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Melanotan-1: Sɛgɛsɛgɛli ni baarakɛcogo cɛɲi baara la

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Fɛn minnu bɛ di nin siti in kan, olu dabɔra ɲininiw dɔrɔn kama in vitro. Sɛgɛsɛgɛli in vitro (latinkan na: *in glass*, o kɔrɔ ye gilasi minɛnw na) bɛ kɛ hadamaden farikolo kɔkan. Nin fura ninnu tɛ furaw ye, Ameriki dumuniko ni furako ɲɛmɔgɔso (FDA) ma sɔn u ma, wa u man kan ka kɛ ka furakɛli bana, bana walima bana si bali, k’a furakɛ, walima k’a furakɛ. A dagalen don kosɛbɛ sariya fɛ ka nin fɛn ninnu don hadamaden walima bagan farikolo la cogo o cogo.




Kuma bɛɛ lajɛlen


Melanotan-1 (MT-1) ye pepitiri ye min bɛ kɛ ka melanositɛriw lawuli, a bɛ se ka kɛ kosɛbɛ, o ye ɔrimɔni melanokɔrini ye min bɛ sɔrɔ a yɛrɛ la, o min ye mɔgɔw ɲɛnajɛ kosɛbɛ cɛɲa baara la. Melanocortin analogues jɔyɔrɔ ka bon farikolo farikoloɲɛnajɛw la, u bɛ ɲɔgɔn sɔrɔ ni a minɛbaga kɛrɛnkɛrɛnnenw ye walasa ka melanin bɔli ɲɛnabɔ. Melanotan - 1 bɛ melanocortin ka baarakɛcogo ladege, a bɛ nɔ bila fari ɲɛjibɔcogo la, o min bɛ kɛ a kɛli basigi ye cɛɲa baara la.


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Jaa 2 Melanotan ka kemikaliya cogoya – 1.


Tariku kɔnɔ, ɲinini minnu kɛra Melanotan-1 kan, olu daminɛna ni farikolo ɲɛjiracogo ɲɛnabɔli fɛɛrɛw ɲinini kuncɛlen ye. Mɔgɔw ​​ka cɛɲi ɲinini bɛ ka caya ka taa a fɛ, kɛrɛnkɛrɛnnenya la farikolojidɛsɛ nɔw ɲinini, ɲininikɛlaw y’u sinsin kosɛbɛ fɛnw kan minnu bɛ se ka melanin bɔli ɲɛnabɔ.




Fɛɛrɛ min bɛ Kɛ ni wale ye


(1) A sirili Melanocortin Recepteurs la

Melanotan-1 ka baarakɛcogo kunba bɛ a seko la ka siri melanocortin receptors (MC1R) la. MC1R ye G protein-coupled receptor ye min bɛ jira fɔlɔ melanositɛriw sanfɛ. Ni Melanotan-1 sirilen don MC1R la, a bɛ taamasiɲɛw cili ko kɛlenw daminɛ selilu kɔnɔ. O sirili bɛ G poroteyini min ni MC1R faralen don ɲɔgɔn kan, o bɛ baara kɛ, o min bɛ adenilati siklazi baara, o bɛ na ni dɔ farali ye selilu kɔnɔ ciden filanan cyclique adenosine monophosphate (cAMP) hakɛ kan. cAMP wulilen bɛ poroteyini kinase A (PKA) baara ka t’a fɛ, o min bɛ melanin sɔrɔli ni ɲɔgɔn cɛ jamu jiracogo ɲɛnabɔ ni duguma sɛbɛnnikɛlan fosforilasi ye, n’o ye mikroftalmie-associé transkripsiyɔn facteur (MITF) ye.


2

Jaa 2 Jɛɲɔgɔnya min bɛ melanin hakɛ caman yeli ni melanin hakɛ basigilen cɛ bolokɔni sanfɛla kɔnɔna na ITT mɔgɔ kelen-kelen bɛɛ la.


(2) Jɛnɛya jiracogo ɲɛnabɔli min bɛ tali kɛ melanin sɔrɔli la

MITF ye sɛbɛnnikɛlan jɔnjɔn ye melanin dilanni na, min bɛ se ka jɛnɛya caman jirali wuli ka taa sanfɛ, minnu bɛ anzimuw kofɔ minnu bɛ melanin dilanni na, ni tirosinizi de nafa ka bon kosɛbɛ. Tirosinizi ye anzimu ye min bɛ dan sigi hakɛ la melanin dilanni na, o bɛ tirosini jiginni dɔɔni dɔɔni ka kɛ dopaquinone ye, o min bɛ sɔrɔ ka kɛ melanin ye. Melanotan-1 bɛ MITF baara sabati, ka dɔ fara tirosinizi ni melanin dilanni ni anzimu wɛrɛw jirali kan, o la, a bɛ melanin dilanni teliya. Melanotan-1 bɛ se ka nɔ bila fana jamu wɛrɛw jirali la minnu bɛ tali kɛ melanin sɔrɔli la, i n’a fɔ dopa-colorin interconverting enzyme (DCT), ani fɛn wɛrɛw. O anzimu ninnu bɛ baara kɛ ɲɔgɔn fɛ walasa ka melanini sɔrɔli ni a dalajɛli sabati, o laban bɛ kɛ sababu ye ka fari kulɛri dibi.


