Ndeapi mashiripiti mhedzisiro uye mabasa eurolithin A? Ndezvipi zvigadzirwa zvinowedzerwa

 Urolithin A chinhu chakakosha bioactive chinhu chinoshandiswa zvakanyanya mukurapa uye hutano hwehutano. Iyo enzyme inonyanya kugadzirwa neitsvo uye ine basa rekunyungudutsa magwamba eropa. Iwo mashiripiti mhedzisiro uye mabasa eUrolithin A anonyanya kuratidzwa mune zvinotevera zvinhu.

Urolithin A inodzivirira kuderera kwemhasuru

1. Kurudzira tsandanyama protein synthesis uye activate mTOR chiratidzo nzira

Chinangwa chemammalian cherapamycin (mTOR) nzira yekuratidzira ndiyo nzira yakakosha yekudzora tsandanyama protein synthesis. Urolithin A inogona kumisa iyo mTOR inoratidzira nzira uye kukurudzira mapuroteni synthesis mumaseru masero.

mTOR inogona kunzwa zviratidzo zvakadai sezvokudya uye kukura kwezvinhu mumasero. Kana yaitwa, inotanga nhevedzano yemamolekemu ekudzika pasi, akadai seribosomal protein S6 kinase (S6K1) uye eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). Urolithin A inomutsa mTOR, phosphorylating S6K1 uye 4E-BP1, nekudaro ichikurudzira kutangwa kweshanduro yemRNA uye kusangana kweribosome, uye nekumhanyisa mapuroteni synthesis.

Semuenzaniso, mukuedza ne in vitro cultured muscle cells, mushure mekuwedzera urolithin A, zvakaonekwa kuti phosphorylation mazinga e mTOR uye mamolekemu ayo ekudzika kwemvura akawedzera, uye kutaura kwemhasuru protein synthesis markers (yakadai semyosin heavy chain) yakawedzera.
Inogadzirisa tsandanyama-specific transcription factor expression

Urolithin A inogona kudzora mataurirwo emhasuru-chaiwo zvinyorwa zvinyorwa zvakakosha kune tsandanyama protein synthesis uye tsandanyama sero kusiyanisa. Semuenzaniso, inogona kusimudzira kutaura kwe myogenic differentiation factor (MyoD) uye myogenin.

MyoD neMyogenin zvinogona kusimudzira kupatsanurwa kwemhasuru stem masero kuita tsandanyama maseru uye kuita kuti kutaura kwemhasuru-chaiyo majini, nekudaro ichikurudzira tsandanyama protein synthesis. Mune tsandanyama atrophy modhi, mushure mekurapa urolithin A, kutaura kweMyoD neMyogenin kwakawedzera, izvo zvinobatsira kuchengetedza tsandanyama uye kudzivirira tsandanyama kuderera.

2. Inhibit muscle protein degradation uye inhibit ubiquitin-proteasome system (UPS)

Iyo UPS ndiyo imwe yenzira huru dzekudzikisa tsandanyama protein. Munguva yemhasuru atrophy, mamwe E3 ubiquitin ligases, akadai semhasuru atrophy F-box protein (MAFbx) uye tsandanyama RING finger protein 1 (MuRF1), inogadziriswa, iyo inogona kuisa mapuroteni emasumbu ne ubiquitin uye yobva yadzikisira kuburikidza neproteasome.

Urolithin A inogona kuvharidzira kutaura uye kuita kweiyi E3 ubiquitin ligases. Mukuedza kwemuenzaniso wemhuka, urolithin A inogona kuderedza mazinga eMAFbx uye MuRF1, kuderedza ubiquitination mark yemapuroteni emasumbu, nokudaro kudzivisa UPS-mediated muscle protein degradation uye zvinobudirira kudzivirira kuderera kwemhasuru.

Kugadziriswa kweiyo autophagy-lysosomal system (ALS)

ALS inoita basa mukuvandudzwa kwemhasuru mapuroteni uye organelles, asi kuwedzeredza kunogona kutungamirira kune tsandanyama atrophy. Urolithin A inogona kudzora ALS kusvika padanho rinonzwisisika. Inogona kuvharidzira yakawandisa autophagy uye kudzivirira zvakanyanya kuderera kwemhasuru mapuroteni.
Semuenzaniso, urolithin A inogona kudzora kutaura kweautophagy-anoenderana mapuroteni (akadai seLC3-II), kuitira kuti igone kuchengetedza iyo homeostasis yemhasuru sero nharaunda ichidzivirira kubviswa kwakanyanya kwemapuroteni emhasuru, nekudaro ichibatsira kuchengetedza mhasuru.

