Kodi zamatsenga ndi ntchito za urolithin A ndi ziti? Zomwe zimawonjezeredwa

 Urolithin A ndi chinthu chofunikira kwambiri cha bioactive chomwe chimagwiritsidwa ntchito kwambiri muzamankhwala ndi chisamaliro chaumoyo. Ndi puloteni yomwe imapangidwa makamaka ndi impso ndipo imakhala ndi ntchito yosungunula magazi. Zotsatira zamatsenga ndi ntchito za Urolithin A zimawonekera makamaka m'mbali zotsatirazi.

Urolithin A imalepheretsa kuwonongeka kwa minofu

1. Limbikitsani kaphatikizidwe ka mapuloteni a minofu ndikuyambitsa njira yowonetsera mTOR

Cholinga cha mammalian cha rapamycin (mTOR) ndi njira yofunikira pakuwongolera kaphatikizidwe ka mapuloteni a minofu. Urolithin A ikhoza kuyambitsa njira yowonetsera mTOR ndikulimbikitsa kaphatikizidwe ka mapuloteni m'maselo a minofu.

mTOR amatha kuzindikira zizindikiro monga zakudya ndi kukula kwa maselo. Ikatsegulidwa, imayamba mamolekyu angapo oyambira pansi, monga ribosomal protein S6 kinase (S6K1) ndi eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). Urolithin A imayambitsa mTOR, phosphorylating S6K1 ndi 4E-BP1, motero imalimbikitsa kuyambitsa kumasulira kwa mRNA ndi msonkhano wa ribosome, ndikufulumizitsa kaphatikizidwe ka mapuloteni.

Mwachitsanzo, poyesera ma cell a mu vitro cultured muscle, atatha kuwonjezera urolithin A, adawona kuti phosphorylation milingo ya mTOR ndi mamolekyu ake owonetsa kumunsi akuwonjezeka, ndipo kufotokozera kwa zizindikiro za mapuloteni a minofu (monga myosin heavy chain) zinawonjezeka.
Imawongolera mawu amtundu wina wa minofu

Urolithin A ikhoza kuwongolera kufotokozera kwa zinthu zolembera za minofu zomwe ndizofunikira pakupanga mapuloteni a minofu ndi kusiyana kwa maselo a minofu. Mwachitsanzo, imatha kuwongolera mawu a myogenic differentiation factor (MyoD) ndi myogenin.

MyoD ndi Myogenin zimatha kulimbikitsa kusiyana kwa maselo amtundu wa minofu kukhala maselo a minofu ndi kuyambitsa mafotokozedwe a majini enieni a minofu, potero kulimbikitsa kaphatikizidwe ka mapuloteni a minofu. Mu chitsanzo cha atrophy ya minofu, pambuyo pa chithandizo cha urolithin A, mawu a MyoD ndi Myogenin adawonjezeka, zomwe zimathandiza kusunga minofu ndikuletsa kuchepa kwa minofu.

2. Kuletsa kuwonongeka kwa mapuloteni a minofu ndikuletsa ubiquitin-proteasome system (UPS)

UPS ndi imodzi mwa njira zazikulu zochepetsera mapuloteni a minofu. Panthawi ya atrophy ya minofu, E3 ubiquitin ligases, monga minofu atrophy F-box protein (MAFbx) ndi minofu RING chala mapuloteni 1 (MuRF1), amatsegulidwa, omwe amatha kulemba mapuloteni a minofu ndi ubiquitin ndiyeno amawasokoneza kudzera mu proteasome.

Urolithin A ikhoza kulepheretsa kufotokoza ndi ntchito za E3 ubiquitin ligases. M'mayesero a zinyama, urolithin A akhoza kuchepetsa mlingo wa MAFbx ndi MuRF1, kuchepetsa chizindikiro cha ubiquitination cha mapuloteni a minofu, motero amalepheretsa kuwonongeka kwa mapuloteni a UPS-mediated minofu ndikuletsa bwino kuchepa kwa minofu.

Kusintha kwa autophagy-lysosomal system (ALS)

ALS imathandizira kukonzanso kwa mapuloteni a minofu ndi organelles, koma kuchitapo kanthu kungayambitsenso minofu atrophy. Urolithin A imatha kuwongolera ALS pamlingo woyenera. Ikhoza kulepheretsa autophagy yambiri ndikuletsa kuwonongeka kwakukulu kwa mapuloteni a minofu.
Mwachitsanzo, urolithin A imatha kuwongolera mafotokozedwe a mapuloteni okhudzana ndi autophagy (monga LC3-II), kotero kuti athe kukhalabe ndi homeostasis ya chilengedwe cha cell cell ndikupewa kutulutsa kwamphamvu kwa mapuloteni a minofu, potero kuthandizira kusunga minofu.

3. Kupititsa patsogolo mphamvu ya metabolism ya maselo a minofu

Kuthamanga kwa minofu kumafuna mphamvu zambiri, ndipo mitochondria ndi malo akuluakulu opanga mphamvu. Urolithin A imatha kupititsa patsogolo ntchito ya minofu ya mitochondria ndikuwongolera kupanga mphamvu. Ikhoza kulimbikitsa biogenesis ya mitochondrial ndikuwonjezera chiwerengero cha mitochondria.

