Isayensi Ngemuva kwe-Urolithin A: Okufanele Ukwazi

I-Urolithin A (UA)iyinhlanganisela ekhiqizwa yi-metabolism yezitshalo zamathumbu ekudleni okucebile ngama-ellagitannins (njengamahalananda, ama-raspberries, njll.). Ibhekwa njenge-anti-inflammatory, anti-aging, antioxidant, induction of mitophagy, njll., futhi ingawela umgoqo wegazi-ubuchopho. Ucwaningo oluningi luye lwaqinisekisa ukuthi i-urolithin A ingabambezela ukuguga, futhi izifundo zomtholampilo nazo zibonise imiphumela emihle.

Iyini i-urolithin A?

I-Urolithin A (Uro-A) iwuhlobo lwe-ellagitannin (ET)-uhlobo lwe-metabolite yamathumbu yamathumbu. Yatholwa ngokusemthethweni futhi yaqanjwa ngo-2005. Ifomula yayo yamangqamuzana ithi C13H8O4, futhi isisindo sayo samangqamuzana esihlobene singama-228.2. Njengesandulela se-metabolic ye-Uro-A, imithombo yokudla eyinhloko ye-ET amahalananda, ama-strawberry, ama-raspberries, ama-walnuts newayini elibomvu. I-UA ingumkhiqizo we-ETs owenziwe nge-metabolized microorganisms zamathumbu. I-UA inamathuba amaningi okusebenza ekuvimbeleni nasekwelapheni izifo eziningi. Ngesikhathi esifanayo, i-UA inezinhlobonhlobo zemithombo yokudla.

Ucwaningo ngemiphumela ye-antioxidant ye-urolithins yenziwe. I-Urolithin-A ayikho esimweni semvelo, kodwa ikhiqizwa uchungechunge lwezinguquko ze-ET ngezitshalo zamathumbu. I-UA ingumkhiqizo we-ETs owenziwe nge-metabolized microorganisms zamathumbu. Ukudla okucebile ku-ET kudlula esiswini namathumbu amancane emzimbeni womuntu, futhi ekugcineni kugaywe ngokuyinhloko ku-Uro-A kukholoni. Inani elincane le-Uro-A lingatholwa futhi emathunjini amancane angaphansi.

Njengezinhlanganisela zemvelo ze-polyphenolic, ama-ET adonse ukunakwa okukhulu ngenxa yemisebenzi yawo yezinto eziphilayo ezifana ne-antioxidant, anti-inflammatory, anti-allergic and anti-viral. Ngaphezu kokutholakala ekudleni okufana namahalananda, ama-strawberries, ama-walnuts, ama-raspberries nama-alimondi, ama-ET atholakala kuma-gallnuts, ama-pomegranate peels, i-myrobalan, i-Dimininus, i-geranium, i-betel nut, amaqabunga e-sea buckthorn, i-Phyllanthus, i-Uncaria, i-Sanguisorba, e-Chinese. Imithi efana nePhyllanthus emblica ne-Agrimony.

Iqembu le-hydroxyl esakhiweni samangqamuzana e-ETs lifana ne-polar, elingahambisani nokumuncwa ngodonga lwamathumbu, futhi i-bioavailability yayo iphansi kakhulu. Ucwaningo oluningi luye lwathola ukuthi ngemva kokuba ama-ET efakwe emzimbeni womuntu, ahlanganiswa yizitshalo zamathumbu emathunjini futhi aguqulwe abe yi-urolithin ngaphambi kokumuncwa. I-ETs i-hydrolyzed ibe yi-ellagic acid (EA) endaweni engenhla ye-gastrointestinal tract, futhi i-EA idlula emathunjini. Izitshalo zebhaktheriya ziqhubeka nokusebenza futhi zilahlekelwe indandatho ye-lactone futhi zibhekana nokusabela kwe-dehydroxylation okuqhubekayo ukuze kukhiqizwe i-urolithin. Kunemibiko yokuthi i-urolithin ingaba yisisekelo sezinto eziphilayo ze-ETs emzimbeni.

