Sayenzi Kuseri kweUrolithin A: Zvaunoda Kuziva

Urolithin A (UA)ikamu rinogadzirwa nemetabolism yemaruva emudumbu mune zvekudya zvakapfuma mu ellagitannins (senge mapomegranati, raspberries, nezvimwewo). Inofungidzirwa kuva ne-anti-inflammatory, anti-aging, antioxidant, induction ye mitophagy, nezvimwewo, uye inogona kuyambuka ropa-brain barriers. Zvidzidzo zvakawanda zvakasimbisa kuti urolithin A inogona kunonoka kuchembera, uye zvidzidzo zvekiriniki zvakaratidzawo mhedzisiro yakanaka.

Chii chinonzi urolithin A?

Urolithin A (Uro-A) is ellagitannin (ET) -rudzi rwemukati memaruva metabolite. Yakawanikwa zviri pamutemo uye yakatumidzwa zita muna 2005. Mushonga wayo wemolecular iC13H8O4, uye huwandu hwayo hwema molecular i228.2. Seye metabolic precursor yeUro-A, iwo makuru echikafu masosi eET mapomegranati, sitirobheri, raspberries, walnuts uye waini tsvuku. UA chigadzirwa cheETs chakagadziriswa nematumbo microorganisms. UA ine tarisiro yakakura yekushandisa mukudzivirira uye kurapwa kwezvirwere zvakawanda. Panguva imwecheteyo, UA ine huwandu hwakawanda hwezvekudya.

Tsvagiridzo pamusoro peiyo antioxidant mhedzisiro yeurolithin yakaitwa. Urolithin-A haipo mumamiriro echisikigo, asi inobudiswa nenhevedzano yekushandurwa kweET nemaruva emukati. UA chigadzirwa cheETs chakagadziriswa nematumbo microorganisms. Zvokudya zvakapfuma muET zvinopfuura nemudumbu uye mudumbu mudiki mumuviri wemunhu, uye pakupedzisira zvinogadziriswa zvakanyanya muUro-A mukoloni. Huwandu hudiki hweUro-A hunogonawo kuwonekwa mudumbu rezasi.

Semasikirwo epolyphenolic compounds, ETs dzakakwevera kutarisa zvakanyanya nekuda kwemabasa avo ehupenyu akadai se antioxidant, anti-inflammatory, anti-allergic uye anti-viral. Pamusoro pekutorwa kubva pakudya zvakaita semapomegranati, sitirobheri, walnuts, raspberries nemaarumondi, maETs anowanikwawo mugallnuts, pomegranate peels, myrobalan, Dimininus, geranium, betel nut, sea buckthorn mashizha, Phyllanthus, Uncaria, Sanguisorba, In Chinese. mishonga yakadai sePhyllanthus emblica uye Agrimony.

Iro hydroxyl boka mune molecular structure yeETs inenge iine polar, iyo isingakodzeri kutorwa nemadziro emukati, uye bioavailability yayo yakaderera zvikuru. Zvidzidzo zvakawanda zvakaona kuti mushure mokunge maET apindwa nemuviri wemunhu, anogadziriswa nemaruva emukati mukoloni uye anoshandurwa kuva urolithin asati abatwa. ETs inonzi hydrolyzed mu ellagic acid (EA) munzvimbo yepamusoro yegumbo, uye EA inodarika nemuura. Huru hwebhakitiriya hunowedzera kushanda uye hunorasa mhete yelactone uye hunoenderera mberi nekuita dehydroxylation kuita urolithin. Pane mishumo yekuti urolithin inogona kunge iri hwaro hwezvinhu zvebiological mhedzisiro yeETs mumuviri.

Chii chinonzi bioavailability yeurolithin ine hukama?

Uchiona izvi, kana wakangwara, unogona kutoziva kuti bioavailability yeUA ine hukama nei.

Chinhu chinonyanya kukosha ndeyekuumbwa kweiyo microbiome, nekuti kwete ese marudzi ehutachiona anogona kuburitsa. Iyo mbishi yeUA ndeye ellagitannins inowanikwa kubva muchikafu. Iyi precursor inowanikwa zviri nyore uye inenge iri pese pese mumasikirwo.

Ellagitannins inoiswa hydrolyzed muura kuti ibudise ellagic acid, iyo inozogadziriswazve nemaruva emudumbu kuita urolithin A.

Zvinoenderana neongororo yakaitwa mujenari Cell, makumi mana muzana chete evanhu vanogona kushandura urolithin A kubva kune inotangira kuita urolithin A.

