Ziziphi iziphumo zomlingo kunye nemisebenzi ye-urolithin A? Zeziphi iimveliso ezongeziweyo

 I-Urolithin A yinto ebalulekileyo ye-bioactive esetyenziswa ngokubanzi kumayeza kunye nokhathalelo lwempilo. Yi-enzyme eveliswa ikakhulu zizintso kwaye inomsebenzi wokunyibilikisa amahlwili egazi. Iziphumo zomlingo kunye nemisebenzi ye-Urolithin A ibonakaliswa ikakhulu kule miba ilandelayo.

I-Urolithin A ikhusela ukuhla kwemisipha

1. Ukukhuthaza i-protein ye-muscle synthesis kunye nokuvula indlela yokubonisa i-mTOR

Ithagethi ye-mammalian ye-rapamycin (mTOR) indlela yomqondiso yindlela ephambili yokulawula i-protein ye-muscle synthesis. I-Urolithin A inokusebenzisa indlela yokubonisa i-mTOR kwaye ikhuthaze ukuhlanganiswa kweeprotheyini kwiiseli ze-muscle.

I-mTOR inokubona iimpawu ezifana nezondlo kunye nezinto zokukhula kwiiseli. Xa ivuliwe, iya kuqalisa uchungechunge lweeamolekyu ezisezantsi, ezifana ne-ribosomal protein S6 kinase (S6K1) kunye ne-eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). I-Urolithin A yenza i-mTOR, i-phosphorylating S6K1 kunye ne-4E-BP1, ngaloo ndlela ikhuthaza ukuqaliswa koguqulo lwe-mRNA kunye nendibano ye-ribosome, kunye nokukhawulezisa ukuhlanganiswa kweeprotheyini.

Ngokomzekelo, kwiimvavanyo kunye neeseli ze-muscle ezikhuliswe kwi-in vitro, emva kokongeza i-urolithin A, kwaphawulwa ukuba amanqanaba e-phosphorylation ye-mTOR kunye ne-athomu ye-signing ye-downstream yanda, kunye nokubonakaliswa kweempawu ze-protein synthesis markers (ezifana ne-myosin chain chain) zanda.
Ilawula imbonakalo yento yokubhala ngokwezihlunu

Urolithin A inokulawula ukubonakaliswa kwezinto ezikhutshelweyo zemisipha eziyimfuneko kwi-protein ye-muscle synthesis kunye nokwahlula kweeseli ze-muscle. Ngokomzekelo, inokulawula ukubonakaliswa kwe-myogenic differentiation factor (MyoD) kunye ne-myogenin.

I-MyoD kunye ne-Myogenin inokukhuthaza ukuhlukana kweeseli ze-muscle ze-muscle kwiiseli ze-muscle kwaye isebenze ukubonakaliswa kwe-genes-specific genes, ngaloo ndlela ikhuthaza i-protein ye-muscle synthesis. Kwimodeli ye-atrophy ye-muscle, emva konyango lwe-urolithin A, ukubonakaliswa kwe-MyoD kunye ne-Myogenin kwanda, okunceda ukugcina ubunzima bemisipha kunye nokuthintela ukuhla kwemisipha.

2. Ukuthintela ukuchithwa kweprotheyini ye-muscle kunye nokuthintela inkqubo ye-ubiquitin-proteasome (UPS)

I-UPS yenye yeendlela eziphambili zokuthotywa kweprotheyini yemisipha. Ngexesha le-atrophy ye-muscle, ezinye i-E3 ubiquitin ligases, ezifana ne-muscle atrophy ye-protein ye-F-box (MAFbx) kunye ne-muscle RING iprotheni yeminwe ye-1 (i-MuRF1), isebenze, enokuthi ifake iiprotheni ze-muscle kunye ne-ubiquitin kwaye emva koko zithobe nge-proteasome.

