Ni izihe ngaruka zubumaji nibikorwa bya urolithin A? Nibihe bicuruzwa byongeweho

 Urolithin A ni ikintu cyingenzi cyibinyabuzima gikoreshwa cyane mubuvuzi no kwita kubuzima. Ni enzyme ikorwa cyane cyane nimpyiko kandi ifite umurimo wo gushonga amaraso. Ingaruka zubumaji nibikorwa bya Urolithin A bigaragarira cyane mubice bikurikira.

Urolithin A irinda kwangirika kwimitsi

1. Gutezimbere intungamubiri za poroteyine no gukora mTOR yerekana inzira

Intego y’inyamabere ya rapamycin (mTOR) yerekana inzira ninzira yingenzi yo kugenzura intungamubiri za poroteyine. Urolithin A irashobora gukora mTOR yerekana inzira kandi igatera intungamubiri za poroteyine mu ngirabuzimafatizo.

mTOR irashobora kumva ibimenyetso nkintungamubiri nibintu bikura muri selile. Iyo ikora, izatangira urukurikirane rwibintu byerekana ibimenyetso bya molekile, nka poroteyine ya ribosomal S6 kinase (S6K1) hamwe na eukaryotic yo gutangiza ibintu 4E-ihuza poroteyine 1 (4E-BP1). Urolithin A ikora mTOR, fosifora S6K1 na 4E-BP1, bityo igateza imbere mRNA yo gutangiza no guteranya ribosome, no kwihutisha intungamubiri za poroteyine.

Kurugero, mubushakashatsi bwakozwe na vitro zifite imitsi ya vitamine zifite umuco, nyuma yo kongeramo urolithine A, byagaragaye ko urugero rwa fosifora ya mTOR hamwe na molekile yo hepfo yerekana ibimenyetso bya molekile byiyongereye, kandi imvugo yerekana ibimenyetso bya sintezamubiri ya protein (nk'urunigi ruremereye rwa myosine) yariyongereye.
Igenga imitsi yihariye yo kwandukura ibintu

Urolithin A. Irashobora kugenzura imvugo yimitsi yihariye yo kwandikirana ingirakamaro muguhindura imitsi ya protein no gutandukanya imitsi. Kurugero, irashobora kugenzura imvugo yibintu bitandukanya myogenic (MyoD) na myogenin.

MyoD na Myogenin birashobora guteza imbere gutandukanya ingirangingo z'imitsi mu ngirabuzimafatizo no gukora imvugo ya genes yihariye, bityo bigatera intungamubiri za poroteyine. Muri moderi ya atrophy yimitsi, nyuma ya urolithin Ubuvuzi, imvugo ya MyoD na Myogenin yariyongereye, ifasha kugumana imitsi no kwirinda kugabanuka kwimitsi.

2. Kubuza kwangirika kwa poroteyine yimitsi no kubuza sisitemu ya ubiquitin-proteasome (UPS)

UPS ni imwe mu nzira nyamukuru zo kwangirika kwa poroteyine. Mugihe cyimitsi yimitsi, ligase zimwe na zimwe za E3 ubiquitin, nka atrophy yimitsi ya F-box protein (MAFbx) hamwe na proteine ​​RING urutoki rwa poroteyine 1 (MuRF1), zirakora, zishobora kuranga poroteyine yimitsi hamwe na ubiquitin hanyuma ikayitesha agaciro binyuze muri proteasome.

Urolithin A irashobora guhagarika imvugo nigikorwa cyiyi E3 ubiquitin ligase. Mu bushakashatsi bw’icyitegererezo cy’inyamaswa, urolithin A irashobora kugabanya urwego rwa MAFbx na MuRF1, igabanya ibimenyetso bya poroteyine zo mu mitsi hose, bityo bikabuza kwangirika kwa poroteyine UPS yifashishijwe no kwirinda imitsi.

Guhindura sisitemu ya autophagy-lysosomal (ALS)

ALS igira uruhare mukuvugurura poroteyine n'imitsi, ariko gukora cyane birashobora no gutuma imitsi itabaho. Urolithin A irashobora kugenga ALS kurwego rwumvikana. Irashobora kubuza autofagy ikabije kandi ikarinda kwangirika gukabije kwa poroteyine.
Kurugero, urolithine A irashobora kugenga imvugo ya poroteyine ziterwa na autofagy (nka LC3-II), kugirango ibashe gukomeza homeostasis yimiterere yimitsi yimitsi mugihe yirinze gukuraho poroteyine nyinshi, bityo bigafasha kugumana imitsi.