Ndeapi mabasa eurolithin A?

Anti-kuchembera

Iyo yemahara radical dzidziso yekuchembera inotenda kuti reactive okisijeni mhando dzakagadzirwa mumitochondrial metabolism inokonzera oxidative kusagadzikana mumuviri uye kutungamirira mukukwegura, uye mitophagy inoita basa rinokosha mukuchengetedza hutano hwemitochondrial uye kuvimbika. Zvinonzi UA inogona kudzora mitophagy uye nokudaro kuratidza mukana wekunonoka kuchembera. Ryu et al. akawana kuti UA yakaderedza kusagadzikana kwemitochondrial uye yakawedzera hupenyu muCaenorhabditis elegans nekuita mitophagy; mumakonzo, UA inogona kudzosera zera-ane mhasuru basa kuderera, zvichiratidza kuti UA inovandudza mitochondrial basa nekusimudzira Muscle mass uye kuwedzera hupenyu hwemuviri. Liu et al. akashandisa UA kupindira mukuchembera ganda fibroblasts. Mhedzisiro yacho yakaratidza kuti UA yakawedzera zvakanyanya kutaura kwerudzi I collagen uye yakaderedza kutaura kwematrix metalloproteinase-1 (MMP-1). Yakagadzirisawo nyukliya Factor E2-inoenderana ne2 (nuclear factor erythroid 2-inoenderana chinhu 2, Nrf2) -mediated antioxidant mhinduro inoderedza intracellular ROS, nokudaro ichiratidza simba rinopesana nekukwegura.

Antioxidant effect

Parizvino, zvidzidzo zvakawanda zvakaitwa nezve antioxidant mhedzisiro yeurolithin. Pakati pese urolithin metabolites, Uro-A ine yakasimba antioxidant basa, yechipiri chete kune proanthocyanidin oligomers, makatechini, epicatechin uye 3,4-dihydroxyphenylacetic acid. Iyo oxygen radical absorbance capacity (ORAC) bvunzo yeplasma yevanozvipira vane hutano yakawana kuti iyo antioxidant simba yakawedzera ne32% mushure memaawa 0.5 ekumedzwa kwepomegranate muto, asi mwero weiyo reactive okisijeni mhando haina kuchinja zvakanyanya, panguva yeNeuro- In. vitro kuyedza pamasero e2a yakaona kuti Uro-A inogona kuderedza mwero weiyo inoshanda oksijeni mhando mumasero. Mhedzisiro iyi inoratidza kuti Uro-A ine yakasimba antioxidant mhedzisiro.

03. Urolithin A uye zvirwere zvemwoyo uye cerebrovascular

Chiitiko chepasi rose chechirwere chemoyo (CVD) chiri kuwedzera gore negore, uye huwandu hwevanhu vanofa hunoramba huri pamusoro. Haingowedzeri mutoro wemagariro nehupfumi chete, asiwo inokanganisa zvakanyanya hupenyu hwevanhu. CVD chirwere chemultifactorial. Kuzvimba kunogona kuwedzera njodzi yeCVD. Oxidative stress inoenderana neiyo pathogenesis yeCVD. Kune mishumo yekuti metabolites inotorwa kubva mumatumbo ma microorganisms inosanganiswa nenjodzi yeCVD.

UA inonzi ine simba rinopesana nekuputika uye antioxidant migumisiro, uye zvidzidzo zvakakodzera zvakatsigira kuti UA inogona kuita basa rinobatsira muCVD. Savi et al. akashandisa chimiro chechirwere cheshuga chekuita mu vivo zvidzidzo zvechirwere cheshuga chemoyo uye akawana kuti UA inogona kuderedza mhinduro yekutanga yekuputika kwemyocardial tissue kune hyperglycemia, kuvandudza myocardial microenvironment, uye kukurudzira kupora kwe cardiomyocyte contractility uye calcium dynamics, zvichiratidza kuti UA inogona inogona kushandiswa semubatsiri mushonga kudzora chirwere cheshuga cardiomyopathy uye kudzivirira matambudziko ayo.

UA inogona kuvandudza mitochondrial basa uye tsandanyama basa nekuita mitophagy. Mwoyo mitochondria ndiwo akakosha organelles ane basa rekuburitsa simba-rakapfuma ATP. Mitochondrial dysfunction ndicho chinokonzera kukanganisa kwemoyo. Mitochondrial dysfunction parizvino inoonekwa seyaigona kurapa chinangwa. Naizvozvo, UA yave zvakare mushonga mutsva wekukwikwidza kurapwa kweCVD.