3. Kuvandudza simba remetabolism yemasero emhasuru

Kubata tsandanyama kunoda simba rakawanda, uye mitochondria ndiyo nzvimbo huru yekugadzira simba. Urolithin A inogona kuwedzera kushanda kwemhasuru cell mitochondria uye kunatsiridza kugadzirwa kwesimba. Inogona kukurudzira mitochondrial biogenesis uye kuwedzera nhamba ye mitochondria.

Semuenzaniso, urolithin A inogona kushandura peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), inova mutongi mukuru wemitochondrial biogenesis, inokurudzira mitochondrial DNA replication uye inoenderana neprotein synthesis. Panguva imwecheteyo, urolithin A inogonawo kuvandudza basa remitochondrial respiratory chain, kuwedzera synthesis yeadenosine triphosphate (ATP), inopa simba rakakwana rekugadzirisa tsandanyama, uye kuderedza kuderera kwemhasuru kunokonzerwa nekushaya simba.

Inogadzirisa shuga uye lipid metabolism uye inotsigira basa remhasuru

Urolithin A inogona kudzora glucose uye lipid metabolism yemasero emhasuru. Panyaya yeglucose metabolism, inogona kukwidziridza kutora uye kushandiswa kweglucose nemasero emhasuru, uye kuve nechokwadi chekuti masero emhasuru ane akakwana emagetsi substrates nekuita iyo insulin yekusaina nzira kana imwe nzira yekufambisa yeglucose ine chekuita nemasaini.

Panyaya ye lipid metabolism, urolithin A inogona kusimudzira mafuta acid oxidation, ichipa imwe sosi yesimba rekumisikidza tsandanyama. Nekugadzirisa glucose uye lipid metabolism, urolithin A inochengetedza simba remasero emhasuru uye inobatsira kudzivirira kuderera kwemhasuru.

Urolithin A inovandudza metabolism

1. Regulate shuga metabolism uye kuvandudza insulin senitivity
Urolithin A inogona kuwedzera insulin senitivity, iyo yakakosha pakuchengetedza kugadzikana kweshuga yeropa. Inogona kuita pamamorekuru akakosha munzira yekusaina insulin, senge insulin receptor substrate (IRS) mapuroteni.

Mumamiriro ekudzivirira insulini, tyrosine phosphorylation ye IRS protein inodziviswa, zvichiita kuti kukundikana kwepasi pasi phosphatidylinositol 3-kinase (PI3K) nzira yekuratidzira kuti ishandiswe zvakajairika, uye sero rinopindura insulin rinopera simba.

Urolithin A inogona kusimudzira tyrosine phosphorylation ye IRS protein, nekudaro ichimisa PI3K-protein kinase B (Akt) nzira yekusaina, zvichiita kuti masero atore zvirinani uye ashandise glucose. Semuenzaniso, mukuedza kwemhando yemhuka, mushure mekutonga kweurolithin A, kunzwisiswa kwemhasuru uye adipose tishu kune insulin yakagadziridzwa zvakanyanya, uye mazinga ehuga eropa akadzorwa zvinobudirira.

Inogadzirisa glycogen synthesis uye kuora

Glycogen ndiyo nzira huru yekuchengetedza glucose mumuviri, inonyanya kuchengetwa muchiropa uye mhasuru tishu. Urolithin A inogona kudzora kuumbwa uye kuparara kweglycogen. Inogona kumisa glycogen synthase, kukurudzira synthesis yeglycogen, uye kuwedzera kuchengetwa kweglycogen.

Panguva imwecheteyo, urolithin A inogonawo kudzivisa kushanda kweglycogenolytic enzymes, yakadai se glycogen phosphorylase, uye kuderedza kuwanda kweglycogen yakasvibiswa kuva glucose uye yakasunungurwa muropa. Izvi zvinobatsira kudzikamisa huwandu hweshuga yeropa uye kudzivirira kuchinjika kwakanyanya muropa. Muchidzidzo chechirwere cheshuga, mushure mekurapa urolithin A, glycogen iri muchiropa nemisungo yakawedzera, uye kutonga kweshuga yeropa kwakavandudzwa.

2. Kugadzirisa lipid metabolism uye inhibit fatty acid synthesis

Urolithin A ine inhibitory mhedzisiro pane lipid synthesis process. Muchiropa uye adipose tishu, inogona kuvharidzira ma enzymes akakosha mumafuta acid synthesis, senge fatty acid synthase (FAS) uye acetyl-CoA carboxylase (ACC).