I-Urolithin A inokuthintela ukubonakaliswa kunye nomsebenzi wale E3 ubiquitin ligases. Kwiimvavanyo zemodeli yezilwanyana, i-urolithin A inokunciphisa amanqanaba e-MAFbx kunye ne-MuRF1, ukunciphisa uphawu lwe-ubiquitination yeeprotheni ze-muscle, ngaloo ndlela inqanda ukuchithwa kweprotheyini ye-muscle ye-UPS-mediated kunye nokuthintela ngokufanelekileyo ukuhla kwemisipha.

Ukumodareyitha kwe-autophagy-lysosomal system (ALS)

I-ALS idlala indima ekuhlaziyweni kweeprotheyini ze-muscle kunye ne-organelles, kodwa ukusetyenziswa ngokugqithiseleyo kunokukhokelela kwi-muscle atrophy. I-Urolithin A inokulawula i-ALS ukuya kwinqanaba elifanelekileyo. Inokuthintela i-autophagy egqithisileyo kwaye ithintele ukuthotywa okugqithisileyo kweeprotheni zemisipha.
Ngokomzekelo, i-urolithin A inokulawula ukubonakaliswa kweeprotheyini ezinxulumene ne-autophagy (ezifana ne-LC3-II), ukwenzela ukuba ikwazi ukugcina i-homeostasis yendawo yeseli ye-muscle ngelixa igwema ukuchithwa ngokugqithiseleyo kweeprotheni ze-muscle, ngaloo ndlela inceda ukugcina ubunzima bemisipha.

3. Ukuphucula i-metabolism yamandla kwiiseli zemisipha

Ukutshatyalaliswa kwemisipha kufuna amandla amaninzi, kwaye i-mitochondria yindawo ephambili yokuvelisa amandla. I-Urolithin A inokuphucula umsebenzi we-muscle cell mitochondria kunye nokuphucula ukusebenza kakuhle kokuveliswa kwamandla. Inokukhuthaza i-biogenesis ye-mitochondrial kunye nokwandisa inani le-mitochondria.

Ngokomzekelo, i-urolithin A inokusebenzisa i-peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), eyona nto ingumlawuli oyintloko we-mitochondrial biogenesis, ukukhuthaza ukuphindaphinda kwe-DNA ye-mitochondrial kunye ne-protein synthesis. Ngelo xesha, i-urolithin A inokuphucula umsebenzi wekhonkco lokuphefumula kwe-mitochondrial, ukwandisa i-synthesis ye-adenosine triphosphate (ATP), inike amandla aneleyo okunciphisa imisipha, kunye nokunciphisa ukuhla kwemisipha okubangelwa amandla anganeleyo.

Ilawula iswekile kunye ne-lipid metabolism kwaye ixhasa umsebenzi wemisipha

I-Urolithin A inokulawula i-glucose kunye ne-lipid metabolism yeeseli zemisipha. Ngokubhekiselele kwi-glucose metabolism, inokuphucula ukunyuswa kunye nokusetyenziswa kwe-glucose ngamaseli e-muscle, kwaye iqinisekise ukuba iiseli ze-muscle zinee-substrates zamandla ezaneleyo ngokuvula indlela yokubonakalisa i-insulin okanye ezinye iindlela zokubonisa i-glucose ezinxulumene nokuthutha.

Ngokubhekiselele kwi-lipid metabolism, i-urolithin A inokukhuthaza i-oxidation ye-fatty acid, inika omnye umthombo wamandla wokunqanda kwemisipha. Ngokulungisa i-glucose kunye ne-lipid metabolism, i-urolithin A igcina ukunikezelwa kwamandla kwiiseli ze-muscle kwaye inceda ukukhusela ukuhla kwemisipha.

I-Urolithin A iphucula imetabolism

1. Ukulawula i-metabolism yeswekile kunye nokuphucula ukuvakalelwa kwe-insulin
I-Urolithin A inokwandisa uvakalelo lwe-insulin, oluyimfuneko ekugcineni uzinzo lweswekile yegazi. Inokuthi isebenze kwiimolekyuli eziphambili kwindlela yokubonisa i-insulin, njenge-insulin receptor substrate (IRS) iiprotheni.

