Melatonin

Vikipediya, ochiq ensiklopediya


Melatonin o'simlik va hayvonlarda mavjud bo'lgan tabiiy mahsulotdir. U asosan hayvonlarda tunda miyadagi pineal bez tomonidan chiqariladigan gormon sifatida tanilgan va uzoq vaqt davomida uyqu-uyg'onish siklini nazorat qilish bilan bog'liq[1][2].

Umurtqali hayvonlarda melatonin sirkadiyalik ritmlarni sinxronlashtirishda, shu jumladan uyqu-uyg'onish vaqtini va qon bosimini tartibga solishda va mavsumiy ritmiklikni nazorat qilishda, shu jumladan ko'payish, semizlik, mo'rtlashish va qish uyqusida ishtirok etadi[3]. Uning ko'p ta'siri melatonin retseptorlarini faollashtirish orqali, boshqalari esa antioksidant roli bilan bog'liq. O'simliklarda u oksidlovchi stressdan himoya qilish vazifasini bajaradi. U turli xil ovqatlarda ham mavjud[4].

Biologik faollik[tahrir | manbasini tahrirlash]

Odamlarda melatonin melatonin retseptorlari 1 (pikomolyar bog'lanish yaqinligi) va melatonin retseptorlari 2 (nanomolyar bog'lanish yaqinligi) ning to'liq agonisti bo'lib, ikkalasi ham G-oqsil bilan bog'langan retseptorlari (GPCR) sinfiga tegishli. Melatonin retseptorlari 1 va 2 ikkalasi ham Gi/o-bog'langan GPCR hisoblanadi, garchi melatonin 1 retseptorlari ham Gq bilan bog'langan. Melatonin, shuningdek, mitoxondriya ichidagi yuqori sig'imli erkin radikallarni tozalash vositasi sifatida ishlaydi, shuningdek, melatonin retseptorlari orqali signal o'tkazish orqali superoksid dismutaza, glutation peroksidaza, glutation reduktaza va katalaza kabi antioksidant fermentlarning ifodalanishiga yordam beradi[5][6][7][8][9][10].

Biologik funksiyalar[tahrir | manbasini tahrirlash]

Ko'zlarga quyosh nuri tushganda, epifizda melatonin ishlab chiqarilishi inhibe qilinadi va ishlab chiqarilgan gormonlar odamni hushyor ushlab turadi. Ko'zlarga yorug'lik tushmasa, pineal bezda melatonin ishlab chiqariladi va odam charchaydi.

Antioksidant[tahrir | manbasini tahrirlash]

Melatonin birinchi marta kuchli antioksidant va erkin radikallarni tozalash vositasi sifatida 1993-yilda xabar qilingan. In vitroda melatonin kislorod radikallarini, shu jumladan OH•, O2−• va reaktiv azot turlarini NO• kabi toʻgʻridan-toʻgʻri tozalovchi vazifasini bajaradi. O'simliklarda melatonin har bir antioksidantning umumiy samaradorligini oshirish uchun boshqa antioksidantlar bilan ishlaydi. Melatonin E vitaminiga qaraganda ikki baravar faol ekanligi isbotlangan, u eng samarali lipofil antioksidant hisoblanadi. Melatonin retseptorlari orqali signal o'tkazish melatonin superoksid dismutaza, glutation peroksidaza, glutation reduktaza va katalaza kabi antioksidant fermentlarning ifodalanishiga yordam beradi[5][6].

Immun tizimi[tahrir | manbasini tahrirlash]

Melatonin immunitet tizimi bilan o'zaro ta'sir qilishi ma'lum bo'lsa-da, bu o'zaro ta'sirlarning tafsilotlari aniq emas. Yallig'lanishga qarshi ta'sir eng dolzarb bo'lib tuyuladi. Kasallikni davolashda melatoninning samaradorligini baholash uchun bir nechta sinovlar o'tkazildi. Mavjud ma'lumotlarning aksariyati kichik, to'liq bo'lmagan sinovlarga asoslangan. Har qanday ijobiy immunologik ta'sir immunokompetent hujayralarda ifodalangan yuqori afinitetli retseptorlarga (MT1 va MT2) ta'sir qiluvchi melatoninning natijasi deb hisoblanadi. Preklinik tadqiqotlarda melatonin sitokin ishlab chiqarishni kuchaytirishi mumkin va bu orqali orttirilgan immunitet tanqisligiga qarshi kurashadi. Ba'zi tadqiqotlar shuni ko'rsatadiki, melatonin yuqumli kasalliklarga, shu jumladan OIV va bakterial infektsiyalarga qarshi kurashda va saraton kasalligini davolashda foydali bo'lishi mumkin[11][12].