Urolithin A uye neurological zvirwere

Neuroinflammation inzira yakakosha mukuitika uye kukura kwechirwere cheurourodegenerative (ND). Apoptosis inokonzerwa neoxidative kusagadzikana uye abnormal protein aggregation inowanzo konzeresa neuroinflammation, uye pro-inflammatory cytokines inoburitswa neuroinflammation inobva yakanganisa neurodegeneration.

Zvidzidzo zvakawana kuti UA inopindirana nekurwisa-kuzvimba chiitiko nekuita autophagy uye activate silent chiratidzo regulator 1 (SIRT-1) deacetylation mechanism, inhibiting neuroinflammation uye neurotoxicity, uye kudzivirira neurodegeneration, zvichiratidza kuti UA inoshanda Neuroprotective agent. Panguva imwecheteyo, zvimwe zvidzidzo zvakawana kuti UA inogona kushandisa neuroprotective mhedzisiro nekutsvaira zvakananga radicals emahara uye kuvharira oxidase.

Zvidzidzo zvakaratidza kuti muto wepomegranate unobata neuroprotective basa nekuwedzera mitochondrial aldehyde dehydrogenase basa, kuchengetedza chiyero che anti-apoptotic protein Bcl-xL, kuderedza α-synuclein aggregation uye kukuvara kweoxidative, uye kukanganisa neuronal basa nekugadzikana. Urolithin makomponi ndiwo mametabolites uye mhedzisiro zvikamu zve ellagitannins mumuviri uye ane zvipenyu zviitiko senge anti-inflammation, anti-oxidative stress, uye anti-apoptosis. Urolithin inogona kuita neuroprotective chiitiko kuburikidza neropa-brain barriers uye inogona kushanda diki molecule yekupindira mune neurodegenerative zvirwere.

Urolithin A uye majoini uye spinal degenerative zvirwere

Degenerative zvirwere zvinokonzerwa nezvakawanda zvinhu zvakadai sekuchembera, kuomerwa, uye kushungurudzika. Zvirwere zvinotapukira zvemajoini ndeye osteoarthritis (OA) uye degenerative spinal chirwere intervertebral disc degeneration (IDD). Zviitiko zvinogona kukonzera marwadzo uye kuita zvishoma, zvichikonzera kurasikirwa kwebasa uye kuisa hutano hwevanhu pangozi. Iyo nzira yeUA mukurapa musana wechirwere chinokanganisa IDD inogona kunge yakabatana nekunonoka nucleus pulposus (NP) cell apoptosis. NP chikamu chinokosha che intervertebral disc. Iyo inochengetedza biological basa re intervertebral disc nekugovera kumanikidza uye kuchengetedza matrix homeostasis. Zvidzidzo zvakawana kuti UA induces mitophagy nekuita iyo AMPK chiratidzo nzira, nokudaro inhibiting tert-butyl hydroperoxide (t-BHP) -induced apoptosis yevanhu osteosarcoma cell NP masero uye kuderedza intervertebral disc degeneration.

Urolithin A uye metabolic zvirwere

Chiitiko chezvirwere zvemagetsi zvakadai sokufutisa uye chirwere cheshuga chiri kuwedzera gore negore, uye migumisiro inobatsira yezvokudya zvepolyphenols pahutano hwevanhu zvakasimbiswa nemapato akawanda uye zvakaratidza kukwanisa mukudzivirira uye kurapwa kwezvirwere zvemagetsi. Pomegranate polyphenols uye intestinal metabolite UA inogona kuvandudza zviratidzo zvekliniki zvine chokuita nezvirwere zvemagetsi, zvakadai se lipase, α-glucosidase (α-glucosidase) uye dipeptidyl peptidase-4 (dipeptidyl peptidase-4) inobatanidzwa muglucose uye mafuta acid metabolism. 4), pamwe chete nemajeni ane hukama akadai seadiponectin, PPARγ, GLUT4 uye FABP4 iyo inokanganisa adipocyte kusiyana uye triglyceride (TG) kuunganidza.

