Inzululwazi ngasemva kwe-Urolithin A: Yintoni ekufuneka uyazi

I-Urolithin A (UA)i-compound eveliswa yi-metabolism ye-intestinal flora ekudleni okucebile kwi-ellagitannins (njengeerharnati, i-raspberries, njl.). Ithathwa njenge-anti-inflammatory, anti-aging, antioxidant, induction of mitophagy, njl., kwaye inokuwela umqobo wegazi-ingqondo. Izifundo ezininzi ziqinisekisile ukuba i-urolithin A inokulibazisa ukuguga, kwaye izifundo zeklinikhi nazo zibonise iziphumo ezilungileyo.

Yintoni urolithin A?

I-Urolithin A (i-Uro-A) yi-ellagitannin (ET) -uhlobo lwamathumbu e-intestinal metabolite. Yafunyanwa ngokusemthethweni yaza yathiywa igama ngo-2005. Ifomula yayo yemolekyuli yi-C13H8O4, kwaye ubunzima bayo bemolekyuli bungama-228.2. Njengomanduleli we-metabolic we-Uro-A, eyona mithombo yokutya iphambili ye-ET ziirharnati, amaqunube, amaqunube, iwalnuts kunye newayini ebomvu. I-UA yimveliso yee-ETs ze-metabolized yi-intestinal microorganisms. I-UA inethuba elibanzi lokusetyenziswa kuthintelo nakunyango lwezifo ezininzi. Ngaxeshanye, i-UA inoluhlu olubanzi lwemithombo yokutya.

Uphando malunga neziphumo ze-antioxidant ze-urolithin zenziwe. I-Urolithin-A ayikho kwimeko yendalo, kodwa iveliswa ngoluhlu lweenguqu ze-ET nge-intestinal flora. I-UA yimveliso yee-ETs ze-metabolized yi-intestinal microorganisms. Ukutya okutyebileyo kwi-ET kudlula isisu kunye namathumbu amancinci emzimbeni womntu, kwaye ekugqibeleni i-metabolized ikakhulu kwi-Uro-A kwikholoni. Isixa esincinci se-Uro-A sinokubonwa kumathumbu amancinci amancinci.

Njengendalo ye-polyphenolic compounds, ii-ETs ziye zatsala ingqalelo enkulu ngenxa yemisebenzi yazo yezinto eziphilayo ezifana ne-antioxidant, i-anti-inflammatory, anti-allergic kunye ne-anti-viral. Ukongeza ekuthathweni kokutya okunje ngeerharnati, amaqunube, iwalnuts, amaqunube kunye neealmonds, ii-ETs zikwafumaneka kwigallnuts, i-pomegranate peels, myrobalan, Dimininus, geranium, betel nut, sea buckthorn amagqabi, Phyllanthus, Uncaria, Sanguisorba, In Chinese. amayeza afana nePhyllanthus emblica kunye neAgrimony.

Iqela le-hydroxyl kwisakhiwo se-molecular ye-ETs i-polar, engafanelekanga ukuba ifakwe eludongeni lwamathumbu, kwaye i-bioavailability yayo iphantsi kakhulu. Izifundo ezininzi ziye zafumanisa ukuba emva kokuba i-ET ifakwe ngumzimba womntu, i-metabolized yi-intestinal flora kwi-colon kwaye iguqulelwe kwi-urolithin ngaphambi kokuba ifakwe. I-ETs i-hydrolyzed kwi-ellagic acid (EA) kwindawo ephezulu yesisu, kwaye i-EA idlula emathunjini. Iintyatyambo zebhaktiriya ziqhubela phambili kwaye ziphulukene neringi ye-lactone kwaye ifumana iziphumo eziqhubekayo ze-dehydroxylation ukwenza i-urolithin. Kukho iingxelo zokuba i-urolithin ingaba sisiseko sezinto eziphathekayo kwimiphumo ye-biological ye-ETs emzimbeni.

Yintoni i-bioavailability ye-urolithin enxulumene nayo?

