Gastrodia elata is a famous traditional Chinese herb with medicinal and edible application.In this study,three new polybenzyls,gastropolybenzylols G-I(1-3)were isolated from the EtOAc extract of G.elata.Their structur...Gastrodia elata is a famous traditional Chinese herb with medicinal and edible application.In this study,three new polybenzyls,gastropolybenzylols G-I(1-3)were isolated from the EtOAc extract of G.elata.Their structures were identified by extensive spectroscopic analyses involving HRESIMS,UV,IR,1D and 2D NMR.Compound 1 showed agonistic effects on MT1 and MT_(2) receptors with agonistic rates of 55.91±4.84%and 165.13±5.65%at the concentration of 0.5 mM,respectively,and an EC_(50) value of 76.24μM on MT_(2) receptor.展开更多
Melatonin,the hormone of darkness and messenger of the photoperiod,is also well known to exhibit strong direct and indirect antioxidant properties. Melatonin has previously been demonstrated to be a powerful organ pro...Melatonin,the hormone of darkness and messenger of the photoperiod,is also well known to exhibit strong direct and indirect antioxidant properties. Melatonin has previously been demonstrated to be a powerful organ protective substance in numerous models of injury; these beneficial effects have been attributed to the hormone's intense radical scavenging capacity. The present report reviews the hepatoprotective potential of the pineal hormone in various models of oxidative stress in vivo,and summarizes the extensive literature showing that melatonin may be a suitable experimental substance to reduce liver damage after sepsis,hemorrhagic shock,ischemia/reperfusion,and in numerous models of toxic liver injury. Melatonin's influence on hepatic antioxidant enzymes and other potentially relevant pathways,such as nitric oxide signaling,hepatic cytokine and heat shock protein expression,are evaluated. Based on recent literature demonstrating the functional relevance of melatonin receptor activation for hepatic organ protection,this article finally suggests that melatonin receptors could mediate the hepatoprotective actions of melatonin therapy.展开更多
Melatonin receptor 1B(MT2,encoded by the MTNR1B gene),a high-affinity receptor for melatonin,is associated with glucose homeostasis including glucose uptake and transport.The rs10830963 variant in the MTNR1B gene is l...Melatonin receptor 1B(MT2,encoded by the MTNR1B gene),a high-affinity receptor for melatonin,is associated with glucose homeostasis including glucose uptake and transport.The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus(GDM);however,the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood.This article aims to investigate the relationship between rs10830963 variants and GDM development,as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts.TaqMan-MGB(minor groove binder)probe quantitative realtime polymerase chain reaction(qPCR)assays were used for rs10930963 genotyping.MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence,western blot,and qPCR.The relationship between MT2 and glucose transporters(GLUTs)or peroxisome proliferator-activated receptorγ(PPARγ)was established by western blot,and glucose consumption of trophoblasts was measured by a glucose assay kit.The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women(P<0.05).The fasting,1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers(P<0.05).Besides,the protein and messenger RNA(mRNA)expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women(P<0.05).Melatonin could stimulate glucose uptake and GLUT4 and PPARγprotein expression in trophoblasts,which could be attenuated by MT2 receptor knockdown.In conclusion,the rs10830963 variant was associated with an increased risk of GDM.The MT2 receptor is essential for melatonin to raise glucose uptake and transport,which may be mediated by PPARγ.展开更多
Objective： To explore the effects of Kaixin Powder （开心散, KXP） on melatonin receptor （MR） expression and 1261-Mel binding affinity in a depression rat model. Methods： Seventy-two male Wistar rats were divided ...Objective： To explore the effects of Kaixin Powder （开心散, KXP） on melatonin receptor （MR） expression and 1261-Mel binding affinity in a depression rat model. Methods： Seventy-two male Wistar rats were divided into six groups： a blank control group, model group, ramelteon group, KXP high-dosage group （HKXP）, medium-dosage group （MKXP） and low-dosage group （LKXP）. To establish the depression model, all groups except the blank control group were singly housed and exposed to chronic unpredictable mild stress. Weight gain, sucrose consumption and the open-field test were used to evaluate induction of depression. KXP at 260, 130 and 65 mg/（kg·d） was also respectively administered to the rats in the HKXP, MKXP and LKXP groups for 21 days. Ramelteon [0.83 mg/（kg·d）] was given to the positive drug control group. An equivalent volume of physiological saline was given to