Kwimeko yokumelana ne-insulin, i-tyrosine phosphorylation yeprotheni ye-IRS ivinjelwe, okubangelwa ukungaphumeleli kwe-phosphatidylinositol ephantsi kwe-3-kinase (PI3K) indlela yokubonisa ukuba isebenze ngokuqhelekileyo, kwaye impendulo yeseli kwi-insulin iyancipha.

I-Urolithin A inokukhuthaza i-tyrosine phosphorylation yeprotheni ye-IRS, ngaloo ndlela isebenze i-PI3K-protein kinase B (Akt) indlela yokubonisa, eyenza iiseli ukuba zifunxe ngcono kwaye zisebenzise i-glucose. Ngokomzekelo, kwiimvavanyo zemodeli yezilwanyana, emva kokulawulwa kwe-urolithin A, ukuvakalelwa kwe-muscle kunye ne-adipose tissue kwi-insulin kuphuculwe kakhulu, kwaye amanqanaba eshukela egazi alawulwa ngokufanelekileyo.

Ilawula ukuhlanganiswa kwe-glycogen kunye nokuthotywa

IGlycogen yeyona ndlela iphambili yokugcina iswekile emzimbeni, ikakhulu igcinwe kwisibindi kunye nezicubu zomzimba. I-Urolithin A inokulawula i-synthesis kunye nokubola kwe-glycogen. Iyakwazi ukwenza i-glycogen synthase isebenze, ikhuthaze ukuhlanganiswa kwe-glycogen, kwaye yandise ukugcinwa kwe-glycogen.

Ngelo xesha, i-urolithin A inokuthintela umsebenzi we-glycogenolytic enzymes, njenge-glycogen phosphorylase, kunye nokunciphisa inani le-glycogen ebolileyo kwi-glucose kwaye ikhutshwe egazini. Oku kunceda ukuzinzisa amanqanaba eswekile yegazi kunye nokuthintela ukuguquguquka okugqithisileyo kweswekile yegazi. Kuphononongo lwemodeli yesifo sikashukela, emva konyango lwe-urolithin A, umxholo we-glycogen kwisibindi kunye nezihlunu zanda, kwaye ukulawula iswekile yegazi kwaphuculwa.

2. Lungiselela i-lipid metabolism kwaye unqande i-fatty acid synthesis

I-Urolithin A inempembelelo yokuthintela kwinkqubo ye-lipid synthesis. Kwisibindi kunye nezicubu ze-adipose, inokuthintela i-enzymes eziphambili kwi-fatty acid synthesis, njenge-fatty acid synthase (FAS) kunye ne-acetyl-CoA carboxylase (ACC).

I-FAS kunye ne-ACC zibalulekile ii-enzymes zokulawula kwi-de novo synthesis ye-fatty acids. I-Urolithin A inokunciphisa ukuhlanganiswa kwe-fatty acids ngokuthintela umsebenzi wabo. Ngokomzekelo, kwimodeli yesibindi esinamafutha esibangelwa kukutya okunamafutha amaninzi, i-urolithin A inokunciphisa umsebenzi we-FAS kunye ne-ACC kwisibindi, ukunciphisa i-synthesis ye-triglycerides, kwaye ngaloo ndlela inciphisa ukuqokelelwa kwe-lipid esibindini.

Ikhuthaza i-fatty acid oxidation

Ukongeza ekuvimbeleni i-fatty acid synthesis, i-urolithin A inokukhuthaza ukubola kwe-oxidative ye-fatty acids. Iyakwazi ukuvuselela iindlela zokubonisa kunye ne-enzymes ezinxulumene ne-fatty acid oxidation. Ngokomzekelo, inokunyusa umsebenzi we-carnitine palmitoyltransferase-1 (CPT-1).

I-CPT-1 yi-enzyme ephambili kwi-acid e-fatty β-oxidation, ejongene nokuthutha i-fatty acids kwi-mitochondria yokubola kwe-oxidative. I-Urolithin A ikhuthaza i-β-oxidation ye-fatty acids ngokuvula i-CPT-1, ukwandisa ukusetyenziswa kwamandla kwamafutha, inceda ukunciphisa ukugcinwa kwamafutha omzimba, kunye nokuphucula i-lipid metabolism.