Iyini i-bioavailability ye-urolithin ehlobene nayo?

Ngokubona lokhu, uma uhlakaniphile, kungenzeka usuyazi ukuthi i-bioavailability ye-UA ihlobene nani.

Into ebaluleke kakhulu ukwakheka kwe-microbiome, ngoba akuzona zonke izinhlobo ze-microbial ezingakhiqiza. Impahla eluhlaza ye-UA i-ellagitannins etholakala ekudleni. Lesi sandulela sitholakala kalula futhi cishe sitholakala yonke indawo ngemvelo.

I-Ellagitannins i-hydrolyzed emathunjini ukuze ikhulule i-ellagic acid, ephinde icutshungulwe yizitshalo zamathumbu zibe i-urolithin A.

Ngokocwaningo kujenali Cell, bangama-40% kuphela abantu abangaguqula ngokwemvelo i-urolithin A isuke kumanduleli wayo iyenze i-urolithin A esebenzisekayo.

Iyini imisebenzi ye-urolithin A?

Anti-ukuguga

I-radical theory yamahhala yokuguga ikholelwa ukuthi izinhlobo ze-oksijeni ezisebenzayo ezikhiqizwa ku-metabolism ye-mitochondrial zibangela ukucindezeleka kwe-oxidative emzimbeni futhi kuholele ekugugeni, futhi i-mitophagy idlala indima ebalulekile ekugcineni impilo ye-mitochondrial nobuqotho. Kuye kwabikwa ukuthi i-UA ingalawula i-mitophagy futhi ngaleyo ndlela ibonise amandla okubambezela ukuguga. Ryu et al. ithole ukuthi i-UA yehlisa ukungasebenzi kahle kwe-mitochondrial kanye neminyaka yokuphila enwetshiwe ku-Caenorhabditis elegans ngokwenza i-mitophagy; kumagundane, i-UA ingahlehlisa ukwehla kokusebenza kwemisipha okuhlobene nobudala, okubonisa ukuthi i-UA ithuthukisa ukusebenza kwe-mitochondrial ngokuthuthukisa i-Muscle mass nokwelula impilo yomzimba. Liu et al. wasebenzisa i-UA ukungenelela ekugugeni kwe-fibroblasts yesikhumba. Imiphumela yabonisa ukuthi i-UA yandisa kakhulu inkulumo yohlobo lwe-collagen futhi yanciphisa ukubonakaliswa kwe-matrix metalloproteinase-1 (MMP-1). Iphinde yasebenza i-nuclear Factor E2-related factor 2 (i-nuclear factor erythroid 2-related factor 2, Nrf2) -mediated antioxidant response inciphisa i-ROS ye-intracellular, ngaleyo ndlela ibonise amandla aqinile okulwa nokuguga.

Umphumela we-Antioxidant

Njengamanje, kuye kwenziwa izifundo eziningi ngomphumela we-antioxidant we-urolithin. Phakathi kwawo wonke ama-metabolites e-urolithin, i-Uro-A inomsebenzi onamandla we-antioxidant, owesibili kuphela kuma-oligomers we-proanthocyanidin, ama-catechin, i-epicatechin kanye ne-3,4-dihydroxyphenylacetic acid. Ukuhlolwa kwe-oxygen radical absorbance capacity (ORAC) ye-plasma yamavolontiya anempilo kutholwe ukuthi amandla e-antioxidant anyuke ngo-32% ngemva kwamahora angu-0.5 okuphuza ijusi yehalananda, kodwa izinga lezinhlobo zomoya-mpilo osebenzayo alizange lishintshe kakhulu, ngenkathi ku-Neuro- In. ukuhlolwa kwe-vitro kumaseli angu-2a kwathola ukuthi i-Uro-A inganciphisa izinga lezinhlobo zomoya-mpilo osebenzayo kumaseli. Le miphumela ikhombisa ukuthi i-Uro-A inemiphumela enamandla ye-antioxidant.

