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Melatonin: Versiyalar orasidagi farq

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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<ref name="Auld2017">{{cite journal | vauthors = Auld F, Maschauer EL, Morrison I, Skene DJ, Riha RL | title = Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders | journal = Sleep Medicine Reviews | volume = 34 | pages = 10–22 | date = August 2017 | pmid = 28648359 | doi = 10.1016/j.smrv.2016.06.005 | hdl = 20.500.11820/0e890bda-4b1d-4786-a907-a03b1580fd07 | url = http://epubs.surrey.ac.uk/813219/1/Riha%20accepted%20MS%202016.pdf | hdl-access = free }}</ref><ref>{{cite book | vauthors = Faraone SV |title=ADHD: Non-Pharmacologic Interventions, An Issue of Child and Adolescent Psychiatric Clinics of North America, E-Book |date=2014 |publisher=Elsevier Health Sciences |isbn=978-0-323-32602-5 |page=888 |url=https://books.google.com/books?id=lNSlBAAAQBAJ&pg=PA888}}</ref>.
'''Melatonin''' epifez bezining asosiy [[Gormonlar|gormoni]] bo'lib, barcha tirik organizmlarning sirkad ritmini tartibga soluvchidir. Melatoninning boshqa muhim funktsiyalari hayvonlarda uning [[Antioksidlovchilar|antioksidant]] faolligini o'z ichiga oladi. Melatoninning antioksidant ta'siri o'simliklarda ham topilgan. Melatonin asosan tunda [[uyqu]] paytida ishlab chiqarilganligi sababli, u "uyqu gormoni" nomini olgan.

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<ref name="Altun2007">{{cite journal|vauthors=Altun A, Ugur-Altun B|title=Melatonin: therapeutic and clinical utilization|journal=International Journal of Clinical Practice|volume=61|issue=5|pages=835–45|date=May 2007|pmid=17298593|doi=10.1111/j.1742-1241.2006.01191.x|s2cid=18050554}}</ref>. 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<ref name="Drugs2019">{{cite web|title=Melatonin: Side Effects, Uses, Dosage (Kids/Adults)|url=https://www.drugs.com/melatonin.html|access-date=9 January 2019|website=Drugs.com}}</ref>.

== Biologik faollik ==
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<ref name="pmid28400824">{{cite journal | vauthors = Sharafati-Chaleshtori R, Shirzad H, Rafieian-Kopaei M, Soltani A | title = Melatonin and human mitochondrial diseases | journal = Journal of Research in Medical Sciences | volume = 22 | pages = 2 | date = 2017 | pmid = 28400824 | pmc = 5361446 | doi = 10.4103/1735-1995.199092 }}</ref><ref name="IUPHAR – melatonin receptors review">{{cite journal|vauthors=Jockers R, Delagrange P, Dubocovich ML, Markus RP, Renault N, Tosini G, Cecon E, Zlotos DP|display-authors=6|title=Update on melatonin receptors: IUPHAR Review 20|journal=British Journal of Pharmacology|volume=173|issue=18|pages=2702–25|date=September 2016|pmid=27314810|pmc=4995287|doi=10.1111/bph.13536|quote=Hence, one melatonin molecule and its associated metabolites could scavenge a large number of reactive species, and thus, the overall antioxidant capacity of melatonin is believed to be greater than that of other well‐known antioxidants, such as vitamin C and vitamin E, under in vitro or in vivo conditions (Gitto et al., 2001; Sharma and Haldar, 2006; Ortiz et al., 2013).}}</ref><ref name="Melatonin as a mitochondrial antioxidant – 2017 Review">{{cite journal | vauthors = Reiter RJ, Rosales-Corral S, Tan DX, Jou MJ, Galano A, Xu B | title = Melatonin as a mitochondria-targeted antioxidant: one of evolution's best ideas | journal = Cellular and Molecular Life Sciences | volume = 74 | issue = 21 | pages = 3863–3881 | date = November 2017 | pmid = 28864909 | doi = 10.1007/s00018-017-2609-7 | s2cid = 23820389 | quote = melatonin is specifically targeted to the mitochondria where it seems to function as an apex antioxidant&nbsp;... The measurement of the subcellular distribution of melatonin has shown that the concentration of this indole in the mitochondria greatly exceeds that in the blood. }}</ref><ref name="Melatonin – 2016 Review">{{cite journal | vauthors = Reiter RJ, Mayo JC, Tan DX, Sainz RM, Alatorre-Jimenez M, Qin L | title = Melatonin as an antioxidant: under promises but over delivers | journal = Journal of Pineal Research | volume = 61 | issue = 3 | pages = 253–78 | date = October 2016 | pmid = 27500468 | doi = 10.1111/jpi.12360 | s2cid = 35435683 | quote = There is credible evidence to suggest that melatonin should be classified as a mitochondria-targeted antioxidant. }}</ref><ref name="pmid26272235">{{cite journal | vauthors = Manchester LC, Coto-Montes A, Boga JA, Andersen LP, Zhou Z, Galano A, Vriend J, Tan DX, Reiter RJ | display-authors = 6 | title = Melatonin: an ancient molecule that makes oxygen metabolically tolerable | journal = Journal of Pineal Research | volume = 59 | issue = 4 | pages = 403–19 | date = November 2015 | pmid = 26272235 | doi = 10.1111/jpi.12267 | s2cid = 24373303 | quote = While originally thought to be produced exclusively in and secreted from the vertebrate pineal gland [53], it is now known that the indole is present in many, perhaps all, vertebrate organs [54] and in organs of all plants that have been investigated [48, 55, 56]. That melatonin is not relegated solely to the pineal gland is also emphasized by the reports that it is present in invertebrates [57–59], which lack a pineal gland and some of which consist of only a single cell. }}</ref><ref name="Melatonin transporters – 2017 review">{{cite journal | vauthors = Mayo JC, Sainz RM, González-Menéndez P, Hevia D, Cernuda-Cernuda R | title = Melatonin transport into mitochondria | journal = Cellular and Molecular Life Sciences | volume = 74 | issue = 21 | pages = 3927–3940 | date = November 2017 | pmid = 28828619 | doi = 10.1007/s00018-017-2616-8 | s2cid = 10920415 }}</ref>.