Og'irlikni tartibga solish[tahrir | manbasini tahrirlash]

Melatoninning kilogramm ortishini boshqarishi mumkin bo'lgan mexanizm uning leptinga inhibitiv ta'siridir. Leptin inson organizmidagi energiya holatining uzoq muddatli ko'rsatkichi sifatida ishlaydi. Uyg'onish vaqtidan tashqarida leptin ta'sirini bostirish orqali melatonin leptin qarshiligini yumshatib, kunduzi leptin sezgirligini tiklashga yordam beradi[13][14].

Biokimyo[tahrir | manbasini tahrirlash]

Biosintez[tahrir | manbasini tahrirlash]

Melatonin biosinteziga umumiy nuqtai

Hayvonlarda melatoninning biosintezi gidroksillanish, dekarboksillanish, atsetillanish va L-triptofan bilan boshlangan metillanish orqali sodir bo'ladi. L-triptofan xorizmatdan shikimat yo'lida ishlab chiqariladi yoki oqsil katabolizmidan olinadi. Birinchi L-triptofan 5-gidroksitriptofan hosil qilish uchun triptofan gidroksilaz tomonidan indol halqasida gidroksillanadi. Ushbu oraliq mahsulot (5-HTP) serotonin ishlab chiqarish uchun piridoksal fosfat va 5-gidroksitriptofan dekarboksilaza tomonidan dekarboksillanadi.

Mexanizm[tahrir | manbasini tahrirlash]

Melatonin biosintezi mexanizmi.

L-triptofanni gidroksillash uchun kofaktor tetrahidrobiopterin (THB) birinchi navbatda kislorod va triptofan gidroksilazaning faol joyi temir bilan reaksiyaga kirishishi kerak. Ushbu mexanizm yaxshi tushunilmagan, ammo ikkita mexanizm taklif qilingan:

1. Bir elektronning THB dan O2 ga sekin oʻtishi THB radikali bilan rekombinatsiyalanib, 4a-peroksipterin hosil qilishi mumkin boʻlgan superoksid hosil qilishi mumkin. Keyin 4a-peroksipterin faol temir (II) bilan reaksiyaga kirishib, temir-peroksipterin oraliq mahsulotini hosil qilishi yoki kislorod atomini to'g'ridan-to'g'ri temirga o'tkazishi mumkin.

2. O2 birinchi navbatda faol joy temir (II) bilan reaksiyaga kirishib, temir (III) superoksidini ishlab chiqarishi mumkin, keyinchalik u THB bilan reaksiyaga kirishib, temir-peroksipterin oraliq mahsulotini hosil qilishi mumkin.

Temir-peroksipterin oraliq mahsulotidan olingan temir (IV) oksidi indol halqasining C5 pozitsiyasida karbokatiya hosil qilish uchun qo'sh bog' bilan tanlab hujumga uchraydi. Vodorodning 1,2 siljishi va keyin C5 dagi ikkita vodorod atomidan birining yo'qolishi 5-gidroksi-L-triptofanni berish uchun aromatiklikni tiklaydi[15].

N-asetilserotonin gidroksil holatida S-adenozil metionin (SAM) tomonidan metillanadi va S-adenozil homosistein (SAH) va melatonin hosil bo'ladi[16][17].

Tibbiy foydalanish[tahrir | manbasini tahrirlash]

Melatonin uyqusizlik va sirkadiyalik ritm buzilishi kabi uyqu buzilishlarini davolashda dori sifatida ishlatiladi, masalan, kechikkan uyqu fazasi buzilishi, jet lag buzilishi va smenali ish buzilishi[18]. Tibbiyotda melatonindan tashqari, ramelteon, tasimelteon va agomelatin kabi sintetik melatonin retseptorlari agonistlari ham qo'llaniladi[19][20].