3. Kunoza imbaraga metabolism yingirabuzimafatizo

Kugabanuka kw'imitsi bisaba imbaraga nyinshi, kandi mitochondriya nicyo kibanza nyamukuru gitanga ingufu. Urolithin A irashobora kongera imikorere yimitsi mitochondriya yimitsi no kunoza umusaruro. Irashobora guteza imbere mitochondrial biogenez no kongera umubare wa mitochondria.

Kurugero, urolithin A irashobora gukora peroxisome prolifator-ikora reseptor γ coactivator-1α (PGC-1α), ikaba ari igenzura rikomeye rya biogenezi ya mitochondrial, iteza imbere kwigana ADN ya mitochondial hamwe na sintezamubiri ya poroteyine. Muri icyo gihe, urolithine A irashobora kandi kunoza imikorere yumuyoboro wubuhumekero wa mitochondrial, kongera synthesis ya adenosine triphosphate (ATP), gutanga imbaraga zihagije zo kugabanuka kwimitsi, no kugabanya imitsi iterwa ningufu zidahagije.

Igenga isukari na lipide metabolism kandi ishyigikira imikorere yimitsi

Urolithin A irashobora kugenga glucose na lipid metabolism ya selile yimitsi. Kubijyanye na glucose metabolism, irashobora kongera gufata no gukoresha glucose ningirangingo zimitsi, kandi ikemeza ko ingirangingo z'imitsi zifite insimburangingo zihagije mugukoresha inzira ya insuline yerekana inzira cyangwa izindi nzira zijyanye no gutwara glucose.

Kubijyanye na lipid metabolism, urolithin A irashobora guteza imbere okiside ya aside irike, itanga indi soko yingufu zo kugabanuka kwimitsi. Muguhindura glucose na lipid metabolism, urolithin A ikomeza ingufu zingirabuzimafatizo kandi ifasha kwirinda kugabanuka kwimitsi.

Urolithin A itezimbere metabolism

1.Genzura isukari metabolisme kandi utezimbere insuline
Urolithine A irashobora kongera insuline ikenera insuline, ikaba ari ngombwa mu gukomeza isukari mu maraso. Irashobora gukora kuri molekile zingenzi munzira yerekana insuline, nka proteine ​​insuline insuline (IRS).

Muri leta irwanya insuline, fosifori ya tyrosine ya poroteyine ya IRS irabujijwe, bikaviramo kunanirwa kwa fosifatidylinositol 3-kinase (PI3K) byerekana inzira yo gukora bisanzwe, kandi igisubizo cyakagari kuri insuline kiracika intege.

Urolithin A irashobora guteza imbere fosifori ya tirozine ya poroteyine ya IRS, bityo igakora inzira ya PI3K-protein kinase B (Akt) yerekana inzira, bigatuma selile zifata neza kandi zigakoresha glucose. Kurugero, mubushakashatsi bwikitegererezo cyinyamanswa, nyuma yubuyobozi bwa urolithine A, ibyiyumvo byimitsi hamwe na adipose tissue kuri insuline byateye imbere cyane, kandi isukari yamaraso yagenzuwe neza.

Igenga synthesis ya glycogene no gutesha agaciro

Glycogene nuburyo nyamukuru bwo kubika glucose mu mubiri, cyane cyane ibikwa mu mwijima no mu ngingo. Urolithin A irashobora kugenga synthesis no kubora kwa glycogene. Irashobora gukora glycogene synthase, igatera synthesis ya glycogene, kandi ikongera ububiko bwa glycogene.

Muri icyo gihe, urolithine A irashobora kandi guhagarika ibikorwa byimisemburo ya glycogenolytike, nka fosifori ya glycogene, ikanagabanya urugero rwa glycogene yangirika muri glucose ikarekurwa mu maraso. Ibi bifasha guhagarika urugero rwisukari rwamaraso no kwirinda ihindagurika ryinshi ryisukari yamaraso. Mu bushakashatsi bw’icyitegererezo cya diyabete, nyuma yo kuvura urolithine A, glycogene iri mu mwijima no mu mitsi yariyongereye, kandi isukari yo mu maraso iratera imbere.

2. Hindura metabolisme ya lipide kandi uhagarike synthesis ya fatty

Urolithin A igira ingaruka zo kubuza inzira ya lipide. Mu mwijima no mu mubiri wa adipose, irashobora guhagarika imisemburo yingenzi muri synthesis ya fatty acide, nka synthase ya fatty acide (FAS) na acetyl-CoA carboxylase (ACC).