== Biologik funksiyalar ==
[[File:Circadian rhythm.svg|thumb|300px|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 ===
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<ref name="pmid28400824" /><ref name="IUPHAR – melatonin receptors review" />.

=== Immun tizimi ===
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<ref name="pmid16729718">{{cite journal | vauthors = Carrillo-Vico A, Reiter RJ, Lardone PJ, Herrera JL, Fernández-Montesinos R, Guerrero JM, Pozo D | title = The modulatory role of melatonin on immune responsiveness | journal = Current Opinion in Investigational Drugs | volume = 7 | issue = 5 | pages = 423–31 | date = May 2006 | pmid = 16729718 }}</ref><ref name="Pp">{{cite journal | vauthors = Maestroni GJ | title = The immunotherapeutic potential of melatonin | journal = Expert Opinion on Investigational Drugs | volume = 10 | issue = 3 | pages = 467–76 | date = March 2001 | pmid = 11227046 | doi = 10.1517/13543784.10.3.467 | s2cid = 6822594 }}</ref>.

=== Og'irlikni tartibga solish ===
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<ref name=":2">{{cite journal|vauthors=Suriagandhi V, Nachiappan V|title=Protective Effects of Melatonin against Obesity-Induced by Leptin Resistance|journal=Behavioural Brain Research|volume=417|pages=113598|date=January 2022|pmid=34563600|doi=10.1016/j.bbr.2021.113598}}</ref><ref>{{cite journal | vauthors = Buonfiglio D, Parthimos R, Dantas R, Cerqueira Silva R, Gomes G, Andrade-Silva J, Ramos-Lobo A, Amaral FG, Matos R, Sinésio J, Motta-Teixeira LC, Donato J, Reiter RJ, Cipolla-Neto J | display-authors = 6 | title = Melatonin Absence Leads to Long-Term Leptin Resistance and Overweight in Rats | journal = Frontiers in Endocrinology | volume = 9 | pages = 122 | date = 2018 | pmid = 29636725 | pmc = 5881424 | doi = 10.3389/fendo.2018.00122 }}</ref>.

== Biokimyo ==

=== Biosintez ===
[[File:Mealtonin biosynth.jpg|thumb|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====
[[File:Melatonin mechanism.jpg|thumb|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 o‘tishi THB radikali bilan rekombinatsiyalanib, 4a-peroksipterin hosil qilishi mumkin bo‘lgan 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<ref>{{cite journal|vauthors=Roberts KM, Fitzpatrick PF|title=Mechanisms of tryptophan and tyrosine hydroxylase|journal=IUBMB Life|volume=65|issue=4|pages=350–7|date=April 2013|pmid=23441081|pmc=4270200|doi=10.1002/iub.1144}}</ref>.

N-asetilserotonin gidroksil holatida S-adenozil metionin (SAM) tomonidan metillanadi va S-adenozil homosistein (SAH) va melatonin hosil bo'ladi<ref name="ReferenceA">{{cite book|vauthors=Dewick PM|year=2002|title=Medicinal Natural Products. A Biosynthetic Approach|edition=2nd|publisher=Wiley|isbn=978-0-471-49640-3}}</ref><ref>{{cite journal | vauthors = Donohue SJ, Roseboom PH, Illnerova H, Weller JL, Klein DC | title = Human hydroxyindole-O-methyltransferase: presence of LINE-1 fragment in a cDNA clone and pineal mRNA | journal = DNA and Cell Biology | volume = 12 | issue = 8 | pages = 715–27 | date = October 1993 | pmid = 8397829 | doi = 10.1089/dna.1993.12.715 | url = https://zenodo.org/record/1235255 }}</ref>.