the blank and model groups. The liquid chip method was used to measure the concentration of plasma melatonin （MT）. Mell a （MT1） and Mellb （MT2） expression levels were determined by Western blotting. In addition, a radioactive ligand-binding assay was used to analyze the specific binding properties and dynamic characteristics between MR and 125I-Mel. Results： The results of weight gain, sucrose consumption and the open-field test showed that our model successfully produced depressive symptoms and depressive-like behavior. The concentration of plasma MT in the model group decreased significantly at night but increased in the MKXP group （P〈0.05）. The HKXP group showed significantly increased expression of MT1 （P〈0.05）; however, the expression of MT2 in all groups exhibited no significant differences （P〉0.05）. The maximum binding capacity （Bmax） for specific binding between MR and 125I-Mel in the MKXP group was significantly higher than that in the model group （P〈0.05）, but no significant differences were found in the equilibrium dissociation constant （Kd） of each group （P〉0.05）. Conclusions： KXP may have a similar effect as ramelteon. KXP improved depressive-like behavior by increasing the concentration of plasma MT and MT1 expression, thereby increasing three Bmax of MR tO achieve the desired antidepressant effect.展开更多
In most fish,reproduction is seasonal or periodic under the suitable conditions.In turbot(Scophthalmus maximus)farms,one of the most economically important marine flatfish species,changes in daylength could cause chan...In most fish,reproduction is seasonal or periodic under the suitable conditions.In turbot(Scophthalmus maximus)farms,one of the most economically important marine flatfish species,changes in daylength could cause changes in the spawning time.In this study,to characterize the regulation of reproductive physiology following light signals,three melatonin receptors(Mtnr)investigated in turbot were named sm Mtnr1,sm Mtnr2,and sm Mtnr1 c.Distinct expression profiles demonstrated that Mtnr m RNAs were concentrated in the brain(as detected in the hypothalamus(Hy)and mesencephalon(Me)),gonad and eye.The most abundant Mtnr1 and Mtnr2 m RNA expression levels were detected in the central nervous system at the beginning of the breeding season,suggesting that Mtnr1 and Mtnr2 may play vital roles in the regulation of turbot gonadal development.In addition,the melatonin profiles gradually increased and reached to the highest level at the spawning stage,indicating that melatonin is a potent hormone in the regulation of fish oocyte growth and maturation.The results of this study suggested that melatonin is the primary factor that transduces the light signal and regulates the physiological functions of turbot seasonal reproduction.Moreover,the results of this study may establish a foundation for further research seeking to identify fish melatonin receptors involved in the gonadal development and gamete maturation.展开更多
Melatonin (MEL) has been reported to have acute enhancing effects on some aspects of cognition. Recently, we revealed that N1-acetyl-5-methoxyquinuramine (AMK), a brain metabolite of MEL, is much more potent than MEL ...Melatonin (MEL) has been reported to have acute enhancing effects on some aspects of cognition. Recently, we revealed that N1-acetyl-5-methoxyquinuramine (AMK), a brain metabolite of MEL, is much more potent than MEL in converting short-term memory (STM) to long-term memory (LTM) with a single administration immediately after the acquisition trial of the novel object recognition (NOR) task. These data suggest that the memory-enhancing effects of MEL may be mediated by mechanisms independent of the activation of MEL MT1 and MT2 receptors. In the present study, we examined the contribution of MT1 and MT2 receptor-mediated and non-receptor-mediated mechanisms to the acute memory-enhancing effects of MEL using NOR task. Mice were administered with either MEL, AMK, or a highly selective MT1/MT2 receptor agonist ramelteon (RAM) immediately after the acquisition trial and the effects of varying doses of these drugs on both STM and LTM performance were compared. We found that both AMK and RAM were more potent than MEL in both facilitating STM and promoting LTM formation. We also found that pretreatment with luzindole, a MT1/MT2 receptor antagonist, markedly suppressed only the effects of RAM. These results suggest that acutely administered MEL enhances NOR memory through both MT1 and MT2 receptor-mediated and non-receptor-mediated mechanisms.展开更多
