Yimiphi imiphumela yemilingo nemisebenzi ye-urolithin A? Yimiphi imikhiqizo engeziwe

 I-Urolithin A iyisithako esibalulekile esisebenzayo esisetshenziswa kakhulu kwezokwelapha nasekunakekelweni kwezempilo. Iyi-enzyme ekhiqizwa kakhulu yizinso futhi inomsebenzi wokuncibilikisa amahlule egazi. Imiphumela eyisimangaliso nemisebenzi ye-Urolithin A ibonakala kakhulu kulezi zici ezilandelayo.

I-Urolithin A ivimbela ukuwohloka kwemisipha

1. Khuthaza ukwakheka kwamaprotheni emisipha futhi usebenzise indlela yokubonisana ye-mTOR

Inhloso yendlela yokubonisana ye-rapamycin (mTOR) yezilwane ezincelisayo iyindlela eyinhloko yokulawula ukwakheka kwamaprotheni emisipha. I-Urolithin A ingasebenzisa indlela yokubonisana ye-mTOR futhi ikhuthaze ukwakheka kwamaprotheni emaseli emisipha.

I-mTOR ingakwazi ukuzwa izimpawu ezifana nezakhamzimba kanye nezici zokukhula kumaseli. Uma isebenza, izoqala uchungechunge lwama-molecule okubonisa izimpawu angezansi, njenge-ribosomal protein S6 kinase (S6K1) kanye ne-eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). I-Urolithin A isebenza ku-mTOR, i-phosphorylating S6K1 kanye ne-4E-BP1, ngaleyo ndlela ikhuthaze ukuqaliswa kokuhumusha kwe-mRNA kanye nokuhlanganiswa kwe-ribosome, futhi isheshise ukwakheka kwamaprotheni.

Isibonelo, ekuhlolweni kwamaseli emisipha akhuliswe ngaphakathi kwe-vitro, ngemuva kokufaka i-urolithin A, kwaphawulwa ukuthi amazinga e-phosphorylation e-mTOR kanye nama-molecule ayo okubonisa izimpawu akhuphuka, futhi ukubonakaliswa kwezimpawu zokwenziwa kwamaprotheni emisipha (njenge-myosin heavy chain) kwanda.
Ilawula ukubonakaliswa kwe-transcription factor ethile yemisipha

I-Urolithin A ingalawula ukuvezwa kwezinto ezichaza ukubhalwa kwemisipha ezibalulekile ekwakhiweni kwamaprotheni emisipha kanye nokwehlukaniswa kwamaseli emisipha. Isibonelo, ingakhuphula ukuvezwa kwe-myogenic differentiation factor (MyoD) kanye ne-myogenin.

I-MyoD ne-Myogenin zingakhuthaza ukuhlukaniswa kwamaseli emisipha abe amaseli emisipha futhi zisebenze ukubonakaliswa kwezakhi zofuzo ezithile zemisipha, ngaleyo ndlela zikhuthaze ukwakheka kwamaprotheni emisipha. Kumodeli yokuwohloka kwemisipha, ngemuva kokwelashwa kwe-urolithin A, ukubonakaliswa kwe-MyoD ne-Myogenin kwanda, okusiza ukugcina ubukhulu bemisipha nokuvimbela ukwehla kwemisipha.

2. Vimbela ukuwohloka kwamaprotheni emisipha futhi uvimbele uhlelo lwe-ubiquitin-proteasome (UPS)

I-UPS ingenye yezindlela eziyinhloko zokuwohloka kwamaprotheni emisipha. Ngesikhathi sokuqina kwemisipha, amanye ama-ligase e-E3 ubiquitin, njenge-muscle atrophy F-box protein (MAFbx) kanye ne-muscle RING finger protein 1 (MuRF1), ayasebenza, angamaka amaprotheni emisipha nge-ubiquitin bese ewawohloza nge-proteasome.