(3) Selilu kɔnɔ taamasiɲɛw siraw ka jɛɲɔgɔnya nɔ minnu bɛ sɔrɔ ɲɔgɔn fɛ

Ka fara cAMP-PKA-MITF taamasiɲɛw sira klasiki kan min kofɔlen don sanfɛ, Melanotan-1 bɛ se ka melanin sɔrɔli fana ɲɛnabɔ ni taamasiɲɛ sira wɛrɛw ye minnu bɛ kɛ selilɛri kɔnɔ. A bɛ se ka nɔ bila mitogène-activé proteine ​​kinase (MAPK) taamasiɲɛw sira la. Melanocytes kɔnɔ, MAPK taamasiɲɛw sira bɛ a sen don ɲɛnamaya kɛcogo suguya caman labɛnni na i n’a fɔ selilɛriw caya, u danfara ani u ka ɲɛnamaya. Melanotan-1 bɛ se ka MAPK taamasiɲɛw sira baara walasa ka melanositɛri caya ni melanin sɔrɔli sabati ka taa a fɛ. PI3K-Akt taamasiɲɛw sira fana bɛ se ka kɛ ni Melanotan-1 nɔw ye. O sira in jɔyɔrɔ ka bon kosɛbɛ farikolokisɛw falenni na, u ka ɲɛnamaya la, ani u ka farikoloɲɛnajɛw labɛnni na, a bɛ se ka kɛ sababu ye ka farikoloɲɛnajɛ jusigilan wajibiyalen di melanin sɔrɔli ma, a kɛtɔ ka farikolokisɛw kɔnɔ farikoloɲɛnajɛw labɛn.




Jɔrɔ min bɛ cɛɲa baara la


(1) Farikolo sɔgɔli sabatili

Tanning (Tanni) nɔw jiracogo

Melanotan-1 ka ɲɛgɛnw kɛcogo min ka bon kosɛbɛ, o ye a seko ye ka fari ɲɛ jɛya. Kɔlɔsiliw y’a jira ko Melanotan-1 pikiri kɛlen kɔ farikolo jukɔrɔ walima a tali sira bɛnnen wɛrɛw fɛ, fari kulɛri dibiba bɛ se ka ye mɔgɔ minnu na. Sɛgɛsɛgɛli dɔ la min kɛra ni cɛ kɛnɛmanw ye minnu y’u yɛrɛ di, Melanotan-1 pikiri kɛra farikolo jukɔrɔ ni a tata hakɛ ye miligaramu 0,08–0,21 ye kilogaramu kelen o kilogaramu kelen na, o kɛra ka a to tile 5 kɔnɔ dɔgɔkun 2 kɔnɔ (a tata hakɛ 10). Jateminɛw y’a jira ko farikolojidɛsɛba bɛ kɛ yɔrɔw la i n’a fɔ mɔgɔ minnu ɲɛda, u bolokɔniw ani u kɔ. Nin farikolojidɛsɛ in tɛ sɔrɔ tiɲɛni fɛ min bɛ sɔrɔ UV fɛ, nka a bɛ sɔrɔ melanini sɔrɔli caya fɛ farikolo kɔnɔ, o bɛ na ni fari ɲɛ ye min bɛ kɛ cogo kelen na ani min bɛ kɛ cogo la min bɛ kɛ a yɛrɛ la.


Tanni kɛcogo kuntaala

Fari ɲɛgɛnɛsira min bɛ sɔrɔ Melanotan-1 fɛ, o bɛ to senna hakɛ dɔ la. Kɔlɔsiliw y’a jira ko farikolojidɛsɛ nɔ sera a dan na dɔgɔkun kelen ɲɔgɔn tali kɔfɛ, ani hali dɔgɔkun saba furakisɛ tan kɛcogo dafalen kɔfɛ, fari kulɛri bɛ to ka dibi ye ka tɛmɛ furakɛli ɲɛfɛ. O b’a jira ko Melanotan-1 tɛ melanin sɔrɔli sabati dɔrɔn ka ɲɛ, nka a bɛ melanin min sɔrɔ o dilancogo in fɛ, o bɛ se ka mara fari la waati dɔ kɔnɔ, o la, farikolojidɛsɛ cogoya bɛ sabati.