Uncariae Ramulus Cum Uncis(Gou-Teng),the dried hook-bearing stems of several Uncaria plants(Rubiaceae),is a wellknown herbal medicine in China.The clinical application of Gou-Teng is bewildered for the morphological a...Uncariae Ramulus Cum Uncis(Gou-Teng),the dried hook-bearing stems of several Uncaria plants(Rubiaceae),is a wellknown herbal medicine in China.The clinical application of Gou-Teng is bewildered for the morphological and chemical similarity between diferent species.In order to discern their chemical and biological diference,an ultra-fast liquid chromatography equipped with ion trap time-of-fight mass spectrometry(UFLC-IT/TOF-MS)combining with melatonin(MT1 and MT2)and 5-hydroxytryptamine(5-HT1A and 5-HT2C)receptors agonistic assay in vitro was conducted on seven Uncaria species.As a result,57 compounds including 35 indole alkaloids,ten favonoids,fve triterpenoids,fve chlorogenic analogues,and two other compounds were characterized based on their MS/MS patterns and UV absorptions.Specifcally,cadambine-type and corynanthein-type alkaloids were exclusively present in U.rhynchophylla and U.scandens,whereas corynoxine-type alkaloids were commonly detected in all the seven Uncaria plants.Three Uncaria species,U.rhynchophylla,U.macrophylla,and U.yunnanensis showed obviously agnostic activity on four neurotransmitter receptors(MT1,MT2,5-HT1A,and 5-HT_(2C)).This frst-time UFLCMS-IT-TOF analyses integrated with biological assay on seven Uncaria plants will provide scientifc viewpoints for the clinical application of Gou-Teng.展开更多
Melatonin plays a critical role in regulating photoperiodic signals and has recently been shown to decrease immunosenescence with age. In this study, we examined whether melatonin activates T lymphocytes as major adap...Melatonin plays a critical role in regulating photoperiodic signals and has recently been shown to decrease immunosenescence with age. In this study, we examined whether melatonin activates T lymphocytes as major adaptive immune cells in in vitro and in vivo models. Splenocytes, CD4＋, and naive CD4 T lymphocytes were isolated from the spleen of BALB/c mice and the cell population patterns and mRNA profiles associated with T cell activation （CD28 and p21） and the melatonin receptor （MT1A and MT1B） were assessed. The T cell activation- related proteins Ki67 and Bcl2 were also evaluated to confirm the relationship between gene and protein levels. Our data clearly revealed that CD28, p21, MT 1 A, and MT 1B mRNA were highly expressed in the presence of melatonin. Co-culture of CD4＋ T lymphocyte and peritoneal macrophage 7 days after melatonin administration to young and aged mice significantly increased APRIL mRNA, suggesting induction or maintenance of T lymphocyte responses. We also found that the intracellular amount of Ki67 and Bcl2 proteins were significantly upregulated in aged CD4＋ T lymphocytes, suggesting enhancing T cell proliferation and ling-term maintenance of memory T cells. Taken together, we conclude that melatonin supplementation may enhance immunity in aged individuals by upregulating immunosenescence indices in association with T lymphocytes and may be an attractive pharmacological candidate for aged and immunocompromised individuals.展开更多
Melatonin is a circulating hormone that is mainly re- leased from the pineal gland. It is best known as a regulator of seasonal and circadian rhythms, its levels being high during the night and low during the day. Int...Melatonin is a circulating hormone that is mainly re- leased from the pineal gland. It is best known as a regulator of seasonal and circadian rhythms, its levels being high during the night and low during the day. Interestingly, insulin levels are also adapted to day/night changes through melatonin-dependent synchronization. This regulation may be explained by the inhibiting action of melatonin on insulin release, which is transmitted through both the pertussis-toxin-sensitive membrane receptors MT1 and MT2 and the second messengers 3',5' -cyclic adenosine monophosphate, 3',5'-cyclic guanosine monophosphate and inositol 1,4,5-trisphosphate. Melatonin may influence diabetes and associated metabolic disturbances not only by regulating insulin secretion, but also by providing protection against reactive oxygen species, since pancreatic β-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity. On the other hand, in several genetic association studies, single nucleotide polymorphysms of the human MT2 receptor have been described as being causally linked to an elevated risk of developing type 2 diabetes. This suggests that these individuals maybe more sensitive to the actions of melatonin, thereby leading to impaired insulin secretion. Therefore, block- ing the melatonin-induced inhibition of insulin secretion may be a novel therapeutic avenue for type 2 diabetes.展开更多
