Isayensi Engasemva kwe-Urolithin A: Oko Ufanele Ukwazi

I-Urolithin A (UA)yikhompawundi eveliswa yimetabolism yezityalo zamathumbu ekutyeni okutyebileyo kwi-ellagitannins (ezifana neepomegranate, iirasbheri, njl.njl.). Ithathwa njengene-anti-inflammatory, anti-aging, antioxidant, induction of mitophagy, njl.njl., kwaye inokunqumla umqobo wegazi-ubuchopho. Izifundo ezininzi ziqinisekisile ukuba i-urolithin A inokulibazisa ukuguga, kwaye izifundo zeklinikhi nazo zibonise iziphumo ezilungileyo.

Yintoni i-urolithin A?

I-Urolithin A (Uro-A) yi-metabolite ye-intestinal flora yohlobo lwe-ellagitannin (ET). Yafunyanwa ngokusesikweni yaza yathiywa igama ngo-2005. Ifomula yayo ye-molecular yi-C13H8O4, kwaye ubunzima bayo be-molecular buyi-228.2. Njengomphambili we-metabolism ye-Uro-A, imithombo yokutya ephambili ye-ET yiipomegranate, iistrawberry, iiraspberries, iiwalnuts kunye newayini ebomvu. I-UA yimveliso ye-ETs ezixutywe ziintsholongwane zamathumbu. I-UA inamathuba amaninzi okusetyenziswa ekuthinteleni nasekunyangeni izifo ezininzi. Kwangaxeshanye, i-UA inoluhlu olubanzi lwemithombo yokutya.

Kuye kwenziwa uphando malunga nemiphumo ye-antioxidant ye-urolithins. I-Urolithin-A ayikho kwimeko yendalo, kodwa iveliswa luchungechunge lotshintsho lwe-ET yizityalo zamathumbu. I-UA yimveliso ye-ETs exutywe ziintsholongwane zamathumbu. Ukutya okutyebileyo kwi-ET kudlula esiswini namathumbu amancinci emzimbeni womntu, kwaye ekugqibeleni kuxutywe ikakhulu kwi-Uro-A kumathumbu amakhulu. Inani elincinci le-Uro-A linokufunyanwa nakwimathumbu amancinci asezantsi.

Njengeekhompawundi ze-polyphenolic zendalo, ii-ET zitsale ingqalelo enkulu ngenxa yemisebenzi yazo yebhayoloji efana ne-antioxidant, anti-inflammatory, anti-allergy kunye ne-anti-viral. Ukongeza ekufumanekeni kokutya okufana neepomegranate, amastrawberry, ii-walnuts, ii-raspberries kunye nee-almond, ii-ET zikwafumaneka kwi-gallnuts, amaxolo epomegranate, i-myrobalan, i-Dimininus, i-geranium, i-betel nut, amagqabi e-sea buckthorn, i-Phyllanthus, i-Uncaria, i-Sanguisorba, Kumayeza aseTshayina afana ne-Phyllanthus emblica kunye ne-Agrimony.

Iqela le-hydroxyl kwisakhiwo se-molecular se-ETs likwi-polar, nto leyo engayivumeliyo ukufunxwa ludonga lwamathumbu, kwaye ukufumaneka kwayo kuphantsi kakhulu. Izifundo ezininzi zifumanise ukuba emva kokuba ii-ET zityiwe ngumzimba womntu, ziyaguqulwa yi-intestinal flora kwi-colon kwaye ziguqulwe zibe yi-urolithin ngaphambi kokuba zifunxwe. Ii-ETs zifunxwa zibe yi-ellagic acid (EA) kwindawo ephezulu yesisu, kwaye i-EA idluliselwa emathunjini. I-bacterial flora iyaqhubeka nokusebenza kwaye ilahlekelwe yi-lactone ring kwaye idlula kwiimpendulo ze-dehydroxylation eziqhubekayo ukuvelisa i-urolithin. Kukho iingxelo zokuba i-urolithin inokuba sisiseko sezinto ezibonakalayo zeziphumo zebhayoloji ze-ETs emzimbeni.

Yintoni enxulumene nokufumaneka kwe-urolithin?

