Sayensị Dị n'azụ Urolithin A: Ihe Ị Kwesịrị Ịma

Urolitin A (UA)bụ ihe mejupụtara nke na-esi na metabolism nke osisi eriri afọ apụta n'ime nri ndị bara ụba na ellagitannins (dịka pomegranate, raspberries, wdg). A na-ewere ya dị ka ihe na-egbochi mbufụt, ihe na-egbochi ịka nká, ihe na-egbochi antioxidant, ihe na-akpali mitophagy, wdg, ma nwee ike ịgafe ihe mgbochi ọbara-ụbụrụ. Ọtụtụ nnyocha egosila na urolithin A nwere ike igbu oge ịka nká, ọmụmụ ihe ahụike egosikwala ezigbo nsonaazụ.

Kedu ihe bụ urolithin A?

Urolithin A (Uro-A) bụ ụdị ellagitannin (ET). A chọpụtara ya n'ihu ọha ma kpọọ ya aha na 2005. Usoro molekul ya bụ C13H8O4, oke molekul ya dịkwa 228.2. Dịka ihe na-ebute metabolism nke Uro-A, isi iyi nri ET bụ pomegranate, strọberị, raspberries, walnuts na mmanya uhie. UA bụ ngwaahịa nke ETs nke microorganisms eriri afọ na-eme ka ọ dị iche. UA nwere ohere itinye ya n'ọrụ sara mbara n'igbochi na ọgwụgwọ nke ọtụtụ ọrịa. N'otu oge ahụ, UA nwere ọtụtụ isi mmalite nri.

Emeela nnyocha gbasara mmetụta antioxidant nke urolithins. Urolithin-A adịghị na ọnọdụ ebumpụta ụwa, mana ọ na-emepụta site na usoro mgbanwe nke ET site na flora eriri afọ. UA bụ ngwaahịa nke ETs nke microorganisms eriri afọ na-eme ka ọ dị iche. Nri bara ụba na ET na-agafe n'afọ na obere eriri afọ n'ahụ mmadụ, ma mechaa na-agbanwe ya ka ọ bụrụ Uro-A n'ime eriri afọ. Enwere ike ịchọpụta obere Uro-A n'ime obere eriri afọ dị ala.

Dịka ihe ndị sitere n'okike sitere n'okike, ET adọtala ọtụtụ mmasị n'ihi ọrụ ha dị ka antioxidant, anti-inflammatory, anti-allergic na anti-virus. Na mgbakwunye na ha sitere na nri dịka pomegranate, strọberị, walnuts, raspberries na almọnd, a na-ahụkwa ET na gallnut, pomegranate peels, myrobalan, Dimininus, geranium, betel nut, sea buckthorn leaf, Phyllanthus, Uncaria, Sanguisorba, na ọgwụ ndị China dịka Phyllanthus emblica na Agrimony.

Otu hydroxyl dị na nhazi molekul nke ETs dịtụ polar, nke na-adịghị mma maka ịmịkọrọ site na mgbidi eriri afọ, a na-ahụkwa bioavailability ya dị obere. Ọtụtụ nnyocha achọpụtala na mgbe ahụ mmadụ riri ETs, a na-eme ka ha dị na eriri afọ ma gbanwee ha ka ha bụrụ urolithin tupu ha abanye. A na-eme ka ETs dị na hydrolyzes ghọọ ellagic acid (EA) na tract eriri afọ elu, EA na-agafekwa site na eriri afọ. Osisi nje na-arụ ọrụ ma na-efunahụ mgbanaka lactone ma na-enweta mmeghachi omume dehydroxylation na-aga n'ihu iji mepụta urolithin. E nwere akụkọ na urolithin nwere ike ịbụ ihe ndabere maka mmetụta bayọlọji nke ETs n'ahụ.

Gịnị ka e ji mara bioavailability nke urolithin?

Mgbe ị hụrụ nke a, ọ bụrụ na ị maara ihe, ị nwere ike ịmaworị ihe metụtara bioavailability nke UA.

Ihe kacha mkpa bụ ihe mejupụtara microbiome ahụ, n'ihi na ọ bụghị ụdị nje niile nwere ike imepụta. Ihe e ji mee UA bụ ellagitannins sitere na nri. Ihe a dị mfe ịnweta ma fọrọ nke nta ka ọ bụrụ ebe niile n'okike.

A na-eme ka Ellagitannins dị n'ime eriri afọ ha wee wepụta ellagic acid, nke a na-ejikwa eriri afọ ha eme ihe n'ime urolithin A.

