Sayansi Kumbuyo kwa Urolithin A: Zomwe Muyenera Kudziwa

Urolithin A (UA)ndi pawiri opangidwa ndi kagayidwe ka matumbo zomera mu zakudya wolemera ellagitannins (monga makangaza, raspberries, etc.). Amaonedwa kuti ali ndi anti-inflammatory, anti-aging, antioxidant, induction of mitophagy, etc., ndipo amatha kuwoloka chotchinga cha ubongo. Kafukufuku wambiri watsimikizira kuti urolithin A imatha kuchedwetsa kukalamba, ndipo maphunziro azachipatala awonetsanso zotsatira zabwino.

Kodi urolithin A ndi chiyani?

Urolithin A (Uro-A) ndi mtundu wa ellagitannin (ET) wamtundu wa m'matumbo metabolite. Zinapezeka mwalamulo ndipo zinatchulidwa mu 2005. Mapangidwe ake a molekyulu ndi C13H8O4, ndipo ma molekyulu ake ndi 228.2. Monga kalambulabwalo wa metabolic wa Uro-A, magwero akulu azakudya a ET ndi makangaza, sitiroberi, raspberries, walnuts ndi vinyo wofiira. UA ndi chinthu cha ETs chopangidwa ndi tizilombo ta m'matumbo. UA ili ndi chiyembekezo chogwiritsa ntchito popewa komanso kuchiza matenda ambiri. Panthawi imodzimodziyo, UA ili ndi mitundu yambiri ya zakudya.

Kafukufuku wokhudza antioxidant zotsatira za urolithin zachitika. Urolithin-A kulibe mu chilengedwe, koma amapangidwa ndi mndandanda wa kusintha kwa ET ndi zomera za m'mimba. UA ndi chinthu cha ETs chopangidwa ndi tizilombo ta m'matumbo. Zakudya zolemera mu ET zimadutsa m'mimba ndi m'matumbo aang'ono m'thupi la munthu, ndipo pamapeto pake zimasinthidwa makamaka mu Uro-A m'matumbo. Uro-A wochepa amatha kupezekanso m'matumbo aang'ono.

Monga mankhwala achilengedwe a polyphenolic, ETs akopa chidwi kwambiri chifukwa cha zochita zawo zamoyo monga antioxidant, anti-inflammatory, anti-allergenic and anti-viral. Kuphatikiza pa zimachokera ku zakudya monga makangaza, sitiroberi, walnuts, raspberries ndi amondi, ETs amapezekanso mu gallnuts, makangaza peels, myrobalan, Dimininus, geranium, betel nut, sea buckthorn masamba, Phyllanthus, Uncaria, Sanguisorba, In Chinese. mankhwala monga Phyllanthus emblica ndi Agrimony.

Gulu la hydroxyl mu mawonekedwe a mamolekyu a ETs ndi ofanana ndi polar, omwe sangathandize kuyamwa ndi khoma la m'mimba, ndipo bioavailability yake ndi yochepa kwambiri. Kafukufuku wambiri apeza kuti ma ET atatha kulowetsedwa ndi thupi la munthu, amasinthidwa ndi zomera za m'matumbo m'matumbo ndipo amasandulika urolithin asanatengedwe. ETs ndi hydrolyzed mu ellagic acid (EA) m'matumbo a m'mimba, ndipo EA imadutsa m'matumbo. Tizilombo ta bakiteriya timachitanso ndikutaya mphete ya lactone ndikupitilirabe dehydroxylation kuti apange urolithin. Pali malipoti oti urolithin ikhoza kukhala maziko achilengedwe a ETs m'thupi.

Kodi bioavailability ya urolithin ikugwirizana ndi chiyani?

Powona izi, ngati ndinu anzeru, mutha kudziwa kale zomwe bioavailability ya UA ikugwirizana nazo.

Chinthu chofunika kwambiri ndi mapangidwe a microbiome, chifukwa si mitundu yonse ya tizilombo toyambitsa matenda yomwe ingatulutse. Zopangira za UA ndi ellagitannins zomwe zimachokera ku chakudya. Kalambulabwaloyi imapezeka mosavuta komanso imapezeka paliponse.

Ellagitannins amapangidwa ndi hydrolyzed m'matumbo kuti atulutse ellagic acid, yomwe imasinthidwanso ndi zomera zam'mimba kukhala urolithin A.

Malinga ndi kafukufuku yemwe adachitika mu nyuzipepala ya Cell, 40% yokha ya anthu amatha kusintha urolithin A kuchokera kalambulabwalo wake kukhala urolithin A.

Kodi ntchito za urolithin A ndi ziti?