Ukubona oku, ukuba uhlakaniphile, usenokuba sele uyazi ukuba i-bioavailability ye-UA inxulumene nantoni.

Into ebaluleke kakhulu kukubunjwa kwe-microbiome, kuba akuzona zonke iintlobo ze-microbial ezinokuvelisa. Impahla ekrwada ye-UA yi-ellagitannins efunyenwe ekutyeni. Le precursor ifumaneka lula kwaye iphantse yafumaneka yonke indawo ngendalo.

I-Ellagitannins i-hydrolyzed emathunjini ukuze ikhuphe i-ellagic acid, ephinda iqhutywe yizityalo zamathumbu zibe yi-urolithin A.

Ngokophononongo olukwijenali yeSeli, ngama-40 ekhulwini kuphela abantu abanokuguqula ngokwendalo i-urolithin A ukusuka kumanduleli wayo ukuya kwi-urolithin A enokusetyenziswa.

Yintoni imisebenzi ye-urolithin A?

Ukuchasa ukuguga

Ithiyori yamahhala yokuguga ikholelwa ukuba iintlobo ze-oksijini ezisebenzayo ezenziwe kwi-mitochondrial metabolism zibangela uxinzelelo lwe-oxidative emzimbeni kwaye lukhokelela ekugugeni, kwaye i-mitophagy idlala indima ebalulekileyo ekugcineni impilo ye-mitochondrial kunye nokunyaniseka. Kuye kwaxelwa ukuba i-UA inokulawula i-mitophagy kwaye ngaloo ndlela ibonise amandla okulibazisa ukuguga. URyu et al. yafumanisa ukuba i-UA yanciphisa ukungasebenzi kwe-mitochondrial kunye nokwandisa ubomi be-Caenorhabditis elegans ngokubangela i-mitophagy; kwiimpuku, i-UA inokubuyisela umva umsebenzi we-muscle onxulumene neminyaka yobudala, ebonisa ukuba i-UA iphucula umsebenzi we-mitochondrial ngokuphucula ubunzima be-Muscle kunye nokwandisa ubomi bomzimba. ULiu et al. wasebenzisa i-UA ukungenelela kwi-fibroblasts yesikhumba eguga. Iziphumo zibonise ukuba i-UA yandisa kakhulu ukubonakaliswa kohlobo lwe-collagen kunye nokunciphisa ukubonakaliswa kwe-matrix metalloproteinase-1 (MMP-1). Iphinde isebenze i-nuclear Factor E2-related factor 2 (i-nuclear factor erythroid 2-related factor 2, Nrf2) -mediated antioxidant response iyanciphisa i-ROS ye-intracellular, ngaloo ndlela ibonisa amandla anamandla okulwa nokuguga.

Isiphumo se-Antioxidant

Okwangoku, uphando oluninzi luye lwenziwa kwi-antioxidant ye-urolithin. Phakathi kwazo zonke i-metabolites ye-urolithin, i-Uro-A inomsebenzi onamandla we-antioxidant, okwesibini kuphela kwi-oligomers ye-proanthocyanidin, i-catechin, i-epicatechin kunye ne-3,4-dihydroxyphenylacetic acid. Uvavanyo lwe-oxygen radical absorbance capacity (ORAC) yeplasma yamavolontiya asempilweni yafumanisa ukuba amandla e-antioxidant anyuke nge-32% emva kwe-0.5 h yokungeniswa kwejusi yerharnati, kodwa inqanaba leentlobo ze-oksijini ezisebenzayo alizange litshintshe kakhulu, ngelixa i-Neuro- In. Uvavanyo lwe-vitro kwiiseli ze-2a zafumanisa ukuba i-Uro-A inokunciphisa inqanaba leentlobo ze-oksijini ezisebenzayo kwiiseli. Ezi ziphumo zibonisa ukuba i-Uro-A ineempembelelo ezinamandla ze-antioxidant.