== Tibbiy foydalanish ==
{{Main|Melatonin (supplement/medication)}}

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<ref name="pmid30148726">{{cite journal|vauthors=Riha RL|title=The use and misuse of exogenous melatonin in the treatment of sleep disorders|journal=Curr Opin Pulm Med|volume=24|issue=6|pages=543–548|date=November 2018|pmid=30148726|doi=10.1097/MCP.0000000000000522|url=}}</ref>. Tibbiyotda melatonindan tashqari, ramelteon, tasimelteon va agomelatin kabi sintetik melatonin retseptorlari agonistlari ham qo'llaniladi<ref name="pmid27500861">{{cite journal | vauthors = Williams WP, McLin DE, Dressman MA, Neubauer DN | title = Comparative Review of Approved Melatonin Agonists for the Treatment of Circadian Rhythm Sleep-Wake Disorders | journal = Pharmacotherapy | volume = 36 | issue = 9 | pages = 1028–41 | date = September 2016 | pmid = 27500861 | pmc = 5108473 | doi = 10.1002/phar.1822 | url = }}</ref><ref name="pmid29487083">{{cite journal | vauthors = Atkin T, Comai S, Gobbi G |author3-link=Gabriella Gobbi| title = Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery | journal = Pharmacol Rev | volume = 70 | issue = 2 | pages = 197–245 | date = April 2018 | pmid = 29487083 | doi = 10.1124/pr.117.014381 | url = }}</ref>.

== Oziq-ovqat qo'shimchasi sifatida ==
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<ref name=":0">{{cite journal | vauthors = Grigg-Damberger MM, Ianakieva D | title = Poor Quality Control of Over-the-Counter Melatonin: What They Say Is Often Not What You Get | journal = Journal of Clinical Sleep Medicine | volume = 13 | issue = 2 | pages = 163–165 | date = February 2017 | pmid = 28095978 | pmc = 5263069 | doi = 10.5664/jcsm.6434 }}</ref>. Ba'zi qo'shimchalar reklama qilingan melatonin miqdorining >400% ni o'z ichiga olgan<ref name=":0" />.

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.<ref name=":1">{{cite journal | vauthors = Gooneratne NS, Edwards AY, Zhou C, Cuellar N, Grandner MA, Barrett JS | title = Melatonin pharmacokinetics following two different oral surge-sustained release doses in older adults | journal = Journal of Pineal Research | volume = 52 | issue = 4 | pages = 437–445 | date = May 2012 | pmid = 22348451 | pmc = 3682489 | doi = 10.1111/j.1600-079X.2011.00958.x }}</ref><ref>{{cite journal | vauthors = Li J, Somers VK, Xu H, Lopez-Jimenez F, Covassin N | title = Trends in Use of Melatonin Supplements Among US Adults, 1999-2018 | journal = Jama | volume = 327 | issue = 5 | pages = 483–485 | date = February 2022 | pmid = 35103775 | doi = 10.1001/jama.2021.23652 }}</ref> 4mg of controlled release melatonin has been found to cause excessive melatonin levels upon waking (>50pg/ml), possibly contributing to lethargy in the morning.<ref name=":1" /> By contrast,.4mg of controlled release melatonin was not found to cause elevated melatonin levels upon waking.<ref name=":1" />

==Tarixi==
Melatonin birinchi bo'lib ba'zi amfibiyalar va sudraluvchilar teri rangini o'zgartirish mexanizmi bilan bog'liq holda topilgan<ref name="Filadelfi1996">{{cite journal | vauthors = Filadelfi AM, Castrucci AM | title = Comparative aspects of the pineal/melatonin system of poikilothermic vertebrates | journal = Journal of Pineal Research | volume = 20 | issue = 4 | pages = 175–86 | date = May 1996 | pmid = 8836950 | doi = 10.1111/j.1600-079X.1996.tb00256.x | s2cid = 41959214 }}</ref><ref name="Sugden2004">{{cite journal | vauthors = Sugden D, Davidson K, Hough KA, Teh MT | title = Melatonin, melatonin receptors and melanophores: a moving story | journal = Pigment Cell Research | volume = 17 | issue = 5 | pages = 454–60 | date = October 2004 | pmid = 15357831 | doi = 10.1111/j.1600-0749.2004.00185.x | doi-access = free }}</ref>. 1917-yildayoq Keri Pratt Makkord va Floyd P. Allen sigirlarning pineal bezlarini boqish ekstrakti qoramtir epidermal melanoforlarni qisqartirish orqali kurtak terisini oqartirishini aniqladilar<ref name="Coates">{{cite book | vauthors = Coates PM, Blackman MR, Cragg GM, Levine M, Moss J, White JD| title = Encyclopedia of dietary supplements | publisher = Marcel Dekker | location = New York, N.Y | year = 2005 | pages = 457–66 | isbn = 978-0-8247-5504-1 | url = https://books.google.com/books?id=Sfmc-fRCj10C&q=Lerner+melatonin+history&pg=PA457 }}</ref><ref name="McCord">{{cite journal |vauthors=McCord CP, Allen FP |title=Evidences associating pineal gland function with alterations in pigmentation |date=January 1917 |journal=J Exp Zool |volume= 23 |issue=1 |pages=206–24 |url=https://books.google.com/books?id=OOM1AQAAMAAJ&pg=PA207 |doi=10.1002/jez.1400230108 }}</ref>.