I-Urolithin A ingavimbela ukuvezwa kanye nomsebenzi walezi ligases ze-E3 ubiquitin. Ekuhlolweni kwemodeli yezilwane, i-urolithin A inganciphisa amazinga e-MAFbx kanye ne-MuRF1, inciphise uphawu lwe-ubiquitination lwamaprotheni emisipha, ngaleyo ndlela ivimbele ukuwohloka kwamaprotheni emisipha okubangelwa yi-UPS futhi ivimbele ngempumelelo ukwehla kwemisipha.

Ukuguqulwa kwesistimu ye-autophagy-lysosomal (ALS)

I-ALS idlala indima ekuvuseleleni amaprotheni emisipha kanye nama-organelle, kodwa ukusebenza ngokweqile kungaholela nasekuwohlokeni kwemisipha. I-Urolithin A ingalawula i-ALS ngezinga elifanele. Ingavimbela i-autophagy ngokweqile futhi ivimbele ukuwohloka ngokweqile kwamaprotheni emisipha.
Isibonelo, i-urolithin A ingalawula ukuvezwa kwamaprotheni ahlobene ne-autophagy (njenge-LC3-II), ukuze ikwazi ukugcina i-homeostasis yendawo yamaseli emisipha ngenkathi igwema ukususwa ngokweqile kwamaprotheni emisipha, ngaleyo ndlela isize ekugcineni isisindo semisipha.

3. Thuthukisa ukusebenza kwamandla kwamangqamuzana emisipha

Ukufinyela kwemisipha kudinga amandla amaningi, futhi i-mitochondria iyindawo eyinhloko yokukhiqizwa kwamandla. I-Urolithin A ingathuthukisa ukusebenza kwe-mitochondria yamaseli emisipha futhi ithuthukise ukusebenza kahle kokukhiqizwa kwamandla. Ingakhuthaza i-biogenesis ye-mitochondria futhi yandise inani le-mitochondria.

Isibonelo, i-urolithin A ingavuselela i-peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), ewumlawuli oyinhloko we-mitochondrial biogenesis, ikhuthaza ukuphindaphindwa kwe-DNA ye-mitochondrial kanye nokwakheka kwamaprotheni ahlobene. Ngesikhathi esifanayo, i-urolithin A ingathuthukisa futhi umsebenzi we-mitochondrial respiratory chain, yandise ukwakheka kwe-adenosine triphosphate (ATP), inikeze amandla anele okunciphisa imisipha, futhi inciphise ukwehla kwemisipha okubangelwa amandla anganele.

Ilawula ukwakheka kukashukela kanye namafutha futhi isekela ukusebenza kwemisipha

I-Urolithin A ingalawula ukwakheka kwe-glucose kanye ne-lipid kwamaseli emisipha. Ngokuphathelene nokwakheka kwe-glucose, ingathuthukisa ukumuncwa nokusetshenziswa kwe-glucose ngamaseli emisipha, futhi iqinisekise ukuthi amaseli emisipha anezakhi zamandla ezanele ngokusebenzisa indlela yokubonisa i-insulin noma ezinye izindlela zokubonisa ezihlobene nokuthutha kwe-glucose.

Ngokuphathelene nokusetshenziswa kwe-lipid metabolism, i-urolithin A ingakhuthaza ukushiswa kwe-fatty acid, inikeze omunye umthombo wamandla wokufinyela kwemisipha. Ngokwenza ngcono ukusetshenziswa kwe-glucose kanye ne-lipid metabolism, i-urolithin A igcina ukuphakelwa kwamandla kwamaseli emisipha futhi isiza ekuvimbeleni ukwehla kwemisipha.

I-Urolithin A ithuthukisa imetabolism

1. Lawula ukusebenza kwe-metabolism kashukela futhi uthuthukise ukuzwela kwe-insulin
I-Urolithin A ingathuthukisa ukuzwela kwe-insulin, okubalulekile ekugcineni ukuqina kukashukela egazini. Ingasebenza kuma-molecule abalulekile endleleni yokubonisana kwe-insulin, njengamaprotheni e-insulin receptor substrate (IRS).

Esimweni sokumelana ne-insulin, i-tyrosine phosphorylation yeprotheyini ye-IRS iyavinjelwa, okuholela ekuhlulekeni kwendlela yokubonisana ye-phosphatidylinositol 3-kinase (PI3K) engezansi ukusebenza ngendlela evamile, futhi impendulo yeseli ku-insulin iba buthaka.