Melatonin is a hormone with endocrine, paracrine andautocrine actions. It is involved in the regulation of multiple functions, including the control of the gastroin-testinal (GI) system under physiological and pathoph...Melatonin is a hormone with endocrine, paracrine andautocrine actions. It is involved in the regulation of multiple functions, including the control of the gastroin-testinal (GI) system under physiological and pathophys-iological conditions. Since the gut contains at least 400times more melatonin than the pineal gland, a reviewof the functional importance of melatonin in the gutseems useful, especially in the context of recent clinicaltrials. Melatonin exerts its physiological effects throughspecific membrane receptors, named melatonin-1 re-ceptor (MT1), MT2 and MT3. These receptors can befound in the gut and their involvement in the regulationof GI motility, inflammation and pain has been reportedin numerous basic and clinical studies. Stable levels ofmelatonin in the lower gut that are unchanged follow-ing a pinealectomy suggest local synthesis and, further more, implicate physiological importance of endogenous melatonin in the GI tract. Presently, only a small number of human studies report possible beneficial and also possible harmful effects of melatonin in case reports and clinical trials. These human studies include patients with lower GI diseases, especially patients with irritable bowel syndrome, inflammatory bowel disease and colorectal cancer. In this review, we summarize the presently available information on melatonin effects in the lower gut and discuss available in vitro and in vivo data. We furthermore aim to evaluate whether melatonin may be useful in future treatment of symptoms or diseases involving the lower gut.展开更多
Diabetes mellitus is a chronic, life-threatening metabolic disorder that occurs worldwide. Despite an increase in the knowledge of the risk factors that are associated with diabetes mellitus, its worldwide prevalence ...Diabetes mellitus is a chronic, life-threatening metabolic disorder that occurs worldwide. Despite an increase in the knowledge of the risk factors that are associated with diabetes mellitus, its worldwide prevalence has continued to rise; thus, necessitating more research into its aetiology. Recent researches are beginning to link a dysregulation of the circadian rhythm to impairment of intermediary metabolism; with evidences that circadian rhythm dysfunction might play an important role in the aetiology, course or prognosis of some cases of diabetes mellitus. These evidences thereby suggest possible relationships between the circadian rhythm regulator melatonin, and diabetes mellitus. In this review, we discuss the roles of the circadian rhythm in the regulation of the metabolism of carbohydrates and other macronutrients; with emphasis on the importance of melatonin and the impacts of its deficiency on car-bohydrate homeostasis. Also, the possibility of using melatonin and its analogs for the "prophylaxis" or management of diabetes mellitus is also considered.展开更多
The diurnal variations of 2-[125I]iodomelatonin binding densities and affinities in the bursa of pinealectomized and shamoperated chickens were studied.The pineals of 2-day-old chickens were removed,and 7 chickens fro...The diurnal variations of 2-[125I]iodomelatonin binding densities and affinities in the bursa of pinealectomized and shamoperated chickens were studied.The pineals of 2-day-old chickens were removed,and 7 chickens from each group were decapitated at 6 wee展开更多
Objective To analyse the potential involvement of the opioid receptor gene expression in the mechanisms of the analgesic action of melatonin.Methods A trauma-pain model was established in Wistar rats by combining righ...Objective To analyse the potential involvement of the opioid receptor gene expression in the mechanisms of the analgesic action of melatonin.Methods A trauma-pain model was established in Wistar rats by combining right-hind limb amputation with 50 ℃ tail-flick test.Antinociception was determined by tail-flick latency to hot waster at 50 ℃.RT-PCR was used to observe the the expression of the M1OR and KOR gene.Results Melatonin produced the antinociceptive effect in dose-dependent manner after i.p or i.c.v.administration.Injected i.c.v.to rats,naloxone(10 μg)obviously antagonized the antinociceptive effect induced by i.p.melatonin.The expression of the M1OR gene in the rat hypothalamus and the KOR gene in the hippocampus was both significantly reduced at day 3 after injury,which was parallel to the reduction of the rat pain thresholds.However,the expression of the M1OR gene in the hippocampus and the KOR gene in the hypothalamus was not changed.Treatment of trauma-pain rats with melatonin(30-120 mg·kg-1)i.p.administrated induced the up-regulation of M1OR mRNA in the hypothalamus and the KOR mRNA in the hippocampus in a concentration-dependent manner.Conclusions The present observations suggest that Melatonin-induced antinociceptive effect may partially contribute to the up-regulation of M1OR mRNA level in the hypothalamus and the KOR mRNA level in the hippocampus.展开更多
基金This work was supported by the Program of Yunling Scholar,the Youth Innovation Promotion Association,CAS(2013252)the Applied Basic Research Programs of Yunnan Province(2017FB137).