(2) Fari tangacogo minnu bɛ se ka kɛ

UV lakanani fɛɛrɛ

Melanin bɛ kɛ farikolo barikalan nafama ye min bɛ se ka kɛ sababu ye ka UV fiɲɛ kɛlɛ. Ni dɔ farala melanin sɔrɔli kan, Melanotan-1 bɛ fari ka se ka UV fiɲɛw minɛ ani k’u jɛnsɛn, o bɛ dɔ bɔ farikolokisɛw tiɲɛni na min bɛ sɔrɔ UV fɛ. Melanin bɛ UV fanga minɛ k’a sɛmɛntiya ka kɛ funteni fanga ye walasa ka bɔ, o la, a bɛ dɔ bɔ UV ka tiɲɛni na fɛnɲɛnamaw ka makɔrɔmolekuliw la i n’a fɔ ADN ani farikolojɔlifɛnw. Ka fara o kan, melanin bɛ se ka fari farikolo tangacogo ɲɛnabɔ walasa ka dɔ bɔ funu jaabiw la minnu bɛ sɔrɔ UV fɛ, o bɛ fari tanga ka taa a fɛ tiɲɛni ma.


Sɛgɛsɛgɛli dalilu minnu bɛ tali kɛ o la

Hali ni kɛnɛyaso ka sɛgɛsɛgɛliw kɛra Melanotan-1 farikolo lakanani nɔ tilennenw kan, olu dan ye sisan, a seko bɛ se ka kɛ UV lakanani na, ka da melanin farikolo baarakɛcogo kan ani Melanotan-1 ka se ka melanin sɔrɔli sabati. Sɛgɛsɛgɛli dɔw kɛra in vitro la, olu y’a jira ko melanositɛri minnu furakɛra ni Melanotan-1 ye, olu bɛ oksizɛni suguya minnu bɛ se ka kɛ (ROS) hakɛ dɔgɔyara kosɛbɛ ani ka apoptose hakɛ dɔgɔya UV tali kɔfɛ, o b’a jira ko Melanotan-1 bɛ se ka fari muɲuni bonya UV fiɲɛ fɛ ni a bɛ melanin sɔrɔli bonya.


(3) A bɛ se ka nɔ wɛrɛ minnu bila fari cogoya la

Fari cogoya ɲɛnabɔli

Dɔw b’a fɔ ko Melanotan-1 bɛ se ka nɔ ɲuman bila fari cogoya la. Melanin sɔrɔli caya bɛ se ka selilɛriw ka farikoloɲɛnajɛ sabati, ka kolajɛ ni fiɲɛw labɛnni ni u kuraya sabati. Kɔlɔsili sɛgɛsɛgɛli misɛnnin dɔw la, lajɛden dɔw y’a jira k’u fari bɛ gɛlɛya, ka sɔgɔsɔgɔ, wa u ye ɲɛtaa jira jiribolo finmanw ni kurukuruw la, Melanotan-1 tali kɔfɛ. O bɛ tali kɛ farikolo kɔkanna matiriyali farikoloɲɛnajɛ labɛnni na farikolo kɔnɔ taamasiɲɛw siraw fɛ minnu bɛ baara kɛ melanin dilanni senfɛ.


Fari ɲɛgɛnɛsiralabanaw dɔgɔyali

Kalan dɔw fana y’a jira ko Melanotan-1 bɛ se ka 改善 nɔ dɔ bila fari ɲɛci la. Fari ɲɛgɛnɛsiraw sɔrɔli bɛ tali kɛ a ka ca a la melanin farikolojɔli banaw la. Ni a bɛ melanini sɔrɔli ni a jɛnsɛnni ɲɛnabɔ, Melanotan-1 bɛ se ka dɛmɛ don ka melanin tilatila cogo kelen na fari la, o la, a bɛ dɔ bɔ ɲɛgɛnɛsira yecogo la.





Baarakɛcogo minnu bɛ Kɛ ɲɛnajɛko siratigɛ la


Pikiri kɛlen kɔ farikolo jukɔrɔ, Melanotan-1 bɛ minɛ farikolo la pewu, a bɛ biyoavailability jira i n’a fɔ a tali jolisira fɛ. Furakɛcogo sɛgɛsɛgɛli dɔ la min kɛra ni a tali siraw danfaralenw suma ɲɔgɔn na, Melanotan-1 pikiri farikolo jukɔrɔ ni a tata hakɛ ye miligaramu 0,08–0,21 ye kilogaramu kelen o kilogaramu kelen na, o kɛra sababu ye ka fura hakɛ dɔn joli la, ni joli tilancɛ si hakɛ ye sanga 0,07–0,79 ye a tali waati la ani lɛri 0,8–1,7 β waati la. Farikolo jukɔrɔ pikiri nafaw ye a tali nɔgɔman ye ani fura tali sabatili; nka, dan dɔw fana b’a la, i n’a fɔ dimi min bɛ se ka kɛ sigida la, a bilenni, ani pikiri kɛyɔrɔ faritanabana wɛrɛw.