03. I-Urolithin A kanye nezifo zenhliziyo kanye ne-cerebrovascular

Izibalo zomhlaba wonke zesifo senhliziyo (CVD) zikhula unyaka nonyaka, futhi izinga lokufa lisalokhu liphezulu. Akukhulisi nje umthwalo wezenhlalo nezomnotho, kodwa futhi kuthinta kakhulu izinga lempilo yabantu. I-CVD yisifo se-multifactorial. Ukuvuvukala kungandisa ingozi ye-CVD. Ukucindezeleka kwe-oxidative kuhlobene ne-pathogenesis ye-CVD. Kunemibiko yokuthi ama-metabolites atholakala kuma-microorganisms amathumbu ahlotshaniswa nengozi ye-CVD.

I-UA kubikwe ukuthi inemiphumela enamandla yokulwa nokuvuvukala kanye ne-antioxidant, futhi izifundo ezifanele ziqinisekisile ukuthi i-UA ingadlala indima enenzuzo ku-CVD. Savi et al. wasebenzisa imodeli yegundane lesifo sikashukela ukwenza izifundo ze-vivo nge-diabetesic cardiomyopathy futhi wathola ukuthi i-UA inganciphisa impendulo yokuqala yokuvuvukala kwezicubu ze-myocardial ku-hyperglycemia, ithuthukise i-myocardial microenvironment, futhi ikhuthaze ukululama kwe-cardiomyocyte contractility kanye ne-calcium dynamics, okubonisa ukuthi i-UA ingakwazi ingasetshenziswa njengomuthi osizayo wokulawula isifo senhliziyo esinesifo sikashukela futhi uvimbele izinkinga zayo.

I-UA ingathuthukisa ukusebenza kwe-mitochondrial kanye nokusebenza kwemisipha ngokufaka i-mitophagy. I-Mitochondria yenhliziyo yizitho zomzimba ezibalulekile ezinomthwalo wemfanelo wokukhiqiza i-ATP enothe ngamandla. Ukungasebenzi kahle kwe-Mitochondrial kuyimbangela eyinhloko yokuhluleka kwenhliziyo. Ukungasebenzi kahle kwe-Mitochondrial okwamanje kuthathwa njengokuhloswe kokwelapha okungaba khona. Ngakho-ke, i-UA isiphinde yaba umuthi omusha wokwelapha i-CVD.

Urolithin A kanye nezifo zezinzwa

I-Neuroinflammation iyinqubo ebalulekile ekuveleni nasekuthuthukisweni kwesifo se-neurodeergenerative (ND). I-apoptosis ebangelwa ingcindezi ye-oxidative kanye nokuhlangana okungajwayelekile kwamaprotheni kuvame ukubangela i-neuroinflammation, futhi ama-cytokines abangela ukuvuvukala akhishwa yi-neuroinflammation abe esethinta ukwakheka kwe-neurodegeneration.

Ucwaningo luye lwathola ukuthi i-UA ilamula umsebenzi wokulwa nokuvuvukala ngokwenza i-autophagy futhi isebenze isilawuli sesignali esithulile esingu-1 (SIRT-1) se-deacetylation mechanism, ivimbela i-neuroinflammation kanye ne-neurotoxicity, futhi ivimbele i-neurodegeneration, iphakamisa ukuthi i-UA iyi-ejenti ye-Neuroprotective esebenzayo. Ngesikhathi esifanayo, ezinye izifundo zithole ukuthi i-UA ingasebenzisa imiphumela ye-neuroprotective ngokukhipha ngokuqondile ama-radicals mahhala kanye nokuvimbela ama-oxidase.

Ucwaningo luye lwabonisa ukuthi ijusi yegromegranate idlala indima ye-neuroprotective ngokwandisa umsebenzi we-mitochondrial aldehyde dehydrogenase, ukugcina izinga le-anti-apoptotic protein Bcl-xL, ukunciphisa ukuhlanganisa kwe-α-synuclein kanye nokulimala kwe-oxidative, futhi kuthinte umsebenzi we-neuronal nokuzinza. Ama-Urolithin compounds angama-metabolites kanye nezingxenye zomphumela we-ellagitannins emzimbeni futhi anemisebenzi yebhayoloji efana nokulwa nokuvuvukala, ukucindezelwa kwe-anti-oxidative, kanye ne-anti-apoptosis. I-Urolithin ingenza umsebenzi we-neuroprotective ngokusebenzisa umgoqo wegazi nobuchopho futhi iyingqamuzana elincane elinamandla lokungenelela ezifweni ze-neurodegenerative.