Pamusoro pezvo, zvimwe zvidzidzo zvakawanawo kuti UA ine mukana wekudzikisa zviratidzo zvekufutisa. UA chigadzirwa che intestinal metabolism ye polyphenols. Aya metabolites ane kugona kuderedza TG kuunganidza mumasero echiropa uye adipocytes. Abdulrasheed et al. kudyiswa kudya kwemafuta akawanda kumakonzo eWistar kuti afutisa. Kurapa kweUA hakuna kungowedzera kubuda kwemafuta mutsvina, asiwo kwakaderedza visceral adipose tissue mass uye uremu hwemuviri nekugadzirisa majini ane chekuita ne lipogenesis uye fatty acid oxidation. Inoderedza kuunganidzwa kwemafuta echiropa uye ayo oxidative kusagadzikana. Panguva imwecheteyo, UA inogona kuwedzera mashandisirwo esimba nekusimudzira thermogenesis yebrown adipose tishu uye kuita browning yemafuta machena. Iyo nzira ndeyekuwedzera triiodothyronine (T3) mazinga mubrown mafuta uye inguinal mafuta madhiri. Inowedzera kugadzirwa kwekupisa uye nekudaro inopikisa kufutisa.

Uye zvakare, UA inewo mhedzisiro yekudzivisa kugadzirwa kwe melanin. Zvidzidzo zvakawana kuti UA inogona kuderedza zvakanyanya kugadzirwa kwe melanin muB16 melanoma masero. Nzira huru ndeyokuti UA inokanganisa iyo catalytic activation ye tyrosinase kuburikidza nemakwikwi inhibition ye cell tyrosinase, nokudaro kuderedza pigmentation. Naizvozvo, UA ine mukana uye inoshanda kuchena nekurerutsa mavara. Uye tsvagiridzo inoratidza kuti urolithin A ine mhedzisiro yekudzoreredza kuchembera kwe immune system. Tsvagiridzo ichangoburwa yakawana kuti kana urolithin A yawedzerwa sechikafu chekuwedzera, haingoite simba reiyo lymphatic nzvimbo yegonzo immune system, asi zvakare inosimudzira basa rehematopoietic stem masero. Kuita kwese kunoratidza kugona kweurolithin A kurwisa zera-ane hukama immune system kuderera.

Kupfupisa, UA, senge intestinal metabolite yemasikirwo phytochemicals ETs, yakakwezva zvakanyanya mumakore achangopfuura. Nekutsvagisa pamhedzisiro yemishonga uye nzira dzeUA dzichiwedzera uye dzakadzika uye dzakadzika, UA haingoite mugomarara uye CVD (chirwere chemoyo). Iyo ine yakanaka yekudzivirira uye yekurapa maitiro kune akawanda emakiriniki ezvirwere senge ND (neurodegenerative zvirwere) uye metabolic zvirwere. Iyo inoratidzawo yakakura yekushandisa mukana muminda yerunako uye hutano hutano sekunonoka kuchembera kweganda, kuderedza huremu hwemuviri uye kuvharira kugadzirwa kwe melanin.

Suzhou Myland Pharm & Nutrition Inc. ndeye FDA-yakanyoreswa mugadziri inopa yepamusoro-mhando uye yakakwirira-kuchena Urolithin A hupfu.

PaSuzhou Myland Pharm takazvipira kupa zvigadzirwa zvemhando yepamusoro nemitengo yakanakisa. Yedu Urolithin A poda inoedzwa zvakasimba kuchena uye potency, kuve nechokwadi kuti iwe unowana yemhando yepamusoro yekuwedzera iwe yaunogona kuvimba nayo. Kunyangwe iwe uchida kutsigira hutano hweserura, kuwedzera immune system yako kana kuwedzera hutano hwese, yedu Urolithin A poda ndiyo sarudzo yakakwana.

Iine makore makumi matatu echiitiko uye ichisundwa nehunyanzvi hwepamusoro uye akakwenenzverwa zvakanyanya R&D mazano, Suzhou Myland Pharm yakagadzira mhando yezvigadzirwa zvemakwikwi uye ive yekuvandudza hupenyu hwesainzi yekuwedzera, tsika synthesis uye kugadzira masevhisi kambani.

Uye zvakare, Suzhou Myland Pharm zvakare iri FDA-yakanyoreswa mugadziri. Zviwanikwa zvekambani zveR&D, zvivakwa zvekugadzira, uye zviridzwa zvekuongorora ndezvemazuva ano uye zvinoshanda, uye zvinogona kugadzira makemikari kubva kumamirigiramu kusvika kumatani muchiyero, uye zvinoenderana neISO 9001 zviyero uye kugadzirwa kweGMP.