Isayensi Engemuva Kwe-Urolithin A: Okudingeka Ukwazi

I-Urolithin A (UA)iyinhlanganisela ekhiqizwa yi-metabolism yezitshalo zamathumbu ekudleni okucebile ngama-ellagitannins (njenge-pomegranate, ama-raspberry, njll.). Kucatshangwa ukuthi ine-anti-inflammatory, anti-aging, antioxidant, induction of mitophagy, njll., futhi ingawela isithiyo segazi-ubuchopho. Izifundo eziningi ziqinisekisile ukuthi i-urolithin A ingalibazisa ukuguga, kanti izifundo zezokwelapha nazo zibonise imiphumela emihle.

Iyini i-urolithin A?

I-Urolithin A (Uro-A) iyi-metabolite yezitshalo zamathumbu yohlobo lwe-ellagitannin (ET). Yatholakala ngokusemthethweni futhi yaqanjwa ngo-2005. Ifomula yayo yama-molecule yi-C13H8O4, kanti isisindo sayo sama-molecule singu-228.2. Njengesandulela se-metabolic se-Uro-A, imithombo yokudla eyinhloko ye-ET amapomegranate, ama-strawberry, ama-raspberry, ama-walnuts kanye newayini elibomvu. I-UA ingumkhiqizo wama-ET acutshungulwa yizinto ezincane zamathumbu. I-UA inamathemba amaningi okusetshenziswa ekuvimbeleni nasekwelapheni izifo eziningi. Ngesikhathi esifanayo, i-UA inemithombo eminingi yokudla.

Ucwaningo ngemiphumela ye-urolithin yokulwa ne-antioxidant luye lwenziwa. I-Urolithin-A ayikho esimweni semvelo, kodwa ikhiqizwa uchungechunge lwezinguquko ze-ET yizitshalo zamathumbu. I-UA ingumkhiqizo wama-ET acutshungulwa yizinto ezincane zamathumbu. Ukudla okucebile ku-ET kudlula esiswini nasemathunjini amancane emzimbeni womuntu, futhi ekugcineni kucutshungulwa ikakhulukazi ku-Uro-A emathunjini amancane. Inani elincane le-Uro-A lingatholakala futhi emathunjini amancane angaphansi.

Njengamakhemikhali e-polyphenolic emvelo, ama-ET adonsele ukunaka okukhulu ngenxa yemisebenzi yawo yebhayoloji efana ne-antioxidant, anti-inflammatory, anti-allergic kanye ne-anti-viral. Ngaphezu kokutholwa ekudleni okufana namapomegranate, ama-strawberry, ama-walnuts, ama-raspberry nama-alimondi, ama-ET atholakala futhi kuma-gallnuts, amakhasi epomegranate, i-myrobalan, i-Dimininus, i-geranium, i-betel nut, amaqabunga e-sea buckthorn, i-Phyllanthus, i-Uncaria, i-Sanguisorba, Emithini yaseShayina efana ne-Phyllanthus emblica kanye ne-Agrimony.

Iqembu le-hydroxyl esakhiweni sama-molecule e-ET liphansi kakhulu, okuyinto engavumeli ukumuncwa udonga lwamathumbu, futhi ukutholakala kwalo kuphansi kakhulu. Izifundo eziningi zithole ukuthi ngemva kokuba ama-ET egwinywe ngumzimba womuntu, aguqulwa yizitshalo zamathumbu emathunjini bese eguqulwa abe yi-urolithin ngaphambi kokuba amuncwe. Ama-ET aguqulwa abe yi-ellagic acid (EA) endaweni ephezulu yokugaya ukudla, bese i-EA idluliselwa emathunjini. Izitshalo zamagciwane ziyaqhubeka nokusebenza futhi zilahlekelwe yindandatho ye-lactone futhi zenze ukusabela okuqhubekayo kwe-dehydroxylation ukuze kukhiqizwe i-urolithin. Kunemibiko yokuthi i-urolithin ingaba yisisekelo semiphumela yezinto eziphilayo ze-ET emzimbeni.

Kuhlobene kanjani nokutholakala kwe-urolithin?