I-Urolithin A kanye nezifo ezihlangene nezomgogodla

Izifo eziwohlokayo zibangelwa izici eziningi njengokuguga, ubunzima, nokuhlukumezeka. Izifo ezivame kakhulu zokuwohloka kwamalunga yi-osteoarthritis (OA) kanye nesifo esiwohlokayo somgogodla we-intervertebral disc degeneration (IDD). Ukwenzeka kungabangela ubuhlungu kanye nomsebenzi olinganiselwe, okuholela ekulahlekelweni komsebenzi futhi kubeke engozini impilo yomphakathi. Indlela ye-UA ekwelapheni i-IDD yesifo somgogodla ingase ihlobane nokubambezeleka kwe-nucleus pulposus (NP) cell apoptosis. I-NP iyingxenye ebalulekile ye-intervertebral disc. Igcina umsebenzi wezinto eziphilayo we-intervertebral disc ngokusabalalisa ingcindezi nokugcina i-homeostasis ye-matrix. Ucwaningo luye lwathola ukuthi i-UA idala i-mitophagy ngokuvula indlela yokubonisa i-AMPK, ngaleyo ndlela ivimbele i-tert-butyl hydroperoxide (t-BHP) -i-apoptosis eyenziwe yamaseli we-osteosarcoma cell NP kanye nokunciphisa ukuwohloka kwe-intervertebral disc.

I-Urolithin A kanye nezifo ze-metabolic

Izigameko zezifo ze-metabolic ezifana nokukhuluphala nesifo sikashukela ziyanda unyaka nonyaka, futhi imiphumela enenzuzo ye-polyphenols yokudla empilweni yabantu iqinisekiswe amaqembu amaningi futhi ibonise amandla ekuvimbeleni nasekwelapheni izifo ze-metabolic. Ipomegranate polyphenols kanye ne-metabolite yayo yamathumbu i-UA ingathuthukisa izinkomba zomtholampilo ezihlobene nezifo ze-metabolic, njenge-lipase, i-α-glucosidase (α-glucosidase) kanye ne-dipeptidyl peptidase-4 (i-dipeptidyl peptidase-4) ehilelekile ku-glucose kanye ne-fatty acid metabolism. 4), kanye nezakhi zofuzo ezihlobene ezifana ne-adiponectin, i-PPARγ, i-GLUT4 ne-FABP4 ezithinta ukuhlukaniswa kwe-adipocyte kanye nokuqoqwa kwe-triglyceride (TG).

Ngaphezu kwalokho, ezinye izifundo zithole ukuthi i-UA inamandla okunciphisa izimpawu zokukhuluphala. I-UA ingumkhiqizo we-metabolism yamathumbu we-polyphenols. Lawa ma-metabolites anamandla okunciphisa ukuqoqwa kwe-TG kumaseli esibindi nama-adipocyte. Abdulrasheed et al. udlise amagundane e-Wistar ukudla okunamafutha amaningi ukuze enze ukukhuluphala. Ukwelashwa kwe-UA akugcini nje ngokukhulisa ukukhishwa kwamafutha endle, kodwa futhi kunciphisa izicubu ze-visceral adipose nesisindo somzimba ngokulawula izakhi zofuzo ezihlobene ne-lipogenesis kanye ne-fatty acid oxidation. Yehlisa ukunqwabelana kwamafutha esibindi kanye nengcindezi ye-oxidative. Ngesikhathi esifanayo, i-UA ingakhuphula ukusetshenziswa kwamandla ngokuthuthukisa i-thermogenesis yezicubu ze-adipose ensundu kanye nokwenza kube nsundu kwamafutha amhlophe. Indlela yokukhulisa amazinga e-triiodothyronine (T3) kumadepho wamafutha ansundu nama-inguinal fat. Khulisa ukukhiqizwa kokushisa futhi ngaleyo ndlela kuphikisane nokukhuluphala.

