Molecules

Research

Jump to: Review

16 pages, 15832 KiB

Open AccessArticle

The Improved Milk Quality and Enhanced Anti-Inflammatory Effect in Acetylserotonin-O-methyltransferase (ASMT) Overexpressed Goats: An Association with the Elevated Endogenous Melatonin Production

by Hao Wu, Xudai Cui, Shengyu Guan, Guangdong Li, Yujun Yao, Haixin Wu, Jinlong Zhang, Xiaosheng Zhang, Tuan Yu, Yunxiang Li, Zhengxing Lian, Lu Zhang and Guoshi Liu

Molecules 2022, 27(2), 572; https://doi.org/10.3390/molecules27020572 - 17 Jan 2022

Cited by 2 | Viewed by 2950

Abstract

Background: Transgenic animal production is an important means of livestock breeding and can be used to model pharmaceutical applications. Methods: In this study, to explore the biological activity of endogenously produced melatonin, Acetylserotonin-O-methyltransferase (ASMT)-overexpressed melatonin-enriched dairy goats were successfully generated through [...] Read more.

Background: Transgenic animal production is an important means of livestock breeding and can be used to model pharmaceutical applications. Methods: In this study, to explore the biological activity of endogenously produced melatonin, Acetylserotonin-O-methyltransferase (ASMT)-overexpressed melatonin-enriched dairy goats were successfully generated through the use of pBC1-ASMT expression vector construction and prokaryotic embryo microinjection. Results: These transgenic goats have the same normal phenotype as the wild-type goats (WT). However, the melatonin levels in their blood and milk were significantly increased (p < 0.05). In addition, the quality of their milk was also improved, showing elevated protein content and a reduced somatic cell number compared to the WT goats. No significant changes were detected in the intestinal microbiota patterns between groups. When the animals were challenged by the intravenous injection of E. coli, the ASMT-overexpressed goats had a lower level of pro-inflammatory cytokines and higher anti-inflammatory cytokines compared to the WT goats. Metabolic analysis uncovered a unique arachidonic acid metabolism pattern in transgenic goats. Conclusions: The increased melatonin production due to ASMT overexpression in the transgenic goats may have contributed to their improved milk quality and enhanced the anti-inflammatory ability compared to the WT goats. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Graphical abstract

23 pages, 11571 KiB

Open AccessArticle

Embryonic Development of Avian Pineal Secretory Activity—A Lesson from the Goose Pineal Organs in Superfusion Culture

by Maria Hanuszewska-Dominiak, Kamila Martyniuk and Bogdan Lewczuk

Molecules 2021, 26(21), 6329; https://doi.org/10.3390/molecules26216329 - 20 Oct 2021

Cited by 2 | Viewed by 1876

Abstract

The embryonic ontogeny of pineal secretory activity in birds has been investigated almost exclusively in chickens. This study aimed to characterize this process in domestic geese. The pineal organs of embryos aged 18–28 days were incubated in superfusion culture under different light conditions [...] Read more.

The embryonic ontogeny of pineal secretory activity in birds has been investigated almost exclusively in chickens. This study aimed to characterize this process in domestic geese. The pineal organs of embryos aged 18–28 days were incubated in superfusion culture under different light conditions for 4–5 days and treated with norepinephrine (NE). Melatonin (MLT) was measured by radioimmunoassay and other indoles by HPLC with fluorescence detection. Additionally, pineal organs were collected from embryos at 14–28 days of age and used to measure catecholamines by HPLC with electrochemical detection. MLT secretion increased with embryo age, most intensively between the 22nd and 24th days of life. The daily changes in MLT secretion under the 12 L:12D cycle occurred on the first day of culture, starting from an embryonic age of 24 days. MLT secretion was controlled by the light-dark cycle in all age groups studied. However, exposure to light during the scotophase did not alter the secretion of MLT. The endogenous oscillator expressed its activity in regulating MLT secretion in the pineal organs of embryos aged 24 days and older but could not generate a rhythm after one cycle. The rhythm of 5-hydroxytryptophan release during the first day of culture was found in the pineal organs of all embryos, while the rhythmic release of N-acetylserotonin and 5-methoxyindole acetic acid started at the age of 24 days. The proportion of released indoles changed with embryo age. NE caused a decrease in MLT secretion and provoked an increase in serotonin release. Incubation of the pineal organs induced the development of MLT secretory machinery and its diurnal rhythmicity. The pineal content of catecholamines increased prominently at the end of embryonic development. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Figure 1