Dịka otu nnyocha e mere n'akwụkwọ akụkọ Cell si kwuo, naanị pasentị iri anọ nke mmadụ nwere ike ịgbanwe urolithin A site na ihe mbụ ya ka ọ bụrụ urolithin A a na-eji eme ihe.

Kedu ọrụ urolithin A?

Mgbochi ịka nká

Echiche nnwere onwe nke ịka nká kwenyere na ụdị oxygen reactive nke emepụtara na mitochondrial metabolism na-akpata nrụgide oxidative n'ahụ ma na-eduga n'ịka nká, mitophagy na-arụkwa ọrụ dị mkpa n'ịnọgide na-enwe ahụike na iguzosi ike n'ezi ihe mitochondrial. Akọpụtala na UA nwere ike ịchịkwa mitophagy ma si otú a gosipụta ike igbu oge ịka nká. Ryu et al. chọpụtara na UA belatara nsogbu mitochondrial na ogologo ndụ na Caenorhabditis elegans site na ịkpalite mitophagy; na òké, UA nwere ike ịgbanwe ọdịda ọrụ akwara metụtara afọ, na-egosi na UA na-eme ka ọrụ mitochondrial ka mma site na ime ka oke akwara dịkwuo mma na ịgbatị ndụ ahụ. Liu et al. jiri UA tinye aka na fibroblasts akpụkpọ ahụ ịka nká. Nsonaazụ gosiri na UA mụbara ngosipụta nke collagen ụdị I nke ukwuu ma belata ngosipụta nke matrix metalloproteinase-1 (MMP-1). Ọ rụkwara ọrụ mmeghachi omume antioxidant nke nuclear Factor E2-related factor 2 (nuclear factor erythroid 2-related factor 2, Nrf2) na-ebelata ROS intracellular, si otú a na-egosi ike mgbochi ịka nká siri ike.

Mmetụta antioxidant

Ugbu a, e meela ọtụtụ nnyocha gbasara mmetụta antioxidant nke urolithin. N'ime metabolites urolithin niile, Uro-A nwere ọrụ antioxidant kachasị ike, nke abụọ naanị na proanthocyanidin oligomers, catechins, epicatechin na 3,4-dihydroxyphenylacetic acid. Nnwale ikike nnabata oxygen radical (ORAC) nke plasma nke ndị ọrụ afọ ofufo ahụike chọpụtara na ikike antioxidant mụbara site na 32% mgbe awa 0.5 nke ịṅụ mmiri pọmigranet gasịrị, mana ọkwa nke ụdị oxygen reactive agbanweghị nke ukwuu, ebe na nnwale Neuro-In vitro na mkpụrụ ndụ 2a chọpụtara na Uro-A nwere ike ibelata ọkwa nke ụdị oxygen reactive na mkpụrụ ndụ. Nsonaazụ ndị a na-egosi na Uro-A nwere mmetụta antioxidant siri ike.

03. Urolithin A na ọrịa obi na akwara ụbụrụ

Ọrịa obi na akwara obi (CVD) na-amụba kwa afọ, ọnụọgụ ọnwụ ka dịkwa elu. Ọ bụghị naanị na ọ na-eme ka ibu arọ ọha na eze na akụ na ụba dịkwuo elu, kamakwa ọ na-emetụta ụdị ndụ mmadụ nke ukwuu. CVD bụ ọrịa na-akpata ọtụtụ ihe. Mbufụt nwere ike ime ka ohere nke CVD dịkwuo elu. Nrụgide oxidative metụtara ọrịa CVD. E nwere akụkọ na metabolites sitere na obere nje eriri afọ na-ejikọta ya na ihe egwu nke CVD.

Akọpụtala na UA nwere mmetụta dị ike nke mgbochi mkpali na antioxidant, ọmụmụ ihe ndị dị mkpa egosila na UA nwere ike ịrụ ọrụ bara uru na CVD. Savi et al. jiri ụdị oke shuga mee ọmụmụ ihe na vivo na ọrịa obi ma chọpụta na UA nwere ike ibelata nzaghachi mkpali mbụ nke anụ ahụ myocardial na hyperglycemia, melite microenvironment myocardial, ma kwalite mgbake nke cardiomyocyte contractivity na calcium dynamics, na-egosi na UA nwere ike iji ya dị ka ọgwụ enyemaka iji chịkwaa cardiomyopathy ọrịa shuga ma gbochie nsogbu ya.

UA nwere ike imeziwanye ọrụ mitochondrial na ọrụ akwara site na ịkpalite mitophagy. Obi mitochondria bụ akụkụ ahụ dị mkpa na-ahụ maka mmepụta ATP bara ụba na ike. Nsogbu Mitochondrial bụ isi ihe na-akpata nkụda obi. A na-ewere nsogbu Mitochondrial ugbu a dị ka ihe nwere ike ibute ọgwụgwọ. Ya mere, UA aghọwokwa ọgwụ ọhụrụ maka ọgwụgwọ CVD.

