Sayensị N'azụ Urolithin A: Ihe Ị Kwesịrị Ịma

Urolitin A (UA)bụ ihe na-emepụta site na metabolism nke ahịhịa eriri afọ na nri ndị nwere ellagitannins (dị ka pọmigranet, raspberries, wdg). A na-ewere ya na ọ nwere mgbochi mkpali, mgbochi ịka nká, antioxidant, ntinye nke mitophagy, wdg, ma nwee ike ịgafe ihe mgbochi ụbụrụ ọbara. Ọtụtụ nchọpụta ekwenyela na urolithin A nwere ike igbu oge ịka nká, na ọmụmụ ụlọ ọgwụ egosiwokwa ezigbo nsonaazụ.

Kedu ihe bụ urolitin A?

Urolithin A (Uro-A) bụ ellagitannin (ET) - ụdị nsia flora metabolite. Achọpụtara ya n'ihu ọha wee kpọọ ya n'afọ 2005. Usoro ihe omimi ya bụ C13H8O4, na mkpokọta molecular ya bụ 228.2. Dị ka usoro metabolic nke Uro-A, isi ihe oriri nke ET bụ mkpụrụ pọmigranet, strawberries, raspberries, walnuts na mmanya uhie. UA bụ ngwaahịa nke ET metabolized site na microorganisms nke eriri afọ. UA nwere atụmanya ngwa sara mbara na mgbochi na ọgwụgwọ nke ọtụtụ ọrịa. N'otu oge ahụ, UA nwere ọtụtụ ụdị nri nri.

Emeela nyocha maka mmetụta antioxidant nke urolitins. Urolithin-A adịghị adị na ọnọdụ eke, mana a na-emepụta ya site na mgbanwe mgbanwe nke ET site na osisi intestinal. UA bụ ngwaahịa nke ET metabolized site na microorganisms nke eriri afọ. Nri bara ụba na ET na-esi n'ime afọ na eriri afọ dị n'ime ahụ mmadụ, ma emesịa metabolized na-abanye na Uro-A na colon. Enwere ike ịhụ obere Uro-A n'ime obere eriri afọ.

Dị ka ogige polyphenolic eke, ET adọtala nlebara anya nke ukwuu n'ihi ọrụ ndụ ha dị ka antioxidant, mgbochi mkpali, mgbochi nrịanrịa na mgbochi nje. Na mgbakwunye na-esi na nri ndị dị ka pọmigranet, strawberries, walnuts, raspberries na almọnd, ET na-ahụkwa na gallnuts, peels pọmigranet, myrobalan, Dimininus, geranium, betel nut, sea buckthorn epupụta, Phyllanthus, Uncaria, Sanguisorba, na Chinese. ọgwụ ndị dị ka Phyllanthus emblica na Agrimony.

Otu hydroxyl dị n'ụdị molecular nke ET bụ obere polar, nke na-adịghị anabata nnabata site na mgbidi eriri afọ, na bioavailability ya dị ntakịrị. Ọtụtụ nchọpụta achọpụtala na mgbe ahụ mmadụ richara ET, a na-emegharị ya site na intestinal flora na colon ma ghọọ urolithin tupu etinye ya. A na-agbanye ET n'ime ellagic acid (EA) na traktị eriri afọ nke elu, EA na-agafekwa n'ime eriri afọ. Osisi nje na-aga n'ihu na-arụkwa ọrụ wee tufuo mgbanaka lactone ma na-enweta mmeghachi omume dehydroxylation na-aga n'ihu iji mepụta urolithin. Enwere akụkọ na urolithin nwere ike ịbụ ihe ndabere ihe maka mmetụta ndu nke ET n'ime ahụ.

Kedu ihe jikọrọ bioavailability nke urolithin?

Ịhụ nke a, ọ bụrụ na ị maara ihe, ị nwere ike maralarị ihe metụtara bioavailability nke UA.

Ihe kachasị mkpa bụ ihe mejupụtara microbiome, n'ihi na ọ bụghị ụdị microbial niile nwere ike ịmepụta. Ngwa ngwa nke UA bụ ellagitannins nwetara site na nri. Nke a precursor dị mfe dị na ihe fọrọ nke nta ka ọ bụrụ ebe niile na okike.

Elagitannin na-edobe hydrolyzed n'ime eriri afọ iji hapụ ellagic acid, bụ nke a na-ahazi ya site na intestinal flora n'ime urolithin A.

Dị ka nnyocha e mere n'akwụkwọ akụkọ Cell si kwuo, nanị 40% nke ndị mmadụ nwere ike gbanwee urolithin A site na mmalite ya gaa na urolithin A.