13 pages, 4136 KiB

Open AccessArticle

Effects of Duodenal 5-Hydroxytryptophan Perfusion on Melatonin Synthesis in GI Tract of Sheep

by Jun Pan, Fengming Li, Caidie Wang, Xiaobin Li, Shiqi Zhang, Wenjie Zhang, Guodong Zhao, Chen Ma, Guoshi Liu and Kailun Yang

Molecules 2021, 26(17), 5275; https://doi.org/10.3390/molecules26175275 - 31 Aug 2021

Cited by 8 | Viewed by 2520

Abstract

The purpose of this study is to investigate the potential effects of 5-hydroxytryptophan (5-HTP) duodenal perfusion on melatonin (MT) synthesis in the gastrointestinal (GI) tract of sheep. 5-hydroxytryptophan is a precursor in the melatonin synthetic pathway. The results showed that this method significantly [...] Read more.

The purpose of this study is to investigate the potential effects of 5-hydroxytryptophan (5-HTP) duodenal perfusion on melatonin (MT) synthesis in the gastrointestinal (GI) tract of sheep. 5-hydroxytryptophan is a precursor in the melatonin synthetic pathway. The results showed that this method significantly increased melatonin production in the mucosa of all segments in GI tract including duodenum, jejunum, ileum, cecum and colon. The highest melatonin level was identified in the colon and this indicates that the microbiota located in the colon may also participate in the melatonin production. In addition, portion of the melatonin generated by the GI tract can pass the liver metabolism and enters the circulation via portal vein. The current study provides further evidence to support that GI tract is the major site for melatonin synthesis and the GI melatonin also contributes to the circulatory melatonin level since plasma melatonin concentrations in 5-HTP treated groups were significantly higher than those in the control group. In conclusion, the results show that 10–50 mg of 5-HTP flowing into the duodenum within 6 h effectively improve the production of melatonin in the GI tract and melatonin concentration in sheep blood circulation during the day. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Figure 1

16 pages, 1777 KiB

Open AccessArticle

Lipoic Acid Combined with Melatonin Mitigates Oxidative Stress and Promotes Root Formation and Growth in Salt-Stressed Canola Seedlings (Brassica napus L.)

by Hafiz Muhammad Rashad Javeed, Mazhar Ali, Milan Skalicky, Fahim Nawaz, Rafi Qamar, Atique ur Rehman, Maooz Faheem, Muhammad Mubeen, Muhammad Mohsin Iqbal, Muhammad Habib ur Rahman, Pavla Vachova, Marian Brestic, Alaa Baazeem and Ayman EL Sabagh

Molecules 2021, 26(11), 3147; https://doi.org/10.3390/molecules26113147 - 25 May 2021

Cited by 48 | Viewed by 3805

Abstract

Lipoic acid (LA) and melatonin (MT) are pleiotropic molecules participating in plant stress resistance by modulating cellular biochemical changes, ion homeostasis, and antioxidant enzyme activities. However, the combined role of these two molecules in counteracting the detrimental impacts of salinity stress is still [...] Read more.

Lipoic acid (LA) and melatonin (MT) are pleiotropic molecules participating in plant stress resistance by modulating cellular biochemical changes, ion homeostasis, and antioxidant enzyme activities. However, the combined role of these two molecules in counteracting the detrimental impacts of salinity stress is still unknown. In the present study, we determined the effects of exogenous LA (0.5 µM), MT (1 µM) and their combination (LA + MT) on growth performance and biomass accumulation, photosynthetic pigments, enzymatic and non-enzymatic antioxidant activities, and ions homeostatic in canola (Brassica napus L.) seedlings under salinity stress (0, 100 mM) for 40 days. The results indicate that exogenous application of LA + MT improved the phenotypic growth (by 25 to 45%), root thickness (by 68%), number of later lateral roots (by 52%), root viability (by 44%), and root length (by 50%) under salinity stress. Moreover, total soluble protein, chlorophyll pigments, the concentration of superoxide dismutase (SOD), catalase peroxidase (CAT), and ascorbic peroxidase (ASA) increased with the presence of salt concentration into the growth media and then decreased with the addition of LA + MT to saline solution. Leaf protein contents and the degradation of photosynthetic pigments were lower when LA + MT treatments were added into NaCl media. The proline and phenol contents decreased in the exogenous application of LA + MT treatments more than individual LA or MT treatments under the salinity stress. The incorporation of LA or MT or a combination of LA + MT to saline solution decreased salinity-induced malondialdehyde and electrolyte leakage. In conclusion, the alteration of metabolic pathways, redox modulation, and ions homeostasis in plant tissues by the combined LA and MT application are helpful towards the adaptation of Brassica napus L. seedlings in a saline environment. The results of this study provide, for the first time, conclusive evidence about the protective role of exogenous LA + MT in canola seedlings under salinity stress. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Figure 1