Uma ubona lokhu, uma uhlakaniphile, ungase wazi kakade ukuthi ukutholakala kwe-UA kuhlobene kanjani.

Into ebaluleke kakhulu ukwakheka kwe-microbiome, ngoba akuzona zonke izinhlobo zamagciwane ezingakhiqiza. Izinto zokusetshenziswa ze-UA ziyi-ellagitannins ezitholakala ekudleni. Lesi sandulela sitholakala kalula futhi cishe sitholakala yonke indawo.

Ama-Ellagitannins afakwa emanzini ukuze akhiphe i-ellagic acid, ephinde icutshungulwe yizitshalo zamathumbu ibe yi-urolithin A.

Ngokusho kocwaningo olushicilelwe kumagazini i-Cell, abantu abangu-40% kuphela abangaguqula ngokwemvelo i-urolithin A kusukela ku-precursor yayo ibe yi-urolithin A esebenzisekayo.

Yimiphi imisebenzi ye-urolithin A?

Ukulwa nokuguga

Ithiyori yama-free radical yokuguga ikholelwa ukuthi izinhlobo ze-oxygen ezisabelayo ezikhiqizwa ku-metabolism ye-mitochondrial zibangela ukucindezeleka kwe-oxidative emzimbeni futhi ziholele ekugugeni, kanti i-mitophagy idlala indima ebalulekile ekugcineni impilo ye-mitochondrial kanye nobuqotho. Kubikwe ukuthi i-UA ingalawula i-mitophagy futhi ngaleyo ndlela ibonise amandla okubambezela ukuguga. URyu et al. bathole ukuthi i-UA inciphise ukungasebenzi kahle kwe-mitochondrial kanye nokuphila isikhathi eside kuma-elegans e-Caenorhabditis ngokubangela i-mitophagy; kumagundane, i-UA ingabuyisela emuva ukwehla kokusebenza kwemisipha okuhlobene nokuguga, okubonisa ukuthi i-UA ithuthukisa ukusebenza kwe-mitochondrial ngokuthuthukisa isisindo semisipha nokwandisa impilo yomzimba. ULiu et al. basebenzise i-UA ukungenelela kuma-fibroblast esikhumba agugayo. Imiphumela ikhombisile ukuthi i-UA yandise kakhulu ukubonakaliswa kwe-type I collagen futhi yanciphisa ukubonakaliswa kwe-matrix metalloproteinase-1 (MMP-1). Iphinde yasebenza impendulo ye-antioxidant ephethwe yi-nuclear Factor E2-related factor 2 (nuclear factor erythroid 2-related factor 2, Nrf2) inciphisa i-ROS yangaphakathi kweseli, ngaleyo ndlela ibonise amandla aqinile okulwa nokuguga.

Umphumela we-Antioxidant

Njengamanje, kuye kwenziwa izifundo eziningi ngomphumela we-urolithin wokulwa ne-antioxidant. Phakathi kwazo zonke i-metabolites ze-urolithin, i-Uro-A inomsebenzi onamandla kakhulu we-antioxidant, owesibili kuphela kuma-oligomers e-proanthocyanidin, ama-catechins, ama-epicatechin kanye ne-3,4-dihydroxyphenylacetic acid. Ukuhlolwa kwamandla okungenisa i-oxygen radical absorbance (ORAC) kwe-plasma yamavolontiya anempilo kuthole ukuthi amandla e-antioxidant akhuphuke ngo-32% ngemuva kwamahora angu-0.5 okugwinya ijusi lepomegranate, kodwa izinga lezinhlobo ze-oxygen ezisabelayo alishintshanga kakhulu, kanti ekuhlolweni kwe-Neuro-In vitro kumaseli e-2a kuthole ukuthi i-Uro-A inganciphisa izinga lezinhlobo ze-oxygen ezisabelayo kumaseli. Le miphumela ikhombisa ukuthi i-Uro-A inemiphumela enamandla ye-antioxidant.