I-Urolithin A ingakhuthaza i-tyrosine phosphorylation yeprotheyini ye-IRS, ngaleyo ndlela isebenze indlela yokubonisana ye-PI3K-protein kinase B (Akt), okwenza amaseli akwazi ukumunca nokusebenzisa i-glucose kangcono. Isibonelo, ekuhlolweni kwemodeli yezilwane, ngemuva kokuphathwa kwe-urolithin A, ukuzwela kwezicubu zemisipha nezicubu zamafutha ku-insulin kwathuthukiswa kakhulu, futhi amazinga kashukela egazini alawulwa ngempumelelo.

Ilawula ukwakheka kwe-glycogen kanye nokuwohloka kwayo

I-Glycogen iyindlela eyinhloko yokugcina ushukela emzimbeni, egcinwa kakhulu esibindini nasemisipheni. I-Urolithin A ingalawula ukwakheka nokubola kwe-glycogen. Ingenza kusebenze i-glycogen synthase, ikhuthaze ukwakheka kwe-glycogen, futhi yandise inqolobane ye-glycogen.

Ngesikhathi esifanayo, i-urolithin A ingavimbela nomsebenzi wama-enzyme e-glycogenolytic, njenge-glycogen phosphorylase, futhi inciphise inani le-glycogen ebolile ibe yi-glucose bese ikhishwa egazini. Lokhu kusiza ekuqiniseni amazinga kashukela egazini futhi kuvimbele ukuguquguquka okukhulu kushukela egazini. Esifundweni semodeli yesifo sikashukela, ngemva kokwelashwa kwe-urolithin A, okuqukethwe kwe-glycogen esibindini nasemisipheni kwanda, futhi ukulawulwa koshukela egazini kwathuthukiswa.

2. Lungiselela i-lipid metabolism futhi uvimbele ukwakheka kwama-fatty acid

I-Urolithin A inomphumela wokuvimbela inqubo yokwenziwa kwamafutha. Ezicutshini zesibindi nezama-adipose, ingavimbela ama-enzyme abalulekile ekwenziweni kwamafutha, njenge-fatty acid synthase (FAS) kanye ne-acetyl-CoA carboxylase (ACC).

I-FAS kanye ne-ACC ziyi-enzyme ebalulekile yokulawula ekwakhiweni okusha kwama-fatty acid. I-Urolithin A inganciphisa ukwakheka kwama-fatty acid ngokuvimbela umsebenzi wawo. Isibonelo, kumodeli yesibindi esinamafutha ebangelwa ukudla okunamafutha amaningi, i-urolithin A inganciphisa umsebenzi we-FAS kanye ne-ACC esibindini, inciphise ukwakheka kwama-triglycerides, ngaleyo ndlela inciphise ukuqongelela kwama-lipid esibindini.

Ikhuthaza ukushiswa kwe-fatty acid

Ngaphezu kokuvimbela ukwakheka kwe-fatty acid, i-urolithin A ingakhuthaza nokubola kwe-oxidative kwama-fatty acid. Ingavuselela izindlela zokubonisana nama-enzyme ahlobene ne-fatty acid oxidation. Isibonelo, ingakhuphula umsebenzi we-carnitine palmitoyltransferase-1 (CPT-1).

I-CPT-1 iyi-enzyme ebalulekile ekufakweni kwe-fatty acid β-oxidation, enesibopho sokuthutha ama-fatty acids aye kuma-mitochondria ukuze kubole i-oxidative. I-Urolithin A ikhuthaza ukufakwa kwe-β-oxidation kwama-fatty acids ngokwenza i-CPT-1 isebenze, ikhulisa ukusetshenziswa kwamandla amafutha, isiza ekunciphiseni ukugcinwa kwamafutha emzimbeni, futhi ithuthukise i-lipid metabolism.