12 pages, 1708 KiB

Open AccessArticle

Melatonin Administration Accelerates Puberty Onset in Mice by Promoting FSH Synthesis

by Chan Yang, Zaohong Ran, Guoshi Liu, Rong Hou, Changjiu He, Qinghua Liu, Yingjun Chen, Yuliang Liu, Xiaodong Wang, Chuqi Ling, Fang Fang and Xiang Li

Molecules 2021, 26(5), 1474; https://doi.org/10.3390/molecules26051474 - 9 Mar 2021

Cited by 9 | Viewed by 4098

Abstract

Although melatonin has been extensively studied in animal reproduction, the mechanism of melatonin in puberty remains elusive. This study was designed to explore the effect of intraperitoneal administration of melatonin on puberty onset in female mice. The injection of melatonin into postnatal days [...] Read more.

Although melatonin has been extensively studied in animal reproduction, the mechanism of melatonin in puberty remains elusive. This study was designed to explore the effect of intraperitoneal administration of melatonin on puberty onset in female mice. The injection of melatonin into postnatal days 10 mice at a dose of 15 mg/kg accelerated the puberty onset in mice. Mechanistically, there was no difference in physical growth and serum Leptin levels after melatonin administration. Meanwhile, the serum levels of reproductive hormones involved in hypothalamic-pituitary-ovarian axis, such as FSH and estrogen level in serum were increased. The mRNA levels of GnRH and GnRHr were not affected by melatonin, while the expressions of FSHβ in pituitary and Cyp19a1 in ovary were significantly up-regulated. In addition, melatonin still promoted FSH synthesis after ovariectomy. Furthermore, the enhanced activity of ERK1/2 signaling verified that the expression of FSHβ increased in pituitary. We confirmed that melatonin promoted the FSH synthesis in pituitary, thereby increased serum estrogen levels and ultimately accelerated puberty onset. However, these effects of melatonin may be pharmacological due to the high dose. This study would help us to understand the functions of melatonin in pubertal regulation comprehensively. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Figure 1

13 pages, 13504 KiB

Open AccessArticle

Induction of Low Temperature Tolerance in Wheat by Pre-Soaking and Parental Treatment with Melatonin

by Hua Zhang, Lei Liu, Zongshuai Wang, Guozhong Feng, Qiang Gao and Xiangnan Li

Molecules 2021, 26(4), 1192; https://doi.org/10.3390/molecules26041192 - 23 Feb 2021

Cited by 30 | Viewed by 3015

Abstract

Low temperatures seriously depress germination and seedling establishment in wheat and it is of great significance to explore approaches to improve wheat tolerance to low temperatures. In this study, the effects of seed pre-soaking and parental treatment with melatonin on seed germination and [...] Read more.

Low temperatures seriously depress germination and seedling establishment in wheat and it is of great significance to explore approaches to improve wheat tolerance to low temperatures. In this study, the effects of seed pre-soaking and parental treatment with melatonin on seed germination and low temperature tolerance during the early growing stage in wheat were studied. The results showed that pre-soaking with melatonin increased the germination rate, improved antioxidant capacity and accelerated starch degradation under low temperature, which alleviated low temperature-induced damage to the chloroplasts in coleoptiles of wheat seedlings. Parental melatonin treatment during grain filling stage significantly decreased the grain weight. Seeds from parental melatonin-treated plants showed higher germination rates and higher antioxidant enzyme activity than the control seeds under low temperature. In addition, parental treatment with melatonin modulated the activities of carbohydrate metabolism enzymes, which contributes to enhanced low temperature tolerance in wheat offspring. It was suggested that both seed pre-soaking and parental treatment with melatonin could be the effective approaches for low temperature tolerance induction in wheat. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Figure 1

18 pages, 2857 KiB

Open AccessArticle

RORα Regulates Odontoblastic Differentiation and Mediates the Pro-Odontogenic Effect of Melatonin on Dental Papilla Cells

by Jun Kang, Haoling Chen, Fuping Zhang, Tong Yan, Wenguo Fan, Liulin Jiang, Hongwen He and Fang Huang

Molecules 2021, 26(4), 1098; https://doi.org/10.3390/molecules26041098 - 19 Feb 2021

Cited by 10 | Viewed by 2737

Abstract

Dental papilla cells (DPCs), precursors of odontoblasts, are considered promising seed cells for tissue engineering. Emerging evidence suggests that melatonin promotes odontoblastic differentiation of DPCs and affects tooth development, although the precise mechanisms remain unknown. Retinoid acid receptor-related orphan receptor α (RORα) is [...] Read more.