Anti-kukalamba

Lingaliro laulere la ukalamba limakhulupirira kuti mitundu yokhazikika ya okosijeni yomwe imapangidwa mu kagayidwe ka mitochondrial imayambitsa kupsinjika kwa okosijeni m'thupi ndikuyambitsa ukalamba, ndipo mitophagy imagwira ntchito yofunika kwambiri pakusunga thanzi la mitochondrial ndi kukhulupirika. Zanenedwa kuti UA imatha kuwongolera mitophagy ndipo motero ikuwonetsa kuthekera kochedwetsa kukalamba. Ryu ndi al. adapeza kuti UA idachepetsa kulephera kwa mitochondrial ndikuwonjezera moyo mu Caenorhabditis elegans poyambitsa mitophagy; mu makoswe, UA imatha kusintha kutsika kwa minofu yokhudzana ndi ukalamba, zomwe zikuwonetsa kuti UA imathandizira ntchito ya mitochondrial mwa kukulitsa Minofu ndi kukulitsa moyo wathupi. Liu et al. amagwiritsa ntchito UA kuti alowerere mu ukalamba wa fibroblasts. Zotsatira zake zidawonetsa kuti UA idakulitsa kwambiri mawonekedwe amtundu wa collagen ndikuchepetsa matrix metalloproteinase-1 (MMP-1). Inayambitsanso nyukiliya ya Factor E2-related factor 2 (nuclear factor erythroid 2-related factor 2, Nrf2) -mediated antioxidant response imachepetsa ROS ya intracellular, motero imasonyeza mphamvu zotsutsa kukalamba.

Antioxidant zotsatira

Pakadali pano, kafukufuku wambiri wachitika pa antioxidant zotsatira za urolithin. Pakati pa metabolites yonse ya urolithin, Uro-A imakhala ndi antioxidant yamphamvu kwambiri, yachiwiri ndi proanthocyanidin oligomers, makatekini, epicatechin ndi 3,4-dihydroxyphenylacetic acid. Mayeso a oxygen radical absorbance capacity (ORAC) a madzi a m'magazi a anthu odzipereka athanzi anapeza kuti mphamvu ya antioxidant inawonjezeka ndi 32% pambuyo pa maola 0.5 atamwa madzi a makangaza, koma mlingo wa okosijeni wokhazikika sunasinthe kwambiri, pamene Neuro- In Kuyesa kwa vitro pa ma cell a 2a adapeza kuti Uro-A imatha kuchepetsa kuchuluka kwa mitundu ya okosijeni yokhazikika m'maselo. Zotsatira izi zikuwonetsa kuti Uro-A ili ndi mphamvu ya antioxidant.

03. Urolithin A ndi matenda a mtima ndi cerebrovascular

Chiwopsezo chapadziko lonse cha matenda amtima (CVD) chikuchulukirachulukira chaka ndi chaka, ndipo chiwopsezo cha kufa chimakhalabe chokwera. Sizimangowonjezera mavuto azachuma komanso zachuma, komanso zimakhudza kwambiri moyo wa anthu. CVD ndi matenda osiyanasiyana. Kutupa kumatha kuonjezera chiopsezo cha CVD. Kupsinjika kwa okosijeni kumagwirizana ndi pathogenesis ya CVD. Pali malipoti oti ma metabolites opangidwa kuchokera ku tizilombo tating'onoting'ono tamatumbo amalumikizidwa ndi chiopsezo cha CVD.

UA yanenedwa kuti ili ndi mphamvu zotsutsa-kutupa ndi antioxidant zotsatira, ndipo maphunziro oyenerera atsimikizira kuti UA ikhoza kukhala ndi gawo lopindulitsa mu CVD. Savi et al. adagwiritsa ntchito makoswe amtundu wa shuga kuti achite maphunziro a vivo pa matenda a shuga a cardiomyopathy ndipo adapeza kuti UA imatha kuchepetsa kuyankha kotupa kwa minofu ya myocardial ku hyperglycemia, kupititsa patsogolo microenvironment ya myocardial, ndikulimbikitsa kuchira kwa cardiomyocyte contractility ndi calcium dynamics, kuwonetsa kuti UA imatha Itha kugwiritsidwa ntchito ngati mankhwala othandizira kuthana ndi matenda a shuga a cardiomyopathy ndikuletsa zovuta zake.

UA ikhoza kupititsa patsogolo ntchito ya mitochondrial ndi ntchito ya minofu poyambitsa mitophagy. Mtima mitochondria ndi ziwalo zofunika kwambiri zomwe zimapanga ATP yolemera kwambiri. Kulephera kugwira ntchito kwa mitochondrial ndizomwe zimayambitsa kulephera kwa mtima. Kulephera kwa Mitochondrial pakadali pano kumawonedwa ngati njira yochiritsira yomwe ingatheke. Chifukwa chake, UA yakhalanso mankhwala atsopano ochizira CVD.