03. I-Urolithin A kunye ne-cardiovascular and cerebrovascular disease

Iziganeko zehlabathi jikelele ze-cardiovascular disease (CVD) zinyuka unyaka nonyaka, kwaye izinga lokufa lihlala liphezulu. Akwandisi umthwalo wentlalo noqoqosho kuphela, kodwa ikwachaphazela ngokunzulu umgangatho wobomi babantu. I-CVD sisifo sezinto ezininzi. Ukudumba kunokunyusa umngcipheko weCVD. Uxinzelelo lwe-oxidative lunxulumene ne-pathogenesis ye-CVD. Kukho iingxelo zokuba i-metabolites ephuma kwi-intestinal microorganisms ihambelana nomngcipheko we-CVD.

I-UA iye yaxelwa ukuba ineempembelelo ezinamandla ezichasayo kunye ne-antioxidant, kwaye izifundo ezifanelekileyo ziqinisekisile ukuba i-UA inokudlala indima enenzuzo kwi-CVD. Savi et al. wasebenzisa imodeli yegundane lesifo seswekile ukuqhuba izifundo ze-vivo kwi-diabetic cardiomyopathy kwaye yafumanisa ukuba i-UA inokunciphisa impendulo yokuqala yokuvuvukala kwezicubu ze-myocardial kwi-hyperglycemia, iphucule i-myocardial microenvironment, kwaye ikhuthaze ukubuyiswa kwe-cardiomyocyte contractility kunye ne-calcium dynamics, ebonisa ukuba i-UA inako. ingasetyenziswa njengechiza elincedisayo ukulawula isifo sentliziyo kunye nokuthintela iingxaki zayo.

I-UA inokuphucula umsebenzi we-mitochondrial kunye nokusebenza kwemisipha ngokubangela i-mitophagy. Intliziyo ye-mitochondria zii-organelles eziphambili ezinoxanduva lokuvelisa i-ATP etyebileyo ngamandla. Ukungasebenzi kakuhle kweMitochondrial yingcambu yesizathu sokungaphumeleli kwentliziyo. Ukungasebenzi kweMitochondrial okwangoku kuthathwa njengento ekujoliswe kuyo yonyango. Ke ngoko, i-UA iye yaba lichiza elitsha lomviwa kunyango lwe-CVD.

Urolithin A kunye nezifo ze-neurological

I-Neuroinflammation yinkqubo ebalulekileyo kwisehlo kunye nophuhliso lwesifo se-neurodeergenerative (ND). I-apoptosis ebangelwa luxinzelelo lwe-oxidative kunye nokudityaniswa kweprotheyini engaqhelekanga ihlala ibangela i-neuroinflammation, kwaye i-pro-inflammatory cytokines ekhutshwe yi-neuroinflammation emva koko ichaphazele i-neurodegeneration.

Uphononongo lufumene ukuba i-UA ilamla umsebenzi wokuchasana nokudumba ngokubangela i-autophagy kwaye isebenze isilawuli se-signal esithe cwaka 1 (SIRT-1) i-deacetylation mechanism, inqanda i-neuroinflammation kunye ne-neurotoxicity, kunye nokuthintela i-neurodegeneration, ebonisa ukuba i-UA yi-agent esebenzayo ye-Neuroprotective. Kwangaxeshanye, ezinye izifundo zifumanise ukuba i-UA inokusebenzisa iziphumo ze-neuroprotective ngokukhupha ngokuthe ngqo iiradicals zasimahla kunye nokuthintela i-oxidases.

Ucwaningo luye lwabonisa ukuba ijusi yegromegranate idlala indima ye-neuroprotective ngokunyusa umsebenzi we-mitochondrial aldehyde dehydrogenase, ukugcina inqanaba le-anti-apoptotic protein Bcl-xL, ukunciphisa i-α-synuclein aggregation kunye nomonakalo oxidative, kunye nokuchaphazela umsebenzi we-neuronal kunye nokuzinza. Iikhompawundi ze-Urolithin ziyi-metabolites kunye neempembelelo ze-ellagitannins emzimbeni kwaye zinemisebenzi ye-biological efana ne-anti-inflammation, i-anti-oxidative stress, kunye ne-anti-apoptosis. I-Urolithin inokusebenzisa umsebenzi we-neuroprotective ngokusebenzisa umqobo wegazi-ubuchopho kwaye iyindawo encinci esebenzayo yokungenelela kwizifo ze-neurodeergenerative.