Mwachitsanzo, urolithin A imatha kuyambitsa receptor γ coactivator-1α (PGC-1α) ya peroxisome proliferator (PGC-1α), yomwe imayendetsa mitochondrial biogenesis, kulimbikitsa kubwereza kwa DNA ya mitochondrial ndi kaphatikizidwe ka mapuloteni. Panthawi imodzimodziyo, urolithin A imathanso kupititsa patsogolo ntchito ya mitochondrial kupuma kwa mpweya, kuonjezera kaphatikizidwe ka adenosine triphosphate (ATP), kupereka mphamvu zokwanira kuti minofu ikhale yolimba, komanso kuchepetsa kuchepa kwa minofu chifukwa cha kuchepa kwa mphamvu.

Imawongolera shuga ndi lipid metabolism ndipo imathandizira kugwira ntchito kwa minofu

Urolithin A amatha kuyendetsa shuga ndi lipid metabolism m'maselo a minofu. Pankhani ya kagayidwe ka glucose, imatha kupititsa patsogolo kuyamwa ndi kugwiritsidwa ntchito kwa shuga ndi maselo am'minyewa, ndikuwonetsetsa kuti ma cell a minofu amakhala ndi mphamvu zokwanira poyambitsa njira yolumikizira insulin kapena njira zina zolumikizirana ndi glucose.

Pankhani ya lipid metabolism, urolithin A imatha kulimbikitsa mafuta acid oxidation, kupereka gwero linanso lamphamvu pakudumpha kwa minofu. Mwa kukhathamiritsa shuga ndi lipid metabolism, urolithin A imasunga mphamvu zama cell a minofu ndikuthandizira kupewa kuchepa kwa minofu.

Urolithin A imathandizira metabolism

1. Kuwongolera kagayidwe ka shuga ndikuwongolera chidwi cha insulin
Urolithin A imatha kukulitsa chidwi cha insulin, chomwe ndi chofunikira kuti shuga wamagazi akhazikike. Imatha kuchitapo kanthu pa mamolekyu ofunikira omwe ali m'njira yowonetsera insulin, monga mapuloteni a insulin receptor substrate (IRS).

Munthawi ya insulin kukana, tyrosine phosphorylation ya protein ya IRS imaletsedwa, zomwe zimapangitsa kulephera kwa njira yolozera ya phosphatidylinositol 3-kinase (PI3K) kuti iyambike bwino, ndipo kuyankha kwa selo ku insulin kumachepa.

Urolithin A imatha kulimbikitsa tyrosine phosphorylation ya mapuloteni a IRS, motero kuyambitsa PI3K-protein kinase B (Akt) njira yowonetsera, kupangitsa kuti maselo azitha kuyamwa bwino ndi kugwiritsa ntchito shuga. Mwachitsanzo, pakuyesa kwachitsanzo cha nyama, pambuyo poyendetsa urolithin A, kukhudzika kwa minofu ndi minofu ya adipose ku insulin kunasintha kwambiri, ndipo kuchuluka kwa shuga m'magazi kumayendetsedwa bwino.

Imawongolera kaphatikizidwe ka glycogen ndi kuwonongeka

Glycogen ndiye njira yayikulu yosungira shuga m'thupi, makamaka yosungidwa m'chiwindi ndi minofu. Urolithin A amatha kuwongolera kaphatikizidwe ndi kuwonongeka kwa glycogen. Imatha kuyambitsa glycogen synthase, kulimbikitsa kaphatikizidwe ka glycogen, ndikuwonjezera nkhokwe ya glycogen.

Nthawi yomweyo, urolithin A imathanso kulepheretsa ntchito ya michere ya glycogenolytic, monga glycogen phosphorylase, ndikuchepetsa kuchuluka kwa glycogen wowola kukhala shuga ndikutulutsidwa m'magazi. Izi zimathandiza kukhazikika kwa shuga m'magazi ndikuletsa kusinthasintha kwakukulu kwa shuga m'magazi. Pakufufuza kwachitsanzo cha matenda a shuga, pambuyo pa chithandizo cha urolithin A, kuchuluka kwa glycogen m'chiwindi ndi minofu kumawonjezeka, ndikuwongolera shuga wamagazi.

2. Konzani lipid metabolism ndikuletsa kaphatikizidwe ka mafuta acid

Urolithin A imakhala ndi zoletsa pakupanga lipid kaphatikizidwe. Mu chiwindi ndi minofu ya adipose, imatha kuletsa ma enzymes ofunikira mu kaphatikizidwe ka mafuta acid, monga fatty acid synthase (FAS) ndi acetyl-CoA carboxylase (ACC).

FAS ndi ACC ndi ma enzymes ofunikira mu de novo synthesis yamafuta acid. Urolithin A imatha kuchepetsa kaphatikizidwe kamafuta acid ndikulepheretsa ntchito yawo. Mwachitsanzo, m'chiwindi chamafuta omwe amapangidwa ndi zakudya zamafuta ambiri, urolithin A imatha kuchepetsa ntchito ya FAS ndi ACC m'chiwindi, kuchepetsa kaphatikizidwe ka triglycerides, motero kumachepetsa kuchuluka kwa lipid m'chiwindi.