Urolithin A ndi matenda a minyewa

Kutupa kwa Neuroinflammation ndi njira yofunika kwambiri pazochitika ndi chitukuko cha matenda a neurodegenerative (ND). Apoptosis yoyambitsidwa ndi kupsinjika kwa okosijeni komanso kusanjidwa bwino kwa mapuloteni nthawi zambiri kumayambitsa neuroinflammation, ndipo ma cytokines oyambitsa kutupa omwe amatulutsidwa ndi neuroinflammation amakhudza neurodegeneration.

Kafukufuku wapeza kuti UA imayimira ntchito yolimbana ndi zotupa poyambitsa autophagy ndikuyambitsa makina owongolera ma siginecha 1 (SIRT-1) deacetylation, kuletsa neuroinflammation ndi neurotoxicity, ndikuletsa neurodegeneration, kutanthauza kuti UA ndi neuroprotective wothandizira. Nthawi yomweyo, kafukufuku wina wapeza kuti UA imatha kukhala ndi zotsatira za neuroprotective mwa kuwononga mwachindunji ma free radicals ndi kuletsa ma oxidase.

Kafukufuku wasonyeza kuti madzi a makangaza amagwira ntchito ya neuroprotective mwa kuwonjezera ntchito ya mitochondrial aldehyde dehydrogenase, kusunga mlingo wa anti-apoptotic protein Bcl-xL, kuchepetsa α-synuclein aggregation ndi kuwonongeka kwa okosijeni, ndi kukhudza ntchito ya neuronal ndi kukhazikika. Urolithin mankhwala ndi metabolites ndi zotsatira zigawo zikuluzikulu za ellagitannins m'thupi ndipo ali ndi zochita zamoyo monga anti-kutupa, anti-oxidative stress, ndi anti-apoptosis. Urolithin imatha kuchita zinthu zoteteza ubongo kudzera mu chotchinga chamagazi-muubongo ndipo ndi molekyulu yaying'ono yomwe ingathe kulowererapo matenda a neurodegenerative.

Urolithin A ndi matenda olowa ndi msana

Matenda a degenerative amayamba chifukwa cha zinthu zingapo monga ukalamba, kupsinjika, ndi kuvulala. Matenda osokonekera kwambiri a mafupa ndi mafupa a osteoarthritis (OA) ndi matenda osokoneza bongo a intervertebral disc degeneration (IDD). Kuchitika kungayambitse ululu ndi ntchito zochepa, zomwe zimapangitsa kutaya ntchito ndikuika pangozi thanzi la anthu. Njira ya UA pochiza matenda a msana IDD ikhoza kukhala yokhudzana ndi kuchedwa kwa nucleus pulposus (NP) cell apoptosis. NP ndi gawo lofunikira la intervertebral disc. Imasunga ntchito yachilengedwe ya intervertebral disc pogawa kukakamiza ndi kusunga matrix homeostasis. Kafukufuku wapeza kuti UA imapangitsa mitophagy mwa kuyambitsa njira yowonetsera AMPK, motero imalepheretsa tert-butyl hydroperoxide (t-BHP) -induced apoptosis ya osteosarcoma cell NP maselo ndi kuchepetsa intervertebral disc degeneration.

Urolithin A ndi matenda a metabolic

Kuchuluka kwa matenda a kagayidwe kachakudya monga kunenepa kwambiri ndi shuga kumawonjezeka chaka ndi chaka, ndipo zotsatira zopindulitsa za ma polyphenols pazaumoyo wa anthu zatsimikiziridwa ndi maphwando ambiri ndipo zawonetsa kuthekera kopewera ndi kuchiza matenda a metabolic. Pomegranate polyphenols ndi matumbo metabolite UA amatha kusintha zizindikiro zachipatala zokhudzana ndi matenda a kagayidwe kake, monga lipase, α-glucosidase (α-glucosidase) ndi dipeptidyl peptidase-4 (dipeptidyl peptidase-4) yomwe imakhudzidwa ndi shuga ndi mafuta acid metabolism. 4), komanso majini okhudzana ndi adiponectin, PPARγ, GLUT4 ndi FABP4 zomwe zimakhudza kusiyana kwa adipocyte ndi triglyceride (TG) kudzikundikira.

