwenziwa kanye nocwaningo lomtholampilo olujulile, kungase kube esinye sezithako eziyinhloko zokubambezela ukuguga kanye nokwenza ngcono izinga lempilo. Kubathengi, ukukhetha imikhiqizo ye-ergothioneine ehlanzekile, eyenziwe ngokwesayensi kungaba yisihluthulelo sokulwa nemiphumela yesikhathi.