Dental papilla cells (DPCs), precursors of odontoblasts, are considered promising seed cells for tissue engineering. Emerging evidence suggests that melatonin promotes odontoblastic differentiation of DPCs and affects tooth development, although the precise mechanisms remain unknown. Retinoid acid receptor-related orphan receptor α (RORα) is a nuclear receptor for melatonin that plays a critical role in cell differentiation and embryonic development. This study aimed to explore the role of RORα in odontoblastic differentiation and determine whether melatonin exerts its pro-odontogenic effect via RORα. Herein, we observed that RORα was expressed in DPCs and was significantly increased during odontoblastic differentiation in vitro and in vivo. The overexpression of RORα upregulated the expression of odontogenic markers, alkaline phosphatase (ALP) activity and mineralized nodules formation (p < 0.05). In contrast, odontoblastic differentiation of DPCs was suppressed by RORα knockdown. Moreover, we found that melatonin elevated the expression of odontogenic markers, which was accompanied by the upregulation of RORα (p < 0.001). Utilising small interfering RNA, we further demonstrated that RORα inhibition attenuated melatonin-induced odontogenic gene expression, ALP activity and matrix mineralisation (p < 0.01). Collectively, these results provide the first evidence that RORα can promote odontoblastic differentiation of DPCs and mediate the pro-odontogenic effect of melatonin. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Figure 1

10 pages, 2124 KiB

Open AccessArticle

Suppression of Rice Cryptochrome 1b Decreases Both Melatonin and Expression of Brassinosteroid Biosynthetic Genes Resulting in Salt Tolerance

by Ok Jin Hwang and Kyoungwhan Back

Molecules 2021, 26(4), 1075; https://doi.org/10.3390/molecules26041075 - 18 Feb 2021

Cited by 9 | Viewed by 2650

Abstract

We investigated the relationship between the blue-light photoreceptor cryptochrome (CRY) and melatonin biosynthesis by generating RNA interference (RNAi) transgenic rice plants that suppress the cryptochrome 1b gene (CRY1b). The resulting CRY1b RNAi rice lines expressed less CRY1b mRNA, but not CRY1a [...] Read more.

We investigated the relationship between the blue-light photoreceptor cryptochrome (CRY) and melatonin biosynthesis by generating RNA interference (RNAi) transgenic rice plants that suppress the cryptochrome 1b gene (CRY1b). The resulting CRY1b RNAi rice lines expressed less CRY1b mRNA, but not CRY1a or CRY2 mRNA, suggesting that the suppression is specific to CRY1b. The growth of CRY1b RNAi rice seedlings was enhanced under blue light compared to wild-type growth, providing phenotypic evidence for impaired CRY function. When these CRY1b RNAi rice plants were challenged with cadmium to induce melatonin, wild-type plants produced 100 ng/g fresh weight (FW) melatonin, whereas CRY1b RNAi lines produced 60 ng/g FW melatonin on average, indicating that melatonin biosynthesis requires the CRY photoreceptor. Due to possible feedback regulation, the expression of melatonin biosynthesis genes such as T5H, SNAT1, SNAT2, and COMT was elevated in the CRY1b RNAi lines compared to the wild-type plants. In addition, laminar angles decreased in the CRY1b RNAi lines via the suppression of brassinosteroid (BR) biosynthesis genes such as DWARF. The main cause of the BR decrease in the CRY1b RNAi lines seems to be the suppression of CRY rather than decreased melatonin because the melatonin decrease suppressed DWARF4 rather than DWARF. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Figure 1

11 pages, 545 KiB

Open AccessArticle

Effects of Melatonin on Dairy Herd Improvement (DHI) of Holstein Cow with High SCS

by Hao Wu, Songyang Yao, Tiankun Wang, Jun Wang, Kang Ren, Hai Yang, Wenkui Ma, Pengyun Ji, Yongqiang Lu, Hui Ma, Changwang He, Wenjuan Wei, Lu Zhang and Guoshi Liu

Molecules 2021, 26(4), 834; https://doi.org/10.3390/molecules26040834 - 5 Feb 2021

Cited by 13 | Viewed by 3182

Abstract

Mastitis is a common disease in cows breeding. The milk quality will be significantly reduced with increased milk somatic cells, which often occurs in cows with mastitis. In this study, the influence of seasonal changes, age and lactation stages in the Dairy Herd [...] Read more.