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 [[pineal gland#Other animals|bovine pineal gland]] extracts and named it melatonin.<ref name="pmid14415935">{{cite journal | vauthors = Lerner AB, Case JD, Takahashi Y | title = Isolation of melatonin and 5-methoxyindole-3-acetic acid from bovine pineal glands | journal = The Journal of Biological Chemistry | volume = 235 | pages = 1992–7 | date = July 1960 | issue = 7 | doi = 10.1016/S0021-9258(18)69351-2 | pmid = 14415935 | doi-access = free }}</ref> In the mid-70s Lynch ''et al.'' demonstrated that the production of melatonin exhibits a circadian rhythm in human pineal glands.<ref name="pmid1167425">{{cite journal | vauthors = Lynch HJ, Wurtman RJ, Moskowitz MA, Archer MC, Ho MH | title = Daily rhythm in human urinary melatonin | journal = Science | volume = 187 | issue = 4172 | pages = 169–71 | date = January 1975 | pmid = 1167425 | doi = 10.1126/science.1167425 | bibcode = 1975Sci...187..169L }}</ref>

== Boshqa turlarda ==

===Boshqa jonzotlar===
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<ref>{{cite journal|vauthors=Foster RG|title=Sleep, circadian rhythms and health|journal=Interface Focus|volume=10|issue=3|pages=20190098|date=June 2020|pmid=32382406|pmc=7202392|doi=10.1098/rsfs.2019.0098}}</ref>.

Kechasi melatonin [[leptin]] darajasini tartibga solib, uning darajasini pasaytiradi.

Ketasianlar melatonin sintezi uchun barcha genlarni, shuningdek, melatonin retseptorlari uchun genlarni yo'qotdilar.<ref name="Huelsmann2019">{{cite journal | vauthors = Huelsmann M, Hecker N, Springer MS, Gatesy J, Sharma V, Hiller M | title = Genes lost during the transition from land to water in cetaceans highlight genomic changes associated with aquatic adaptations | journal = Science Advances | volume = 5 | issue = 9 | pages = eaaw6671 | date = September 2019 | pmid = 31579821 | pmc = 6760925 | doi = 10.1126/sciadv.aaw6671 | bibcode = 2019SciA....5.6671H }}</ref> 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<ref name="Huelsmann2019" />.

===Plants===
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<ref name="Tan_2012">{{cite journal|vauthors=Tan DX, Hardeland R, Manchester LC, Korkmaz A, Ma S, Rosales-Corral S, Reiter RJ|title=Functional roles of melatonin in plants, and perspectives in nutritional and agricultural science|journal=Journal of Experimental Botany|volume=63|issue=2|pages=577–97|date=January 2012|pmid=22016420|doi=10.1093/jxb/err256|doi-access=free}}</ref><ref>{{cite journal | vauthors = Paredes SD, Korkmaz A, Manchester LC, Tan DX, Reiter RJ | title = Phytomelatonin: a review | journal = Journal of Experimental Botany | volume = 60 | issue = 1 | pages = 57–69 | date = 1 January 2009 | pmid = 19033551 | doi = 10.1093/jxb/ern284 | s2cid = 15738948 }}</ref>. 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<ref name="hardeland2015">{{cite journal | vauthors = Hardeland R | title = Melatonin in plants and other phototrophs: advances and gaps concerning the diversity of functions | journal = Journal of Experimental Botany | volume = 66 | issue = 3 | pages = 627–46 | date = February 2015 | pmid = 25240067 | doi = 10.1093/jxb/eru386 | doi-access = free }}</ref><ref name="Bonnefont-Rousselot 2010 55–67">{{cite journal | vauthors = Bonnefont-Rousselot D, Collin F | title = Melatonin: action as antioxidant and potential applications in human disease and aging | journal = Toxicology | volume = 278 | issue = 1 | pages = 55–67 | date = November 2010 | pmid = 20417677 | doi = 10.1016/j.tox.2010.04.008 }}</ref>. 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<ref name="hardeland2015" /><ref name="reiter2015">{{cite journal | vauthors = Reiter RJ, Tan DX, Zhou Z, Cruz MH, Fuentes-Broto L, Galano A | title = Phytomelatonin: assisting plants to survive and thrive | journal = Molecules | volume = 20 | issue = 4 | pages = 7396–437 | date = April 2015 | pmid = 25911967 | pmc = 6272735 | doi = 10.3390/molecules20047396 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Arnao MB, Hernández-Ruiz J | title = Functions of melatonin in plants: a review | journal = Journal of Pineal Research | volume = 59 | issue = 2 | pages = 133–50 | date = September 2015 | pmid = 26094813 | doi = 10.1111/jpi.12253 | doi-access = free }}</ref>.

