Urolithin ufa

1.Urolithin A Backgroud

Phindu la khangaza lachititsa ofufuza kuti afufuze momwe zipatso zofiira izi zingatithandizire kukhala athanzi. Pakufufuza kwaposachedwa, ofufuza aku Switzerland apeza molekyulu yatsopano yomwe imadza chifukwa chotsegula mankhwala awiri omwe amapezeka m'makangaza: punicalagins ndi ellagitannins. Molekyu yapaderayi, yotchedwa urolithin A, imathandizira kukonzanso mitochondria, nyumba zathu zamagetsi zamagetsi. Urolithin A imatsegula chitseko cha chithandizo chamankhwala chatsopano chothana ndi zovuta zokhudzana ndi ukalamba, kuphatikiza kufooka, komwe kumayambitsa chiwopsezo cha anthu olumala, ogonekedwa mchipatala, komanso omwalira.

2.Urolithin A mwachidule

Urolithin A ndi mankhwala a metabolite, omwe ali m'gulu la mankhwala omwe amadziwika kuti benzo-coumarins. Ndizopangidwa kumapeto kwa chakudya chomwe chimakhala ndi ellagitannins (polyphenols) ndipo chimagwiritsidwa ntchito ndimatenda amthupi. Mwanjira ina, Urolithin A amapangidwa pamene munthu ameza chakudya chomwe chili ndi ellagitannins.

Urolithin A sichimachitika mwachilengedwe pamapeto pake. Zakudya za Ellagitannin, monga mitundu ina ya zipatso ndi makangaza, ziyenera kupukusidwa ndi mabakiteriya am'mimba kuti apange. Kuti kampaniyo igwiritse ntchito moyenera, imayenera kupangidwa mu labu, kapena mwanjira ina, Urolithin A iyenera kupangidwa kuti izitha kugwiritsidwa ntchito.

3.Urolithin Njira Yogwirira Ntchito

Kodi Urolithin A amagwira ntchito bwanji? Ellagic acids ndi Ellagitannins ndi omwe amatsogolera Urolithin A.

Ellagitannins amatulutsidwa kuchokera m'matumbo kuti atulutse Ellagic acid, ndipo izi zimakonzedwa kuchokera m'matumbo microflora kupita ku urolithins kudzera mukuwonjezeka kochulukirapo mu 1 mwa ma lactones awiri motsatizana kuchotsa magulu a hydroxyl. Mukamadya m'matumbo, Urolithin A ufa umalowa mu dongosolo la m'matumbo.

Mitophagy, malinga ndi tanthauzo la Wikipedia, ndiye kuwonongeka kwa mitochondria yanu mwa kudzipangira. Nthawi zambiri zimapezeka ndi mitochondria yolakwika pambuyo povulala kapena kupsinjika. Komabe, tikamakalamba, ntchito ya Mitophagy imayamba kuchepa. Mwamwayi, Urolithin A imavomerezedwa kuti ipangitse mitophagy m'njira yosungidwa pamitundu yosiyanasiyana.

4. Ubwino/Zotsatira za Urolithin A

❶ Urolithin A Athandiza Kuthetsa Khansa

Ngakhale chithandizo chamankhwala opondereza komanso chemotherapy, pafupifupi 50% ya anthu omwe ali ndi khansa yoyipa amayamba zotupa zobwerezabwereza. Izi zikhoza kukhala chifukwa cha kupulumuka kwa maselo oopsa a khansa ya m'matumbo omwe amatsutsana ndi mankhwala ochiritsira komanso "mbewu" za khansa.
Pazosangalatsa, ofufuza adatulutsa maselo am'magazi a khansa m'matumbo kuchokera kwa wodwala yemwe ali ndi khansa yamtundu wamtundu uliwonse osakaniza okhala ndi 85% urolithin A kapena 30% urolithin A. Zotsatirazo zinali zosangalatsa. Kusakanikirana kwakukulu kwa urolithin Kusakanikirana kwamtunduwu kunali kothandiza kwambiri poletsa kuchuluka ndi kukula kwa maselo am'magazi a khansa ya m'matumbo ndikuletsa ntchito ya aldehyde dehydrogenase, chodziwitsa chemoresistance.