FAS na ACC ni enzymes zingenzi zigenga muri de novo synthesis ya acide acide. Urolithin A irashobora kugabanya synthesis ya acide acide muguhagarika ibikorwa byabo. Kurugero, muburyo bwumwijima bwumwijima buterwa nimirire yuzuye amavuta, urolithine A irashobora kugabanya ibikorwa bya FAS na ACC mumwijima, kugabanya synthesis ya triglyceride, bityo bikagabanya kwirundanya kwa lipide mumwijima.

Itera aside irike

Usibye guhagarika aside irike, urolithine A irashobora kandi guteza imbere kwangirika kwa okiside ya aside irike. Irashobora gukora inzira yerekana inzira na enzymes zijyanye na aside irike. Kurugero, irashobora kugenzura ibikorwa bya karnitine palmitoyltransferase-1 (CPT-1).

CPT-1 ni enzyme yingenzi muri aside irike β-okiside, ishinzwe gutwara aside irike muri mitochondriya kugirango ibashe kwangirika. Urolithin A iteza β-okiside ya aside irike ikora CPT-1, ikongera ingufu zamavuta, ifasha kugabanya ibinure byumubiri, kandi igahindura metabolisme ya lipide.

3. Kunoza imbaraga za metabolism no kongera imikorere ya mito-iyambere

Mitochondria ni "inganda zingufu" za selile, kandi urolithine A irashobora kongera imikorere ya mitochondria. Irashobora kugenga ibinyabuzima bya mitochondrial no guteza imbere synthesis ya mitochondrial no kuvugurura. Kurugero, irashobora gukora peroxisome prolifator-ikora reseptor gamma coactivator-1α (PGC-1α).

PGC-1α ni urufunguzo rwingenzi rwa biogenezi ya mitochondial, rushobora guteza imbere kwigana ADN ya mito-iyambere hamwe no guhuza poroteyine zifitanye isano na mito-iyambere. Urolithin A yongera umubare nubwiza bwa mitochondriya kandi igateza imbere ingufu zingirabuzimafatizo zikora PGC-1α. Muri icyo gihe, urolithin A irashobora kandi kunoza imikorere yubuhumekero bwa mitochondria no kongera synthesis ya adenosine triphosphate (ATP).

4. Kugena gahunda ya Cellular Metabolic Reprogramming

Urolithin A irashobora kuyobora selile gukora progaramu ya metabolike, bigatuma metabolism ya selile ikora neza. Mugihe cy'imihangayiko cyangwa indwara zimwe na zimwe, imiterere ya metabolike ya selile irashobora guhinduka, bigatuma umusaruro ugabanuka mubikorwa byingufu hamwe na synthesis.

Urolithin A irashobora kugenga inzira yerekana ibimenyetso bya metabolike mu ngirabuzimafatizo, nka poroteyine ya AMP ikoreshwa na poroteyine kinase (AMPK) yerekana inzira. AMPK ni "sensor" yingufu za selile metabolism. Nyuma ya urolithin A ikora AMPK, irashobora gutuma ingirabuzimafatizo ziva muri anabolism zikajya muri catabolisme, zigakoresha neza ingufu nintungamubiri, bityo bigatuma imikorere ya metabolike muri rusange.

Gukoresha urolithin A ntabwo bigarukira gusa mubuvuzi. Igenda kandi yitabwaho buhoro buhoro mubicuruzwa byubuzima no kwisiga. Urolithin A yongewe kubicuruzwa byinshi byubuzima kugirango byongere ubudahangarwa, kunoza amaraso no guteza imbere metabolism. Ibicuruzwa mubisanzwe biri muburyo bwa capsules, ibinini cyangwa amazi, bikwiranye nibyifuzo byabantu batandukanye.

Mu rwego rwo kwisiga, urolithin A ikoreshwa cyane mubicuruzwa byita ku ruhu bitewe no kuvugurura ingirabuzimafatizo no kurwanya gusaza. Irashobora guteza imbere umuvuduko wamaraso muruhu kandi igatera synthesis ya kolagen, bityo igahindura uruhu rworoshye kandi rukayangana. Ibirango byinshi byo murwego rwohejuru byita ku ruhu byatangiye gukoresha urolithine A nkibintu byingenzi kugirango utangire ibicuruzwa birwanya gusaza, gusana no gutanga amazi kugirango abakiriya babone uruhu rwiza.

Mu gusoza, nkibintu bioaktike ifite imirimo myinshi, urolithin A yerekanye uburyo bwagutse bwo gukoresha mubijyanye n'ubuvuzi, ubuvuzi n'ubwiza. Hamwe nubushakashatsi bwimbitse, ubushakashatsi bwa urolithin A buzakomeza kwaguka, butange amahitamo menshi kubuzima nubwiza bwabantu.