文摘Gastrodia elata is a famous traditional Chinese herb with medicinal and edible application.In this study,three new polybenzyls,gastropolybenzylols G-I(1-3)were isolated from the EtOAc extract of G.elata.Their structures were identified by extensive spectroscopic analyses involving HRESIMS,UV,IR,1D and 2D NMR.Compound 1 showed agonistic effects on MT1 and MT_(2) receptors with agonistic rates of 55.91±4.84%and 165.13±5.65%at the concentration of 0.5 mM,respectively,and an EC_(50) value of 76.24μM on MT_(2) receptor.
基金Supported by (in part) Grants from the European Society of Anesthesiology and the HOMFOR Homburger Forschungsfrderung
文摘Melatonin,the hormone of darkness and messenger of the photoperiod,is also well known to exhibit strong direct and indirect antioxidant properties. Melatonin has previously been demonstrated to be a powerful organ protective substance in numerous models of injury; these beneficial effects have been attributed to the hormone's intense radical scavenging capacity. The present report reviews the hepatoprotective potential of the pineal hormone in various models of oxidative stress in vivo,and summarizes the extensive literature showing that melatonin may be a suitable experimental substance to reduce liver damage after sepsis,hemorrhagic shock,ischemia/reperfusion,and in numerous models of toxic liver injury. Melatonin's influence on hepatic antioxidant enzymes and other potentially relevant pathways,such as nitric oxide signaling,hepatic cytokine and heat shock protein expression,are evaluated. Based on recent literature demonstrating the functional relevance of melatonin receptor activation for hepatic organ protection,this article finally suggests that melatonin receptors could mediate the hepatoprotective actions of melatonin therapy.
基金This work was supported by the Health Commission of Hubei Province Scientific Research Project(No.WJ2021M129)the National Key Research and Development Program of China(No.2021YFC2701502)。
文摘Melatonin receptor 1B(MT2,encoded by the MTNR1B gene),a high-affinity receptor for melatonin,is associated with glucose homeostasis including glucose uptake and transport.The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus(GDM);however,the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood.This article aims to investigate the relationship between rs10830963 variants and GDM development,as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts.TaqMan-MGB(minor groove binder)probe quantitative realtime polymerase chain reaction(qPCR)assays were used for rs10930963 genotyping.MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence,western blot,and qPCR.The relationship between MT2 and glucose transporters(GLUTs)or peroxisome proliferator-activated receptorγ(PPARγ)was established by western blot,and glucose consumption of trophoblasts was measured by a glucose assay kit.The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women(P<0.05).The fasting,1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers(P<0.05).Besides,the protein and messenger RNA(mRNA)expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women(P<0.05).Melatonin could stimulate glucose uptake and GLUT4 and PPARγprotein expression in trophoblasts,which could be attenuated by MT2 receptor knockdown.In conclusion,the rs10830963 variant was associated with an increased risk of GDM.The MT2 receptor is essential for melatonin to raise glucose uptake and transport,which may be mediated by PPARγ.