❷ Urolithin A - Neuroprotective Effects

Kulumikizana pakati pa makangaza ndi zotsatira zake zoteteza ku matenda a Alzheimer's kwakhazikitsidwa bwino pamaphunziro a zinyama.8 Komabe, zomwe zimayambitsa bioactive pankhaniyi sizimadziwika mpaka pano.
Matenda a Alzheimer akuyembekezeka kukhudza anthu opitilira 115 miliyoni padziko lonse pofika chaka cha 2050. Gulu la ofufuza lidayang'ana kafukufuku wakale wazinyama yemwe adanenapo zakusagwirizana ndi Alzheimer's zotsatira za makangaza.
Gululi linayesa kuthekera kwa zigawozi kudutsa malire a magazi ndi ubongo ndipo anapeza kuti mtundu wa methylated wa urolithin A (mUA), wochokera ku khangaza, pamodzi ndi ma urolithin ena amatha kutero.
Ndipo, ngakhale kuti pakufunika kafukufuku wambiri, olembawo adatsimikiza kuti ma urolithin ndi omwe amathandizira pazomwe zimayambitsa matenda a Alzheimer's omwe amateteza ku neurotoxicity ndi b-amyloid fibrillation. Zotsatirazi zikulonjeza, ndikuwonetsa kufunikira kofufuza njira zina zachilengedwe zopewera zakudya zopewera kapena kuchepetsa kukula kwa matenda a Alzheimer's.
Zotsatira ndi zomwe zapezeka m'maphunziro osiyanasiyanawa zimathandiziranso kufunikira kwa mankhwala a polyphenol metabolite monga urolithin A ochokera ku makangaza ndi gawo lawo polimbana ndi khansa ya m'matumbo ndi matenda opatsirana pogonana.
Kafukufuku adawonetsanso kuti Urolithin A imatha kulimbikitsa kulimba kwa minofu ndi kupirira kwa okalamba. Kafukufuku waposachedwa akuwonetsa kuti umboni woyambirira ukupereka zabwino zina za Urolithin A, kuphatikiza izi:

-Kuthana ndi zotupa
- Anticarcinogenic
-Zosakaniza
-Zosangalatsa
-Tizilombo toyambitsa matenda

Urolithin A imawonekeranso ngati chowonjezera pazopangira mapuloteni kuti athandize kuchita masewera olimbitsa thupi, komanso kuchepetsa kunenepa kwambiri.

5.Urolithin A Zotsatirapo

M'mayesero achipatala a anthu omwe tawatchulawa, palibe choyipa zotsatira zoyipazi zinanenedwa. Pakafukufuku wotsatizana wamaphunziro azachipatala komanso azachipatala, zikuwoneka kuti pali umboni wotsimikizira chitetezo cha kugwiritsa ntchito Urolithin A.

Palibe zotulukapo zowopsa zomwe zafotokozedwapo, ngakhale m'maphunziro omwe amakhudza kwambiri makoswe m'maphunziro amenewo.

6.Urolithin A Zakudya Zakudya

Monga tanenera, Urolithin A pamapeto pake samawoneka mwachilengedwe. Sidziwika kuti amapezeka m'malo aliwonse opangira chakudya. Komabe, choyambirira cha panganolo chitha kupezeka mu zipatso ndi mtedza wina. Zakudya zomwe zimakhala ndi ellagitannins monga makangaza, rasipiberi, strawberries, cloudberries, ndi walnuts ndi zitsanzo.

Ma ellagitannins a zipatso ndi mtedzawu amapangidwa ndi hydrolyzed m'matumbo kuti apange ellagic acid, yomwe imakonzedwa m'matumbo ndikupukutidwa ndi m'matumbo microflora ku Urolithin A.

Ndikofunika kudziwa kuti Urolithin A samachitika nthawi zonse akamamwa. Matumbo a anthu ena alibe microflora yosakanikirana bwino kuti asinthe ellagic acid kukhala Urolithin A. Izi zikutanthauza kuti si aliyense amene angatulutse Urolithin A m'matumbo awo ngati adya makangaza, mtedza, kapena zipatso. Zonse zimadalira m'matumbo mabakiteriya omwe amapezeka mthupi lanu.

7.Urolithin Njira Yopangira

Urolithin A amapangidwa kudzera pamankhwala opangira pogwiritsa ntchito imodzi mwanjira zomwe tafotokozazi. Zonsezi zimakhudza kuyanjana kwa Ullmann, kutsatiridwa ndi mankhwala a Lewis acid kuti apange urolithin A woyeretsedwa kwambiri.

