Zithini iziphumo zomlingo kunye nemisebenzi ye-urolithin A? Zeziphi iimveliso ezongezwayo

 I-Urolithin A sisithako esibalulekileyo esisebenzayo kwi-bioactive esisetyenziswa kakhulu kunyango nakwimpilo. Yi-enzyme eveliswa kakhulu zizintso kwaye inomsebenzi wokunyibilikisa amahlwili egazi. Iziphumo zomlingo kunye nemisebenzi ye-Urolithin A zibonakala kakhulu kwezi zinto zilandelayo.

I-Urolithin A ithintela ukuwohloka kwemisipha

1. Khuthaza ukwenziwa kweproteni yemisipha kwaye usebenzise indlela yokubonisa i-mTOR

Indlela yokubonisa i-rapamycin (mTOR) ekujoliswe kuyo kwizilwanyana ezincancisayo yindlela ephambili yokulawula ukwenziwa kweproteni yemisipha. I-Urolithin A ingenza indlela yokubonisa i-mTOR isebenze kwaye ikhuthaze ukwenziwa kweproteni kwiiseli zemisipha.

I-mTOR iyakwazi ukubona imiqondiso efana nezondlo kunye nezinto ezikhula kwiiseli. Xa isebenza, iya kuqalisa uthotho lweemolekyuli zokubonisa ezisezantsi, ezifana ne-ribosomal protein S6 kinase (S6K1) kunye ne-eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). I-Urolithin A isebenza kwi-mTOR, i-phosphorylating S6K1 kunye ne-4E-BP1, ngaloo ndlela ikhuthaza ukuqaliswa koguqulelo lwe-mRNA kunye nokuhlanganiswa kwe-ribosome, kwaye ikhawulezise ukwenziwa kweproteni.

Umzekelo, kuvavanyo lweeseli zemisipha ezikhuliswe kwi-in vitro, emva kokongeza i-urolithin A, kwabonwa ukuba amanqanaba e-phosphorylation ye-mTOR kunye neemolekyuli zayo zokubonisa ezisezantsi ayanda, kwaye ukubonakaliswa kweempawu zokwenziwa kweproteni yemisipha (ezifana ne-myosin heavy chain) kwanda.
Ilawula ukubonakaliswa kwezinto ezithile ze-transcription factor

I-Urolithin A inokulawula ukubonakaliswa kwezinto ezithile ze-transcription zemisipha ezibalulekileyo ekuqulunqweni kweprotheyini yemisipha kunye nokwahlulwa kweeseli zemisipha. Umzekelo, inokunyusa ukubonakaliswa kwe-myogenic differentiation factor (MyoD) kunye ne-myogenin.

I-MyoD kunye ne-Myogenin zinokukhuthaza ukwahlulwa kweeseli ze-muscle stem kwiiseli ze-muscle kwaye zivuselele ukubonakaliswa kwezakhi zofuzo ezithile ze-muscle, ngaloo ndlela zikhuthaza ukwenziwa kweproteni ye-muscle. Kwimodeli ye-muscle atrophy, emva konyango lwe-urolithin A, ukubonakaliswa kwe-MyoD kunye ne-Myogenin kwanda, okunceda ukugcina ubunzima be-muscle kunye nokuthintela ukwehla kwe-muscle.

2. Ukuthintela ukuwohloka kweproteni yemisipha kunye nokuthintela inkqubo ye-ubiquitin-proteasome (UPS)

I-UPS yenye yezona ndlela ziphambili zokonakala kweprotheyini yemisipha. Ngexesha lokonakala kwemisipha, ezinye ii-ligases ze-E3 ubiquitin, ezifana ne-muscle atrophy F-box protein (MAFbx) kunye ne-muscle RING finger protein 1 (MuRF1), ziyasebenza, ezinokubonisa iiprotheyini zemisipha nge-ubiquitin kwaye emva koko ziwohloke nge-proteasome.