3. Ukuphucula i-metabolism yamandla kunye nokuphucula umsebenzi we-mitochondrial

I-Mitochondria "ziifektri zamandla" zeeseli, kwaye i-urolithin A inokuphucula umsebenzi we-mitochondria. Inokulawula i-biogenesis ye-mitochondrial kwaye ikhuthaze ukuhlanganiswa kwe-mitochondrial kunye nokuhlaziywa. Ngokomzekelo, inokwenza i-peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α).

I-PGC-1α ingumlawuli oyintloko we-mitochondrial biogenesis, enokukhuthaza ukuphindaphinda kwe-DNA ye-mitochondrial kunye nokuhlanganiswa kweeprotheni ezinxulumene ne-mitochondrial. I-Urolithin A yonyusa inani kunye nomgangatho we-mitochondria kwaye iphucula ukusebenza kakuhle kokuveliswa kwamandla kweeseli ngokuvula i-PGC-1α. Ngelo xesha, i-urolithin A inokuphucula umsebenzi wekhonkco lokuphefumla lwe-mitochondria kunye nokwandisa ukuhlanganiswa kwe-adenosine triphosphate (ATP).

4. Ukulawula ukuCwangciswa ngokutsha kweMetabolic yeSelula

I-Urolithin A inokukhokela iiseli ukuba zingene kwi-metabolic reprogramming, yenze i-metabolism yeseli isebenze ngakumbi. Phantsi koxinzelelo oluthile okanye iimeko zesifo, ipateni yemetabolism yeseli inokutshintsha, okukhokelela ekunciphiseni ukusebenza kakuhle kwimveliso yamandla kunye ne-substance synthesis.

I-Urolithin A inokulawula iindlela zokubonisa i-metabolic kwiiseli, ezifana ne-AMP-activated protein kinase (AMPK) indlela yokubonisa. I-AMPK "yinzwa" ye-metabolism yamandla eselula. Emva kokuba i-urolithin A isebenze i-AMPK, inokubangela ukuba iiseli zitshintshe ukusuka kwi-anabolism ukuya kwi-catabolism, zenze ukusetyenziswa ngokufanelekileyo kwamandla kunye nezondlo, ngaloo ndlela kuphuculwe umsebenzi jikelele we-metabolic.

Ukusetyenziswa kwe-urolithin A akuphelelanga kwintsimi yezonyango. Kwakhona ngokuthe ngcembe ifumana ingqalelo kwiimveliso zempilo kunye nezithambiso. I-Urolithin A yongezwa kwiimveliso ezininzi zempilo ukuphucula ukukhuseleka, ukuphucula ukujikeleza kwegazi kunye nokukhuthaza imetabolism. Ezi mveliso zihlala zikwimo yee-capsules, iipilisi okanye ulwelo, ezifanelekileyo kwiimfuno zamaqela ahlukeneyo abantu.

Kwintsimi yezithambiso, i-urolithin A isetyenziswa ngokubanzi kwiimveliso zokunakekelwa kwesikhumba ngenxa yokuvuselelwa kweeseli kunye neempawu zokulwa nokuguga. Inokuphucula ukujikeleza kwegazi esikhumbeni kwaye ikhuthaze i-collagen synthesis, ngaloo ndlela iphucula ukuqina kwesikhumba kunye nokukhanya. Iimveliso ezininzi zokhathalelo lwesikhumba ezikumgangatho ophezulu sele ziqalisile ukusebenzisa i-urolithin A njengesithako esisisiseko sokuqalisa ukuguga, ukulungisa kunye neemveliso ezithambisayo ukuhlangabezana nokusukela kwabathengi ulusu oluhle.

Ukuqukumbela, njenge-bioactive substance enemisebenzi emininzi, i-urolithin A ibonise amathuba okusebenza ngokubanzi kwiinkalo zonyango, ukhathalelo lwempilo kunye nobuhle. Ngokunzulu kophando lwezenzululwazi, intsimi yesicelo se-urolithin A iya kuqhubeka isanda, inika ukhetho olungakumbi kwimpilo yabantu kunye nobuhle.