Chomaliza chimatsukidwa ndi njira zochiritsira zosungunulira, zosefedwa, zotsukidwa, ndi zouma kuti zipeze urolithin A. Chogulitsidwacho pambuyo pake chimachepetsa kukula kwa tinthu.

Malinga ndi njira zokhazikitsidwa bwino, Urolithin A ufa umapangidwa mwaluso ndikuyeretsedwa munjira zingapo zazikulu mpaka 99%. Zida zopangira ndi njira zopangira zomwe zimakhudzidwa ndi kaphatikizidwe ka urolithin A zimaphatikizapo 2-Bromo-5-methoxy benzoic acid, 2-Bromo-5-hydroxy benzoic acid, Resorcinol, 50% sodium hydroxide, Copper sulfate pentahydrate, Methanol, Aluminium chloride, Toluene. , DMSO, Methanol, Acetic Acid, ndi TBME (tert-butyl-methyl ether).

8.Synthetic Urolithin A VS Natural Urolithin A

Monga tafotokozera pamwambapa, Urolithin A ndi m'mimba mwa mabakiteriya a ellagitannins (ET) kapena ellagic acid (EA). Ngati mukufuna kupeza Urolithin A wambiri, muyenera kuyamba kudya zipatso zazikulu, kenako ndikuwadikirira kuti achoke ku ellagitannins ndi ellagic acid kupita ku Urolithin A. Njirayi ndi yayitali, ndipo ndi yoyera kwambiri, ndipo koposa zonse , zikhala zodula kwambiri kutero.

Sikuti aliyense ali ndi microflora yoyenera yomwe imatha kupanga metabolite. Kuphatikiza apo, njirayi siyingagwiritsidwe ntchito popanga misa mu malo opanga ovomerezeka a GMP.

Nkhani yabwino ndiyakuti, ngati chinthu chatsopano, Urolithin A pamapeto pake amapezeka ku 2019 kuchokera ku Cima Science. Tsopano itha kupangidwa mu labu ndi fakitale. Kupanga kwa urolithin A kumafanana mofanana ndi urolithin A. Kuthekera kopanga zinthu kumafika 3000 kgs kapena 2.5 matani / mwezi.

9.Urolithin A Chitetezo

Urolithin A imavomerezedwa ndi European Union ngati chakudya chatsopano.

US Food and Drug Administration (FDA) mu 2018 yapatsa urolithin A momwe GRAS imagwiritsidwira ntchito pazakudya zowonjezera. GRAS imatanthauza kuti Urolithin A nthawi zambiri imawoneka ngati yotetezeka ndi mulingo wa 500mg mpaka 1 gramu pakatumikira.

Urolithin A chitetezo chidafufuzidwa pamayeso angapo azachipatala komanso zamankhwala, zomwe zimalimbikitsa chitetezo chaumoyo pazogwiritsira ntchito. Kuchulukitsa kwamasiku 28 ndi maphunziro a masiku 90 a urolithin A mu makoswe sikunawonetsere kuwopsa kwa zoopsa zina mwa magawo omwe amayesedwa munjira iliyonse yomwe adayesedwa.

10.Mwalandiridwa Kugula Urolithin A/Urolithin A 8-Methyl Ether Bulk Powder kuchokera ku AASraw!

Kupezeka kwa urolithin A, komwe kumachokera ku ma punicalagins ndi ellagitannins omwe amapezeka m'makangaza, kumapereka mipata yatsopano yolimbana ndi kuchepa kwa ntchito ya mitochondrial komanso kufooka ndi kutayika kwa minofu.

Mwa kuthandiza maselo kuti adzikonzenso okha ndikuthandizira kugwira ntchito kwa minofu, makangaza ndi mankhwala ake aposachedwa kwambiri, urolithin A-atha kuchita bwino.

Kuphatikiza pa zomwe apezazi, pali umboni wotsimikizira za mphamvu zomwe urolithin A ali nazo motsutsana ndi matenda a Alzheimer ndi khansa, zomwe zimaperekanso chida china cholimbana ndi mikhalidwe yowonongekayi yomwe imakhudza anthu ambiri okalamba.