Mastitis is a common disease in cows breeding. The milk quality will be significantly reduced with increased milk somatic cells, which often occurs in cows with mastitis. In this study, the influence of seasonal changes, age and lactation stages in the Dairy Herd Improvement (DHI) of cows was investigated. Then, the Dairy Herd Improvement (DHI) of cows with high somatic cell score (SCS) after melatonin treatment was systemically investigated. The results showed that melatonin significantly suppressed the milk somatic cell score under all of the tested conditions. The melatonin treatment also improved the milk nutritional value by reducing its fat but increasing its lactose and protein contents. The application of melatonin significantly improved the DHI. The beneficial effects of melatonin on DHI are likely attributed to the antioxidant and anti-inflammatory activities of melatonin. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Graphical abstract

16 pages, 1621 KiB

Open AccessCommunication

Cyst Reduction by Melatonin in a Novel Drosophila Model of Polycystic Kidney Disease

by Cassandra Millet-Boureima, Roman Rozencwaig, Felix Polyak and Chiara Gamberi

Molecules 2020, 25(22), 5477; https://doi.org/10.3390/molecules25225477 - 23 Nov 2020

Cited by 9 | Viewed by 8467

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) causes progressive cystic degeneration of the renal tubules, the nephrons, eventually severely compromising kidney function. ADPKD is incurable, with half of the patients eventually needing renal replacement. Treatments for ADPKD patients are limited and new effective therapeutics [...] Read more.

Autosomal dominant polycystic kidney disease (ADPKD) causes progressive cystic degeneration of the renal tubules, the nephrons, eventually severely compromising kidney function. ADPKD is incurable, with half of the patients eventually needing renal replacement. Treatments for ADPKD patients are limited and new effective therapeutics are needed. Melatonin, a central metabolic regulator conserved across all life kingdoms, exhibits oncostatic and oncoprotective activity and no detected toxicity. Here, we used the Bicaudal C (BicC) Drosophila model of polycystic kidney disease to test the cyst-reducing potential of melatonin. Significant cyst reduction was found in the renal (Malpighian) tubules upon melatonin administration and suggest mechanistic sophistication. Similar to vertebrate PKD, the BicC fly PKD model responds to the antiproliferative drugs rapamycin and mimics of the second mitochondria-derived activator of caspases (Smac). Melatonin appears to be a new cyst-reducing molecule with attractive properties as a potential candidate for PKD treatment. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Graphical abstract

Review

Jump to: Research

14 pages, 553 KiB

Open AccessReview

The Reserve/Maximum Capacity of Melatonin’s Synthetic Function for the Potential Dimorphism of Melatonin Production and Its Biological Significance in Mammals

by Dun-Xian Tan and Rüdiger Hardeland

Molecules 2021, 26(23), 7302; https://doi.org/10.3390/molecules26237302 - 2 Dec 2021

Cited by 9 | Viewed by 2884

Abstract

In this article, we attempt to classify a potential dimorphism of melatonin production. Thus, a new concept of “reserve or maximum capacity of melatonin synthetic function” is introduced to explain the subtle dimorphism of melatonin production in mammals. Considering ASMT/ASMTL genes [...] Read more.

In this article, we attempt to classify a potential dimorphism of melatonin production. Thus, a new concept of “reserve or maximum capacity of melatonin synthetic function” is introduced to explain the subtle dimorphism of melatonin production in mammals. Considering ASMT/ASMTL genes in the pseudoautosomal region of sex chromosomes with high prevalence of mutation in males, as well as the sex bias of the mitochondria in which melatonin is synthesized, we hypothesize the existence of a dimorphism in melatonin production to favor females, which are assumed to possess a higher reserve capacity for melatonin synthesis than males. Under physiological conditions, this subtle dimorphism is masked by the fact that cells or tissues only need baseline melatonin production, which can be accomplished without exploiting the full potential of melatonin’s synthetic capacity. This capacity is believed to exceed the already remarkable nocturnal increase as observed within the circadian cycle. However, during aging or under stressful conditions, the reserve capacity of melatonin’s synthetic function is required to be activated to produce sufficiently high levels of melatonin for protective purposes. Females seem to possess a higher reserve/maximum capacity for producing more melatonin than males. Thus, this dimorphism of melatonin production becomes manifest and detectable under these conditions. The biological significance of the reserve/maximum capacity of melatonin’s synthetic function is to improve the recovery rate of organisms from injury, to increase resistance to pathogen infection, and even to enhance their chances of survival by maximizing melatonin production under stressful conditions. The higher reserve/maximum capacity of melatonin synthesis in females may also contribute to the dimorphism in longevity, favoring females in mammals. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Figure 1