Gerbitsidlar keltirib chiqaradigan oksidlovchi stress in vivo jonli ravishda yuqori melatoninli transgenik guruchda yumshatilgan<ref name="Park-et-al-2012">{{cite journal | vauthors = Park S, Lee DE, Jang H, Byeon Y, Kim YS, Back K | title = Melatonin-rich transgenic rice plants exhibit resistance to herbicide-induced oxidative stress | journal = Journal of Pineal Research | volume = 54 | issue = 3 | pages = 258–63 | date = April 2013 | pmid = 22856683 | doi = 10.1111/j.1600-079x.2012.01029.x | publisher = [[Wiley Publishing|Wiley]] | s2cid = 6291664 }}</ref><ref name="Arnao-Hernandez-Ruiz-2014">{{cite journal | vauthors = Arnao MB, Hernández-Ruiz J | title = Melatonin: plant growth regulator and/or biostimulator during stress? | journal = Trends in Plant Science | volume = 19 | issue = 12 | pages = 789–97 | date = December 2014 | pmid = 25156541 | doi = 10.1016/j.tplants.2014.07.006 | publisher = [[Elsevier]] | s2cid = 38637203 }}</ref>.

Qo'ziqorin kasalliklariga chidamlilik boshqa rol o'ynaydi. Qo'shilgan melatonin Malus prunifolia ning Diplocarpon mali ga qarshi chidamliligini oshiradi<ref name="Arnao-Hernandez-Ruiz-2014" /><ref name="Arnao-Hernandez-Ruiz-2015">{{cite journal | vauthors = Arnao MB, Hernández-Ruiz J | title = Functions of melatonin in plants: a review | journal = Journal of Pineal Research | volume = 59 | issue = 2 | pages = 133–50 | date = September 2015 | pmid = 26094813 | doi = 10.1111/jpi.12253 | publisher = [[Wiley Publishing|Wiley]] | s2cid = 19887642 | doi-access = free }}</ref>. 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<ref name="Arnao-Hernandez-Ruiz-2015" />.

=== Zamburug'lar ===
Melatonin o'simlik-patogen tizimlarida Phytophthora infestansda stressga chidamlilikni kamaytirishi kuzatilgan<ref name="Socaciu-et-al-2020">{{cite journal|vauthors=Socaciu AI, Ionuţ R, Socaciu MA, Ungur AP, Bârsan M, Chiorean A, Socaciu C, Râjnoveanu AG|display-authors=6|title=Melatonin, an ubiquitous metabolic regulator: functions, mechanisms and effects on circadian disruption and degenerative diseases|journal=Reviews in Endocrine & Metabolic Disorders|volume=21|issue=4|pages=465–478|date=December 2020|pmid=32691289|doi=10.1007/s11154-020-09570-9|s2cid=220657247}}</ref>.

== Hodisa ==

=== Oziq-ovqat mahsulotlari ===
Tabiiy melatonin 0,17–13,46 ng/g gacha bo'lgan tort gilos<ref name="pmid11600041">{{cite journal|vauthors=Burkhardt S, Tan DX, Manchester LC, Hardeland R, Reiter RJ|title=Detection and quantification of the antioxidant melatonin in Montmorency and Balaton tart cherries (Prunus cerasus)|journal=Journal of Agricultural and Food Chemistry|volume=49|issue=10|pages=4898–902|date=October 2001|pmid=11600041|doi=10.1021/jf010321}}</ref>, banan, olxo'ri, uzum, guruch, don, o'tlar, zaytun moyi<ref>{{cite journal|vauthors=González-Flores D, Velardo B, Garrido M, González-Gómez D, Lozano M, Ayuso MC, Barriga C, Paredes SD, Rodríguez AB|year=2011|url=https://www.researchgate.net/publication/259983119|title=Ingestion of Japanese plums (Prunus salicina Lindl. cv. Crimson Globe) increases the urinary 6-sulfatoxymelatonin and total antioxidant capacity levels in young, middle-aged and elderly humans: Nutritional and functional characterization of their content|journal=Journal of Food and Nutrition Research|volume=50|issue=4|pages=229–36}}</ref>, sharob<ref name="pmid21342247">{{cite journal|vauthors=Lamont KT, Somers S, Lacerda L, Opie LH, Lecour S|title=Is red wine a SAFE sip away from cardioprotection? Mechanisms involved in resveratrol- and melatonin-induced cardioprotection|journal=Journal of Pineal Research|volume=50|issue=4|pages=374–80|date=May 2011|pmid=21342247|doi=10.1111/j.1600-079X.2010.00853.x|s2cid=8034935}}</ref> va pivoda<ref>{{cite journal|vauthors=Salehi B|date=5 July 2019|title=Melatonin in Medicinal and Food Plants|url=https://schlaf.fit/Melatonin_in_Plants_and_Food.pdf|journal=[[Cells (journal)|Cells]]|volume=681}}</ref> tabiiy ravishda uchraydi<ref>{{cite journal|vauthors=Pereira N, Naufel MF, Ribeiro EB, Tufik S, Hachul H|title=Influence of Dietary Sources of Melatonin on Sleep Quality: A Review|journal=Journal of Food Science|volume=85|issue=1|pages=5–13|date=January 2020|pmid=31856339|doi=10.1111/1750-3841.14952|publisher=Wiley|doi-access=free}}</ref>. 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<ref name="pmid23137025">{{cite journal|vauthors=Sae-Teaw M, Johns J, Johns NP, Subongkot S|title=Serum melatonin levels and antioxidant capacities after consumption of pineapple, orange, or banana by healthy male volunteers|journal=Journal of Pineal Research|volume=55|issue=1|pages=58–64|date=August 2013|pmid=23137025|doi=10.1111/jpi.12025|s2cid=979886}}</ref>.