03. I-Urolithin A kanye nezifo zenhliziyo nemithambo yegazi

Ukwanda kwesifo senhliziyo (CVD) emhlabeni wonke kuyanda unyaka nonyaka, kanti izinga lokufa lihlala liphezulu. Akugcini nje ngokwandisa umthwalo wezenhlalo nezomnotho, kodwa futhi kuthinta kakhulu ikhwalithi yokuphila kwabantu. I-CVD iyisifo esithinta izici eziningi. 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.

Kubikwe ukuthi i-UA inemiphumela enamandla yokulwa nokuvuvukala kanye ne-antioxidant, futhi izifundo ezifanele ziqinisekisile ukuthi i-UA ingadlala indima enenzuzo ku-CVD. USavi nabanye basebenzise imodeli yegundane lesifo sikashukela ukwenza izifundo ezi-in vivo nge-cardiomyopathy yesifo sikashukela futhi bathola ukuthi i-UA inganciphisa impendulo yokuqala yokuvuvukala kwezicubu ze-myocardial ku-hyperglycemia, ithuthukise i-microenvironment ye-myocardial, futhi ikhuthaze ukubuyiselwa kwe-cardiomyocyte contractility kanye ne-calcium dynamics, okubonisa ukuthi i-UA ingasetshenziswa njengomuthi osizayo ukulawula i-cardiomyopathy yesifo sikashukela nokuvimbela izinkinga zayo.

I-UA ingathuthukisa ukusebenza kwe-mitochondrial kanye nokusebenza kwemisipha ngokubangela i-mitophagy. I-mitochondria yenhliziyo yi-organelles ebalulekile ebangela ukukhiqiza i-ATP ecebile ngamandla. Ukungasebenzi kahle kwe-mitochondrial kuyimbangela eyinhloko yokwehluleka kwenhliziyo. Ukungasebenzi kahle kwe-mitochondrial okwamanje kubhekwa njengento engaba yingozi yokwelapha. Ngakho-ke, i-UA nayo isibe umuthi omusha ofanele ukwelashwa kwe-CVD.

I-Urolithin A kanye nezifo zezinzwa

Ukuvuvukala kwe-neuroinflammation kuyinqubo ebalulekile ekuveleni nasekuthuthukisweni kwesifo sokuwohloka kwemizwa (ND). I-apoptosis ebangelwa ukucindezeleka kwe-oxidative kanye nokuhlangana kwamaprotheni okungajwayelekile ivame ukubangela ukuvuvukala kwemizwa, kanti ama-cytokine abangela ukuvuvukala akhishwa yi-neuroinflammation abe esethinta ukonakala kwemizwa.

Izifundo zithole ukuthi i-UA ilawula umsebenzi wokulwa nokuvuvukala ngokubangela i-autophagy kanye nokusebenzisa indlela yokulawula isignali esithule 1 (SIRT-1) yokuqeda acetylation, ivimbele ukuvuvukala kwe-neuroinflammation kanye nobuthi be-neuro, futhi ivimbele ukonakala kwe-neuro, okuphakamisa ukuthi i-UA iyi-ejenti evikela i-Neuro. Ngesikhathi esifanayo, ezinye izifundo zithole ukuthi i-UA ingaba nemiphumela yokuvikela i-neuro ngokususa ngqo ama-free radicals kanye nokuvimbela ama-oxidases.

Izifundo zibonise ukuthi ijusi lepomegranate lidlala indima yokuvikela izinzwa ngokwandisa umsebenzi we-mitochondrial aldehyde dehydrogenase, ukugcina izinga leprotheyini yokulwa ne-apoptotic i-Bcl-xL, ukunciphisa ukuhlanganiswa kwe-α-synuclein kanye nomonakalo we-oxidative, futhi kuthinta umsebenzi we-neuronal kanye nokuzinza. Ama-Urolithin compounds ayi-metabolites kanye nezingxenye zomphumela we-ellagitannins emzimbeni futhi anemisebenzi yebhayoloji efana nokulwa nokuvuvukala, ukucindezeleka kwe-anti-oxidative, kanye ne-anti-apoptosis. I-Urolithin ingasebenza umsebenzi wokuvikela izinzwa ngokusebenzisa isithiyo segazi nobuchopho futhi iyi-molecule encane engase isebenze yokungenelela ezifweni ze-neurodegenerative.