I-Urolithin A kunye nezifo ezidibeneyo kunye ne-spinal degenerative

Izifo eziwohlokayo zibangelwa zizinto ezininzi ezifana nokuguga, ukuxinezeleka, kunye nokwenzakala. Izifo ezixhaphakileyo ezixhaphakileyo zamalungu yi-osteoarthritis (OA) kunye ne-degenerative spinal disease intervertebral disc degeneration (IDD). Ukwenzeka kunokubangela intlungu kunye nomsebenzi omncinci, okukhokelela ekulahlekelweni kwabasebenzi kunye nokubeka impilo yoluntu engozini. Indlela ye-UA ekuphatheni i-IDD yesifo somgogodla inokunxulumana nokulibazisa i-nucleus pulposus (NP) ye-cell apoptosis. I-NP yinxalenye ebalulekileyo yediski ye-intervertebral. Igcina umsebenzi we-biological we-disc intervertebral ngokusabalalisa uxinzelelo kunye nokugcina i-homeostasis ye-matrix. Izifundo ziye zafumanisa ukuba i-UA ibangela i-mitophagy ngokuvula indlela yokubonisa i-AMPK, ngaloo ndlela inqanda i-tert-butyl hydroperoxide (t-BHP) -i-apoptosis eyenziwa yi-osteosarcoma yeseli ye-NP ye-cell kunye nokunciphisa i-intervertebral disc degeneration.

Urolithin A kunye nezifo ze-metabolic

Iziganeko zezifo ze-metabolic ezifana nokukhuluphala kunye nesifo sikashukela zikhula unyaka nonyaka, kwaye imiphumo enenzuzo ye-polyphenols yokutya kwimpilo yabantu iqinisekisiwe ngamaqela amaninzi kwaye ibonise amandla okukhusela kunye nokunyangwa kwezifo ze-metabolic. I-pomegranate polyphenols kunye ne-intestinal metabolite UA inokuphucula izikhombisi zeklinikhi ezinxulumene nezifo ze-metabolic, ezifana ne-lipase, i-α-glucosidase (α-glucosidase) kunye ne-dipeptidyl peptidase-4 (i-dipeptidyl peptidase-4) echaphazelekayo kwi-glucose kunye ne-fatty acid metabolism. I-4), kunye neegenes ezinxulumene nazo ezifana ne-adiponectin, i-PPARγ, i-GLUT4 kunye ne-FABP4 echaphazela ukuhlukana kwe-adipocyte kunye ne-triglyceride (TG) yokuqokelela.

Ukongeza, ezinye izifundo zikwafumanise ukuba i-UA inamandla okunciphisa iimpawu zokutyeba. I-UA yimveliso ye-intestinal metabolism yeepolyphenols. Ezi metabolites zinamandla okunciphisa ukuqokelela kwe-TG kwiiseli zesibindi kunye ne-adipocytes. Abdulrasheed et al. bondliwe ukutya okunamafutha aphezulu kwiimpuku zeWistar ukuphembelela ukutyeba. Unyango lwe-UA alunyusi nje ukukhutshelwa kwamafutha kwilindle, kodwa luphinde lunciphise ubunzima bezicubu ze-adipose ze-visceral kunye nobunzima bomzimba ngokulawula izakhi zofuzo ezinxulumene ne-lipogenesis kunye ne-fatty acid oxidation. Inciphisa ukuqokelelwa kwamafutha esibindi kunye noxinzelelo lwe-oxidative. Kwangaxeshanye, i-UA inokonyusa ukusetyenziswa kwamandla ngokuphucula i-thermogenesis ye-brown adipose tissue kunye nokubangela ukubomvu kwamafutha amhlophe. Umatshini kukunyusa amanqanaba e-triiodothyronine (T3) kwi-brown fat kunye ne-inguinal fat depot. Yandisa imveliso yobushushu kwaye ngaloo ndlela ichasene nokutyeba.

