Sainzi Iri Kuseri kweUrolithin A: Zvaunofanira Kuziva

Urolithin A (UA)imusanganiswa unogadzirwa nekushandiswa kwezvirimwa zvemudumbu muzvikafu zvakapfuma mu ellagitannins (senge mapomegranati, raspberries, nezvimwewo). Inofungidzirwa kuti ine anti-inflammatory, anti-aging, antioxidant, induction of mitophagy, nezvimwewo, uye inogona kuyambuka chipingamupinyi cheropa-uropi. Zvidzidzo zvakawanda zvakasimbisa kuti urolithin A inogona kunonoka kukwegura, uye zvidzidzo zvekiriniki zvakaratidzawo mhedzisiro yakanaka.

Chii chinonzi urolithin A?

Urolithin A (Uro-A) imhando ye ellagitannin (ET) mudumbu. Yakawanikwa zviri pamutemo uye yakatumidzwa zita muna 2005. Fomura yayo yemamorekuru iC13H8O4, uye huwandu hwayo hwemamorekuru i228.2. Senzira yekutanga metabolic yeUro-A, manyuko makuru eET ndiwo mapomegranate, mastrawberry, maraspberry, walnuts newaini tsvuku. UA chigadzirwa cheETs dzakagadziriswa nehutachiona hwemudumbu. UA ine mikana yakawanda yekushandiswa mukudzivirira nekurapa zvirwere zvakawanda. Panguva imwe chete, UA ine mhando dzakasiyana dzezvikafu.

Tsvagiridzo pamusoro pemhedzisiro ye urolithin ine antioxidant yakaitwa. Urolithin-A haipo muchimiro chechisikigo, asi inogadzirwa nekushanduka kweET nemaruva emudumbu. UA chigadzirwa cheETs chinogadziriswa netupukanana twemudumbu. Zvikafu zvakapfuma muET zvinopfuura nemudumbu nemudumbu mudiki mumuviri wemunhu, uye pakupedzisira zvinogadziriswa zvakanyanya muUro-A muura. Hushoma hweUro-A hunogonawo kuonekwa mudumbu diki rezasi.

Sezvinhu zvakasikwa zve polyphenolic, ma ET akakwezva vanhu vakawanda nekuda kwemabasa avo ehupenyu akadai se antioxidant, anti-inflammatory, anti-allergic uye anti-viral. Kuwedzera pakuva anobva muzvikafu zvakaita semapomegranate, mastrawberry, walnuts, raspberries uye almonds, ma ET anowanikwawo mu gallnuts, pomegranate peels, myrobalan, Dimininus, geranium, betel nut, sea buckthorn leaves, Phyllanthus, Uncaria, Sanguisorba, Mumishonga yeChinese yakaita sePhyllanthus emblica neAgrimony.

Boka rehydroxyl riri muchimiro chemamorekuru eETs rakati pfuurei, izvo zvisingakodzeri kunyudzwa nemadziro emudumbu, uye bioavailability yaro yakaderera zvikuru. Ongororo dzakawanda dzakawana kuti mushure mekunge maETs anyikwa nemuviri wemunhu, anogadziriswa nezvinomera zvemudumbu muura uye anoshandurwa kuita urolithin asati anyudzwa. MaETs anonyudzwa kuita ellagic acid (EA) mudumbu repamusoro, uye EA inopfuudzwa nemudumbu. Zvinomera zvebhakitiriya zvinoenderera mberi nekugadzirisa uye kurasikirwa ne lactone ring uye zvinoitwa ne dehydroxylation reactions kuti zvigadzire urolithin. Kune mishumo yekuti urolithin inogona kunge iri hwaro hwemhedzisiro ye ETs mumuviri.

Chii chinobatanidzwa ne bioavailability ye urolithin?

Kana uchiona izvi, kana wakangwara, ungatove uchiziva kuti kuwanika kweUA kune chekuita nei.

Chinhu chinonyanya kukosha ndechekuumbwa kwe microbiome, nekuti hazvisi zvese zvipenyu zvinogona kubereka. Zvinhu zveUA zvinonzi ellagitannins zvinowanikwa kubva muchikafu. Izvi zvinowanikwa nyore nyore uye zvinowanikwa pese pese.

MaEllagitannins anonyungudika muura kuti abudise ellagic acid, iyo inozogadziriswazve nemaruva emudumbu kuita urolithin A.

Sekureva kweongororo yakaitwa mumagazini inonzi Cell, vanhu 40% chete ndivo vanogona kushandura urolithin A kubva pakutanga kwayo kuita urolithin A inoshandiswa.