I-Urolithin A inokuthintela ukubonakaliswa kunye nomsebenzi wezi ligases ze-E3 ubiquitin. Kwizilingo zemodeli yezilwanyana, i-urolithin A inokunciphisa amanqanaba e-MAFbx kunye ne-MuRF1, inciphise uphawu lwe-ubiquitination lweeproteni zemisipha, ngaloo ndlela ithintele ukuwohloka kweproteni yemisipha ebangelwa yi-UPS kwaye ithintele ngokufanelekileyo ukuwohloka kwemisipha.

Ukuguqulwa kwenkqubo ye-autophagy-lysosomal (ALS)

I-ALS idlala indima ekuvuseleleni iiproteni zemisipha kunye nee-organelles, kodwa ukusebenza kakhulu kunokukhokelela ekuwohlokeni kwemisipha. I-Urolithin A inokulawula i-ALS kwinqanaba elifanelekileyo. Ingathintela i-autophagy egqithisileyo kwaye ithintele ukuwohloka okugqithisileyo kweeproteni zemisipha.
Umzekelo, i-urolithin A inokulawula ukubonakaliswa kweeproteni ezinxulumene ne-autophagy (ezifana ne-LC3-II), ukuze ikwazi ukugcina i-homeostasis yendawo yeeseli zemisipha ngelixa ithintela ukususwa okugqithisileyo kweeproteni zemisipha, ngaloo ndlela inceda ukugcina ubunzima bemisipha.

3. Ukuphucula imetabolism yamandla kwiiseli zemisipha

Ukucutheka kwemisipha kufuna amandla amaninzi, kwaye i-mitochondria yindawo ephambili yokuvelisa amandla. I-Urolithin A inokuphucula ukusebenza kwe-mitochondria yeeseli zemisipha kwaye iphucule ukusebenza kakuhle kwemveliso yamandla. Inokukhuthaza i-mitochondrial biogenesis kwaye inyuse inani le-mitochondria.

Umzekelo, i-urolithin A ingavuselela i-peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), elawula i-mitochondrial biogenesis, ikhuthaza ukuphindaphinda kwe-DNA ye-mitochondrial kunye nokuhlanganiswa kweproteni enxulumene nayo. Kwangaxeshanye, i-urolithin A inokuphucula umsebenzi we-mitochondrial respiratory chain, inyuse ukwenziwa kwe-adenosine triphosphate (ATP), inike amandla aneleyo okucutheka kwemisipha, kwaye inciphise ukwehla kwemisipha okubangelwa kukungabikho kwamandla aneleyo.

Ilawula iswekile kunye ne-lipid metabolism kwaye ixhasa ukusebenza kwemisipha

I-Urolithin A inokulawula i-glucose kunye ne-lipid metabolism yeeseli zemisipha. Ngokuphathelele i-glucose metabolism, inokuphucula ukufunxwa nokusetyenziswa kwe-glucose ziiseli zemisipha, kwaye iqinisekise ukuba iiseli zemisipha zinamandla aneleyo ngokusebenzisa indlela ye-insulin signaling okanye ezinye iindlela ze-glucose transport-related transportation pathways.

Ngokuphathelele imetabolism yamafutha, i-urolithin A inokukhuthaza i-oxidation ye-fatty acid, inike omnye umthombo wamandla wokucutheka kwemisipha. Ngokuphucula imetabolism yeglucose kunye ne-lipid, i-urolithin A igcina ukunikezelwa kwamandla kwiiseli zemisipha kwaye inceda ukuthintela ukuwohloka kwemisipha.

I-Urolithin A iphucula imetabolism

1. Lawula imetabolism yeswekile kwaye uphucule uvakalelo lwe-insulin
I-Urolithin A inokuphucula uvakalelo lwe-insulin, oluyimfuneko ekugcineni uzinzo lweswekile egazini. Ingasebenza kwiimolekyuli ezibalulekileyo kwindlela yokubonisa i-insulin, njengeeproteni ze-insulin receptor substrate (IRS).

Kwimeko yokuxhathisa i-insulin, i-tyrosine phosphorylation yeprotheyini ye-IRS iyathintelwa, nto leyo ebangela ukuba indlela yokubonisa i-phosphatidylinositol 3-kinase (PI3K) esezantsi ingasebenzi kakuhle, kwaye impendulo yeseli kwi-insulin ibuthathaka.

