I-Urolithin (1143-70-0) (1139-83-9) - Ifektri yomkhiqizi

I-Urolithin

ICofftek inamandla okukhiqiza ngobuningi kanye nokuhlinzeka nge-urolithin a ne-urolithin b ngaphansi kwesimo se-cGMP.

Isingeniso ku-Urolithins

Ama-Urolithin angama-metabolites wesibili we-ellagic acid asuselwa kuma-ellagitannins. Kubantu ama-ellagitannins aguqulwa yi-gut microflora ibe yi-ellagic acid ephinde iguqulwe ibe ama-urolithins A, urolithin B, urolithin C kanye ne-urolithin D emathunjini amakhulu.

I-Urolithin A (UA) yi-metabolite edume kakhulu yama-ellagitannins. Kodwa-ke, i-urolithin A ayaziwa ukuthi ivela ngokwemvelo kunoma iyiphi imithombo yokudla.

I-Urolithin B (UB) iyi-metabolite eningi ekhiqizwa emathunjini ngokuguqulwa kwama-ellagitannins. I-Urolithin B ingumkhiqizo wokugcina ngemuva kokuthi wonke amanye ama-urolithin derivatives ehlehlisiwe. I-Urolithin B itholakala emchameni njenge-urolithin B glucuronide.

  I-Urolithin A 8-Methyl Ether ingumkhiqizo ophakathi ngesikhathi sokuhlanganiswa kwe-Urolithin A. I-metabolite yesibili ephawulekayo ye-ellagitannin futhi inezakhiwo ze-antioxidant nezokulwa nokuvuvukala.

Indlela yokusebenza kwe-urolithin A no-B

● I-Urolithin A iheha i-mitophagy
I-Mitophagy enye indlela ye-autophagy esiza ukuqeda i-mitochondrial eyonakele ekusebenzeni kwayo okuhle. I-Autophagy isho inqubo esetshenziswayo lapho okuqukethwe kwe-cytoplasmic kuncekelwa khona futhi ngenxa yalokho kuphinde kusetshenziswe kabusha ngenkathi i-mitophagy kungukuwohloka nokuphinda kusetshenziswe kabusha i-mitochondria.

Ngesikhathi sokuguga ukwehla kokuzenzakalela ngesici esisodwa esiholela ekwehleni komsebenzi we-mitochondrial. Ngaphezu kwalokho, ukucindezelwa kwe-oxidative nakho kungaholela ekuzenzakaleni okuphansi. I-Urolithin A inekhono lokususa i-mitochondria eyonakele ngokusebenzisa i-autophagy ekhethiwe.

● Izakhi ze-antioxidant
Ukucindezela kwe-Oxidative kwenzeka lapho kunokungalingani phakathi kwama-radicals mahhala ne-antioxidant emzimbeni. Le radicals yamahhala ngokweqile ivame ukuhlotshaniswa nezifo eziningi ezingamahlalakhona ezinjengezifo zenhliziyo, isifo sikashukela nomdlavuza.

Ama-Urolithins A no-B abonisa imiphumela ye-antioxidant ngokusebenzisa amandla abo ukunciphisa ama-radicals wamahhala futhi ikakhulukazi amazinga we-oksijini we-oxygen (ROS) we-intracellular futhi enhibit peroxidation ezinhlotsheni ezithile zeseli.

Ngaphezu kwalokho, ama-urolithin akwazi ukuvimbela ama-enzyme athile e-oxidizing, kufaka phakathi i-monoamine oxidase A ne-tyrosinase.

● Izakhiwo ezilwa nokuvuvukala
Ukuvuvukala kuyinqubo engokwemvelo lapho imizimba yethu ilwa nanoma yikuphi ukuwa okufana nokutheleleka, ukulimala, namagciwane. Kodwa-ke, ukuvuvukala okungamahlalakhona kungaba yingozi emzimbeni ngoba lokhu kuhlotshaniswa nokuphazamiseka okuhlukahlukene okufana nesifuba somoya, izinkinga zenhliziyo, nomdlavuza. Ukuvuvukala okungamahlalakhona kungenzeka ngenxa yokuvuvukala okukhulu okungalashwa, ukutheleleka noma ama-radicals mahhala emzimbeni.

Ama-Urolithins A no-B abonisa izakhiwo ezilwa nokuvuvukala ngokuvimbela ukukhiqizwa kwe-nitric oxide. Zinqabela ngokuthe ngqo i-nitric oxide synthase (iNOS) ye-nitric oxide synthase (iNOS) ne-mRNA enesibopho sokuvuvukala.