12 pages, 1219 KiB

Open AccessReview

Role of Melatonin in Angiotensin and Aging

by Ahmet Ozer Sehirli, Serkan Sayıner, Ugochukwu Chukwunyere and Nedime Serakinci

Molecules 2021, 26(15), 4666; https://doi.org/10.3390/molecules26154666 - 31 Jul 2021

Cited by 6 | Viewed by 5158

Abstract

The cellular utilization of oxygen leads to the generation of free radicals in organisms. The accumulation of these free radicals contributes significantly to aging and several age-related diseases. Angiotensin II can contribute to DNA damage through oxidative stress by activating the NAD(P)H oxidase [...] Read more.

The cellular utilization of oxygen leads to the generation of free radicals in organisms. The accumulation of these free radicals contributes significantly to aging and several age-related diseases. Angiotensin II can contribute to DNA damage through oxidative stress by activating the NAD(P)H oxidase pathway, which in turn results in the production of reactive oxygen species. This radical oxygen-containing molecule has been linked to aging and several age-related disorders, including renal damage. Considering the role of angiotensin in aging, melatonin might relieve angiotensin-II-induced stress by enhancing the mitochondrial calcium uptake 1 pathway, which is crucial in preventing the mitochondrial calcium overload that may trigger increased production of reactive oxygen species and oxidative stress. This review highlights the role and importance of melatonin together with angiotensin in aging and age-related diseases. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Figure 1

28 pages, 2709 KiB

Open AccessEditor’s ChoiceReview

Melatonin, Its Metabolites and Their Interference with Reactive Nitrogen Compounds

by Rüdiger Hardeland

Molecules 2021, 26(13), 4105; https://doi.org/10.3390/molecules26134105 - 5 Jul 2021

Cited by 23 | Viewed by 5238

Abstract

Melatonin and several of its metabolites are interfering with reactive nitrogen. With the notion of prevailing melatonin formation in tissues that exceeds by far the quantities in blood, metabolites come into focus that are poorly found in the circulation. Apart from their antioxidant [...] Read more.

Melatonin and several of its metabolites are interfering with reactive nitrogen. With the notion of prevailing melatonin formation in tissues that exceeds by far the quantities in blood, metabolites come into focus that are poorly found in the circulation. Apart from their antioxidant actions, both melatonin and N¹-acetyl-5-methoxykynuramine (AMK) downregulate inducible and inhibit neuronal NO synthases, and additionally scavenge NO. However, the NO adduct of melatonin redonates NO, whereas AMK forms with NO a stable product. Many other melatonin metabolites formed in oxidative processes also contain nitrosylatable sites. Moreover, AMK readily scavenges products of the CO₂-adduct of peroxynitrite such as carbonate radicals and NO₂. Protein AMKylation seems to be involved in protective actions. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Figure 1

26 pages, 2851 KiB

Open AccessReview

Melatonin-Loaded Nanocarriers: New Horizons for Therapeutic Applications

by Luiz Gustavo de Almeida Chuffa, Fábio Rodrigues Ferreira Seiva, Adriana Alonso Novais, Vinícius Augusto Simão, Virna Margarita Martín Giménez, Walter Manucha, Debora Aparecida Pires de Campos Zuccari and Russel J. Reiter

Molecules 2021, 26(12), 3562; https://doi.org/10.3390/molecules26123562 - 10 Jun 2021

Cited by 31 | Viewed by 7806

Abstract

The use of nanosized particles has emerged to facilitate selective applications in medicine. Drug-delivery systems represent novel opportunities to provide stricter, focused, and fine-tuned therapy, enhancing the therapeutic efficacy of chemical agents at the molecular level while reducing their toxic effects. Melatonin ( [...] Read more.