基金Supported by the National Natural Science Foundation of China(No.81072744)
文摘Objective： To explore the effects of Kaixin Powder （开心散, KXP） on melatonin receptor （MR） expression and 1261-Mel binding affinity in a depression rat model. Methods： Seventy-two male Wistar rats were divided into six groups： a blank control group, model group, ramelteon group, KXP high-dosage group （HKXP）, medium-dosage group （MKXP） and low-dosage group （LKXP）. To establish the depression model, all groups except the blank control group were singly housed and exposed to chronic unpredictable mild stress. Weight gain, sucrose consumption and the open-field test were used to evaluate induction of depression. KXP at 260, 130 and 65 mg/（kg·d） was also respectively administered to the rats in the HKXP, MKXP and LKXP groups for 21 days. Ramelteon [0.83 mg/（kg·d）] was given to the positive drug control group. An equivalent volume of physiological saline was given to the blank and model groups. The liquid chip method was used to measure the concentration of plasma melatonin （MT）. Mell a （MT1） and Mellb （MT2） expression levels were determined by Western blotting. In addition, a radioactive ligand-binding assay was used to analyze the specific binding properties and dynamic characteristics between MR and 125I-Mel. Results： The results of weight gain, sucrose consumption and the open-field test showed that our model successfully produced depressive symptoms and depressive-like behavior. The concentration of plasma MT in the model group decreased significantly at night but increased in the MKXP group （P〈0.05）. The HKXP group showed significantly increased expression of MT1 （P〈0.05）; however, the expression of MT2 in all groups exhibited no significant differences （P〉0.05）. The maximum binding capacity （Bmax） for specific binding between MR and 125I-Mel in the MKXP group was significantly higher than that in the model group （P〈0.05）, but no significant differences were found in the equilibrium dissociation constant （Kd） of each group （P〉0.05）. Conclusions： KXP may have a similar effect as ramelteon. KXP improved depressive-like behavior by increasing the concentration of plasma MT and MT1 expression, thereby increasing three Bmax of MR tO achieve the desired antidepressant effect.
基金The National Natural Science Foundation of China under contract No.31802319the Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)under contract No.GML2019ZD0402+7 种基金the National Key Research and Development Program under contract No.2018YFD0901204the Major Agricultural Application Technology Innovation Project of Shandong Province under contract No.SD2019YY011the Natural Science Foundation of Shandong Province under contract No.ZR2018BC053the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao)under contract No.2018SDKJ0502-2the Fund of China Agriculture Research System under contract No.CARS-47the Major Science and Technology for Scientific and Technological Innovation Projects(Shandong)under contract No.2019JZZY020710the Science and Technology Service Network Initiative Project under contract Nos KFZD-SW-106,ZSSD-019,2017T3017 and 2019T3022the Advanced Talents Foundation of Qingdao Agricultural University under contract No.6631119055。
文摘In most fish,reproduction is seasonal or periodic under the suitable conditions.In turbot(Scophthalmus maximus)farms,one of the most economically important marine flatfish species,changes in daylength could cause changes in the spawning time.In this study,to characterize the regulation of reproductive physiology following light signals,three melatonin receptors(Mtnr)investigated in turbot were named sm Mtnr1,sm Mtnr2,and sm Mtnr1 c.Distinct expression profiles demonstrated that Mtnr m RNAs were concentrated in the brain(as detected in the hypothalamus(Hy)and mesencephalon(Me)),gonad and eye.The most abundant Mtnr1 and Mtnr2 m RNA expression levels were detected in the central nervous system at the beginning of the breeding season,suggesting that Mtnr1 and Mtnr2 may play vital roles in the regulation of turbot gonadal development.In addition,the melatonin profiles gradually increased and reached to the highest level at the spawning stage,indicating that melatonin is a potent hormone in the regulation of fish oocyte growth and maturation.The results of this study suggested that melatonin is the primary factor that transduces the light signal and regulates the physiological functions of turbot seasonal reproduction.Moreover,the results of this study may establish a foundation for further research seeking to identify fish melatonin receptors involved in the gonadal development and gamete maturation.
文摘Melatonin (MEL) has been reported to have acute enhancing effects on some aspects of cognition. Recently, we revealed that N1-acetyl-5-methoxyquinuramine (AMK), a brain metabolite of MEL, is much more potent than MEL in converting short-term memory (STM) to long-term memory (LTM) with a single administration immediately after the acquisition trial of the novel object recognition (NOR) task. These data suggest that the memory-enhancing effects of MEL may be mediated by mechanisms independent of the activation of MEL MT1 and MT2 receptors. In the present study, we examined the contribution of MT1 and MT2 receptor-mediated and non-receptor-mediated mechanisms to the acute memory-enhancing effects of MEL using NOR task. Mice were administered with either MEL, AMK, or a highly selective MT1/MT2 receptor agonist ramelteon (RAM) immediately after the acquisition trial and the effects of varying doses of these drugs on both STM and LTM performance were compared. We found that both AMK and RAM were more potent than MEL in both facilitating STM and promoting LTM formation. We also found that pretreatment with luzindole, a MT1/MT2 receptor antagonist, markedly suppressed only the effects of RAM. These results suggest that acutely administered MEL enhances NOR memory through both MT1 and MT2 receptor-mediated and non-receptor-mediated mechanisms.