● Imiphumela elwa namagciwane
Imicrobes kufaka phakathi amagciwane, isikhunta kanye namagciwane kwenzeka ngokwemvelo emvelo futhi nasemzimbeni womuntu. Kodwa-ke, amagciwane ambalwa abizwa ngokuthi ama-pathogen angadala izifo ezithathelwanayo njengomkhuhlane, isimungumungwane kanye nomalaleveva.

I-Urolithin A no-B ziyakwazi ukubonisa umsebenzi we-antimicrobial ngokuvimbela umuzwa we-quorum. Ukuzwela i-Quorum kuyindlela yokuxhumana kwamagciwane enikeza ama-bacterium ukubona futhi alawule izinqubo ezihlobene nokutheleleka ezifana ne-virulence and motility.

● Ukuvimbela amaprotheni glycation
I-Glycation isho okunamathiselwe ushukela okungewona okwama-enzymatic kashukela ku-lipid noma iprotheni. I-biomarker ebalulekile kushukela nezinye izifo kanye nokuguga.

I-glycation ephezulu yamaphaphu ngumphumela wesibili we-hyperglycemia onendima enkulu ekuphazamisekeni okuhlobene nenhliziyo njengesifo sikashukela nesifo i-Alzheimer's.

I-Urolithin A ne-B inezindawo zokulwa ne-glycative ezixhomekeke kumthamo ezizimele zomsebenzi wazo we-antioxidant.

Izinzuzo ze-Urolithin A no-B

Ama-Urolithin anemiphumela eminingi ezuzisayo esekelwa ngubufakazi obususelwa ocwaningweni bezinto ezilwa nokuvuvukala, i-anti-carcinogenic, antioxidant, ne-antimicrobial. Izinzuzo ze-Urolithin A zihlobene kakhulu nezinzuzo ze-urolithin B. Ngezansi kunezinye izinzuzo ezibikwe kuma-urolithin;
Izinzuzo ze-Urolithin A
(1) Ingangezela isikhathi sokuphila
I-Urolithin A ifaka i-mitophagy ngokukhetha ukususa i-mitochondria eyonakalisiwe. Lokhu futhi kuqinisekisa ukwenziwa kabusha kwe-mitochondria yokusebenza kahle. IMitochondria imvamisa ilimala ngeminyaka futhi futhi ngenxa yengcindezi. Ukuqeda i-mitochondria eyonakalisiwe kudlala indima ekwandiseni isikhathi sokuphila.

Ekutadisheni izibungu, i-urolithin Isengezo esilawulwa ku-50 µM kusuka esigabeni seqanda kuze kube sekufeni kutholakele ukwelula isikhathi sabo sokuphila ngo-45.4%.

Kwesinye isifundo esenziwe ngo-2019 kusetshenziswa ama-fibroblasts womuntu we-senescent, i-urolithin A supplement yatholakala ukukhombisa amandla wokulwa nokuguga. Ikwazile ukwandisa uhlobo lwe-1 collagen expression futhi yehlisa nencazelo ye-matrix metalloproteinase 1.

Ucwaningo oluncane lwabantu lubonisa nokuthi i-UA yayikwazi ukuthuthukisa ukusebenza kwe-mitochondrial nempilo yamathambo kubantu asebekhulile lapho iphathwa ngomlomo ku-500-1000mg isikhathi esingamasonto amane.

(2) Siza ukuvimbela umdlavuza wendlala yesinye
Ama-urolithin kanye nomanduleli wawo, ama-ellagitannins, anezinto ezilwa nomdlavuza. Bayakwazi ukuvimbela ukwanda komdlavuza weseli ngokuboshwa komjikelezo wamaseli nangokufaka i-apoptosis. I-Apoptosis isho ukufa okuhleliwe okuhleliwe lapho umzimba ususa khona umdlavuza-amaseli namanye amaseli angenwe yileli gciwane.

Ocwaningweni lwamagundane ajovwe ngamaseli womdlavuza womuntu, kwatholakala ukuthi i-ellagitannins metabolites (Urolithin A) ivimbela ukukhula komdlavuza wendlala yesinye. Ucwaningo luphinde lwabika ukugcwala okuphezulu kwama-metabolites emzimbeni we-Prostate gland, colon kanye nezicubu zamathumbu.

(3) Ukuthuthukiswa kwengqondo
I-Urolithin A iyakwazi ukuvikela ama-neurons ekufeni futhi ingadala neurogeneis ngokusebenzisa ukusayina okulwa nokuvuvukala.

Esifundweni samagundane kanye nokukhubazeka kwememori, kutholakale ukuthi i-urolithin A ilungisa ukungalungiswa kwengqondo futhi ivikele nama-neurons ekuqopheni. Lokhu kuphakamisa ukuthi i-UA ingasetshenziswa ekwelapheni isifo se-Alzheimer's (AD).