Ukongeza, i-UA nayo inefuthe lokuthintela ukuveliswa kwe-melanin. Uphononongo lufumene ukuba i-UA inokunciphisa kakhulu ukuveliswa kwe-melanin kwiiseli ze-melanoma ze-B16. Eyona ndlela iphambili yeyokuba i-UA ichaphazela ukusebenza kwe-catalytic ye-tyrosinase ngokuthintela ukhuphiswano lwe-cell tyrosinase, ngaloo ndlela inciphisa umbala. Ke ngoko, i-UA inamandla kwaye iyasebenza ukwenza mhlophe kwaye ikhanyise amabala. Kwaye uphando lubonisa ukuba i-urolithin A inefuthe lokubuyisela umva ukuguga kwamajoni omzimba. Uphando lwamva nje lufumanise ukuba xa i-urolithin A yongezwa njengesongezelelo sokutya, ayisebenzi nje kuphela amandla ommandla we-lymphatic we-immune system, kodwa inyusa umsebenzi weeseli ze-hematopoietic stem. Ukusebenza ngokubanzi kubonisa ukubanakho kwe-urolithin A ukulwa nokuhla kwe-immune system.

Ukushwankathela, i-UA, njenge-metabolite yamathumbu e-phytochemicals yendalo ye-ETs, iye yatsala ingqalelo enkulu kwiminyaka yamuva. Ngophando malunga neempembelelo ze-pharmacological kunye neendlela ze-UA ziba zibanzi kwaye zinzulu kwaye zinzulu, i-UA ayisebenzi kuphela kumhlaza kunye ne-CVD (izifo zentliziyo). Inefuthe elihle lokuthintela kunye nonyango kwizifo ezininzi zeklinikhi ezifana ne-ND (izifo ze-neurodeergenerative) kunye nezifo ze-metabolic. Ikwabonisa amandla amakhulu okusebenza kwiinkalo zobuhle kunye nokhathalelo lwempilo njengokulibazisa ukuguga kwesikhumba, ukunciphisa ubunzima bomzimba kunye nokuthintela ukuveliswa kwe-melanin.

I-Suzhou Myland Pharm & Nutrition Inc. ngumvelisi obhalisiwe we-FDA obonelela ngomgangatho ophezulu kunye nococeko oluphezulu lwe-Urolithin A powder.

ESuzhou Myland Pharm sizimisele ukubonelela ngezona mveliso zikumgangatho ophezulu ngamaxabiso angcono. I-Urolithin yethu ye-powder ihlolwe ngokugqithiseleyo ukucoceka kunye namandla, ukuqinisekisa ukuba ufumana isongezelelo esiphakamileyo esinokuthembela kuso. Nokuba ufuna ukuxhasa impilo yeselula, ukonyusa amajoni akho omzimba okanye ukuphucula impilo yonke, i-Urolithin A powder yethu lukhetho olugqibeleleyo.

Ineminyaka engama-30 yamava kwaye iqhutywa bubuchwepheshe obuphezulu kunye nezicwangciso ze-R&D eziphuculwe kakhulu, iSuzhou Myland Pharm iphuhlise uluhlu lweemveliso ezikhuphisanayo kwaye ibe sisongezelelo sesayensi yobomi, ukudibanisa isiko kunye nenkampani yeenkonzo zokuvelisa.

Ukongeza, iSuzhou Myland Pharm ikwangumvelisi obhalisiweyo we-FDA. Izixhobo ze-R&D zenkampani, izixhobo zemveliso, kunye nezixhobo zohlalutyo zezanamhlanje kwaye zinemisebenzi emininzi, kwaye zinokuvelisa iikhemikhali ukusuka kwimilligrams ukuya kwiitoni kwisikali, kwaye zithobela imigangatho ye-ISO 9001 kunye neenkcukacha zemveliso ye-GMP.