Amathandizira kukhazikika kwamafuta acid

Kuphatikiza pa kuletsa kaphatikizidwe ka mafuta acid, urolithin A imatha kulimbikitsanso kuwonongeka kwa okosijeni kwamafuta acid. Ikhoza kuyambitsa njira zowonetsera ndi ma enzyme okhudzana ndi mafuta acid oxidation. Mwachitsanzo, ikhoza kupititsa patsogolo ntchito ya carnitine palmitoyltransferase-1 (CPT-1).

CPT-1 ndi puloteni yofunika kwambiri mumafuta acid β-oxidation, yomwe imayang'anira kutumiza mafuta acid kupita ku mitochondria kuti awonongeke. Urolithin A imalimbikitsa β-oxidation ya mafuta acids poyambitsa CPT-1, imawonjezera kugwiritsa ntchito mphamvu zamafuta, imathandizira kuchepetsa kusungidwa kwamafuta am'thupi, ndikuwongolera lipid metabolism.

3. Kupititsa patsogolo mphamvu ya metabolism ndikuwonjezera ntchito ya mitochondrial

Mitochondria ndi "mafakitale amphamvu" a maselo, ndipo urolithin A imatha kupititsa patsogolo ntchito ya mitochondria. Ikhoza kulamulira mitochondrial biogenesis ndikulimbikitsa kaphatikizidwe ka mitochondrial ndi kukonzanso. Mwachitsanzo, imatha kuyambitsa peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α).

PGC-1α ndiwowongolera kwambiri wa mitochondrial biogenesis, yomwe ingalimbikitse kubwereza kwa DNA ya mitochondrial ndi kaphatikizidwe ka mapuloteni okhudzana ndi mitochondrial. Urolithin A imawonjezera kuchuluka kwa mitochondria ndi mtundu wa mitochondria ndikuwongolera kupanga mphamvu zama cell poyambitsa PGC-1α. Panthawi imodzimodziyo, urolithin A imathanso kupititsa patsogolo ntchito ya mitochondria yopuma ndikuwonjezera kaphatikizidwe ka adenosine triphosphate (ATP).

4. Kuwongolera Ma Cellular Metabolic Reprogramming

Urolithin A imatha kutsogolera ma cell kuti ayambenso kukonza kagayidwe kachakudya, kupangitsa kuti kagayidwe kake ka cell kakhale kothandiza kwambiri. Pansi pa zovuta zina kapena matenda, kagayidwe kachakudya ka maselo amatha kusintha, zomwe zimapangitsa kuti pakhale kuchepa kwamphamvu pakupanga mphamvu komanso kaphatikizidwe kazinthu.

Urolithin A imatha kuyendetsa njira zowonetsera kagayidwe kachakudya m'maselo, monga AMP-activated protein kinase (AMPK) njira yowonetsera. AMPK ndi "sensor" ya ma cell metabolism. Urolithin A itayambitsa AMPK, imatha kuyambitsa ma cell kuchoka ku anabolism kupita ku catabolism, kugwiritsa ntchito bwino mphamvu ndi michere, potero kumapangitsa kuti kagayidwe kake kagwire ntchito bwino.

Kugwiritsa ntchito urolithin A sikungokhudza zachipatala zokha. Komanso pang'onopang'ono akupeza chidwi mu mankhwala mankhwala ndi zodzoladzola. Urolithin A amawonjezedwa kuzinthu zambiri zathanzi kuti apititse patsogolo chitetezo chamthupi, kusintha magazi komanso kulimbikitsa kagayidwe. Mankhwalawa nthawi zambiri amakhala ngati makapisozi, mapiritsi kapena zakumwa, oyenera zosowa zamagulu osiyanasiyana a anthu.

M'munda wa zodzoladzola, urolithin A imagwiritsidwa ntchito kwambiri pazinthu zosamalira khungu chifukwa cha kusinthika kwa ma cell komanso anti-kukalamba. Ikhoza kupititsa patsogolo kayendedwe ka magazi pakhungu ndikulimbikitsa kaphatikizidwe ka collagen, potero kumapangitsa kuti khungu likhale losalala komanso lowala. Mitundu yambiri yosamalira khungu yapamwamba yayamba kugwiritsa ntchito urolithin A ngati chinthu chofunikira kwambiri poyambitsa anti-kukalamba, kukonza ndi kunyowa kuti akwaniritse zofuna za ogula pakhungu lokongola.

Pomaliza, monga bioactive mankhwala ndi ntchito zingapo, urolithin A wasonyeza chiyembekezo ntchito mu mankhwala, chisamaliro chaumoyo ndi kukongola. Ndi kuzama kwa kafukufuku wa sayansi, gawo logwiritsira ntchito urolithin A lipitiriza kukula, kupereka zosankha zambiri za thanzi ndi kukongola kwa anthu.