Kuphatikiza apo, kafukufuku wina wapezanso kuti UA imatha kuchepetsa zizindikiro za kunenepa kwambiri. UA ndi mankhwala a matumbo metabolism a polyphenols. Ma metaboliteswa amatha kuchepetsa kuchuluka kwa TG m'maselo a chiwindi ndi adipocytes. Abdulrasheed et al. kudyetsedwa zakudya zamafuta ambiri kwa makoswe a Wistar kuti apangitse kunenepa kwambiri. Kuchiza kwa UA sikungowonjezera kutulutsa kwamafuta mu ndowe, komanso kumachepetsa minofu ya visceral adipose ndi kulemera kwa thupi mwa kuwongolera majini okhudzana ndi lipogenesis ndi mafuta acid oxidation. Amachepetsa kuchuluka kwa mafuta m'chiwindi ndi kupsinjika kwake kwa okosijeni. Nthawi yomweyo, UA imatha kukulitsa kugwiritsa ntchito mphamvu powonjezera thermogenesis yamafuta a bulauni komanso kupangitsa kuyanika kwamafuta oyera. Njirayi ndikuwonjezera milingo ya triiodothyronine (T3) m'malo osungira mafuta a bulauni ndi inguinal mafuta. Amachulukitsa kutentha ndipo potero amalimbana ndi kunenepa kwambiri.

Kuphatikiza apo, UA imakhalanso ndi zotsatira zoletsa kupanga melanin. Kafukufuku wapeza kuti UA imatha kufooketsa kwambiri kupanga melanin m'maselo a melanoma a B16. Njira yayikulu ndikuti UA imakhudza kuyambitsa kwa tyrosinase kudzera mumpikisano woletsa cell tyrosinase, potero amachepetsa mtundu wa pigmentation. Chifukwa chake, UA ili ndi kuthekera komanso kothandiza kuyeretsa ndikuwunikira mawanga. Ndipo kafukufuku akuwonetsa kuti urolithin A imakhala ndi zotsatira zobwezeretsa ukalamba wa chitetezo chamthupi. Kafukufuku waposachedwa adapeza kuti urolithin A ikawonjezeredwa ngati chowonjezera pazakudya, sikuti imangoyambitsa mphamvu ya chitetezo chamthupi cha mbewa, komanso imathandizira ntchito ya maselo amtundu wa hematopoietic. Ntchito yonseyi ikuwonetsa kuthekera kwa urolithin A polimbana ndi kuchepa kwa chitetezo chamthupi chokhudzana ndi ukalamba.

Pomaliza, UA, monga matumbo a metabolite achilengedwe a phytochemicals ETs, yakopa chidwi kwambiri m'zaka zaposachedwa. Ndi kafukufuku wokhudzana ndi zotsatira za mankhwala ndi njira za UA kukhala zowonjezereka komanso zozama, UA sikuti imagwira ntchito pa khansa ndi CVD (matenda a mtima). Imakhala ndi chitetezo chabwino komanso chochizira matenda ambiri azachipatala monga ND (matenda a neurodegenerative) ndi matenda a metabolic. Ikuwonetsanso kuthekera kwakukulu kogwiritsa ntchito pazinthu za kukongola ndi chisamaliro chaumoyo monga kuchedwetsa kukalamba kwa khungu, kuchepetsa kulemera kwa thupi komanso kuletsa kupanga melanin.

Suzhou Myland Pharm & Nutrition Inc. ndi wopanga olembetsedwa ndi FDA yemwe amapereka ufa wapamwamba kwambiri komanso woyeretsedwa kwambiri wa Urolithin A.

Ku Suzhou Myland Pharm tadzipereka kupereka zinthu zapamwamba kwambiri pamitengo yabwino kwambiri. Urolithin A ufa wathu umayesedwa mwamphamvu kuti ukhale woyera ndi potency, kuonetsetsa kuti mumapeza chowonjezera chapamwamba chomwe mungakhulupirire. Kaya mukufuna kuthandizira thanzi la ma cell, kulimbikitsa chitetezo chamthupi kapena kukulitsa thanzi labwino, Urolithin A ufa wathu ndiye chisankho chabwino kwambiri.

Ndi zaka 30 zachidziwitso komanso motsogozedwa ndiukadaulo wapamwamba komanso njira zokongoletsedwa bwino za R&D, Suzhou Myland Pharm yapanga zinthu zambiri zampikisano ndikukhala kampani yotsogola ya sayansi ya moyo, kaphatikizidwe kazinthu ndi ntchito zopanga.

Kuphatikiza apo, Suzhou Myland Pharm ndiwopanganso zolembedwa ndi FDA. Zothandizira zamakampani za R&D, malo opangira zinthu, ndi zida zowunikira ndi zamakono komanso zogwira ntchito zambiri, ndipo zimatha kupanga mankhwala kuchokera ku ma milligrams mpaka matani mumlingo, ndikutsata miyezo ya ISO 9001 ndi zopangira GMP.