Ukuba ulumkile, usenokuba sele uyazi ukuba i-bioavailability ye-UA inxulumene nantoni na.

Eyona nto ibalulekileyo kukwakheka kwe-microbiome, kuba ayizizo zonke iintlobo ze-microbial ezinokuvelisa. Izinto eziluhlaza ze-UA zii-ellagitannins ezifumaneka ekutyeni. Le nto isandul’ ukwenzeka ifumaneka lula kwaye iphantse ibe kuyo yonke indawo kwindalo.

Ii-Ellagitannins zifakwa kwi-hydrolyzed emathunjini ukuze zikhuphe i-ellagic acid, ethi icutshungulwe ngakumbi yi-intestinal flora ibe yi-urolithin A.

Ngokutsho kophando olukwiphephabhuku iCell, ngabantu abangama-40% kuphela abanokuguqula i-urolithin A ukusuka kwi-precursor yayo ibe yi-urolithin A esebenzisekayo.

Zithini imisebenzi ye-urolithin A?

Ukuthintela ukwaluphala

Ithiyori ye-free radical yokwaluphala ikholelwa ukuba iintlobo ze-oxygen ezisabelayo eziveliswa kwi-metabolism ye-mitochondrial zibangela uxinzelelo lwe-oxidative emzimbeni kwaye zikhokelela ekwaluphaleni, kwaye i-mitophagy idlala indima ebalulekileyo ekugcineni impilo ye-mitochondrial kunye nokuthembeka. Kuye kwaxelwa ukuba i-UA inokulawula i-mitophagy kwaye ngaloo ndlela ibonise amandla okulibazisa ukuguga. URyu et al. bafumanise ukuba i-UA inciphisa ukungasebenzi kakuhle kwe-mitochondrial kunye nobomi obude kwi-elegans ze-Caenorhabditis ngokubangela i-mitophagy; kwiimpuku, i-UA inokubuyisela umva ukuhla komsebenzi wemisipha onxulumene nobudala, okubonisa ukuba i-UA iphucula umsebenzi we-mitochondrial ngokuphucula ubunzima beMisipha kunye nokwandisa ubomi bomzimba. ULiu et al. basebenzise i-UA ukungenelela kwi-fibroblasts yolusu oludala. Iziphumo zibonise ukuba i-UA yonyusa kakhulu ukubonakaliswa kwe-type I collagen kwaye yanciphisa ukubonakaliswa kwe-matrix metalloproteinase-1 (MMP-1). Ikwasebenze ne-nuclear Factor E2-related factor 2 (nuclear factor erythroid 2-related factor 2, Nrf2)-mediated antioxidant response inciphisa i-ROS yangaphakathi kweseli, ngaloo ndlela ibonisa amandla aqinileyo okulwa nokwaluphala

Isiphumo se-antioxidant

Okwangoku, kwenziwe izifundo ezininzi malunga nefuthe le-urolithin le-antioxidant. Phakathi kwazo zonke ii-metabolites ze-urolithin, i-Uro-A inomsebenzi onamandla we-antioxidant, ilandela i-proanthocyanidin oligomers, ii-catechins, i-epicatechin kunye ne-3,4-dihydroxyphenylacetic acid. Uvavanyo lwe-oxygen radical absorbance capacity (ORAC) kwi-plasma yamavolontiya asempilweni lufumanise ukuba amandla e-antioxidant anyuke nge-32% emva kweeyure eziyi-0.5 zokuginya ijusi yepomegranate, kodwa umgangatho weentlobo ze-reactive oxygen awutshintshanga kakhulu, ngelixa kwi-Neuro-In vitro experiments kwiiseli ze-2a zifumanise ukuba i-Uro-A inokunciphisa umgangatho weentlobo ze-reactive oxygen kwiiseli. Ezi ziphumo zibonisa ukuba i-Uro-A inemiphumo enamandla ye-antioxidant.