Ndeapi mabasa e urolithin A?

Kudzivirira kukwegura

Dzidziso yefree radical yekukwegura inotenda kuti mhando dzeokisijeni dzinogadzirwa mumitochondrial metabolism dzinokonzera oxidative stress mumuviri uye dzinotungamira mukukwegura, uye mitophagy inoita basa rakakosha mukuchengetedza hutano hwemitochondrial uye kutendeseka. Zvakataurwa kuti UA inogona kudzora mitophagy nekudaro ichiratidza mukana wekunonoka kukwegura. Ryu et al. vakawana kuti UA yakaderedza kusashanda zvakanaka kwemitochondrial uye yakawedzera hupenyu muCaenorhabditis elegans nekukurudzira mitophagy; mumakonzo, UA inogona kudzosera kudzikira kwekushanda kwemhasuru dzine chekuita nekukwegura, zvichiratidza kuti UA inovandudza kushanda kwemitochondrial nekuwedzera tsandanyama uye kuwedzera hupenyu hwemuviri. Liu et al. vakashandisa UA kupindira mukukura kweganda fibroblasts. Mhedzisiro yacho yakaratidza kuti UA yakawedzera zvakanyanya kutaura kwerudzi rweI collagen uye yakaderedza kutaura kwe matrix metalloproteinase-1 (MMP-1). Yakabatsirawo nuclear Factor E2-related factor 2 (nuclear factor erythroid 2-related factor 2, Nrf2)-mediated antioxidant response inoderedza intracellular ROS, nokudaro ichiratidza simba rakasimba rekurwisa kukwegura.

Mhedzisiro yeAntioxidant

Parizvino, zvidzidzo zvakawanda zvakaitwa pamusoro pemhedzisiro ye urolithin inodzivirira kukuvadza kwemasero. Pakati pemetabolites ese e urolithin, Uro-A ine simba guru rekudzivirira kukuvadza, yechipiri kune proanthocyanidin oligomers, catechins, epicatechin uye 3,4-dihydroxyphenylacetic acid. Kuyedzwa kwe oxygen radical absorbance capacity (ORAC) yeplasma yevazvipiri vane hutano kwakawana kuti simba rekudzivirira kukuvadza kwakawedzera ne32% mushure memaawa 0.5 ekudya pomegranate juice, asi huwandu hwemhando dzeokisijeni dzinoshanda hauna kuchinja zvakanyanya, nepo mukuyedza kweNeuro-In vitro pamasero e2a kwakawana kuti Uro-A inogona kuderedza huwandu hwemhando dzeokisijeni dzinoshanda mumasero. Mhedzisiro iyi inoratidza kuti Uro-A ine simba guru rekudzivirira kukuvadza.

03. Urolithin A nezvirwere zvemwoyo netsinga dzeropa

Kuwanda kwezvirwere zvemwoyo pasi rose (CVD) kuri kuwedzera gore negore, uye huwandu hwevanhu vanofa huchiri pamusoro. Hazvingowedzeri mutoro wemagariro evanhu nehupfumi chete, asiwo zvinokanganisa hupenyu hwevanhu zvakanyanya. CVD chirwere chinokonzerwa nezvinhu zvakawanda. Kuzvimba kunogona kuwedzera njodzi yeCVD. Kushushikana kwe oxidative kune chekuita nekukura kweCVD. Kune mishumo yekuti metabolites dzinobva mutupukanana twemudumbu dzine chekuita nenjodzi yeCVD.

UA inonzi ine simba rekudzivirira kuzvimba uye antioxidant, uye zvidzidzo zvakakosha zvakasimbisa kuti UA inogona kuita basa rinobatsira muCVD. Savi nevamwe vake vakashandisa modhi yemakonzo echirwere cheshuga kuita zvidzidzo zve in vivo nezvechirwere cheshuga cardiomyopathy uye vakaona kuti UA inogona kuderedza kupindura kwekutanga kwekuzvimba kwenyama yemyocardial kune hyperglycemia, kuvandudza microenvironment yemyocardial, uye kukurudzira kudzoreredzwa kwe cardiomyocyte contractility uye calcium dynamics, zvichiratidza kuti UA inogona Inogona kushandiswa semushonga wekubatsira kudzora chirwere cheshuga cardiomyopathy uye kudzivirira matambudziko ayo.