Oziq-ovqat qo'shimchasi sifatida[tahrir | manbasini tahrirlash]

Melatonin rejalashtirilgan dori bo'lmagan mamlakatlarda parhez qo'shimchasi sifatida sotiladi. AQShda melatonin oziqaviy qo'shimcha hisoblanadi va rejalashtirilgan yoki faqat retsept bo'yicha beriladigan dori-darmonlarga nisbatan qattiqroq FDA qoidalaridan ozod qilinadi. 2017-yilda AQSh bozorida so'ralgan melatonin qo'shimchalarining 70 foizi reklama qilingan melatonin tarkibining <10 foizini o'z ichiga olgan[21]. Ba'zi qo'shimchalar reklama qilingan melatonin miqdorining >400% ni o'z ichiga olgan[21].

There is evidence to suggest that the typical advertised dose of most melatonin supplements (>1mg) are excessive for the treatment of insomnia and may even be detrimental to overall sleep quality.[22][23] 4mg of controlled release melatonin has been found to cause excessive melatonin levels upon waking (>50pg/ml), possibly contributing to lethargy in the morning.[22] By contrast,.4mg of controlled release melatonin was not found to cause elevated melatonin levels upon waking.[22]

Tarixi[tahrir | manbasini tahrirlash]

Melatonin birinchi bo'lib ba'zi amfibiyalar va sudraluvchilar teri rangini o'zgartirish mexanizmi bilan bog'liq holda topilgan[24][25]. 1917-yildayoq Keri Pratt Makkord va Floyd P. Allen sigirlarning pineal bezlarini boqish ekstrakti qoramtir epidermal melanoforlarni qisqartirish orqali kurtak terisini oqartirishini aniqladilar[26][27].

In 1958, dermatology professor Aaron B. Lerner and colleagues at Yale University, in the hope that a substance from the pineal might be useful in treating skin diseases, isolated the hormone from bovine pineal gland extracts and named it melatonin.[28] In the mid-70s Lynch et al. demonstrated that the production of melatonin exhibits a circadian rhythm in human pineal glands.[29]

Boshqa turlarda[tahrir | manbasini tahrirlash]

Boshqa jonzotlar[tahrir | manbasini tahrirlash]

Umurtqali hayvonlarda melatonin qorong'uda, odatda tunda, miyaning markazida joylashgan, ammo qon-miya to'sig'idan tashqarida joylashgan kichik ichki sekretsiya bezi - pineal bez tomonidan ishlab chiqariladi. Yorug'lik/qorong'i ma'lumotlar melatonin signalidan ko'ra (bir paytlar taxmin qilinganidek) ko'zning to'r pardasining fotosensitiv ganglion hujayralaridan supraxiazmatik yadrolarga etib boradi. "Qorong'ulik gormoni" deb nomlanuvchi melatoninning oqshom chog'ida paydo bo'lishi tungi (tungi faol) hayvonlarning faolligini va kunduzgi hayvonlarning, shu jumladan odamlarning uxlashiga yordam beradi[30].

Kechasi melatonin leptin darajasini tartibga solib, uning darajasini pasaytiradi.

Ketasianlar melatonin sintezi uchun barcha genlarni, shuningdek, melatonin retseptorlari uchun genlarni yo'qotdilar.[31] Bu ularning bir yarim sharik uyqu rejimi (bir vaqtning o'zida bitta miya yarim shari) bilan bog'liq deb taxmin qilinadi. Xuddi shunday tendentsiyalar sireniyaliklarda ham topilgan[31].