Izifo ze-Urolithin A kanye nokuwohloka kwamalunga nomgogodla

Izifo eziwohlokayo zibangelwa izici eziningi ezifana nokuguga, ukucindezeleka, kanye nokulimala. Izifo eziwohlokayo ezivame kakhulu zamalunga yi-osteoarthritis (OA) kanye nesifo somgogodla esiwohlokayo sokuwohloka kwe-intervertebral disc (IDD). Ukwenzeka kungabangela ubuhlungu kanye nomsebenzi olinganiselwe, okuholela ekulahlekelweni umsebenzi futhi kubeke impilo yomphakathi engozini enkulu. Indlela ye-UA ekwelapheni isifo somgogodla esiwohlokayo i-IDD ingase ihlobane nokubambezeleka kwe-nucleus pulposus (NP) cell apoptosis. I-NP iyisici esibalulekile se-intervertebral disc. Igcina umsebenzi webhayoloji we-intervertebral disc ngokusabalalisa ingcindezi nokugcina i-matrix homeostasis. Izifundo zithole ukuthi i-UA ibangela i-mitophagy ngokusebenzisa indlela yokubonisana ye-AMPK, ngaleyo ndlela ivimbele i-tert-butyl hydroperoxide (t-BHP)-induced apoptosis yamaseli e-NP e-osteosarcoma yomuntu kanye nokunciphisa ukuwohloka kwe-intervertebral disc.

I-Urolithin A kanye nezifo ze-metabolic

Ukusabalala kwezifo ze-metabolic ezifana nokukhuluphala ngokweqile nesifo sikashukela kuyanda unyaka nonyaka, futhi imiphumela emihle yama-polyphenol ekudleni empilweni yabantu iqinisekiswe yizinhlangothi eziningi futhi ibonise amandla ekuvimbeleni nasekwelapheni izifo ze-metabolic. Ama-polyphenol e-pomegranate kanye ne-metabolite yayo yamathumbu i-UA ingathuthukisa izinkomba zemitholampilo ezihlobene nezifo ze-metabolic, njenge-lipase, i-α-glucosidase (α-glucosidase) kanye ne-dipeptidyl peptidase-4 (dipeptidyl peptidase-4) ehilelekile ekusetshenzisweni kwe-glucose kanye ne-fatty acid. 4), kanye nezakhi zofuzo ezihlobene njenge-adiponectin, i-PPARγ, i-GLUT4 kanye ne-FABP4 ezithinta ukuhlukaniswa kwama-adipocyte kanye nokuqongelela kwe-triglyceride (TG).

Ngaphezu kwalokho, ezinye izifundo zithole nokuthi i-UA inamandla okunciphisa izimpawu zokukhuluphala. I-UA ingumkhiqizo we-metabolism yamathumbu yama-polyphenols. Lawa ma-metabolites anekhono lokunciphisa ukuqongelela kwe-TG kumaseli esibindi nama-adipocytes. U-Abdulrasheed nabanye banikeze amagundane aseWistar ukudla okunamafutha amaningi ukuze kubangele ukukhuluphala. Ukwelashwa kwe-UA akugcini nje ngokwandisa ukukhishwa kwamafutha endle, kodwa futhi kunciphisa isisindo sezicubu zamafutha ezicutshini kanye nesisindo somzimba ngokulawula izakhi zofuzo ezihlobene ne-lipogenesis kanye ne-oxidation ye-fatty acid. Kunciphisa ukuqongelela kwamafutha esibindi kanye nokucindezeleka kwawo kwe-oxidative. Ngesikhathi esifanayo, i-UA ingandisa ukusetshenziswa kwamandla ngokuthuthukisa i-thermogenesis yezicubu zamafutha ezinsundu kanye nokwenza amafutha amhlophe abe nsundu. Indlela iwukwandisa amazinga e-triiodothyronine (T3) emathunjini amafutha ansundu kanye nama-inguinal fat depots. Kwandisa ukukhiqizwa kokushisa futhi ngaleyo ndlela kulwisane nokukhuluphala.