UA inogona kuvandudza mashandiro emitochondrial uye mashandiro emhasuru nekukonzera mitophagy. Mitochondria yemoyo ndiwo maorganelle akakosha anogadzira ATP ine simba rakawanda. Kusashanda zvakanaka kwemitochondrial ndiko kunokonzera kukundikana kwemoyo. Kusashanda zvakanaka kwemitochondrial parizvino kunoonekwa senzira yekurapa. Saka, UA yavewo mushonga mutsva wekurapa CVD.

Urolithin A uye zvirwere zvetsinga

Kuzvimba kweuropi inzira inokosha mukuitika uye kukura kwechirwere chepfungwa (ND). Kuputika kweuropi kunokonzerwa nekushushikana kwe oxidative uye kuungana kwemapuroteni zvisina kujairika kunowanzo kukonzera kuzvimba kweuropi, uye ma cytokines anokonzera kuzvimba anoburitswa neuropi anobva akanganisa kuora kweuropi.

Zvidzidzo zvakawana kuti UA inodzivirira kuzvimba nekukurudzira autophagy uye kuita kuti silent signal regulator 1 (SIRT-1) deacetylation mechanism, ichidzivisa neuroinflammation uye neurotoxicity, uye ichidzivirira neurodegeneration, zvichiratidza kuti UA inodzivirira Neuro. Panguva imwe chete, zvimwe zvidzidzo zvakawana kuti UA inogona kudzivirira Neurological effects nekubvisa zvakananga ma free radicals uye kudzivirira oxidases.

Zvidzidzo zvakaratidza kuti muto wepomegranate unobatsira kudzivirira tsinga dzemuviri nekuwedzera mitochondrial aldehyde dehydrogenase activity, kuchengetedza mwero weproteni ye anti-apoptotic Bcl-xL, kuderedza kuunganidzwa kweα-synuclein uye kukuvara kwe oxidative, uye kukanganisa mashandiro etsinga dzemuviri uye kugadzikana. MaUrolithin compounds ndiwo metabolites uye zvikamu zve ellagitannins mumuviri uye ane mabasa ehupenyu akadai sekudzivirira kuzvimba, anti-oxidative stress, uye anti-apoptosis. Urolithin inogona kuita basa rekudzivirira tsinga kuburikidza neropa-uropi uye imorekuru diki inogona kushanda yekudzivirira zvirwere zvetsinga.

Urolithin A uye zvirwere zvinokanganisa majoini nemusana

Zvirwere zvinopera simba zvinokonzerwa nezvinhu zvakawanda zvakaita sekukwegura, kusvuta, uye kukuvara. Zvirwere zvinopera simba zvakanyanya zvemajoini iosteoarthritis (OA) uye degenerative spinal disease intervertebral disc degeneration (IDD). Kuitika kwacho kunogona kukonzera kurwadziwa uye kusashanda zvakanaka, zvichikonzera kurasikirwa nebasa uye kuisa hutano hwevanhu panjodzi zvakanyanya. Maitiro eUA mukurapa chirwere chespinal degenerative IDD anogona kunge aine chekuita nekunonoka kwe nucleus pulposus (NP) cell apoptosis. NP chikamu chakakosha che intervertebral disc. Inochengetedza basa re intervertebral disc nekuparadzira kumanikidzwa uye kuchengetedza matrix homeostasis. Zvidzidzo zvakawana kuti UA inokurudzira mitophagy nekushandisa AMPK signaling pathway, nokudaro ichidzivisa tert-butyl hydroperoxide (t-BHP)-induced apoptosis ye human osteosarcoma cell NP cells uye kuderedza intervertebral disc degeneration.

Urolithin A uye zvirwere zve metabolic

Kuwanda kwezvirwere zve metabolic zvakaita sekufuta nechirwere cheshuga kuri kuwedzera gore negore, uye mhedzisiro inobatsira ye polyphenols pahutano hwevanhu yakasimbiswa nemapoka akawanda uye yakaratidza kugona mukudzivirira nekurapa zvirwere zve metabolic. Pomegranate polyphenols uye metabolite yayo yemudumbu UA inogona kuvandudza zviratidzo zvekiriniki zvine chekuita nezvirwere zve metabolic, zvakaita se lipase, α-glucosidase (α-glucosidase) uye dipeptidyl peptidase-4 (dipeptidyl peptidase-4) zvine chekuita ne glucose ne fatty acid metabolism. 4), pamwe chete nemajini ane hukama akadai se adiponectin, PPARγ, GLUT4 ne FABP4 anokanganisa kusiyana kwe adipocyte uye triglyceride (TG) kuunganidza.