Urolithin A na Ọrịa Neuro

Ọrịa neuroinflammation bụ usoro dị mkpa n'ihe gbasara ọrịa neurodegenerative (ND). Apoptosis nke nrụgide oxidative na mkpokọta protein na-adịghị mma na-akpatakarị mbufụt neuroinflammation, cytokines pro-inflammatory nke neuroinflammation wepụtara na-emetụta neurodegeneration.

Nnyocha achọpụtala na UA na-eme ka ọrụ mgbochi mkpali site n'ịkpalite autophagy na ịgbalite usoro deacetylation nke silent signal regulator 1 (SIRT-1), na-egbochi neuroinflammation na neurotoxicity, ma na-egbochi neurodegeneration, na-egosi na UA bụ ihe na-eme ka Neuroprotective dị irè. N'otu oge ahụ, ụfọdụ ọmụmụ achọpụtala na UA nwere ike ime mmetụta neuroprotective site na iwepụ free radicals ozugbo na igbochi oxidases.

Nnyocha egosila na ihe ọṅụṅụ mkpụrụ pọmigranet na-arụ ọrụ nchebe neuron site n'ịbawanye ọrụ mitochondrial aldehyde dehydrogenase, na-eme ka ọkwa nke protein anti-apoptotic Bcl-xL dị, na-ebelata mkpokọta α-synuclein na mmebi oxidative, ma na-emetụta ọrụ na nkwụsi ike nke neuron. Ihe mejupụtara Urolithin bụ metabolites na ihe ndị mejupụtara ellagitannins n'ahụ ma nwee ọrụ bayoloji dịka mgbochi mbufụt, nrụgide anti-oxidative, na anti-apoptosis. Urolithin nwere ike ime ọrụ nchebe neuron site na mgbochi ọbara-ụbụrụ ma bụrụ obere molekul nwere ike ịrụ ọrụ maka itinye aka na ọrịa neurodegenerative.

Urolithin A na-akpata mmebi nke nkwonkwo na ọkpụkpụ azụ

Ọrịa ndị na-emebi emebi na-esite n'ọtụtụ ihe dịka ịka nká, nrụgide, na mmerụ ahụ. Ọrịa ndị na-emebi emebi nke nkwonkwo bụ osteoarthritis (OA) na mmebi diski intervertebral nke ọrịa spinal (IDD). Mmepe nwere ike ibute ihe mgbu na obere ọrụ, na-ebute ọnwụ nke ọrụ ma na-etinye ahụike ọha na eze n'ihe ize ndụ dị ukwuu. Usoro nke UA n'ịgwọ ọrịa na-emebi ọkpụkpụ azụ IDD nwere ike ịbụ njikọ na igbu oge nucleus pulposus (NP) cell apoptosis. NP bụ akụkụ dị mkpa nke diski intervertebral. Ọ na-akwado ọrụ ndu nke diski intervertebral site na ikesa nrụgide na ịnọgide na-enwe matrix homeostasis. Ọmụmụ ihe achọpụtala na UA na-akpali mitophagy site na ịgbalite ụzọ mgbaàmà AMPK, si otú a na-egbochi apoptosis nke mkpụrụ ndụ NP osteosarcoma mmadụ na ibelata mmebi diski intervertebral.

Urolithin A na nsogbu metabolic

Ọrịa metabolic dịka oke ibu na ọrịa shuga na-amụba kwa afọ, ọtụtụ ndị na-akwadokwa uru nke polyphenols nri na ahụike mmadụ, ha egosikwala na ha nwere ike igbochi ma gwọọ ọrịa metabolic. Polyphenols pomegranate na metabolite eriri afọ ya UA nwere ike imeziwanye ihe ngosi ahụike metụtara ọrịa metabolic, dịka lipase, α-glucosidase (α-glucosidase) na dipeptidyl peptidase-4 (dipeptidyl peptidase-4) nke na-emetụta metabolism glucose na abụba acid. 4), yana mkpụrụ ndụ ihe nketa ndị metụtara ya dịka adiponectin, PPARγ, GLUT4 na FABP4 nke na-emetụta ọdịiche adipocyte na mkpokọta triglyceride (TG).