03. I-Urolithin A kunye nezifo zentliziyo kunye nemithambo yegazi

Ukwanda kwesifo sentliziyo (i-CVD) kwihlabathi liphela kuyanda minyaka le, kwaye izinga lokufa lihlala liphezulu. Akugcini nje ngokunyusa umthwalo wentlalo nowezoqoqosho, kodwa kukwachaphazela kakhulu umgangatho wobomi babantu. I-CVD sisifo esibangelwa ziinkalo ezininzi. Ukudumba kunokunyusa umngcipheko we-CVD. Uxinzelelo lwe-oxidative lunxulumene ne-pathogenesis ye-CVD. Kukho iingxelo zokuba ii-metabolites ezivela kwiintsholongwane zamathumbu zinxulunyaniswa nomngcipheko we-CVD.

Kuye kwaxelwa ukuba i-UA ineempembelelo ezinamandla zokulwa nokuvuvukala kunye ne-antioxidant, kwaye izifundo ezifanelekileyo ziqinisekisile ukuba i-UA inokudlala indima eluncedo kwi-CVD. USavi et al. basebenzise imodeli yegundane lesifo seswekile ukwenza izifundo ze-in vivo kwi-cardiomyopathy yesifo seswekile kwaye bafumanisa ukuba i-UA inokunciphisa impendulo yokuqala yokuvuvukala kwezicubu ze-myocardial kwi-hyperglycemia, iphucule imeko-bume ye-myocardial, kwaye ikhuthaze ukubuyiselwa kwe-cardiomyocyte contractility kunye ne-calcium dynamics, nto leyo ebonisa ukuba i-UA ingasetyenziswa njengeyeza elincedisayo ukulawula i-cardiomyopathy yesifo seswekile kunye nokuthintela iingxaki zayo.

I-UA inokuphucula ukusebenza kwe-mitochondrial kunye nokusebenza kwemisipha ngokubangela i-mitophagy. I-mitochondria yentliziyo zii-organelles eziphambili ezinoxanduva lokuvelisa i-ATP etyebileyo kumandla. Ukungasebenzi kakuhle kwe-mitochondrial yimbangela yokusilela kwentliziyo. Ukungasebenzi kakuhle kwe-mitochondrial okwangoku kuthathwa njengento enokwenzeka yokunyanga. Ke ngoko, i-UA ikwaliyeza elitsha elifunekayo kunyango lwe-CVD.

I-Urolithin A kunye nezifo ze-neurological

Ukudumba kwe-neuroinflammation yinkqubo ebalulekileyo ekwakhiweni nasekuphuhlisweni kwesifo se-neurodegenerative (ND). I-apoptosis ebangelwa luxinzelelo lwe-oxidative kunye nokuhlanganiswa kweproteni okungaqhelekanga kudla ngokubangela ukudumba kwe-neuroinflammation, kwaye ii-cytokines ezibangela ukudumba ezikhutshwa yi-neuroinflammation emva koko zichaphazela ukudumba kwe-neuro.

Izifundo zifumanise ukuba i-UA ilawula umsebenzi wokulwa nokuvuvukala ngokubangela i-autophagy kunye nokusebenzisa indlela yokulawula isignali esithuleyo 1 (SIRT-1) deacetylation, ithintela ukudumba kwe-neuroinflammation kunye ne-neurotoxicity, kwaye ithintele ukuwohloka kwe-neuro, nto leyo ebonisa ukuba i-UA yiarhente esebenzayo yokukhusela i-Neuroprotective. Kwangaxeshanye, ezinye izifundo zifumanise ukuba i-UA inokuba nemiphumo yokukhusela i-neuroprotective ngokususa ngokuthe ngqo ii-free radicals kunye nokuthintela ii-oxidases.

Izifundo zibonise ukuba ijusi yepomegranate idlala indima yokukhusela imithambo-luvo ngokwandisa umsebenzi we-mitochondrial aldehyde dehydrogenase, ukugcina inqanaba leprotheyini yokulwa ne-apoptotic i-Bcl-xL, ukunciphisa ukuhlanganiswa kwe-α-synuclein kunye nomonakalo we-oxidative, kunye nokuchaphazela umsebenzi we-neuronal kunye nozinzo. Iikhompawundi ze-Urolithin zii-metabolites kunye neenxalenye zempembelelo ze-ellagitannins emzimbeni kwaye zinemisebenzi yebhayoloji efana nokulwa nokudumba, uxinzelelo lwe-anti-oxidative, kunye ne-anti-apoptosis. I-Urolithin inokusebenzisa umsebenzi wokukhusela imithambo-luvo ngokusebenzisa umqobo wegazi-ingqondo kwaye yimolekyuli encinci enokuthi isebenze ekungeneleleni kwizifo ze-neurodegenerative.