I-Urolithin A inokukhuthaza i-tyrosine phosphorylation yeproteni ye-IRS, ngaloo ndlela isebenze indlela yokubonisa ye-PI3K-protein kinase B (Akt), ivumela iiseli ukuba zifunxe kwaye zisebenzise i-glucose ngcono. Umzekelo, kuvavanyo lwemodeli yezilwanyana, emva kokunikwa kwe-urolithin A, ukuvalelwa kwemisipha kunye nezicubu zamafutha kwi-insulin kuphuculwe kakhulu, kwaye amanqanaba eswekile egazini alawulwa ngempumelelo.

Ilawula ukwenziwa kwe-glycogen kunye nokuwohloka kwayo

I-Glycogen yeyona ndlela iphambili yokugcina i-glucose emzimbeni, igcinwa ikakhulu kwisibindi nakwizihlunu zemisipha. I-Urolithin A inokulawula ukwenziwa kunye nokubola kwe-glycogen. Ingenza i-glycogen synthase isebenze, ikhuthaze ukwenziwa kwe-glycogen, kwaye yonyuse ukugcinwa kwe-glycogen.

Kwangaxeshanye, i-urolithin A inokuthintela umsebenzi wee-enzymes ze-glycogenolytic, ezifana ne-glycogen phosphorylase, kwaye inciphise ubungakanani be-glycogen eboliswe kwi-glucose ize ikhutshwe egazini. Oku kunceda ukuzinzisa amanqanaba eswekile yegazi kwaye kuthintele ukuguquguquka okugqithisileyo kwiswekile yegazi. Kwisifundo semodeli yesifo seswekile, emva konyango lwe-urolithin A, umxholo we-glycogen kwisibindi nakwimisipha wanda, kwaye ulawulo lweswekile egazini lwaphucuka.

2. Yenza ngcono imetabolism ye-lipid kwaye uthintele ukwenziwa kwe-fatty acid

I-Urolithin A inefuthe lokuthintela inkqubo yokwenziwa kwe-lipid. Kwizicubu zesibindi kunye ne-adipose, inokuthintela ii-enzymes ezibalulekileyo ekuqulunqweni kwe-fatty acid, njenge-fatty acid synthase (FAS) kunye ne-acetyl-CoA carboxylase (ACC).

I-FAS kunye ne-ACC zii-enzyme ezibalulekileyo ezilawulayo kwi-de novo synthesis ye-fatty acids. I-Urolithin A inokunciphisa ukwenziwa kwe-fatty acids ngokuthintela umsebenzi wazo. Umzekelo, kwimodeli yesibindi esinamafutha ebangelwa kukutya okunamafutha amaninzi, i-urolithin A inokunciphisa umsebenzi we-FAS kunye ne-ACC kwisibindi, inciphise ukwenziwa kwe-triglycerides, kwaye ngaloo ndlela inciphise ukuqokelelwa kwe-lipid kwisibindi.

Ikhuthaza ukunyibilika kwe-fatty acid

Ukongeza ekuthinteleni ukwenziwa kwe-fatty acid, i-urolithin A inokukhuthaza ukubola kwe-oxidative kwe-fatty acids. Ingavuselela iindlela zokubonisa kunye nee-enzymes ezinxulumene ne-fatty acid oxidation. Umzekelo, inokunyusa umsebenzi we-carnitine palmitoyltransferase-1 (CPT-1).

I-CPT-1 yi-enzyme ephambili kwi-fatty acid β-oxidation, enoxanduva lokuthutha ii-fatty acids ukuya kwi-mitochondria ukuze i-oxidative bole. I-Urolithin A ikhuthaza i-β-oxidation yee-fatty acids ngokusebenzisa i-CPT-1, inyusa ukusetyenziswa kwamandla amafutha, inceda ekunciphiseni ukugcinwa kwamafutha emzimbeni, kwaye iphucula imetabolism ye-lipids.