基金supported by the National Natural Science Foundation of China(81573322)the Yunnan Wanren Project(YNWR-QNBJ-2018-061)+1 种基金the Youth Innovation Promotion Association,CAS(2013252)the Program of Yunling Scholarship,the Yunnan Science Fund for Excellent Young Scholars(2019FI017)。
文摘Uncariae Ramulus Cum Uncis(Gou-Teng),the dried hook-bearing stems of several Uncaria plants(Rubiaceae),is a wellknown herbal medicine in China.The clinical application of Gou-Teng is bewildered for the morphological and chemical similarity between diferent species.In order to discern their chemical and biological diference,an ultra-fast liquid chromatography equipped with ion trap time-of-fight mass spectrometry(UFLC-IT/TOF-MS)combining with melatonin(MT1 and MT2)and 5-hydroxytryptamine(5-HT1A and 5-HT2C)receptors agonistic assay in vitro was conducted on seven Uncaria species.As a result,57 compounds including 35 indole alkaloids,ten favonoids,fve triterpenoids,fve chlorogenic analogues,and two other compounds were characterized based on their MS/MS patterns and UV absorptions.Specifcally,cadambine-type and corynanthein-type alkaloids were exclusively present in U.rhynchophylla and U.scandens,whereas corynoxine-type alkaloids were commonly detected in all the seven Uncaria plants.Three Uncaria species,U.rhynchophylla,U.macrophylla,and U.yunnanensis showed obviously agnostic activity on four neurotransmitter receptors(MT1,MT2,5-HT1A,and 5-HT_(2C)).This frst-time UFLCMS-IT-TOF analyses integrated with biological assay on seven Uncaria plants will provide scientifc viewpoints for the clinical application of Gou-Teng.
基金supported by High Value-added Food Technology Development Program,Ministry of Agriculture,Food and Rural Affairs(MAFRAgrant number 113034-3)
文摘Melatonin plays a critical role in regulating photoperiodic signals and has recently been shown to decrease immunosenescence with age. In this study, we examined whether melatonin activates T lymphocytes as major adaptive immune cells in in vitro and in vivo models. Splenocytes, CD4＋, and naive CD4 T lymphocytes were isolated from the spleen of BALB/c mice and the cell population patterns and mRNA profiles associated with T cell activation （CD28 and p21） and the melatonin receptor （MT1A and MT1B） were assessed. The T cell activation- related proteins Ki67 and Bcl2 were also evaluated to confirm the relationship between gene and protein levels. Our data clearly revealed that CD28, p21, MT 1 A, and MT 1B mRNA were highly expressed in the presence of melatonin. Co-culture of CD4＋ T lymphocyte and peritoneal macrophage 7 days after melatonin administration to young and aged mice significantly increased APRIL mRNA, suggesting induction or maintenance of T lymphocyte responses. We also found that the intracellular amount of Ki67 and Bcl2 proteins were significantly upregulated in aged CD4＋ T lymphocytes, suggesting enhancing T cell proliferation and ling-term maintenance of memory T cells. Taken together, we conclude that melatonin supplementation may enhance immunity in aged individuals by upregulating immunosenescence indices in association with T lymphocytes and may be an attractive pharmacological candidate for aged and immunocompromised individuals.
基金Supported by Ministry of Education (AP2009-0753, to Dr. Javier Espino)
文摘Melatonin is a circulating hormone that is mainly re- leased from the pineal gland. It is best known as a regulator of seasonal and circadian rhythms, its levels being high during the night and low during the day. Interestingly, insulin levels are also adapted to day/night changes through melatonin-dependent synchronization. This regulation may be explained by the inhibiting action of melatonin on insulin release, which is transmitted through both the pertussis-toxin-sensitive membrane receptors MT1 and MT2 and the second messengers 3',5' -cyclic adenosine monophosphate, 3',5'-cyclic guanosine monophosphate and inositol 1,4,5-trisphosphate. Melatonin may influence diabetes and associated metabolic disturbances not only by regulating insulin secretion, but also by providing protection against reactive oxygen species, since pancreatic β-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity. On the other hand, in several genetic association studies, single nucleotide polymorphysms of the human MT2 receptor have been described as being causally linked to an elevated risk of developing type 2 diabetes. This suggests that these individuals maybe more sensitive to the actions of melatonin, thereby leading to impaired insulin secretion. Therefore, block- ing the melatonin-induced inhibition of insulin secretion may be a novel therapeutic avenue for type 2 diabetes.