Izifo ze-Urolithin A kunye nezifo zokuwohloka kwamalungu kunye nomgogodla

Izifo eziwohlokayo zibangelwa zizinto ezininzi ezifana nokwaluphala, ukuxinana, kunye nokwenzakala. Ezona zifo ziqhelekileyo zokuwohloka kwamalungu yi-osteoarthritis (OA) kunye nesifo somgogodla esiwohlokayo sokuwohloka kwe-intervertebral disc (IDD). Ukwenzeka kwazo kunokubangela iintlungu kunye nomsebenzi omncinci, okubangela ukulahleka kwabasebenzi kunye nokubeka impilo yoluntu emngciphekweni omkhulu. Indlela ye-UA ekunyangeni isifo somgogodla esiwohlokayo I-IDD inokunxulunyaniswa nokulibazisa i-nucleus pulposus (NP) cell apoptosis. I-NP yinxalenye ebalulekileyo ye-intervertebral disc. Igcina umsebenzi webhayoloji we-intervertebral disc ngokusasaza uxinzelelo kunye nokugcina i-matrix homeostasis. Izifundo zifumanise ukuba i-UA ikhuthaza i-mitophagy ngokusebenzisa indlela ye-AMPK signaling, ngaloo ndlela ithintela i-tert-butyl hydroperoxide (t-BHP)-induced apoptosis yeeseli ze-NP ze-osteosarcoma cell zabantu kunye nokunciphisa ukuwohloka kwe-intervertebral disc.

I-Urolithin A kunye nezifo ze-metabolic

Ukuxhaphaka kwezifo ze-metabolic ezifana nokutyeba kakhulu nesifo seswekile kuyanda minyaka le, kwaye iziphumo ezilungileyo ze-polyphenols zokutya kwimpilo yabantu ziqinisekisiwe ngamaqela amaninzi kwaye zibonakalise amandla ekuthinteleni nasekunyangeni izifo ze-metabolic. Iipomegranate polyphenols kunye ne-metabolite yayo yamathumbu i-UA inokuphucula izalathisi zeklinikhi ezinxulumene nezifo ze-metabolic, ezifana ne-lipase, i-α-glucosidase (α-glucosidase) kunye ne-dipeptidyl peptidase-4 (dipeptidyl peptidase-4) ebandakanyeka kwi-glucose kunye ne-fatty acid metabolism. 4), kunye neejini ezinxulumene nazo ezifana ne-adiponectin, i-PPARγ, i-GLUT4 kunye ne-FABP4 ezichaphazela ukwahluka kwe-adipocyte kunye nokuqokelelwa kwe-triglyceride (TG).

Ukongeza, ezinye izifundo zifumanise ukuba i-UA inamandla okunciphisa iimpawu zokutyeba kakhulu. I-UA yimveliso ye-metabolism yamathumbu ee-polyphenols. Ezi metabolites zinamandla okunciphisa ukuqokelelwa kwe-TG kwiiseli zesibindi kunye nee-adipocytes. U-Abdulrasheed nabanye. Bondla iimpuku zeWistar ngokutya okunamafutha amaninzi ukuze babangele ukutyeba kakhulu. Unyango lwe-UA aluzange lonyuse kuphela ukukhutshwa kwamafutha kwindle, kodwa lukwanciphise ubunzima bezicubu ze-adipose ze-visceral kunye nobunzima bomzimba ngokulawula iijini ezinxulumene ne-lipogenesis kunye ne-fatty acid oxidation. Lunciphisa ukuqokelelwa kwamafutha esibindi kunye noxinzelelo lwaso lwe-oxidative. Kwangaxeshanye, i-UA inokunyusa ukusetyenziswa kwamandla ngokuphucula i-thermogenesis yezicubu ze-adipose ezimdaka kunye nokukhuthaza ukuntsundu kwamafutha amhlophe. Indlela kukunyusa amanqanaba e-triiodothyronine (T3) kwiindawo zokugcina amafutha amdaka kunye ne-inguinal fat. Lunyusa imveliso yobushushu kwaye ngaloo ndlela luchasa ukutyeba kakhulu.