Njira yazakudya iyi imatsegula mwayi womwe njira zamankhwala zamankhwala sizinafufuzepo. Ngati mukufuna kugula Urolithin A ufa / Urolithin A 8-Methyl Ether ufa, AASraw mwina kusankha bwino.

11.Urolithin A VS Urolithin B

Onse a Urolithin B ndi Urolithin A ufa amagwiritsidwa ntchito pazowonjezera, koma ndi zopindulitsa zosiyanasiyana. Amagwira ntchito ndi njira yosiyana. Urolithin A makamaka ndi njira yolimbana ndi ukalamba pamakina ake a mitophagy pomwe urolithin B ali muzakudya zamasewera ngati chopangira chomanga minofu.

Urolithin A ndi mankhwala ofufuzidwa bwino kwambiri, omwe nthawi zambiri amawaona ngati otetezeka (GRAS) ndi FDA, pamene urolithin B sali. Pali mitundu yowonjezereka yogwiritsira ntchito urolithin A kuposa urolithin B.

Urolithin A ndi Urolithin B ndizogwirizana. Chotsitsa cha makangaza chili ndi ma urolithin onsewa. Makangaza ndi pachimake pa zipatso. Pambuyo pa chimbudzi, zigawo zawo zomwe zili m'matumbo zimatha kusinthidwa ndi zomera za m'matumbo kukhala urolithin C ndiyeno kusinthidwa kukhala Urolithin D ndi A, kenako Urolithin B. M'lingaliro limeneli, urolithin A akhoza kusinthidwa kukhala urolithin B.

Chifukwa chake, urolithin B wochepa amatha kupezeka m'magazi a anthu omwe amadyetsedwa ndi makangaza; komabe, antioxidant ndi anti-inflammatory properties ndi zofooka kwambiri kuposa urolithin A. Komabe, urolithin B ili ndi ubwino wake kuposa urolithin A. Imatha kuwonjezera kukula kwa maselo a minofu ndikufulumizitsa minofu kukula.

12.Urolithin B Kufotokozera

Urolithin B ndi urolithin, mtundu wa mankhwala ochulukitsa omwe amapangidwa m'matumbo amunthu atamwa chakudya cha ellagitannins monga makangaza, sitiroberi, raspberries wofiyira, walnuts kapena vinyo wofiira wazaka. Urolithin B amapezeka mkodzo mumtundu wa urolithin B glucuronide.

Urolithin B ndichinthu chachilengedwe chomwe chimakhala ndi zochita za antiproliferative komanso antioxidant. Urolithin B imapangidwa ndi metabolism kuchokera ku polyphenols omwe amapezeka mtedza ndi zipatso, makamaka makangaza. Urolithin B yawonetsedwa kuti idutsa chotchinga chaubongo wamagazi, ndipo itha kukhala ndi zoteteza ku matenda a Alzheimer's.

13.Urolithin B Mechanism of Action

Amachepetsa kuwonongeka kwa mapuloteni ndipo amachititsa kuti thupi likhale ndi hypertrophy. Urolithin B imaletsa ntchito ya aromatase, enzyme yomwe imasinthitsa estrogen ndi testosterone.

Urolithin B ndi mankhwala achilengedwe omwe ali ndi antiproliferative ndi antioxidant. Urolithin B imapangidwa ndi metabolism kuchokera ku polyphenols omwe amapezeka mtedza ndi zipatso, makamaka makangaza. Urolithin B yawonetsedwa kuti idutsa chotchinga chaubongo wamagazi, ndipo itha kukhala ndi zoteteza ku matenda a Alzheimer's.

14.Urolithin B Kugwiritsa Ntchito

Pomwe amaphunzira za anti-yotupa ndi antioxidant katundu wa urolithin A ndi B, ofufuza a UCL adachitika zindikirani kuti chomalizacho chinali ndi chitetezo pa minofu. 'Maselo a minofu mu chikhalidwe omwe anali okhudzana ndi urolithin B anakhala aakulu kuposa omwe sanali. Tinkafuna kudziwa chifukwa chake.

Choyamba, adaphunzira za vitro ndikupeza kuti urolithin B imakhudza kawiri: imathandizira kuphatikizika kwa mapuloteni ndikuchepetsa kuwonongeka.