The use of nanosized particles has emerged to facilitate selective applications in medicine. Drug-delivery systems represent novel opportunities to provide stricter, focused, and fine-tuned therapy, enhancing the therapeutic efficacy of chemical agents at the molecular level while reducing their toxic effects. Melatonin (N-acetyl-5-methoxytriptamine) is a small indoleamine secreted essentially by the pineal gland during darkness, but also produced by most cells in a non-circadian manner from which it is not released into the blood. Although the therapeutic promise of melatonin is indisputable, aspects regarding optimal dosage, biotransformation and metabolism, route and time of administration, and targeted therapy remain to be examined for proper treatment results. Recently, prolonged release of melatonin has shown greater efficacy and safety when combined with a nanostructured formulation. This review summarizes the role of melatonin incorporated into different nanocarriers (e.g., lipid-based vesicles, polymeric vesicles, non-ionic surfactant-based vesicles, charge carriers in graphene, electro spun nanofibers, silica-based carriers, metallic and non-metallic nanocomposites) as drug delivery system platforms or multilevel determinations in various in vivo and in vitro experimental conditions. Melatonin incorporated into nanosized materials exhibits superior effectiveness in multiple diseases and pathological processes than does free melatonin; thus, such information has functional significance for clinical intervention. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Figure 1

17 pages, 7421 KiB

Open AccessReview

ROR: Nuclear Receptor for Melatonin or Not?

by Haozhen Ma, Jun Kang, Wenguo Fan, Hongwen He and Fang Huang

Molecules 2021, 26(9), 2693; https://doi.org/10.3390/molecules26092693 - 4 May 2021

Cited by 47 | Viewed by 4294

Abstract

Whether the retinoic acid-related orphan receptor (ROR) is a nuclear receptor of melatonin remains controversial. ROR is inextricably linked to melatonin in terms of its expression, function, and mechanism of action. Additionally, studies have illustrated that melatonin functions analogous to ROR ligands, thereby [...] Read more.

Whether the retinoic acid-related orphan receptor (ROR) is a nuclear receptor of melatonin remains controversial. ROR is inextricably linked to melatonin in terms of its expression, function, and mechanism of action. Additionally, studies have illustrated that melatonin functions analogous to ROR ligands, thereby modulating the transcriptional activity of ROR. However, studies supporting these interactions have since been withdrawn. Furthermore, recent crystallographic evidence does not support the view that ROR is a nuclear receptor of melatonin. Some other studies have proposed that melatonin indirectly regulates ROR activity rather than directly binding to ROR. This review aims to delve into the complex relationship of the ROR receptor with melatonin in terms of its structure, expression, function, and mechanism. Thus, we provide the latest evidence and views on direct binding as well as indirect regulation of ROR by melatonin, dissecting both viewpoints in-depth to provide a more comprehensive perspective on this issue. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Figure 1

46 pages, 1599 KiB

Open AccessReview

Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

by Wamidh H. Talib, Ahmad Riyad Alsayed, Alaa Abuawad, Safa Daoud and Asma Ismail Mahmod

Molecules 2021, 26(9), 2506; https://doi.org/10.3390/molecules26092506 - 25 Apr 2021

Cited by 121 | Viewed by 15651

Abstract

Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation [...] Read more.

Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Figure 1

19 pages, 2367 KiB

Open AccessReview

Physiological and Molecular Responses to Acid Rain Stress in Plants and the Impact of Melatonin, Glutathione and Silicon in the Amendment of Plant Acid Rain Stress

by Biswojit Debnath, Ashim Sikdar, Shahidul Islam, Kamrul Hasan, Min Li and Dongliang Qiu

Molecules 2021, 26(4), 862; https://doi.org/10.3390/molecules26040862 - 6 Feb 2021

Cited by 31 | Viewed by 6345

Abstract

Air pollution has been a long-term problem, especially in urban areas, that eventually accelerates the formation of acid rain (AR), but recently it has emerged as a serious environmental issue worldwide owing to industrial and economic growth, and it is also considered a [...] Read more.

Air pollution has been a long-term problem, especially in urban areas, that eventually accelerates the formation of acid rain (AR), but recently it has emerged as a serious environmental issue worldwide owing to industrial and economic growth, and it is also considered a major abiotic stress to agriculture. Evidence showed that AR exerts harmful effects in plants, especially on growth, photosynthetic activities, antioxidant activities and molecular changes. Effectiveness of several bio-regulators has been tested so far to arbitrate various physiological, biochemical and molecular processes in plants under different diverse sorts of environmental stresses. In the current review, we showed that silicon (tetravalent metalloid and semi-conductor), glutathione (free thiol tripeptide) and melatonin (an indoleamine low molecular weight molecule) act as influential growth regulators, bio-stimulators and antioxidants, which improve plant growth potential, photosynthesis spontaneity, redox-balance and the antioxidant defense system through quenching of reactive oxygen species (ROS) directly and/or indirectly under AR stress conditions. However, earlier research findings, together with current progresses, would facilitate the future research advancements as well as the adoption of new approaches in attenuating the consequence of AR stress on crops, and might have prospective repercussions in escalating crop farming where AR is a restraining factor. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Figure 1