Ukongeza, i-UA ikwanefuthe lokuthintela ukuveliswa kwe-melanin. Izifundo zifumanise ukuba i-UA inokwenza buthathaka kakhulu ukuveliswa kwe-melanin kwiiseli ze-melanoma ze-B16. Eyona ndlela iphambili kukuba i-UA ichaphazela ukusebenza kwe-tyrosinase ngokuthintelwa okukhuphisanayo kwe-tyrosinase yeseli, ngaloo ndlela inciphisa umbala. Ke ngoko, i-UA inamandla kunye nokusebenza kakuhle kokwenza mhlophe kwaye kukhanye amabala. Kwaye uphando lubonisa ukuba i-urolithin A inefuthe lokubuyisela ukuguga kwenkqubo yomzimba yokuzikhusela. Uphando lwamva nje lufumanise ukuba xa i-urolithin A yongezwa njengesongezelelo sokutya, ayisebenzi nje kuphela amandla ommandla we-lymphatic kwenkqubo yomzimba yokuzikhusela yegundane, kodwa ikwaphucula umsebenzi weeseli ze-hematopoietic stem. Ukusebenza ngokubanzi kubonisa amandla e-urolithin A okulwa nokuhla kwenkqubo yomzimba yokuzikhusela enxulumene nobudala.

Ngamafutshane, i-UA, njenge-metabolite yamathumbu ye-phytochemicals yendalo ye-ETs, itsale ingqalelo enkulu kwiminyaka yakutshanje. Njengoko uphando malunga nemiphumo ye-pharmacological kunye neendlela ze-UA lusanda kwaye lunzulu, i-UA ayisebenzi kuphela kumhlaza kunye ne-CVD (izifo zentliziyo). Inefuthe elihle lokuthintela kunye nonyango kwizifo ezininzi zeklinikhi ezifana ne-ND (izifo ze-neurodegenerative) kunye nezifo ze-metabolic. Ikwabonisa amandla amakhulu okusetyenziswa kwiindawo zobuhle kunye nokhathalelo lwempilo ezifana nokulibazisa ukuguga kolusu, ukunciphisa ubunzima bomzimba kunye nokuthintela ukuveliswa kwe-melanin.

I-Suzhou Myland Pharm & Nutrition Inc. ngumvelisi obhalisiweyo kwi-FDA obonelela ngomgubo we-Urolithin A okumgangatho ophezulu nococekileyo.

Apha eSuzhou Myland Pharm sizibophelele ekuboneleleni ngeemveliso ezikumgangatho ophezulu ngamaxabiso angcono. Umgubo wethu we-Urolithin A uvavanywa ngokungqongqo ubumsulwa kunye namandla, ukuqinisekisa ukuba ufumana isongezelelo esisemgangathweni onokusithemba. Nokuba ufuna ukuxhasa impilo yeseli, ukukhulisa amajoni akho omzimba okanye ukuphucula impilo iyonke, umgubo wethu we-Urolithin A lukhetho olufanelekileyo.

Ngamava angama-30 eminyaka kwaye eqhutywa bubuchwepheshe obuphezulu kunye namaqhinga ophando nophuhliso aphucukileyo, iSuzhou Myland Pharm iphuhlise uluhlu lweemveliso ezikhuphisanayo kwaye yaba yinkampani yeenkonzo zokongeza izinto ezintsha zesayensi yobomi, ukwenziwa kwezinto ngokwezifiso kunye neenkonzo zokuvelisa.

Ukongeza, iSuzhou Myland Pharm ikwangumvelisi obhalisiweyo yi-FDA. Izixhobo zeR&D zenkampani, izixhobo zemveliso, kunye nezixhobo zokuhlalutya zizinto zanamhlanje kwaye zisebenza ngeendlela ezininzi, kwaye zinokuvelisa iikhemikhali ukusuka kwi-milligrams ukuya kwiitoni ngobukhulu, kwaye zihambelana nemigangatho ye-ISO 9001 kunye neenkcukacha zemveliso ze-GMP.