文摘Melatonin is a hormone with endocrine, paracrine andautocrine actions. It is involved in the regulation of multiple functions, including the control of the gastroin-testinal (GI) system under physiological and pathophys-iological conditions. Since the gut contains at least 400times more melatonin than the pineal gland, a reviewof the functional importance of melatonin in the gutseems useful, especially in the context of recent clinicaltrials. Melatonin exerts its physiological effects throughspecific membrane receptors, named melatonin-1 re-ceptor (MT1), MT2 and MT3. These receptors can befound in the gut and their involvement in the regulationof GI motility, inflammation and pain has been reportedin numerous basic and clinical studies. Stable levels ofmelatonin in the lower gut that are unchanged follow-ing a pinealectomy suggest local synthesis and, further more, implicate physiological importance of endogenous melatonin in the GI tract. Presently, only a small number of human studies report possible beneficial and also possible harmful effects of melatonin in case reports and clinical trials. These human studies include patients with lower GI diseases, especially patients with irritable bowel syndrome, inflammatory bowel disease and colorectal cancer. In this review, we summarize the presently available information on melatonin effects in the lower gut and discuss available in vitro and in vivo data. We furthermore aim to evaluate whether melatonin may be useful in future treatment of symptoms or diseases involving the lower gut.
文摘Diabetes mellitus is a chronic, life-threatening metabolic disorder that occurs worldwide. Despite an increase in the knowledge of the risk factors that are associated with diabetes mellitus, its worldwide prevalence has continued to rise; thus, necessitating more research into its aetiology. Recent researches are beginning to link a dysregulation of the circadian rhythm to impairment of intermediary metabolism; with evidences that circadian rhythm dysfunction might play an important role in the aetiology, course or prognosis of some cases of diabetes mellitus. These evidences thereby suggest possible relationships between the circadian rhythm regulator melatonin, and diabetes mellitus. In this review, we discuss the roles of the circadian rhythm in the regulation of the metabolism of carbohydrates and other macronutrients; with emphasis on the importance of melatonin and the impacts of its deficiency on car-bohydrate homeostasis. Also, the possibility of using melatonin and its analogs for the "prophylaxis" or management of diabetes mellitus is also considered.
文摘The diurnal variations of 2-[125I]iodomelatonin binding densities and affinities in the bursa of pinealectomized and shamoperated chickens were studied.The pineals of 2-day-old chickens were removed,and 7 chickens from each group were decapitated at 6 wee
文摘Objective To analyse the potential involvement of the opioid receptor gene expression in the mechanisms of the analgesic action of melatonin.Methods A trauma-pain model was established in Wistar rats by combining right-hind limb amputation with 50 ℃ tail-flick test.Antinociception was determined by tail-flick latency to hot waster at 50 ℃.RT-PCR was used to observe the the expression of the M1OR and KOR gene.Results Melatonin produced the antinociceptive effect in dose-dependent manner after i.p or i.c.v.administration.Injected i.c.v.to rats,naloxone(10 μg)obviously antagonized the antinociceptive effect induced by i.p.melatonin.The expression of the M1OR gene in the rat hypothalamus and the KOR gene in the hippocampus was both significantly reduced at day 3 after injury,which was parallel to the reduction of the rat pain thresholds.However,the expression of the M1OR gene in the hippocampus and the KOR gene in the hypothalamus was not changed.Treatment of trauma-pain rats with melatonin(30-120 mg·kg-1)i.p.administrated induced the up-regulation of M1OR mRNA in the hypothalamus and the KOR mRNA in the hippocampus in a concentration-dependent manner.Conclusions The present observations suggest that Melatonin-induced antinociceptive effect may partially contribute to the up-regulation of M1OR mRNA level in the hypothalamus and the KOR mRNA level in the hippocampus.