Kedu ọrụ nke urolitin A?

Mgbochi ịka nká

Theory free radical of ịka nká kwenyere na ụdị oxygen na-emeghachi omume na-emepụta na mitochondrial metabolism na-akpata nrụgide oxidative n'ime ahụ ma na-eduga n'ịka nká, na mitophagy na-arụ ọrụ dị mkpa n'ịkwado ahụike na iguzosi ike n'ezi ihe nke mitochondrial. A kọwo na UA nwere ike ịhazi mitophagy ma si otú ahụ gosipụta ikike igbu oge ịka nká. Ryu et al. chọpụtara na UA belatara nrụrụ mitochondrial na ogologo ndụ ogologo na Caenorhabditis elegans site n'ịkwalite mitophagy; N'ime òké, UA nwere ike gbanwee arụ ọrụ akwara afọ metụtara afọ, na-egosi na UA na-eme ka ọrụ mitochondrial dịkwuo mma site n'ịkwalite ọkpụkpụ akwara na ịgbatị ndụ ahụ. Liu et al. ejiri UA tinye aka na fibroblasts akpụkpọ ahụ merela agadi. Nsonaazụ gosiri na UA mụbara okwu nke ụdị collagen nke ukwuu ma belata okwu nke matrix metalloproteinase-1 (MMP-1). Ọ na-arụ ọrụ nuklia Factor E2-related factor 2 (ihe na-akpata erythroid 2-related factor 2, Nrf2) nzaghachi antioxidant na-ebelata ROS intracellular, si otú ahụ na-egosi ike mgbochi ịka nká.

Mmetụta antioxidant

Ka ọ dị ugbu a, e meela ọtụtụ ọmụmụ banyere mmetụta antioxidant nke urolitin. N'ime metabolites urolithin niile, Uro-A nwere ọrụ antioxidant siri ike, nke abụọ bụ proanthocyanidin oligomers, catechins, epicatechin na 3,4-dihydroxyphenylacetic acid. Nnwale nke ikuku oxygen radical absorbance (ORAC) nke plasma nke ndị ọrụ afọ ofufo ahụike chọpụtara na ikike antioxidant mụbara site na 32% mgbe 0,5 h riri mmiri pọmigranet, mana ọkwa nke ụdị oxygen na-emeghachi omume agbanwebeghị nke ukwuu, ebe na Neuro-In. Nnwale vitro na sel 2a chọpụtara na Uro-A nwere ike ibelata ogo ụdị oxygen na-emeghachi omume na sel. Nsonaazụ ndị a na-egosi na Uro-A nwere mmetụta antioxidant siri ike.

03. Urolithin A na ọrịa obi na ụbụrụ cerebrovascular

Ọnụ ọgụgụ zuru ụwa ọnụ nke ọrịa obi (CVD) na-abawanye kwa afọ, ọnụ ọgụgụ ndị na-anwụ anwụ na-adịkwa elu. Ọ bụghị naanị na ọ na-abawanye ibu ọrụ mmekọrịta mmadụ na ibe ya, kamakwa ọ na-emetụta ụdị ndụ ndị mmadụ. CVD bụ ọrịa na-akpata ọtụtụ ihe. Mbufụt nwere ike ịbawanye ohere nke CVD. Nchegbu oxidative metụtara pathogenesis nke CVD. Enwere akụkọ na metabolites sitere na microorganisms intestinal jikọtara ya na ihe ize ndụ nke CVD.

A kọwo UA na ọ nwere mmetụta mgbochi mkpali na antioxidant siri ike, na ọmụmụ ihe ndị dị mkpa ekwenyela na UA nwere ike ịrụ ọrụ bara uru na CVD. Savi et al. jiri ụdị oke ọrịa shuga na-eduzi na vivo ọmụmụ banyere ọrịa obi na-arịa ọrịa shuga wee chọpụta na UA nwere ike belata nzaghachi mbufụt nke anụ ahụ myocardial na hyperglycemia, meziwanye microenvironment myocardial, ma kwalite mgbake nke nkwekọrịta cardiomyocyte na mgbanwe calcium, na-egosi na UA nwere ike enwere ike iji ya dị ka ọgwụ inyeaka iji chịkwaa cardiomyopathy mamịrị ma gbochie nsogbu ya.

UA nwere ike imeziwanye ọrụ mitochondrial na arụ ọrụ akwara site n'ịkwalite mitophagy. Mitochondria obi bụ akụkụ dị mkpa nke na-ahụ maka imepụta ATP nwere ume. Mitochondrial dysfunction bụ isi ihe kpatara nkụda obi. A na-ewere dysfunction Mitochondrial ugbu a dị ka ebumnuche ọgwụgwọ nwere ike. Ya mere, UA aghọwokwa ọgwụ ọhụrụ maka ọgwụgwọ CVD.

