Ndezvipi mhedzisiro yemashiripiti uye mabasa eurolithin A? Ndezvipi zvigadzirwa zvinowedzerwa

 Urolithin A chinhu chakakosha chinoshandiswa zvakanyanya mukurapa nekuchengetedza hutano. Ienzyme inonyanya kugadzirwa neitsvo uye ine basa rekunyungudutsa magaro eropa. Mhedzisiro yemashiripiti nemabasa eUrolithin A zvinonyanya kuratidzwa muzvinhu zvinotevera.

Urolithin A inodzivirira kuora kwetsandanyama

1. Kurudzira kugadzirwa kwemapuroteni emhasuru uye shandisa nzira yekutumira chiratidzo yemTOR

Chinangwa chenzira yekutumira zviratidzo yerapamycin (mTOR) inzira huru yekugadzirisa kugadzirwa kwemapuroteni emhasuru. Urolithin A inogona kumutsa nzira yekutumira zviratidzo yemTOR uye kukurudzira kugadzirwa kwemapuroteni mumasero emhasuru.

mTOR inogona kunzwa zviratidzo zvakaita sekudya zvinovaka muviri uye zvinhu zvinokura mumasero. Kana yashanda, inotanga mamorekuru akawanda ezviratidzo, akadai se ribosomal protein S6 kinase (S6K1) uye eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). Urolithin A inomutsa mTOR, ichiisa phosphorylating S6K1 uye 4E-BP1, nokudaro ichikurudzira kutanga kwekushandurwa kwe mRNA uye kuungana kwe ribosome, uye ichikurumidzisa kugadzirwa kweprotein.

Semuenzaniso, mukuyedza nemasero emhasuru akakurira mu vitro, mushure mekuwedzera urolithin A, zvakaonekwa kuti huwandu hwephosphorylation yemTOR nemamorekuru ayo ekuratidza zviratidzo hwakawedzera, uye kuratidzwa kwezviratidzo zvekugadzira mapuroteni emhasuru (senge myosin heavy chain) kwakawedzera.
Inodzora tsandanyama-yakanangana nekunyorwa kwechinhu chinoshandiswa mutsandanyama

Urolithin A inogona kudzora kuratidzwa kwetsandanyama dzinoenderana netsandanyama dzinodiwa pakugadzirwa kwemapuroteni emhasuru uye kupatsanurwa kwemasero emhasuru. Semuenzaniso, inogona kuwedzera kuratidzwa kwe myogenic differentiation factor (MyoD) uye myogenin.

MyoD neMyogenin zvinogona kukurudzira kupatsanurwa kwemasero emhasuru kuita masero emhasuru uye zvinomutsa kuratidzwa kwemajini emhasuru, nokudaro zvichikurudzira kugadzirwa kwemapuroteni emhasuru. Mumuenzaniso wekushaya simba kwemhasuru, mushure mekurapwa kweurolithin A, kuratidzwa kweMyoD neMyogenin kwakawedzera, izvo zvinobatsira kuchengetedza huremu hwemhasuru uye kudzivirira kudzikira kwemhasuru.

2. Dzivirirai kuputsika kwemapuroteni emhasuru uye dzivirirai ubiquitin-proteasome system (UPS)

UPS ndeimwe yenzira huru dzekuparadza mapuroteni emhasuru. Munguva yekuora kwemhasuru, mamwe maE3 ubiquitin ligases, akadai semuscle atrophy F-box protein (MAFbx) uye muscle RING finger protein 1 (MuRF1), anotanga kushanda, izvo zvinogona kuisa mapuroteni emhasuru muumbi neumbiquitin uye zvobva zvaaparadza kuburikidza neproteasome.

Urolithin A inogona kudzivirira kuratidzwa uye kushanda kweaya maE3 ubiquitin ligases. Mukuyedza kwemhando yemhuka, urolithin A inogona kuderedza huwandu hweMAFbx neMuRF1, kuderedza chiratidzo cheubiquitination chemapuroteni emhasuru, nokudaro ichidzivisa kuora kwemapuroteni emhasuru anokonzerwa neUPS uye kudzivirira kudzikira kwemhasuru zvinobudirira.

Kuchinja kwe autophagy-lysosomal system (ALS)

ALS ine basa guru mukuvandudzwa kwemapuroteni emhasuru uye maorganelles, asi kushanda zvakanyanya kunogonawo kukonzera kupera simba kwemhasuru. Urolithin A inogona kudzora ALS kusvika padanho rakakodzera. Inogona kudzivirira autophagy yakawandisa uye kudzivirira kuora kwakanyanya kwemapuroteni emhasuru.
Semuenzaniso, urolithin A inogona kudzora kuratidzwa kwemapuroteni ane chekuita neautophagy (akadai seLC3-II), kuitira kuti igone kuchengetedza homeostasis yenzvimbo yemasero emhasuru uku ichidzivirira kubviswa kwemapuroteni emhasuru zvakanyanya, nokudaro ichibatsira kuchengetedza huremu hwemhasuru.