3. Ukuphucula imetabolism yamandla kunye nokuphucula ukusebenza kwe-mitochondrial

I-Mitochondria "ziifektri zamandla" zeeseli, kwaye i-urolithin A inokuphucula ukusebenza kwe-mitochondria. Ingalawula i-mitochondrial biogenesis kwaye ikhuthaze ukwenziwa kunye nokuhlaziywa kwe-mitochondrial. Umzekelo, ingenza i-peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) isebenze.

I-PGC-1α ngumlawuli ophambili we-mitochondrial biogenesis, enokukhuthaza ukuphindaphinda kwe-mitochondrial DNA kunye nokuhlanganiswa kweeproteni ezinxulumene ne-mitochondrial. I-Urolithin A yonyusa inani kunye nomgangatho we-mitochondria kwaye iphucula ukusebenza kakuhle kwemveliso yamandla eeseli ngokusebenzisa i-PGC-1α. Kwangaxeshanye, i-urolithin A inokuphucula umsebenzi we-respiration chain ye-mitochondria kwaye yonyuse ukwenziwa kwe-adenosine triphosphate (ATP).

4. Ukulawula uHlaziyo lweMetabolic yeSeli

I-Urolithin A ingakhokela iiseli ukuba ziphinde zicwangciswe ngokutsha kwe-metabolic, nto leyo eyenza ukuba i-metabolism yeseli isebenze kakuhle. Phantsi kweemeko ezithile zoxinzelelo okanye zesifo, ipateni ye-metabolism yeseli inokutshintsha, nto leyo ekhokelela ekunciphiseni ukusebenza kakuhle kwemveliso yamandla kunye nokuhlanganiswa kwezinto.

I-Urolithin A inokulawula iindlela zokubonisa i-metabolic kwiiseli, njenge-AMP-activated protein kinase (AMPK) signaling pathway. I-AMPK "sisiva" se-cell energy metabolism. Emva kokuba i-urolithin A isebenze i-AMPK, inokubangela ukuba iiseli zitshintshe kwi-anabolism ziye kwi-catabolism, zisebenzise amandla kunye nezondlo ngokufanelekileyo, ngaloo ndlela ziphucula umsebenzi we-metabolic iyonke.

Ukusetyenziswa kwe-urolithin A akupheleli nje kwicandelo lezonyango. Kwakhona ifumana ingqalelo kancinci kancinci kwiimveliso zempilo kunye nezinto zokuthambisa. I-Urolithin A yongezwa kwiimveliso ezininzi zempilo ukuze kuphuculwe amasosha omzimba, kuphuculwe ukujikeleza kwegazi kwaye kukhuthazwe imetabolism. Ezi mveliso zihlala zikwimo yeekhaphu, iipilisi okanye ulwelo, ezifanelekileyo kwiimfuno zamaqela ahlukeneyo abantu.

Kwicandelo lezinto zokuthambisa, i-urolithin A isetyenziswa kakhulu kwiimveliso zokhathalelo lolusu ngenxa yokuvuselelwa kweeseli zayo kunye neempawu zayo zokulwa nokwaluphala. Ingaphucula ukujikeleza kwegazi eluswini kwaye ikhuthaze ukwenziwa kwe-collagen, ngaloo ndlela iphucula ukuthamba nokukhanya kolusu. Iimpawu ezininzi zokhathalelo lolusu ezikumgangatho ophezulu ziqalile ukusebenzisa i-urolithin A njengesithako esiphambili ukuqalisa iimveliso zokulwa nokwaluphala, ukulungisa kunye nokufumisa ulusu ukuze kuhlangatyezwane nokufuna kwabathengi ulusu oluhle.

Ukuqukumbela, njengesithako esisebenzayo kwi-bioactive esinemisebenzi emininzi, i-urolithin A ibonise amathuba amaninzi okusetyenziswa kwicandelo lezonyango, ukhathalelo lwempilo kunye nobuhle. Ngokukhula kophando lwesayensi, icandelo lokusetyenziswa kwe-urolithin A liya kuqhubeka likhula, libonelela ngeendlela ezininzi zempilo nobuhle babantu.