4. Ka sanga ni ɲɛnajɛ kɛcogo wɛrɛw ye

Ni a bɛ tali kɛ tilebɔcogo laadalata la

Laadalata tilebɔ ye fɛɛrɛ ye min bɛ kɛ ka fari ɲɛɲini nɔ sɔrɔ, nka o fɛɛrɛ in nafa ka bon. Ni aw bɛ mɛnni kɛ ni fiɲɛ ye min bɛ wele ko ultraviolet (UV), o bɛ dɔ fara fari kansɛri, fotokɔrɔya ani bana wɛrɛw kan, ka sɔrɔ fana a bɛ se ka kɛ sababu ye ka tile jeni, ka a ja ani ka a kurukuru. Melanotan-1 bɛ farikolojidɛsɛ sɔrɔ, o bɛ sɔrɔ ni melanini sɔrɔli caya ye kɔnɔbara la, hakili la, o bɛ a yɛrɛ tanga tiɲɛni ma min bɛ sɔrɔ UV tilennen tali fɛ. Nka, ikomi Melanotan-1 lakanani ma sigi sen kan fɔlɔ, a tɛ se ka tilebɔ laadalata nɔ bila pewu sisan i n’a fɔ farikolojidɛsɛ fɛɛrɛ min tɛ mɔgɔ tɔɔrɔ ani min bɛ se ka da a kan.


Ni a bɛ tali kɛ farikolojidɛsɛ furaw la minnu dilannen don ni fɛn dilannenw ye

Farikolo ɲɛgɛn dilannen dɔw bɛ sɔrɔ sugu la, i n’a fɔ farikolojidɛsɛ furaw, minnu ka teli ka kɛ ni asidi aminiki ye fari la walasa ka kulɛri dɔ dilan min bɛ i n’a fɔ ɲɛgɛn. Ni aw ye a suma ni Melanotan-1 ye, farikolojidɛsɛ fura dilannenw bɛ baara kɛ fari la, o bɛ na ni nɔ ye min tɛ mɛn, wa a bɛ se ka kɛ sababu ye ka ko dɔw lase mɔgɔ ma i n’a fɔ kulɛri min tɛ kelen ye walima min tɛ a yɛrɛ la. Faan wɛrɛ fɛ, melanotan-1 bɛ fari kulɛri Changer ka bɔ a kɔnɔna na, a kɛtɔ ka melanin sɔrɔli labɛn, o bɛ se ka kɛ sababu ye ka nɔ banbali ni nafama sɔrɔ.




Kuncɛli


I n’a fɔ ɔrimɔni pepitiri sintetiki min bɛ melanositɛri lawuli, Melanotan-1 bɛ baara kɛ fɔlɔ ni a sirili ye ɔrimɔni minɛbagaw la minnu bɛ melanositɛri lawuli, ka selilu kɔnɔ taamasiɲɛw siraw baara, ani ka jamu jiracogo ɲɛnabɔ minnu bɛ tali kɛ melanin dilanni na, o la, a bɛ melanin sɔrɔli sabati. Farikoloɲɛnajɛ siratigɛ la, a bɛ fari ɲɛ jɛyali sabati kosɛbɛ ni a bɛ to senna cogo dɔ la, wa a bɛ se ka kɛ fana ko a bɛ se ka fari tanga ani ka nɔ ɲuman wɛrɛw bila fari yecogo la.




Sosow (Sɔrɔyɔrɔw).


[1] Habbema L, Halk A. B., Neumann M., ani mɔgɔ wɛrɛw. Farati minnu bɛ sɔrɔ alfa-melanositɛri-stimulant hormone analogues tali la cogo la min tɛ labɛn: seginnkanni[J]. Duniya kɔnɔ farikoloɲɛnajɛw ka gafe, 2017,56(10):975-980.DOI:10.1111/ijd.13585.


[2] Fitzgerald L. M., Fryer J. L., Dwyer T., ani a ɲɔgɔnnaw. MELANOTAN, [Nle(4), D-Phe(7)]-alpha-MSH, nɔ min bɛ melanin sɔrɔli la hadamadenw na minnu ka MC1R fɛnɲɛnamafagalanw bɛ u la[J]. Pepitidiw, 2006,27(2):388-394.DOI:10.1016/j.pepitidiw.2004.12.038.


[3] Ugwu S, Blanchard J, Dorr R, ani a ɲɔgɔnnaw. Fari ɲɛgɛnɛsira ni melanotan-I furakɛlicogo hadamadenw na[J]. Biofarmasitiki ni furaw tali, 1997,18:259-269.DOI:10.1002/(SICI)1099-081X(199704)18:33.0.CO;2-X.


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