Ngaphezu kwalokho, i-UA nayo inomphumela wokuvimbela ukukhiqizwa kwe-melanin. Izifundo zithole ukuthi i-UA inganciphisa kakhulu ukukhiqizwa kwe-melanin kumaseli e-melanoma e-B16. Indlela eyinhloko ukuthi i-UA ithinta ukusebenza kwe-tyrosinase okubangela ukuguga ngokuvimbela ukuncintisana kwe-tyrosinase yamaseli, ngaleyo ndlela inciphise umbala. Ngakho-ke, i-UA inamandla nokusebenza kahle kokwenza mhlophe nokukhanyisa amabala. Futhi ucwaningo lubonisa ukuthi i-urolithin A inomphumela wokuguqula ukuguga kwesistimu yokuzivikela komzimba. Ucwaningo lwakamuva luthole ukuthi uma i-urolithin A ingezwa njengesengezo sokudla, ayigcini nje ngokusebenza amandla endawo ye-lymphatic yesistimu yokuzivikela komzimba yegundane, kodwa futhi ithuthukisa umsebenzi wamaseli e-hematopoietic stem. Ukusebenza okuphelele kubonisa amandla e-urolithin A okulwa nokwehla kwesistimu yokuzivikela yomzimba okuhlobene nokuguga.

Ngamafuphi, i-UA, njenge-metabolite yamathumbu ye-phytochemicals yemvelo ye-ETs, idonsele ukunaka okukhulu eminyakeni yamuva nje. Njengoba ucwaningo ngemiphumela yezokwelapha kanye nezindlela ze-UA luba lukhulu futhi lujulile, i-UA ayisebenzi nje kuphela emdlavuza kanye ne-CVD (izifo zenhliziyo). Inomphumela omuhle wokuvimbela nokwelapha ezifweni eziningi zezokwelapha ezifana ne-ND (izifo ze-neurodegenerative) kanye nezifo ze-metabolic. Iphinde ibonise amandla amakhulu okusetshenziswa emikhakheni yobuhle nokunakekelwa kwempilo njengokulibazisa ukuguga kwesikhumba, ukunciphisa isisindo somzimba kanye nokuvimbela ukukhiqizwa kwe-melanin.

I-Suzhou Myland Pharm & Nutrition Inc. ingumkhiqizi obhalisiwe yi-FDA ohlinzeka nge-Urolithin A powder esezingeni eliphezulu futhi emsulwa.

KwaSuzhou Myland Pharm sizibophezele ekuhlinzekeni ngemikhiqizo esezingeni eliphezulu ngamanani amahle kakhulu. Impuphu yethu ye-Urolithin A ihlolwe ngokucophelela ukuhlanzeka kanye namandla, okuqinisekisa ukuthi uthola isithasiselo sekhwalithi ephezulu ongasithemba. Kungakhathaliseki ukuthi ufuna ukusekela impilo yamaseli, ukukhulisa amasosha omzimba wakho noma ukuthuthukisa impilo iyonke, impuphu yethu ye-Urolithin A iyisinqumo esifanele.

Njengoba ineminyaka engama-30 yesipiliyoni futhi iqhutshwa ubuchwepheshe obuphezulu kanye namasu e-R&D athuthukisiwe kakhulu, i-Suzhou Myland Pharm ithuthukise imikhiqizo ehlukahlukene encintisanayo futhi yaba yinkampani yezinsizakalo zesayensi yokuphila entsha, ukuhlanganiswa ngokwezifiso kanye nokukhiqiza.

Ngaphezu kwalokho, iSuzhou Myland Pharm nayo ingumkhiqizi obhalisiwe yi-FDA. Izinsizakusebenza ze-R&D zenkampani, izikhungo zokukhiqiza, kanye nezinsimbi zokuhlaziya zisesimanje futhi zisebenza ngezindlela eziningi, futhi zingakhiqiza amakhemikhali kusukela kuma-milligram kuya kumathani ngobukhulu, futhi zihambisana nezindinganiso ze-ISO 9001 kanye nemininingwane yokukhiqiza i-GMP.