Chachiwiri, ofufuzawo adaphunzira momwe urolithin B amagwirira ntchito mu vivo, pa mbewa. 'Zawonjezera kukula kwa minofu yawo', Prof. Francaux akuti. 'Tidaperekanso mbewa ndi mitsempha yoduka yomwe imayambitsa ziwalo za mwendo, ndipo kutayika kwa minofu komwe kunachitika kunachitika 20 mpaka 30% posachedwa komanso pang'ono pang'ono.'

15. Zotsatira za Urolithin B

Urolithin B ndi amodzi mwamatumbo a michere ya ellagitannins, ndipo ali ndi zotsutsana ndi zotupa komanso zoteteza ku antioxidant. Urolithin B imalepheretsa zochitika za NF-κB pochepetsa phosphorylation ndikuwonongeka kwa I VerBcy, ndikupondereza phosphorylation ya JNK, ERK, ndi Akt, ndikukweza phosphorylation ya AMPK. Urolithin B imakhalanso wolamulira mafupa a minofu.

(1). Urolithin B amachepetsa kuchepa kwa minofu kulemera kukhudzidwa ndi kukhumudwa
(2). Urolithin B-yolowetsa mafupa a hypertrophy mu mbewa
(3). Pulogalamu ya mphamvu ya anabolic Urolithin B imayendetsedwa ndi cholandilira cha androgen
(4). Urolithin B imayambitsa mapuloteni mu C2C12 myotubes poyambitsa chizindikiro cha mTORC1
(5). Urolithin B imalepheretsa kuwonongeka kwa mapuloteni pochepetsa ubiquitin-proteasome njira
(6). Urolithin B imathandizira kusiyanitsa kwa myotubes ya C2C12

Reference

[1] Wogwiritsira ntchito, S. et al. DNA ya Mitochondrial imachotsedwa m'maselo amtundu wa satellite: tanthauzo la mankhwala. Hum. Mol. Chibadwa. 22, 4739-4747 (2013).
[2] Milburn, MV & Lawton, KA Kugwiritsa ntchito ma metabolomics kuti azindikire kukana kwa insulin. Annu. Rev. Med. 64, 291-305 (2013).
[3] Laker, RC ndi al. Phosphorylation ya Ampk ya Ulk1 imafunikira pakukakamiza mitochondria kupita ku lysosomes mu mitophagy yolimbitsa thupi. Nat. Commun. 8, 548 (2017).
[4] Singh, R. et al. Kupititsa patsogolo kutsekeka kwamatumbo ndi microbial metabolite kudzera munjira ya Nrf2. Nat. Commun. 10, 89 (2019).
[5] Andreux, PA et al. Ntchito ya mitochondrial imasokonekera m'minyewa ya achikulire omwe alibe zofooka. Sci. Pemphani 8, 8548 (2018).
[6] Gong, Z. ndi al. Urolithin A amachepetsa kufooka kwa kukumbukira komanso kufooka kwa ubongo mu mbewa za APP / PS1. J. Neuroinfigue 16, 62 (2019).
[7] Felder, TK neri Al. Phospholipids, ma acylcarnitines, ma amino acid ndi ma biogenic amene ndimayendedwe olimbitsa thupi. J. Sci. Med. Masewera 20, 700-705 (2017).
[8] Schooneman, MG, Vaz, FM, Houten, SM & Soeters, MR Acylcarnitines: kuwonetsa kapena kuyambitsa kukana kwa insulin? Matenda a shuga 62, 1-8 (2013).
[9] Ndondomeko ya Njira Zomwe Mungadziwire ndi Kuchepetsa Zowopsa Pazoyeserera Zamankhwala Zoyamba-ndi-Zachipatala ndi Investigational Medicinal Products EMEA / CHMP / SWP / 28367/07 (European Medicines Agency, 2007).
[10] Keefe, DM GRAS Chidziwitso nambala GRN 000791 (Food and Drug Administration, 2018).
[11] Drake, JC & Yan, Z. Mitophagy pokhalabe ndi mafupa a mitochondrial proteostasis ndi kagayidwe kachakudya ndi ukalamba. J. Physiol. 595, 6391-6399 (2017).
[12] Choi, AM, Ryter, SW & Levine, B. Autophagy muumoyo wa anthu ndi matenda. N. Engl. J. Med. 368, 651-662 (2013).