Urolitin A na ọrịa akwara ozi

Neuroinflammation bụ usoro dị mkpa na omume na mmepe nke ọrịa neurodegenerative (ND). Apoptosis kpatara nrụgide oxidative na nchịkọta protein na-adịghị mma na-ebutekarị neuroinflammation, na cytokines pro-inflammatory nke neuroinflammation wepụtara na-emetụta neurodegeneration.

Nnyocha achọpụtala na UA na-arụ ọrụ mgbochi mkpali site n'ime ka autophagy na-arụ ọrụ na-eme ka usoro nkwụsị nke 1 (SIRT-1) na-eme ka ọ ghara ịdị jụụ, na-egbochi neuroinflammation na neurotoxicity, na igbochi neurodegeneration, na-atụ aro na UA bụ onye ọrụ Neuroprotective dị irè. N'otu oge ahụ, ụfọdụ ọmụmụ achọpụtala na UA nwere ike ịkpata mmetụta neuroprotective site n'iwepụ radicals n'efu na igbochi oxidases.

Nnyocha egosiwo na ihe ọṅụṅụ pọmigranet na-arụ ọrụ neuroprotective site n'ịbawanye ọrụ mitochondrial aldehyde dehydrogenase, na-edobe ọkwa nke protein anti-apoptotic Bcl-xL, na-ebelata mkpokọta α-synuclein na mmebi oxidative, na-emetụta ọrụ neuronal na nkwụsi ike. Ogige urolithin bụ metabolites na mmetụta akụkụ nke ellagitannins n'ime ahụ ma na-enwe ihe omume ndu dị ka mgbochi mbufụt, mgbochi oxidative stress, na mgbochi apoptosis. Urolithin nwere ike na-arụ ọrụ neuroprotective site na mgbochi ụbụrụ ọbara na ọ bụ obere molekul na-arụ ọrụ maka itinye aka na ọrịa neurodegenerative.

Urolithin A na nkwonkwo na ọrịa degenerative spinal

A na-ebute ọrịa na-emebi emebi site na ọtụtụ ihe dị ka ịka nká, nsogbu, na trauma. Ọrịa ogbu na nkwonkwo na-emekarị bụ ọrịa ogbu na nkwonkwo (OA) na ọrịa intervertebral disc degeneration (IDD). Ihe omume nwere ike ịkpata mgbu na oke ọrụ, na-ebute nkwụsị ọrụ yana itinye ahụike ọha n'ihe egwu. Usoro UA n'ịgwọ ọrịa degenerative spinal IDD nwere ike jikọta ya na igbu oge nucleus pulposus (NP) apoptosis cell. NP bụ akụkụ dị mkpa nke diski intervertebral. Ọ na-ejigide ọrụ ndu nke diski intervertebral site na ikesa nrụgide na idowe matrix homeostasis. Nnyocha achọpụtala na UA na-ebute mitophagy site n'ịkwalite ụzọ akara AMPK, si otú ahụ na-egbochi tert-butyl hydroperoxide (t-BHP) apoptosis nke mmadụ osteosarcoma cell NP cell na ibelata intervertebral disc degeneration.

Urolitin A na ọrịa metabolic

Mmetụta nke ọrịa metabolic dị ka oke ibu na ọrịa shuga na-abawanye kwa afọ, na mmetụta bara uru nke polyphenols nri na ahụike mmadụ ekwenyela na ọtụtụ ndị ọzọ ma gosipụta ikike na mgbochi na ọgwụgwọ nke ọrịa metabolic. Pomegranate polyphenols na eriri afọ ya metabolite UA nwere ike imeziwanye ihe ngosi ahụike metụtara ọrịa metabolic, dị ka lipase, α-glucosidase (α-glucosidase) na dipeptidyl peptidase-4 (dipeptidyl peptidase-4) na-etinye aka na glucose na abụba acid metabolism. 4), yana mkpụrụ ndụ ihe nketa metụtara dị ka adiponectin, PPARγ, GLUT4 na FABP4 nke na-emetụta ọdịiche adipocyte na mkpokọta triglyceride (TG).