FAS neACC zvakakosha kudzora enzymes mu de novo synthesis yemafuta acids. Urolithin A inogona kuderedza kuumbwa kwemafuta acids nekudzivisa basa ravo. Semuenzaniso, mumhando yemafuta echiropa inokonzerwa nekudya kwemafuta akawanda, urolithin A inogona kuderedza basa reFAS neACC muchiropa, kuderedza kuumbwa kwe triglycerides, uye nokudaro kuderedza lipid kuunganidza muchiropa.

Inosimudzira fatty acid oxidation

Pamusoro pekudzivisa fatty acid synthesis, urolithin A inogonawo kukurudzira kuparara kweoxidative yemafuta acids. Inogona kumisa nzira dzechiratidzo uye ma enzyme ane hukama nemafuta acid oxidation. Semuenzaniso, inogona kusimudzira basa recarnitine palmitoyltransferase-1 (CPT-1).

CPT-1 ndiyo enzyme inokosha mumafuta asidhi β-oxidation, iyo inokonzera kutakura mafuta acids kune mitochondria nokuda kwekuparara kweoxidative. Urolithin A inokurudzira β-oxidation yemafuta acids nekuita CPT-1, inowedzera kushandiswa kwesimba remafuta, inobatsira kuderedza kuchengetedza kwemafuta emuviri, uye inovandudza lipid metabolism.

3. Kuvandudza simba remetabolism uye kuwedzera mitochondrial basa

Mitochondria ndiyo "mafekitori emagetsi" emasero, uye urolithin A inogona kuwedzera basa remitochondria. Inogona kudzora mitochondrial biogenesis uye kukurudzira mitochondrial synthesis uye kuvandudzwa. Semuenzaniso, inogona kuita peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α).

PGC-1α ndiyo inogadzirisa mitochondrial biogenesis, iyo inogona kukurudzira kudzokororwa kweDNA mitochondrial uye kuumbwa kwemapuroteni ane chokuita nemitochondrial. Urolithin A inowedzera nhamba uye mhando ye mitochondria uye inovandudza simba rekugadzira simba remasero nekuita PGC-1α. Panguva imwecheteyo, urolithin A inogonawo kuvandudza basa rekufema remitochondria uye kuwedzera synthesis yeadenosine triphosphate (ATP).

4. Kugadzirisa Cellular Metabolic Reprogramming

Urolithin A inogona kutungamira maseru kuti aite metabolic reprogramming, zvichiita kuti masetabolism ishande zvakanyanya. Pasi pemamwe kushushikana kana mamiriro echirwere, sero metabolic pateni inogona kushanduka, zvichikonzera kudzikiswa kwesimba mukugadzira simba uye kugadzirwa kwezvinhu.

Urolithin A inogona kudzora metabolic masaini nzira mumaseru, senge AMP-activated protein kinase (AMPK) yekusaina nzira. AMPK i "sensor" ye cellular energy metabolism. Mushure mekunge urolithin A inobata AMPK, inogona kukurudzira masero kuti abve kubva kuanabolism kuenda ku catabolism, zvichiita kuti simba riwedzere kushandiswa kwesimba uye zvokudya zvinovaka muviri, nokudaro zvichivandudza basa rose remetabolism.

Kushandiswa kweurolithin A hakungogumiri pakurapa. Iri zvakare zvishoma nezvishoma kuwana kutarisisa mune zvehutano zvigadzirwa uye zvizoro. Urolithin A inowedzerwa kune zvakawanda zvehutano zvigadzirwa kuwedzera kusadzivirirwa, kunatsiridza kutenderera kweropa uye kukurudzira metabolism. Izvi zvigadzirwa zvinowanzova mumhando ye capsules, mapiritsi kana zvinwiwa, zvakakodzera kune zvinodiwa nemapoka akasiyana evanhu.

Mumunda wezvizoro, urolithin A inoshandiswa zvakanyanya muzvigadzirwa zvekuchengetedza ganda nekuda kwekuvandudzwa kwesero uye anti-kuchembera zvinhu. Inogona kuvandudza kutenderera kweropa muganda uye kukurudzira collagen synthesis, nekudaro inovandudza ganda elasticity uye kupenya. Mazhinji emhando yepamusoro ekuchengetedza ganda atanga kushandisa urolithin A sechinhu chakakosha kutanga anti-kuchembera, kugadzirisa uye kunyorovesa zvigadzirwa kusangana nevatengi kutsvaga ganda rakanaka.

Mukupedzisa, sechinhu chebioactive chine mabasa akawanda, urolithin A yakaratidza tarisiro yakafara yekushandisa muminda yemishonga, hutano uye runako. Nekudzika kwekutsvagisa kwesainzi, nzvimbo yekushandisa yeurolithin A icharamba ichikura, ichipa sarudzo dzakawanda dzehutano hwevanhu uye runako.