3. Thuthukisa i-metabolism yamandla futhi uthuthukise ukusebenza kwe-mitochondrial

I-Mitochondria "iyizimboni zamandla" zamaseli, futhi i-urolithin A ingathuthukisa ukusebenza kwe-mitochondria. Ingalawula i-mitochondrial biogenesis futhi ikhuthaze ukwakheka kwe-mitochondrial kanye nokuvuselelwa kwayo. Isibonelo, ingenza kusebenze i-peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α).

I-PGC-1α iwumlawuli oyinhloko we-mitochondrial biogenesis, engakhuthaza ukuphindaphindwa kwe-DNA ye-mitochondrial kanye nokwakheka kwamaprotheni ahlobene ne-mitochondrial. I-Urolithin A yandisa inani kanye nekhwalithi ye-mitochondria futhi ithuthukisa ukusebenza kahle kokukhiqizwa kwamandla kwamaseli ngokusebenzisa i-PGC-1α. Ngesikhathi esifanayo, i-urolithin A ingathuthukisa futhi umsebenzi wochungechunge lokuphefumula lwe-mitochondria futhi yandise ukwakheka kwe-adenosine triphosphate (ATP).

4. Ukulawula Ukuhlelwa Kabusha Kwe-Metabolic Yeseli

I-Urolithin A ingaqondisa amaseli ukuthi aphinde ahlelwe kabusha nge-metabolic, okwenza i-metabolism yeseli isebenze kahle kakhulu. Ngaphansi kwezimo ezithile zokucindezeleka noma zesifo, iphethini ye-metabolism yeseli ingashintsha, okuholela ekunciphiseni ukusebenza kahle ekukhiqizweni kwamandla kanye nokuhlanganiswa kwezidakamizwa.

I-Urolithin A ingalawula izindlela zokubonisana kwe-metabolic kumaseli, njengendlela yokubonisana ye-AMP-activated protein kinase (AMPK). I-AMPK "iyinzwa" ye-metabolism yamandla eseli. Ngemva kokuthi i-urolithin A isebenze i-AMPK, ingenza amaseli ashintshe kusuka ku-anabolism aye ku-catabolism, asebenzise amandla nezakhamzimba ngendlela ephumelelayo, ngaleyo ndlela athuthukise ukusebenza kwe-metabolic iyonke.

Ukusetshenziswa kwe-urolithin A akugcini nje emkhakheni wezokwelapha. Kuphinde kuthole ukunakwa kancane kancane emikhiqizweni yezempilo nasezimonyweni. I-Urolithin A yengezwa emikhiqizweni eminingi yezempilo ukuze kuthuthukiswe amasosha omzimba, kuthuthukiswe ukujikeleza kwegazi futhi kukhuthazwe imetabolism. Le mikhiqizo ivame ukuba ngesimo sama-capsule, amaphilisi noma uketshezi, okulungele izidingo zamaqembu ahlukene abantu.

Emkhakheni wezimonyo, i-urolithin A isetshenziswa kabanzi emikhiqizweni yokunakekelwa kwesikhumba ngenxa yokuvuselelwa kwamaseli ayo kanye nezakhiwo zayo zokulwa nokuguga. Ingathuthukisa ukujikeleza kwegazi esikhumbeni futhi ikhuthaze ukwakheka kwe-collagen, ngaleyo ndlela ithuthukise ukuqina kwesikhumba nokukhanya. Imikhiqizo eminingi yokunakekelwa kwesikhumba ephezulu isiqalile ukusebenzisa i-urolithin A njengesithako esiyinhloko ukwethula imikhiqizo yokulwa nokuguga, ukulungisa kanye nokuthambisa isikhumba ukuze kuhlangatshezwane nokuphishekela kwabathengi isikhumba esihle.

Ekuphetheni, njengezinto eziphilayo ezinemisebenzi eminingi, i-urolithin A ibonise amathuba amaningi okusetshenziswa emikhakheni yezokwelapha, ukunakekelwa kwempilo kanye nobuhle. Ngokujula kocwaningo lwesayensi, insimu yokusetshenziswa kwe-urolithin A izoqhubeka nokukhula, inikeze izinketho eziningi zempilo nobuhle babantu.