==Manbalar==
{{Reflist}}

==Tashqi havola==
{{Commons category}}
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/melatonin | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Melatonin }}
* {{cite web | url = https://www.chemwatch.net/resource-center/melatonin/ | publisher = Chemwatch | title = Melatonin }}

{{Authority control}}

[[Category:Melatonin| ]]
[[Category:Acetamides]]
[[Category:Antioxidants]]
[[Category:Aromatase inhibitors]]
[[Category:Circadian rhythm]]
[[Category:Hormones of the pineal gland]]
[[Category:Melatonin receptor agonists]]
[[Category:Methoxy compounds]]
[[Category:Mexamines]]
[[Category:Tryptamine alkaloids]]
[[Category:Wikipedia medicine articles ready to translate]]

2022-yil 21-sentyabr, 10:29 dagi koʻrinishi


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

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

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

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

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

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

Biosintez

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

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 o‘tishi THB radikali bilan rekombinatsiyalanib, 4a-peroksipterin hosil qilishi mumkin bo‘lgan 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

Asosiy maqola: Melatonin (supplement/medication)

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

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

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

Boshqa jonzotlar

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

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

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

Hodisa

Oziq-ovqat mahsulotlari

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

  1. ↑ "Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders". Sleep Medicine Reviews 34: 10–22. August 2017. doi:10.1016/j.smrv.2016.06.005. PMID 28648359. http://epubs.surrey.ac.uk/813219/1/Riha%20accepted%20MS%202016.pdf. 
  2. ↑ ADHD: Non-Pharmacologic Interventions, An Issue of Child and Adolescent Psychiatric Clinics of North America, E-Book. Elsevier Health Sciences, 2014 — 888-bet. ISBN 978-0-323-32602-5. 
  3. ↑ "Melatonin: therapeutic and clinical utilization". International Journal of Clinical Practice 61 (5): 835–45. May 2007. doi:10.1111/j.1742-1241.2006.01191.x. PMID 17298593. 
  4. ↑ „Melatonin: Side Effects, Uses, Dosage (Kids/Adults)“. Drugs.com. Qaraldi: 2019-yil 9-yanvar.
  5. ↑ 5,0 5,1 "Melatonin and human mitochondrial diseases". Journal of Research in Medical Sciences 22: 2. 2017. doi:10.4103/1735-1995.199092. PMID 28400824. PMC 5361446. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5361446. 
  6. ↑ 6,0 6,1 "Update on melatonin receptors: IUPHAR Review 20". British Journal of Pharmacology 173 (18): 2702–25. September 2016. doi:10.1111/bph.13536. PMID 27314810. PMC 4995287. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4995287. "Hence, one melatonin molecule and its associated metabolites could scavenge a large number of reactive species, and thus, the overall antioxidant capacity of melatonin is believed to be greater than that of other well‐known antioxidants, such as vitamin C and vitamin E, under in vitro or in vivo conditions (Gitto et al., 2001; Sharma and Haldar, 2006; Ortiz et al., 2013)." 
  7. ↑ "Melatonin as a mitochondria-targeted antioxidant: one of evolution's best ideas". Cellular and Molecular Life Sciences 74 (21): 3863–3881. November 2017. doi:10.1007/s00018-017-2609-7. PMID 28864909. "melatonin is specifically targeted to the mitochondria where it seems to function as an apex antioxidant ... The measurement of the subcellular distribution of melatonin has shown that the concentration of this indole in the mitochondria greatly exceeds that in the blood." 
  8. ↑ "Melatonin as an antioxidant: under promises but over delivers". Journal of Pineal Research 61 (3): 253–78. October 2016. doi:10.1111/jpi.12360. PMID 27500468. "There is credible evidence to suggest that melatonin should be classified as a mitochondria-targeted antioxidant." 