(4) Amandla wokulwa nokukhuluphala
Ucwaningo lukhombisa ukuthi ama-ellagitannins ayakwazi ukuvimba ukuqongelela i-lipid futhi amaka we-adipogenic anjenge-protein ukukhula kwe-protein 2 kanye ne-protein-binding binding ngokubopha umjikelezo weseli.

I-Urolithin A itholakele ngqo ukuze ithuthukise umuzwa we-insulin ngaleyo ndlela ivimbela ukuthuthukiswa kokukhuluphala.

Ocwaningweni lwamagundane anesifo sokukhuluphala, i-urolithin A supplementation yatholakala ukuvikela ukukhuluphala okubangelwa ukudla kanye nokuphazamiseka kwe-metabolic kumagundane. Ucwaningo luveze ukuthi ukwelashwa kwe-UA kwandisa izindleko zamandla ngakho-ke isisindo somzimba esiphansi.

Izinzuzo ze-Urolithin B
Izithako ze-Urolithin B nazo zinezinzuzo eziningana zezempilo futhi iningi lazo lifana nezinzuzo ze-urolithin A.

(1) Amandla okulwa nomdlavuza
Izici zokulwa nokuvuvukala ze-urolithin B zenza kube yilowo okhetha ukulwa nomdlavuza. Abanye abacwaningi babike la mandla kuma-fibroblasts, microphages namaseli endothelial.

Ucwaningo luye lwabika ukuthi i-UB ivimbela izinhlobo ezahlukene zomdlavuza onjenge-Prostate, ikholoni nomdlavuza wesinye.

Ocwaningweni oluthinta amangqamuzana omdlavuza womuntu we-colon, ama-ellagitannins, ama-ellagic acid kanye ne-urolithins A no-B ahlolwa ukuze akwazi ukuhlasela umdlavuza. Babike ukuthi zonke izindlela zokwelapha zikwazile ukuvimba ukukhula kwamaseli womdlavuza. Zivimbela amaseli omdlavuza ukuba ande ngokuboshwa kwamaselula ngomjikelezo ezigabeni ezahlukahlukene nangokuvuselela i-apoptosis.

(2) Ingasiza ukulwa nokucindezeleka okwenziwe nge-oxidative
I-Urolithin B inezindawo ezinhle kakhulu zokulwa ne-antioxidant ngokunciphisa amazinga ezinhlobo zomoya-mpilo kanye ne-lipid peroxidation ezinhlotsheni ezithile zamaseli. Amazinga aphezulu e-ROS ahlotshaniswa nokuphazamiseka okuningi okufana nesifo i-Alzheimer's.

Ocwaningweni olunamaseli we-neuronal avezwe ekucindezelekeni kwe-oxidative, i-urolithin B supplement kanye ne-urolithin A kutholakale ukuvikela amaseli ekulweni ne-oxidation yingakho kwandise ukusinda kweseli.

(3) Urolithin B ekuthuthukiseni inkumbulo
Kubikwa ukuthi i-Urolithin b yathuthukisa ukutholakala kwegazi-barriers. Lokhu kuthuthukisa ukusebenza kwengqondo.

Ucwaningo lukhombisa ukuthi i-urolithin B ingaba isithuthukisi sememori ngokuthuthukisa ukusebenza kwengqondo okujwayelekile.

(4) Kuvimbela ukulahleka kwemisipha
Ukulahleka kwemisipha kungenzeka ngenxa yezizathu ezahlukahlukene njengokuphazamiseka, ukuguga nokuntuleka kwamaprotheni ekudleni. Izindlela eziningana zokumisa, ukukhawulela noma ukuvikela okungcono ukulahleka kwemisipha kufaka phakathi, ukuzivocavoca, izidakamizwa nama-amino acid kanye nama-polyphenols angaqashwa.

Ama-Urolithins angahlukaniswa njengama-polyphenols futhi adlala indima ekuvimbeleni ukulahleka kwemisipha ngokwenza kusebenze izicubu zamaprotheni omzimba futhi kunciphise nokuncipha kokuwohloka.

Ocwaningweni olwenziwe ngamagundane, izakhamzimba ze-Urolithin B ezilawulwa isikhathi eside zatholakala ukuthuthukisa ukukhula kwemisipha yazo njengoba izicubu bezibonakala zikhula.  

(5) Urolithin B ulwa nokuvuvukala
I-Urolithin B inezindawo ezilwa nokuvuvukala ngokunciphisa izimpawu zokuvuvukala iningi.

 Esicwaningweni samagundane angena nge-renal fibrosis eyenziwe ngeso lokhozi, kutholakale ukuthi i-urolithin B ilungisa ukulimala kwezinso. Kuthuthukise umsebenzi wezinso, i-morphology yezinso futhi yanciphisa abamaki bokulimala bezinso. Lokhu kukhombisa ukuthi i-UB ibikwazi ukunciphisa ukuvuvukala kwe-renal.