Na mgbakwunye, ụfọdụ nnyocha achọpụtakwala na UA nwere ike ibelata mgbaàmà nke oke ibu. UA bụ ngwaahịa nke polyphenols na-emepụta n'ime eriri afọ. Metabolites ndị a nwere ike ibelata mkpokọta TG na mkpụrụ ndụ imeju na adipocytes. Abdulrasheed et al. nyere oke Wistar nri nwere abụba dị elu iji kpalite oke ibu. Ọgwụgwọ UA abụghị naanị ịbawanye mwepụta abụba na nsị, kamakwa belata oke anụ ahụ adipose visceral na ibu ahụ site na ịchịkwa mkpụrụ ndụ ihe nketa metụtara lipogenesis na oxidation acid fatty. Na-ebelata mkpokọta abụba imeju na nrụgide oxidative ya. N'otu oge ahụ, UA nwere ike ịbawanye oriri ike site na ime ka thermogenesis nke anụ ahụ adipose aja aja na ịkpalite browning nke abụba ọcha. Usoro a bụ ịbawanye ọkwa triiodothyronine (T3) na abụba aja aja na ebe nchekwa abụba inguinal. Na-eme ka mmepụta okpomọkụ dịkwuo elu 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 mkpụrụ ndụ melanoma B16 nke ukwuu. Isi usoro bụ na UA na-emetụta mkpali nke tyrosinase site na mgbochi asọmpi nke tyrosinase sel, si otú a na-ebelata agba. Ya mere, UA nwere ike na arụmọrụ iji mee ka ntụpọ dị ọcha ma mee ka ha dị nro. Nnyocha na-egosikwa na urolithin A nwere mmetụta nke ịgbanwe ịka nká nke sistemụ ahụ ji alụso ọrịa ọgụ. Nnyocha kachasị ọhụrụ chọpụtara na mgbe etinyere urolithin A dị ka mgbakwunye nri, ọ bụghị naanị na ọ na-eme ka ike nke mpaghara lymphatic nke sistemụ ahụ ji alụso ọrịa ọgụ òké rụọ ọrụ, kamakwa ọ na-eme ka ọrụ nke mkpụrụ ndụ hematopoietic dịkwuo mma. Arụmọrụ zuru oke na-egosi ike urolithin A nwere iji lụso mbelata nke sistemụ ahụ ji alụso ọrịa ọgụ metụtara afọ ọgụ.

Na nchịkọta, UA, dịka ihe na-eme ka eriri afọ nke phytochemicals ETs dị iche iche, adọtala ọtụtụ mmasị n'afọ ndị na-adịbeghị anya. Ka nnyocha e mere na mmetụta ọgwụ na usoro nke UA na-aghọwanye nke sara mbara ma dị omimi, UA anaghị arụ ọrụ naanị na kansa na CVD (ọrịa obi). Ọ nwere ezigbo mgbochi na ọgwụgwọ na ọtụtụ ọrịa ahụike dịka ND (ọrịa neurodegenerative) na ọrịa metabolic. Ọ na-egosikwa nnukwu ike itinye n'ọrụ n'ọhịa nke ịma mma na nlekọta ahụike dịka igbu oge ịka nká akpụkpọ ahụ, ibelata ibu ahụ na igbochi mmepụta melanin.

Suzhou Myland Pharm & Nutrition Inc. bụ ụlọ ọrụ mmepụta ihe nke FDA debanyere aha ya, nke na-enye ntụ ntụ Urolithin A dị elu ma dị ọcha nke ukwuu.

Na Suzhou Myland Pharm, anyị na-agba mbọ inye ngwaahịa kachasị mma na ọnụ ahịa kacha mma. A na-anwale ntụ ntụ Urolithin A 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 sel, ịkwalite sistemu ahụ ji alụso ọrịa ọgụ gị ma ọ bụ melite ahụike zuru oke, ntụ ntụ Urolithin A anyị bụ nhọrọ zuru oke.

Site na ahụmịhe afọ iri atọ nke teknụzụ dị elu na atụmatụ R&D kachasị mma, Suzhou Myland Pharm emepụtala ọtụtụ ngwaahịa asọmpi ma bụrụ ụlọ ọrụ mgbakwunye sayensị ndụ ọhụrụ, mmepụta omenala na ọrụ mmepụta.

Tinyere nke ahụ, Suzhou Myland Pharm bụkwa onye nrụpụta nke FDA debanyere aha ya. Akụrụngwa nyocha na mmepe nke ụlọ ọrụ ahụ, ebe mmepụta, na ngwa nyocha ya bụ nke ọgbara ọhụrụ ma na-arụ ọrụ nke ọma, ha nwekwara ike imepụta kemịkalụ site na milligram ruo tọn n'ọkwa, ma rube isi n'ụkpụrụ ISO 9001 na nkọwapụta mmepụta GMP.