3. Kuvandudza simba rekushandiswa kwemasero emhasuru

Kusunga tsandanyama kunoda simba rakawanda, uye mitochondria ndiyo nzvimbo huru yekugadzira simba. Urolithin A inogona kuwedzera mashandiro emasero emhasuru mitochondria uye kuvandudza mashandiro ekugadzira simba. Inogona kukurudzira mitochondria biogenesis uye kuwedzera huwandu hwemitochondria.

Semuenzaniso, urolithin A inogona kumutsa peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), iyo inonyanya kudzora mitochondrial biogenesis, ichikurudzira mitochondrial DNA replication uye mapuroteni ane hukama. Panguva imwe chete, urolithin A inogonawo kuvandudza mashandiro emitochondrial respiratory chain, kuwedzera kugadzirwa kweadenosine triphosphate (ATP), kupa simba rakakwana rekudzikira kwetsandanyama, uye kuderedza kudzikira kwetsandanyama kunokonzerwa nekushaikwa kwesimba.

Inodzora metabolism yeshuga uye mafuta uye inotsigira mashandiro emhasuru

Urolithin A inogona kudzora glucose uye lipid metabolism yemasero emhasuru. Panyaya ye glucose metabolism, inogona kuwedzera kutorwa nekushandiswa kweglucose nemasero emhasuru, uye kuve nechokwadi chekuti masero emhasuru ane simba rakakwana nekushandisa insulin signaling pathway kana dzimwe nzira dze glucose transport-related signaling pathway.

Panyaya yekushandiswa kwemafuta mumuviri, urolithin A inogona kukurudzira oxidation yemafuta, ichipa imwe nzira yekusimbisa tsandanyama. Nekuvandudza kushandiswa kweglucose nemafuta mumuviri, urolithin A inochengetedza simba remasero emhasuru uye inobatsira kudzivirira kudzikira kwetsandanyama.

Urolithin A inovandudza metabolism

1. Gadzirisa kushandiswa kweshuga mumuviri uye kuvandudza kunzwa kwe insulin
Urolithin A inogona kuwedzera kunzwa kwe insulin, iyo inokosha pakuchengetedza kugadzikana kweshuga muropa. Inogona kushanda pamamorekuru akakosha ari munzira yekuzivisa insulin, akadai semapuroteni e insulin receptor substrate (IRS).

Kana insulin isingashande zvakanaka, tyrosine phosphorylation yeproteni yeIRS inodziviswa, zvichikonzera kutadza kushanda zvakanaka kwenzira yekutumira masaini yephosphatidylinositol 3-kinase (PI3K) pasi pemasero, uye mhinduro yemasero ku insulin inodzikira.

Urolithin A inogona kukurudzira tyrosine phosphorylation yeproteni yeIRS, nokudaro ichitanga kushanda kwePI3K-protein kinase B (Akt) signaling pathway, zvichiita kuti masero akwanise kupinza nekushandisa glucose zviri nani. Semuenzaniso, mukuyedza kwemhando yemhuka, mushure mekupiwa urolithin A, kunzwa kwetsandanyama nemafuta kune insulin kwakavandudzika zvakanyanya, uye huwandu hweshuga muropa hwakadzorwa zvinobudirira.

Inodzora kugadzirwa kweglycogen uye kuora kwayo

Glycogen ndiyo nzira huru yekuchengetera shuga mumuviri, inonyanya kuchengetwa muchiropa netsandanyama. Urolithin A inogona kudzora kugadzirwa nekuora kweglycogen. Inogona kumutsa glycogen synthase, kukurudzira kugadzirwa kweglycogen, uye kuwedzera huwandu hweglycogen.

Panguva imwe chete, urolithin A inogonawo kudzivirira kushanda kwema enzymes e glycogenolytic, akadai se glycogen phosphorylase, uye kuderedza huwandu hwe glycogen inoora kuita glucose yoburitswa muropa. Izvi zvinobatsira kudzikamisa huwandu hweshuga muropa uye kudzivirira kuchinja-chinja kwakanyanya kweshuga muropa. Muchidzidzo chemuenzaniso wechirwere cheshuga, mushure mekurapwa kwe urolithin A, huwandu hwe glycogen muchiropa netsandanyama hwakawedzera, uye kudzora shuga muropa kwakavandudzika.

2. Gadzirisa metabolism yemafuta uye dzivisa kugadzirwa kwemafuta acid

Urolithin A ine simba rekudzivirira kugadzirwa kwemafuta mumuviri. Muchiropa nemafuta, inogona kudzivirira ma enzyme akakosha mukugadzirwa kwemafuta, akadai se fatty acid synthase (FAS) uye acetyl-CoA carboxylase (ACC).