Pamusoro pezvo, zvimwe zvidzidzo zvakawanawo kuti UA ine mukana wekuderedza zviratidzo zvekufutisa. UA imugumisiro wemetabolism ye polyphenols mudumbu. Aya ma metabolites ane kugona kuderedza kuunganidzwa kweTG mumasero echiropa uye adipocytes. Abdulrasheed nevamwe vake vakapa makonzo eWistar chikafu chine mafuta akawanda kuti vakurudzire kufuta. Kurapa kweUA hakuna kungowedzera kuburitswa kwemafuta mutsvina chete, asiwo kwakaderedza visceral adipose tissue mass nehuremu hwemuviri nekutonga majini ane chekuita ne lipogenesis uye fatty acid oxidation. Kunoderedza kuunganidzwa kwemafuta echiropa uye oxidative stress yayo. Panguva imwecheteyo, UA inogona kuwedzera kushandiswa kwesimba nekuwedzera thermogenesis yebrown adipose tissue uye kukonzera browning yemafuta machena. Maitiro acho ndeekuwedzera mazinga e triiodothyronine (T3) mubrown fat uye inguinal fat depots. Kunowedzera kugadzirwa kwekupisa uye nekudaro kunodzivisa kufuta.

Pamusoro pezvo, UA inewo simba rekudzivisa kugadzirwa kwemelanin. Zvidzidzo zvakawana kuti UA inogona kuderedza zvakanyanya kugadzirwa kwemelanin mumasero eB16 melanoma. Nzira huru ndeyekuti UA inokanganisa catalytic activation yetyrosinase kuburikidza nekudzivisa tyrosinase yemasero kukwikwidzana, nokudaro ichideredza pigmentation. Nokudaro, UA ine simba uye kushanda kwekuchenesa nekujekesa mavara. Uye tsvakurudzo inoratidza kuti urolithin A ine simba rekudzorera kukwegura kweimmune system. Tsvagiridzo yazvino yakawana kuti kana urolithin A ikawedzerwa sechikafu chekuwedzera, haingoiti chete simba renzvimbo ye lymphatic ye immune system yembeva, asiwo inowedzera kushanda kwemasero e hematopoietic stem. Kushanda kwese kunoratidza kugona kwe urolithin A kurwisa kudzikira kwe immune system ine chekuita nekukwegura.

Mukupfupisa, UA, semushonga wemudumbu wemakemikari echisikigo eET, yakakwezva vanhu vakawanda mumakore achangopfuura. Nekutsvaga kwemishonga uye mashandiro eUA kuri kuwedzera uye kwakadzama, UA haingoshandi chete mukenza neCVD (zvirwere zvemwoyo). Ine mhedzisiro yakanaka yekudzivirira uye yekurapa pazvirwere zvakawanda zvekiriniki zvakaita seND (zvirwere zveneurodegenerative) nezvirwere zvemetabolism. Inoratidzawo kugona kukuru kwekushandisa munzvimbo dzerunako nehutano dzakadai sekunonoka kukwegura kweganda, kuderedza huremu hwemuviri uye kudzivirira kugadzirwa kwemelanin.

Suzhou Myland Pharm & Nutrition Inc. ikambani yakanyoreswa neFDA inopa Urolithin A powder yemhando yepamusoro uye yakachena.

KuSuzhou Myland Pharm takazvipira kupa zvigadzirwa zvemhando yepamusoro nemitengo yepamusoro. Upfu hwedu hweUrolithin A hunoongororwa zvakasimba kuti hune kuchena uye simba, zvichiita kuti uwane chinowedzera chemhando yepamusoro chaunogona kuvimba nacho. Kunyangwe uchida kutsigira hutano hwemasero, kusimbisa masoja emuviri wako kana kusimudzira hutano hwese, Upfu hwedu hweUrolithin A ndiyo sarudzo yakakwana.

Nemakore makumi matatu eruzivo uye zvichitungamirirwa netekinoroji yepamusoro uye nzira dzeR&D dzakanyatsogadzirwa, Suzhou Myland Pharm yakagadzira zvigadzirwa zvakasiyana-siyana zvinokwikwidzana uye yakava kambani itsva yekuwedzera sainzi yehupenyu, kugadzira zvinhu zvakagadzirwa uye kugadzira zvinhu.

Pamusoro pezvo, Suzhou Myland Pharm ikambani yakanyoreswa neFDA. Zvishandiso zveR&D zvekambani, nzvimbo dzekugadzira, uye zvishandiso zvekuongorora ndezvemazuva ano uye zvinoshanda zvakawanda, uye zvinogona kugadzira makemikari kubva pamamirigiramu kusvika kumatani muhukuru, uye zvinoenderana neISO 9001 standards uye specifications dzekugadzira GMP.