(6) Izinzuzo ze-synergistic ze-urolithin A no-B
Imiphumela ye-Synergistic nayo ibikiwe ngokuhlanganiswa kwe-urolithin A no-B ekusebenzeni kwengqondo nasemandleni. Ucwaningo luthi le nhlanganisela ingasetshenziswa ekwelapheni noma ekuvimbeleni ukuphazamiseka okuhlobene nokuwohloka komqondo njengokukhathazeka noma ukuphazamiseka kwe-Alzheimer's.

Ezinye izinzuzo ezihambisana nama-urolithins yilezi;
  • neuroprotection
  • I-Ameliorates metabolic syndrome

Imithombo yokudla ye-Urolithin A no-B

Ama-urolithin akwaziwa ukuthi atholakala ngokwemvelo kunoma yimiphi imithombo yokudla. Bawumkhiqizo wokuguqulwa kwama-asidi we-ellagic aqhamuka kuma-ellagitannins. Ama-Ellagitannins aguqulwa aba ama-ellagic acid yi-gut micobiota futhi i-ellagic acid ibuye iguqulwe ibe yi-metabolites yayo (ama-urolithins) emathunjini amakhulu.

  Ama-ellagitannins avela ngokwemvelo emithonjeni yokudla njengamapomegranati, amajikijolo afaka ama-strawberry, ama-raspberries, ama-cloudberries nama-blackberries, amagilebhisi e-muscadine, ama-alimondi, amagwava, itiye namantongomane afana nama-walnuts nama-chestnuts kanye neziphuzo ezineminyaka engama-oki ngokwesibonelo iwayini elibomvu ne-whisky evela imiphongolo ye-oki.

Ngakho-ke singaphetha ngokudla kwe-urolithin A kanye nokudla kwe-urolithin B ukudla okunothe i-ellagitannin. Kubalulekile ukuqaphela ukuthi i-ellagitannin bioavailability incane kakhulu ngenkathi ama-metabolites ayo wesibili (ama-urolithins) etholakala kalula.

Ukukhishwa nokukhiqizwa kwe-Urolithins kuyahlukahluka kakhulu phakathi kwabantu kusukela ukuguqulwa kusuka kuma-ellagitannins kuncike kwi-microbiota esiswini. Kunamagciwane athile athintekayo kulokhu kuguqulwa futhi ayahlukahluka kubantu lapho abanye benama-microbiota aphezulu, aphansi noma engekho. Imithombo yokudla nayo iyahlukahluka emazingeni e-ellagitannins awo. Ngakho-ke izinzuzo ezingaba khona zama-ellagitannins ziyahlukahluka kuye ngomunye umuntu.

Izithasiselo ze-Urolithin A no-B

Izithako ze-Urolithin A kanye nezithasiselo ze-Urolithin B zitholakala kalula emakethe njengezithako zokudla ezinothe nge-ellagitannin. Izithasiselo ze-Urolithin A nazo ziyatholakala kalula. Kakhulu izengezo zamapomegranati zithengiswe kabanzi futhi zasetshenziswa ngempumelelo. Lezi zithasiselo zihlanganiswa nezithelo noma amantongomane bese zenziwa zaba uketshezi noma ifomu lempuphu.

Ngenxa yokuhlukahluka kokugxila kwe-ellagitannins ekudleni okwehlukile, amakhasimende e-urolithin ayithenga ecubungula umthombo wokudla. Okufanayo kusebenza lapho kutholwa i-urolithin B powder noma izengezo zoketshezi.

Izifundo ezimbalwa zomtholampilo zabantu ezenziwa nge-urolithin A powder noma B azange zibike noma yimiphi imiphumela emibi evela ekuphathweni kwalezi zithasiselo.

Izikhombo:

  1. UGarcia-Munoz, uCristina; UVaillant, uFabrice (2014-12-02). "I-Metabolic Fate ye-Ellagitannins: Imiphumela Yezempilo, Nemibono Yocwaningo Yezinto Ezintsha Zokudla Okusebenzayo". Ukubuyekezwa Okubalulekile kuSayensi Yezokudla Nondlekile.
  2. UBialonska D, uKasimsetty SG, uKhan SI, uFerreira D (11 Novemba 2009). "Ama-Urolithins, ama-metabolites amancane emathunjini we-Pomegranate ellagitannins, akhombisa umsebenzi onamandla we-antioxidant ekuhlolweni okususelwa kuseli". J Agric Ukudla Chem.
  3. UBodwell, uGraham; UPottie, u-Ian; INandaluru, iPenchal (2011). "I-Inverse Electron-Demand Diels-Alder-based Total Synthesis ye-Urolithin M7".