  9. ↑ "Melatonin: an ancient molecule that makes oxygen metabolically tolerable". Journal of Pineal Research 59 (4): 403–19. November 2015. doi:10.1111/jpi.12267. PMID 26272235. "While originally thought to be produced exclusively in and secreted from the vertebrate pineal gland [53], it is now known that the indole is present in many, perhaps all, vertebrate organs [54] and in organs of all plants that have been investigated [48, 55, 56]. That melatonin is not relegated solely to the pineal gland is also emphasized by the reports that it is present in invertebrates [57–59], which lack a pineal gland and some of which consist of only a single cell." 
  10. ↑ "Melatonin transport into mitochondria". Cellular and Molecular Life Sciences 74 (21): 3927–3940. November 2017. doi:10.1007/s00018-017-2616-8. PMID 28828619. 
  11. ↑ "The modulatory role of melatonin on immune responsiveness". Current Opinion in Investigational Drugs 7 (5): 423–31. May 2006. PMID 16729718. 
  12. ↑ "The immunotherapeutic potential of melatonin". Expert Opinion on Investigational Drugs 10 (3): 467–76. March 2001. doi:10.1517/13543784.10.3.467. PMID 11227046. 
  13. ↑ "Protective Effects of Melatonin against Obesity-Induced by Leptin Resistance". Behavioural Brain Research 417: 113598. January 2022. doi:10.1016/j.bbr.2021.113598. PMID 34563600. 
  14. ↑ "Melatonin Absence Leads to Long-Term Leptin Resistance and Overweight in Rats". Frontiers in Endocrinology 9: 122. 2018. doi:10.3389/fendo.2018.00122. PMID 29636725. PMC 5881424. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5881424. 
  15. ↑ "Mechanisms of tryptophan and tyrosine hydroxylase". IUBMB Life 65 (4): 350–7. April 2013. doi:10.1002/iub.1144. PMID 23441081. PMC 4270200. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4270200. 
  16. ↑ Medicinal Natural Products. A Biosynthetic Approach, 2nd, Wiley, 2002. ISBN 978-0-471-49640-3. 
  17. ↑ "Human hydroxyindole-O-methyltransferase: presence of LINE-1 fragment in a cDNA clone and pineal mRNA". DNA and Cell Biology 12 (8): 715–27. October 1993. doi:10.1089/dna.1993.12.715. PMID 8397829. https://zenodo.org/record/1235255. 
  18. ↑ "The use and misuse of exogenous melatonin in the treatment of sleep disorders". Curr Opin Pulm Med 24 (6): 543–548. November 2018. doi:10.1097/MCP.0000000000000522. PMID 30148726. 
  19. ↑ "Comparative Review of Approved Melatonin Agonists for the Treatment of Circadian Rhythm Sleep-Wake Disorders". Pharmacotherapy 36 (9): 1028–41. September 2016. doi:10.1002/phar.1822. PMID 27500861. PMC 5108473. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5108473. 
  20. ↑ "Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery". Pharmacol Rev 70 (2): 197–245. April 2018. doi:10.1124/pr.117.014381. PMID 29487083. 
  21. ↑ 21,0 21,1 "Poor Quality Control of Over-the-Counter Melatonin: What They Say Is Often Not What You Get". Journal of Clinical Sleep Medicine 13 (2): 163–165. February 2017. doi:10.5664/jcsm.6434. PMID 28095978. PMC 5263069. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5263069. 
  22. ↑ 22,0 22,1 22,2 "Melatonin pharmacokinetics following two different oral surge-sustained release doses in older adults". Journal of Pineal Research 52 (4): 437–445. May 2012. doi:10.1111/j.1600-079X.2011.00958.x. PMID 22348451. PMC 3682489. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3682489. 
  23. ↑ "Trends in Use of Melatonin Supplements Among US Adults, 1999-2018". Jama 327 (5): 483–485. February 2022. doi:10.1001/jama.2021.23652. PMID 35103775. 
  24. ↑ "Comparative aspects of the pineal/melatonin system of poikilothermic vertebrates". Journal of Pineal Research 20 (4): 175–86. May 1996. doi:10.1111/j.1600-079X.1996.tb00256.x. PMID 8836950. 
  25. ↑ "Melatonin, melatonin receptors and melanophores: a moving story". Pigment Cell Research 17 (5): 454–60. October 2004. doi:10.1111/j.1600-0749.2004.00185.x. PMID 15357831. 
  26. ↑ Encyclopedia of dietary supplements. New York, N.Y: Marcel Dekker, 2005 — 457–66-bet. ISBN 978-0-8247-5504-1. 
  27. ↑ "Evidences associating pineal gland function with alterations in pigmentation". J Exp Zool 23 (1): 206–24. January 1917. doi:10.1002/jez.1400230108. https://books.google.com/books?id=OOM1AQAAMAAJ&pg=PA207. 