Plants[tahrir | manbasini tahrirlash]

1987-yilda o'simliklarda aniqlanmagunga qadar, melatonin o'nlab yillar davomida asosan hayvonlarning neyrogormoni deb hisoblangan. 1970-yillarda qahva ekstraktida melatonin aniqlanganda, u ekstraksiya jarayonining yon mahsuloti ekanligiga ishonishgan. Biroq, keyinchalik, melatonin tekshirilgan barcha o'simliklarda topilgan. U o'simliklarning barcha turli qismlarida, jumladan, barglari, poyalari, ildizlari, mevalari va urug'larida turli nisbatlarda mavjud[32][33]. Melatonin kontsentratsiyasi nafaqat o'simlik turlari, balki agrotexnik o'sish sharoitlariga qarab bir xil turdagi navlar orasida ham farqlanadi, pikogramlardan grammiga bir necha mikrogramgacha o'zgaradi[34][35]. Qahva, choy, vino va pivo kabi mashhur ichimliklar hamda makkajo'xori, guruch, bug'doy, arpa va jo'xori kabi ekinlarda yuqori melatonin kontsentratsiyasi aniqlangan. Ba'zi keng tarqalgan oziq-ovqat va ichimliklar, jumladan, qahva va yong'oqda melatonin kontsentratsiyasi qondagi melatonin darajasini kunduzgi boshlang'ich qiymatlardan oshirish uchun etarli darajada yuqori ekanligi taxmin qilingan yoki o'lchangan.

Melatoninning o'simlik gormoni sifatidagi roli aniq aniqlanmagan bo'lsa-da, uning o'sish va fotosintez kabi jarayonlarda ishtirok etishi yaxshi tasdiqlangan. Ba'zi o'simlik turlarida melatonin darajasidagi endogen sirkadiyalik ritmlarning faqat cheklangan dalillari ko'rsatilgan va hayvonlarda ma'lum bo'lganlarga o'xshash membrana bilan bog'langan retseptorlari tasvirlanmagan. Aksincha, melatonin o'simliklarda o'sish regulyatori, shuningdek, ekologik stressdan himoya qiluvchi muhim rol o'ynaydi. U o'simliklarda biologik stresslarga, masalan, qo'ziqorin infektsiyasiga va haroratning haddan tashqari o'zgarishi, toksinlar, tuproq sho'rlanishining oshishi, qurg'oqchilik va boshqalar kabi biologik bo'lmagan stresslarga duchor bo'lganda sintezlanadi[34][36][37].

Gerbitsidlar keltirib chiqaradigan oksidlovchi stress in vivo jonli ravishda yuqori melatoninli transgenik guruchda yumshatilgan[38][39].

Qo'ziqorin kasalliklariga chidamlilik boshqa rol o'ynaydi. Qo'shilgan melatonin Malus prunifolia ning Diplocarpon mali ga qarshi chidamliligini oshiradi[39][40]. Bundan tashqari, Alternaria, Botrytis va Fusarium spp kabi qo'ziqorin patogenlarida o'sish inhibitori sifatida ishlaydi. INFEKTSION tezligini pasaytiradi. Urug'larni davolash sifatida Lupinus albusni qo'ziqorinlardan himoya qiladi. Pseudomonas syringae pomidorini sezilarli darajada sekinlashtiradi DC3000 Arabidopsis thaliana va Nicotiana benthamiana yuqtiradi[40].

Zamburug'lar[tahrir | manbasini tahrirlash]

Melatonin o'simlik-patogen tizimlarida Phytophthora infestansda stressga chidamlilikni kamaytirishi kuzatilgan[41].

Hodisa[tahrir | manbasini tahrirlash]

Oziq-ovqat mahsulotlari[tahrir | manbasini tahrirlash]

Tabiiy melatonin 0,17–13,46 ng/g gacha bo'lgan tort gilos[42], banan, olxo'ri, uzum, guruch, don, o'tlar, zaytun moyi[43], sharob[44] va pivoda[45] tabiiy ravishda uchraydi[46]. Sut va gilos iste'mol qilish uyqu sifatini yaxshilashi mumkin. Qushlar guruch kabi melatoninga boy o'simlik ozuqalarini iste'mol qilganda, melatonin ularning miyasidagi melatonin retseptorlari bilan bog'lanadi. Odamlar banan, ananas va apelsin kabi melatoninga boy oziq-ovqatlarni iste'mol qilganda, qonda melatonin darajasi sezilarli darajada oshadi[47].

Manbalar[tahrir | manbasini tahrirlash]

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Tashqi havola[tahrir | manbasini tahrirlash]

  • „Melatonin“. Drug Information Portal. U.S. National Library of Medicine.