FAS neACC ma enzyme akakosha mukugadzira mafuta acids. Urolithin A inogona kuderedza kugadzirwa kwemafuta acids nekudzikisa kushanda kwawo. Semuenzaniso, mumuenzaniso wechiropa chine mafuta anokonzerwa nekudya kune mafuta akawanda, urolithin A inogona kuderedza kushanda kweFAS neACC muchiropa, kuderedza kugadzirwa kwetriglycerides, uye nokudaro kuderedza kuunganidzwa kwemafuta muchiropa.

Inokurudzira oxidation yemafuta acid

Pamusoro pekudzivisa kugadzirwa kwemafuta acid, urolithin A inogonawo kukurudzira kuora kwemafuta acids. Inogona kumutsa nzira dzekutumira masaini uye ma enzyme ane chekuita neoxidation yemafuta acid. Semuenzaniso, inogona kuwedzera mashandiro ecarnitine palmitoyltransferase-1 (CPT-1).

CPT-1 ienzyme inokosha mu fatty acid β-oxidation, iyo inotarisira kutakura fatty acids kuenda ku mitochondria kuti iparare oxidative. Urolithin A inokurudzira β-oxidation ye fatty acids nekuita kuti CPT-1 ishande, inowedzera kushandiswa kwesimba remafuta, inobatsira kuderedza kuchengetwa kwemafuta mumuviri, uye inovandudza metabolism yemafuta mumuviri.

3. Kuvandudza kushandiswa kwesimba uye kusimudzira mashandiro emitochondrial

Mitochondria ndiwo "mafekitori esimba" emasero, uye urolithin A inogona kuwedzera mashandiro emitochondria. Inogona kudzora mitochondria biogenesis uye kukurudzira kugadzirwa kwemitochondria nekuvandudzwa. Semuenzaniso, inogona kumutsa peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α).

PGC-1α chinhu chakakosha mukutonga mitochondrial biogenesis, izvo zvinogona kukurudzira kudzokororwa kweDNA yemitochondrial uye kugadzirwa kwemapuroteni ane chekuita nemitochondrial. Urolithin A inowedzera huwandu uye mhando yemitochondria uye inovandudza kushanda kwesimba remasero nekushandisa PGC-1α. Panguva imwe chete, urolithin A inogona zvakare kuvandudza mashandiro ekufema kwemitochondria uye kuwedzera kugadzirwa kweadenosine triphosphate (ATP).

4. Kudzora Kugadziriswazve kweMasero eMetabolic

Urolithin A inogona kutungamira masero kuti agadziriswezve mashandiro emuviri, zvichiita kuti mashandiro emuviri wesero ashande zvakanaka. Kana paine kushushikana kana chirwere, maitiro emuviri wesero anogona kuchinja, zvichikonzera kudzikira kwekushanda kwesimba mukugadzirwa kwesimba uye kugadzirwa kwezvinhu.

Urolithin A inogona kudzora nzira dzekutumira zviratidzo mumasero, dzakadai seAMP-activated protein kinase (AMPK) signaling pathway. AMPK i "sensor" yekushandiswa kwesimba remasero. Mushure mekunge urolithin A yatanga kushanda AMPK, inogona kukurudzira masero kuti achinje kubva pa anabolism kuenda ku catabolism, zvichiita kuti simba nezvinovaka muviri zvishandiswe zvakanaka, nokudaro zvichivandudza mashandiro e metabolic.

Kushandiswa kwe urolithin A hakugumiri pakurapa chete. Zviri kuwedzerawo kutariswa zvishoma nezvishoma muzvigadzirwa zvehutano nezvizoro. Urolithin A inowedzerwa muzvigadzirwa zvakawanda zvehutano kuti iwedzere dziviriro yemuviri, ivandudze kutenderera kweropa uye inokurudzira metabolism. Zvigadzirwa izvi zvinowanzova muchimiro chemakapisi, mapiritsi kana zvinwiwa, zvakakodzera mapoka akasiyana evanhu.

Muchikamu chezvizoro, urolithin A inoshandiswa zvakanyanya muzvigadzirwa zvekuchengetedza ganda nekuda kwekuvandudzwa kwemasero ayo uye hunhu hwayo hwekudzivirira kukwegura. Inogona kuvandudza kutenderera kweropa muganda uye kukurudzira kugadzirwa kwecollagen, nokudaro ichivandudza kutwasuka kweganda uye kupenya kwaro. Makambani mazhinji ekuchengetedza ganda epamusoro-soro atanga kushandisa urolithin A sechinhu chikuru chekugadzira zvigadzirwa zvinodzivirira kukwegura, kugadzirisa uye kunyorovesa kuti zvigutse vatengi vari kutsvaga ganda rakanaka.

Mukupedzisa, sechinobatika mumuviri chine mabasa akawanda, urolithin A yakaratidza mikana yakawanda yekushandiswa muminda yekurapa, hutano uye runako. Nekuwedzera kwekutsvaga kwesainzi, nzvimbo yekushandisa urolithin A icharamba ichikura, ichipa sarudzo dzakawanda dzehutano nerunako rwevanhu.