  28. ↑ "Isolation of melatonin and 5-methoxyindole-3-acetic acid from bovine pineal glands". The Journal of Biological Chemistry 235 (7): 1992–7. July 1960. doi:10.1016/S0021-9258(18)69351-2. PMID 14415935. 
  29. ↑ "Daily rhythm in human urinary melatonin". Science 187 (4172): 169–71. January 1975. doi:10.1126/science.1167425. PMID 1167425. 
  30. ↑ "Sleep, circadian rhythms and health". Interface Focus 10 (3): 20190098. June 2020. doi:10.1098/rsfs.2019.0098. PMID 32382406. PMC 7202392. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=7202392. 
  31. ↑ 31,0 31,1 "Genes lost during the transition from land to water in cetaceans highlight genomic changes associated with aquatic adaptations". Science Advances 5 (9): eaaw6671. September 2019. doi:10.1126/sciadv.aaw6671. PMID 31579821. PMC 6760925. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=6760925. 
  32. ↑ "Functional roles of melatonin in plants, and perspectives in nutritional and agricultural science". Journal of Experimental Botany 63 (2): 577–97. January 2012. doi:10.1093/jxb/err256. PMID 22016420. 
  33. ↑ "Phytomelatonin: a review". Journal of Experimental Botany 60 (1): 57–69. 1 January 2009. doi:10.1093/jxb/ern284. PMID 19033551. 
  34. ↑ 34,0 34,1 "Melatonin in plants and other phototrophs: advances and gaps concerning the diversity of functions". Journal of Experimental Botany 66 (3): 627–46. February 2015. doi:10.1093/jxb/eru386. PMID 25240067. 
  35. ↑ "Melatonin: action as antioxidant and potential applications in human disease and aging". Toxicology 278 (1): 55–67. November 2010. doi:10.1016/j.tox.2010.04.008. PMID 20417677. 
  36. ↑ "Phytomelatonin: assisting plants to survive and thrive". Molecules 20 (4): 7396–437. April 2015. doi:10.3390/molecules20047396. PMID 25911967. PMC 6272735. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=6272735. 
  37. ↑ "Functions of melatonin in plants: a review". Journal of Pineal Research 59 (2): 133–50. September 2015. doi:10.1111/jpi.12253. PMID 26094813. 
  38. ↑ "Melatonin-rich transgenic rice plants exhibit resistance to herbicide-induced oxidative stress". Journal of Pineal Research (Wiley) 54 (3): 258–63. April 2013. doi:10.1111/j.1600-079x.2012.01029.x. PMID 22856683. 
  39. ↑ 39,0 39,1 "Melatonin: plant growth regulator and/or biostimulator during stress?". Trends in Plant Science (Elsevier) 19 (12): 789–97. December 2014. doi:10.1016/j.tplants.2014.07.006. PMID 25156541. 
  40. ↑ 40,0 40,1 "Functions of melatonin in plants: a review". Journal of Pineal Research (Wiley) 59 (2): 133–50. September 2015. doi:10.1111/jpi.12253. PMID 26094813. 
  41. ↑ "Melatonin, an ubiquitous metabolic regulator: functions, mechanisms and effects on circadian disruption and degenerative diseases". Reviews in Endocrine & Metabolic Disorders 21 (4): 465–478. December 2020. doi:10.1007/s11154-020-09570-9. PMID 32691289. 
  42. ↑ "Detection and quantification of the antioxidant melatonin in Montmorency and Balaton tart cherries (Prunus cerasus)". Journal of Agricultural and Food Chemistry 49 (10): 4898–902. October 2001. doi:10.1021/jf010321. PMID 11600041. 
  43. ↑ "Ingestion of Japanese plums (Prunus salicina Lindl. cv. Crimson Globe) increases the urinary 6-sulfatoxymelatonin and total antioxidant capacity levels in young, middle-aged and elderly humans: Nutritional and functional characterization of their content". Journal of Food and Nutrition Research 50 (4): 229–36. 2011. https://www.researchgate.net/publication/259983119. 
  44. ↑ "Is red wine a SAFE sip away from cardioprotection? Mechanisms involved in resveratrol- and melatonin-induced cardioprotection". Journal of Pineal Research 50 (4): 374–80. May 2011. doi:10.1111/j.1600-079X.2010.00853.x. PMID 21342247. 
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  47. ↑ "Serum melatonin levels and antioxidant capacities after consumption of pineapple, orange, or banana by healthy male volunteers". Journal of Pineal Research 55 (1): 58–64. August 2013. doi:10.1111/jpi.12025. PMID 23137025. 

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