Ngaphezu kwalokho, i-UA nayo inomphumela wokuvimbela ukukhiqizwa kwe-melanin. Ucwaningo luthole ukuthi i-UA inganciphisa kakhulu ukukhiqizwa kwe-melanin kumaseli e-melanoma B16. Indlela eyinhloko ukuthi i-UA ithinta ukwenziwa kusebenze okunamandla kwe-tyrosinase ngokuvimbela ngokuncintisana kweseli tyrosinase, ngaleyo ndlela yehlise umbala. Ngakho-ke, i-UA inamandla kanye nempumelelo yokwenza amabala abe mhlophe futhi akhanyise. Futhi ucwaningo lubonisa ukuthi i-urolithin A inomphumela wokubuyisela emuva ukuguga kwamasosha omzimba. Ucwaningo lwakamuva luthole ukuthi uma i-urolithin A yengezwa njengesengezo sokudla, ayisebenzi nje kuphela ubungqabavu bendawo ye-lymphatic yamasosha omzimba wegundane, kodwa futhi ithuthukisa umsebenzi wamaseli e-hematopoietic stem. Ukusebenza kukonke kubonisa amandla e-urolithin A ukulwa nokwehla kwamasosha omzimba ahlobene neminyaka.

Ukufingqa, i-UA, njenge-metabolite yamathumbu emathunjini e-phytochemicals ETs, idonse ukunaka okukhulu eminyakeni yamuva. Ngocwaningo lwemiphumela yemithi kanye nezindlela ze-UA ziya ngokuya ziba ziningi futhi zijule, i-UA ayisebenzi nje kuphela kumdlavuza kanye ne-CVD (izifo zenhliziyo). Inomphumela omuhle wokuvimbela kanye nokwelapha ezifweni eziningi zemitholampilo njenge-ND (izifo ze-neurodeergenerative) kanye nezifo ze-metabolic. Iphinde ibonise amandla amakhulu okusebenza emikhakheni yobuhle nokunakekelwa kwezempilo njengokubambezela ukuguga kwesikhumba, ukunciphisa isisindo somzimba kanye nokuvimbela ukukhiqizwa kwe-melanin.

I-Suzhou Myland Pharm & Nutrition Inc. ingumkhiqizi obhalisiwe we-FDA ohlinzeka ngempushana ye-Urolithin A yekhwalithi ephezulu nemsulwa.

KwaSuzhou Myland Pharm sizibophezele ekuhlinzekeni ngemikhiqizo esezingeni eliphezulu ngamanani angcono kakhulu. I-Urolithin A yethu powder ihlolwe ngokuqinile ukuhlanzeka namandla, iqinisekisa ukuthi uthola isengezo sekhwalithi ephezulu ongayethemba. Kungakhathaliseki ukuthi ufuna ukusekela impilo yeselula, ukuqinisa amasosha akho omzimba noma ukuthuthukisa impilo yonke, i-Urolithin A powder yethu iyisinqumo esihle kakhulu.

Njengoba inesipiliyoni seminyaka engu-30 futhi iqhutshwa ubuchwepheshe obuphezulu kanye namasu e-R&D athuthukiswe kakhulu, i-Suzhou Myland Pharm isungule uhide lwemikhiqizo encintisanayo futhi yaba isithasiselo sesayensi yempilo emisha, ukuhlanganisa ngokwezifiso kanye nenkampani yezinkonzo zokukhiqiza.

Ngaphezu kwalokho, iSuzhou Myland Pharm iphinde ibe ngumkhiqizi obhalisiwe we-FDA. Izinsiza ze-R&D zenkampani, izikhungo zokukhiqiza, namathuluzi okuhlaziya kungokwesimanjemanje futhi kunemisebenzi eminingi, futhi ingakhiqiza amakhemikhali ukusuka kumamiligremu ukuya kumathani esikalini, futhi ihambisane namazinga e-ISO 9001 kanye nemininingwane yokukhiqiza ye-GMP.