Na mgbakwunye, ụfọdụ ọmụmụ achọpụtakwala na UA nwere ikike ibelata mgbaàmà nke oke ibu. UA bụ ngwaahịa nke eriri afọ nke polyphenols. Metabolites ndị a nwere ikike ibelata mkpokọta TG na mkpụrụ ndụ imeju na adipocytes. Abdulrasheed et al. nyere oke Wistar nri nwere oke abụba iji kpalite oke ibu. Ọgwụgwọ UA abụghị naanị mmụba abụba na nsị, kamakwa belata oke anụ ahụ adipose visceral na ịdị arọ ahụ site na ịhazi mkpụrụ ndụ ihe nketa metụtara lipogenesis na fatty acid oxidation. Na-ebelata mkpokọta abụba imeju na nrụgide oxidative. N'otu oge ahụ, UA nwere ike ịbawanye oriri ike site n'ịkwalite thermogenesis nke anụ ahụ adipose na-acha aja aja na ịkpata browning nke abụba ọcha. Usoro a bụ ịbawanye ọkwa triiodothyronine (T3) na abụba aja aja na ebe nchekwa abụba inguinal. Na-abawanye mmepụta okpomọkụ ma si otú a na-emegide oke ibu.

Na mgbakwunye, UA nwekwara mmetụta nke igbochi mmepụta melanin. Nnyocha achọpụtala na UA nwere ike imebi mmepụta melanin na sel B16 melanoma. Usoro bụ isi bụ na UA na-emetụta mkpali catalytic nke tyrosinase site na mgbochi asọmpi nke cell tyrosinase, si otú ahụ na-ebelata pigmentation. Ya mere, UA nwere ikike na ịdị irè iji mee ka ọ dị ọcha ma mee ka ntụpọ dị mfe. Na nyocha na-egosi na urolithin A nwere mmetụta nke ịtụgharị ịka nká nke usoro ahụ ji alụso ọrịa ọgụ. Nnyocha ọhụrụ a chọpụtara na mgbe agbakwunyere urolithin A dị ka ihe mgbakwunye nri, ọ bụghị naanị na ọ na-eme ka ike nke mpaghara lymphatic nke usoro ahụ ji alụso ọrịa ọgụ dịkwuo elu, kamakwa na-eme ka ọrụ nke mkpụrụ ndụ hematopoietic dị elu. Arụmọrụ n'ozuzu ya na-egosiputa ikike nke urolithin A iji lụso usoro mgbochi ọrịa ọgụ metụtara afọ ọgụ.

N'ịchịkọta, UA, dị ka eriri afọ metabolite nke eke phytochemicals ET, dọtara mmasị nke ukwuu n'ime afọ ndị na-adịbeghị anya. Site na nyocha banyere mmetụta ọgwụ na usoro nke UA na-abawanye ụba na omimi, UA abụghị naanị dị irè na ọrịa cancer na CVD (ọrịa obi). Ọ nwere ezigbo mgbochi na ọgwụgwọ ọgwụgwọ na ọtụtụ ọrịa na-adakarị dị ka ND (ọrịa neurodegenerative) na ọrịa metabolic. Ọ na-egosikwa ikike ngwa dị ukwuu n'ihe gbasara ịma mma na nlekọta ahụike dịka igbu oge ịka nká anụ ahụ, ibelata ibu ahụ yana igbochi mmepụta melanin.

Suzhou Myland Pharm & Nutrition Inc. bụ onye na-emepụta aha FDA nke na-enye urolithin A ntụ ntụ dị elu na ịdị ọcha.

Na Suzhou Myland Pharm anyị na-agba mbọ ịnye ngwaahịa kachasị mma na ọnụ ahịa kacha mma. A na-anwale ntụ ntụ Urolithin anyị nke ọma maka ịdị ọcha na ike, na-eme ka ị nweta mgbakwunye dị elu ị nwere ike ịtụkwasị obi. Ma ịchọrọ ịkwado ahụike cellular, kwalite usoro ahụ ji alụso ọrịa ọgụ ma ọ bụ kwalite ahụike zuru oke, Urolithin A ntụ ntụ bụ nhọrọ zuru oke.

Site na ahụmịhe afọ 30 na teknụzụ dị elu na atụmatụ R&D kachasị mma, Suzhou Myland Pharm ewepụtala ngwaahịa dị iche iche nke asọmpi wee bụrụ mgbakwunye sayensị ndụ ọhụrụ, njikọta omenala na ụlọ ọrụ nrụpụta.

Na mgbakwunye, Suzhou Myland Pharm bụkwa onye nrụpụta FDA debanyere aha. Akụrụngwa R&D nke ụlọ ọrụ ahụ, akụrụngwa nrụpụta na ngwa nyocha bụ nke ọgbara ọhụrụ yana ọtụtụ ọrụ, ma nwee ike imepụta kemịkalụ site na milligrams ruo tọn n'ọ̀tụ̀tụ̀, ma na-agbaso ụkpụrụ ISO 9001 na nkọwapụta GMP.