19 pages, 1170 KiB

Open AccessReview

Potential Role of Melatonin as an Adjuvant for Atherosclerotic Carotid Arterial Stenosis

by Rui Zhang, Leng Ni, Xiao Di, Baitao Ma, Shuai Niu, Zhihua Rong and Changwei Liu

Molecules 2021, 26(4), 811; https://doi.org/10.3390/molecules26040811 - 4 Feb 2021

Cited by 12 | Viewed by 3971

Abstract

Carotid artery stenosis (CAS) is an atherosclerotic disease characterized by a narrowing of the artery lumen and a high risk of ischemic stroke. Risk factors of atherosclerosis, including smoking, hypertension, hyperglycemia, hyperlipidemia, aging, and disrupted circadian rhythm, may potentiate atherosclerosis in the carotid [...] Read more.

Carotid artery stenosis (CAS) is an atherosclerotic disease characterized by a narrowing of the artery lumen and a high risk of ischemic stroke. Risk factors of atherosclerosis, including smoking, hypertension, hyperglycemia, hyperlipidemia, aging, and disrupted circadian rhythm, may potentiate atherosclerosis in the carotid artery and further reduce the arterial lumen. Ischemic stroke due to severe CAS and cerebral ischemic/reperfusion (I/R) injury after the revascularization of CAS also adversely affect clinical outcomes. Melatonin is a pluripotent agent with potent anti-inflammatory, anti-oxidative, and neuroprotective properties. Although there is a shortage of direct clinical evidence demonstrating the benefits of melatonin in CAS patients, previous studies have shown that melatonin may be beneficial for patients with CAS in terms of reducing endothelial damage, stabilizing arterial plaque, mitigating the harm from CAS-related ischemic stroke and cerebral I/R injury, and alleviating the adverse effects of the related risk factors. Additional pre-clinical and clinical are required to confirm this speculation. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Figure 1

20 pages, 1498 KiB

Open AccessReview

Role of Melatonin in Plant Tolerance to Soil Stressors: Salinity, pH and Heavy Metals

by Mohamed Moustafa-Farag, Amr Elkelish, Mohamed Dafea, Mumtaz Khan, Marino B. Arnao, Magdi T. Abdelhamid, Aziz Abu El-Ezz, Abdlwareth Almoneafy, Ahmed Mahmoud, Mahrous Awad, Linfeng Li, Yanhong Wang, Mirza Hasanuzzaman and Shaoying Ai

Molecules 2020, 25(22), 5359; https://doi.org/10.3390/molecules25225359 - 17 Nov 2020

Cited by 101 | Viewed by 6077

Abstract

Melatonin (MT) is a pleiotropic molecule with diverse and numerous actions both in plants and animals. In plants, MT acts as an excellent promotor of tolerance against abiotic stress situations such as drought, cold, heat, salinity, and chemical pollutants. In all these situations, [...] Read more.

Melatonin (MT) is a pleiotropic molecule with diverse and numerous actions both in plants and animals. In plants, MT acts as an excellent promotor of tolerance against abiotic stress situations such as drought, cold, heat, salinity, and chemical pollutants. In all these situations, MT has a stimulating effect on plants, fomenting many changes in biochemical processes and stress-related gene expression. Melatonin plays vital roles as an antioxidant and can work as a free radical scavenger to protect plants from oxidative stress by stabilization cell redox status; however, MT can alleviate the toxic oxygen and nitrogen species. Beyond this, MT stimulates the antioxidant enzymes and augments antioxidants, as well as activates the ascorbate–glutathione (AsA–GSH) cycle to scavenge excess reactive oxygen species (ROS). In this review, we examine the recent data on the capacity of MT to alleviate the effects of common abiotic soil stressors, such as salinity, alkalinity, acidity, and the presence of heavy metals, reinforcing the general metabolism of plants and counteracting harmful agents. An exhaustive analysis of the latest advances in this regard is presented, and possible future applications of MT are discussed. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms II

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Related Special Issue

Published Papers (19 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI