Search Results (17)

Indoles are bioactive components found in wine products and are associated with yeast activity. Cava, a Spanish sparkling wine, is characterized by aging in contact with lees, making it a potential matrix for indoles. Therefore, the aim of this study was to determine the indole content in Cava produced at an industrial scale. Nine indoles were analysed by Ultra High-Performance Liquid Chromatography—Tandem Mass Spectrometry in Cava samples with different ageing times (n = 74). Significant amounts of tryptophan (2.3–1680.4 μg/L), tryptophan ethyl ester (0.1–5.2 μg/L), 5-methoxytryptophol (0.3–29.2 µg/L) and n-acetyl serotonin (0.3–2.3 μg/L) were determined. Tryptophan and tryptophan ethyl ester were positively correlated and decreased with ageing time. In fact, a concentration of less than 0.56 μg of the latter indole can become a marker of the most aged Cavas. The ageing time in contact with lees seems to play a key role affecting the indole content, since base wines show high amount of tryptophan and tryptophan ethyl ester while aged sparkling wines have values around the lower 95% confidence limit. Notably, the identification of tryptophan ethyl ester as a potential marker for aging in Cava suggests a new avenue for further research and quality assessment in its production. Full article

Background: Anxiety refers to the pathological persistence and intensification of emotional responses to danger, affecting health from psychological and physical aspects. Serotonin is an important neurotransmitter involved in the onset of anxiety. Methods and Results: To explore the biological changes in the formation of anxiety in crustaceans under the regulation of serotonin, we applied the open field-like test method for assessing anxiety states of larval Portunus trituberculatus, a highly aggressive crustacean species with a more simple neural structure compared with rodents and mammals. Compared with the control group, serotonin treatment resulted in a significant decrease in the time spent by the larvae in the central zone, suggesting anxiety-like behavior. Clonazepam treatment reversed this result and provided further evidence that the behavior of larval P. trituberculatus displayed anxiety. Moreover, a non-targeted metabolomic analysis found a significant alteration in the metabolites involved in tryptophan metabolism pathways associated with anxiety, including L-kynurenine, N-acetyl serotonin, and serotonin. These metabolites are involved in the serotonin pathway, the kynurenine pathway, and other pathways that affect anxiety through tryptophan metabolism. There were no significant differences in tryptophan metabolism levels between the control and clonazepam treatment groups. Conclusions: Our results demonstrate the possible existence of anxiety-like behavior in the larvae of P. trituberculatus from two perspectives. Being a species with a simpler neural structure than that of mammals, the larvae of P. trituberculatus offer a convenient model for studying the mechanisms of anxiety in crustaceans. Full article

The medicinal plant tulsi (Ocimum sanctum L.) is acknowledged for its invigorating and healing properties that enhance resilience to stress in various human and animal models by modulating antioxidant compounds. While extensive research has documented these effects in humans, the adaptogenic potential of tulsi in stressful in vitro plant systems has not been explored. This study aimed to elucidate the adaptogenic properties of tulsi leaf extract on the in vitro regeneration of tobacco leaf explants through an investigation of the indoleamines at different developmental stages. Shoot regeneration from leaf explants on the medium supplemented with tulsi extract (20%) was compared to the control, and the differences in indoleamine compounds were analyzed using ultra-performance liquid chromatography. Treatment of the explants with the extract resulted in an almost two-fold increase in the number of regenerants after four weeks of culture, and 9% of the regenerants resembled somatic embryo-like structures. The occurrence of browning in the extract-treated explants stopped on day 10, shoots began to develop, and a significant concentration of tryptamine and N-acetyl-serotonin accumulated. A comparative analysis of indoleamine compounds in intact and cut tobacco leaves also revealed the pivotal role of melatonin and 2-hydroxymelatonin functioning as antioxidants during stress adaptation. This study demonstrates that tulsi is a potent adaptogen that is capable of modulating plant morphogenesis in vitro, paving the way for further investigations into the role of adaptogens in plant stress biology. Full article

Melatonin (MT), a naturally occurring compound, is found in various species worldwide. In 1958, it was first identified in the pineal gland of dairy cows. MT is an “old friend” but a “new compound” for plant biology. It brings experts and research minds from the broad field of plant sciences due to its considerable influence on plant systems. The MT production process in plants and animals is distinct, where it has been expressed explicitly in chloroplasts and mitochondria in plants. Tryptophan acts as the precursor for the formation of phyto-melatonin, along with intermediates including tryptamine, serotonin, N-acetyl serotonin, and 5-methoxy tryptamine. It plays a vital role in growth phases such as the seed germination and seedling growth of crop plants. MT significantly impacts the gas exchange, thereby improving physio-chemical functions in plant systems. During stress, the excessive generation and accumulation of reactive oxygen species (ROS) causes protein oxidation, lipid peroxidation, nucleic acid damage, and enzyme inhibition. Because it directly acts as an antioxidant compound, it awakens the plant antioxidant defense system during stress and reduces the production of ROS, which results in decreasing cellular oxidative damage. MT can enhance plant growth and development in response to various abiotic stresses such as drought, salinity, high temperature, flooding, and heavy metals by regulating the antioxidant mechanism of plants. However, these reactions differ significantly from crop to crop and are based on the level and kind of stress. The role of MT in the physiological functions of plants towards plant growth and development, tolerance towards various abiotic stresses, and approaches for enhancing the endogenous MT in plant systems are broadly reviewed and it is suggested that MT is a steering compound in directing major physiological functions of plants under the changing climate in future. Full article

Neuropathic pain is a debilitating condition characterized by abnormal signaling within the nervous system, resulting in persistent and often intense sensations of pain. It can arise from various causes, including traumatic nerve injury, neuropathy, and certain diseases. We present an overview of current and emerging pharmacotherapies for neuropathic pain, focusing on novel drug targets and potential therapeutic agents. Current pharmacotherapies, including tricyclic antidepressants, gabapentinoids, and serotonin norepinephrine re-uptake inhibitors, are discussed, as are emerging treatments, such as ambroxol, cannabidiol, and N-acetyl-L-cysteine. Additionally, the article highlights the need for further research in this field to identify new targets and develop more effective and targeted therapies for neuropathic pain management. Full article

Recently, the presence of melatonin in fermented beverages has been correlated with yeast metabolism during alcoholic fermentation. Melatonin, originally considered a unique product of the pineal gland of vertebrates, has been also identified in a wide range of invertebrates, plants, bacteria, and fungi in the last two decades. These findings bring the challenge of studying the function of melatonin in yeasts and the mechanisms underlying its synthesis. However, the necessary information to improve the selection and production of this interesting molecule in fermented beverages is to disclose the genes involved in the metabolic pathway. So far, only one gene has been proposed as involved in melatonin production in Saccharomyces cerevisiae, PAA1, a polyamine acetyltransferase, a homolog of the vertebrate’s aralkylamine N-acetyltransferase (AANAT). In this study, we assessed the in vivo function of PAA1 by evaluating the bioconversion of the different possible substrates, such as 5-methoxytryptamine, tryptamine, and serotonin, using different protein expression platforms. Moreover, we expanded the search for new N-acetyltransferase candidates by combining a global transcriptome analysis and the use of powerful bioinformatic tools to predict similar domains to AANAT in S. cerevisiae. The AANAT activity of the candidate genes was validated by their overexpression in E. coli because, curiously, this system evidenced higher differences than the overexpression in their own host S. cerevisiae. Our results confirm that PAA1 possesses the ability to acetylate different aralkylamines, but AANAT activity does not seem to be the main acetylation activity. Moreover, we also prove that Paa1p is not the only enzyme with this AANAT activity. Our search of new genes detected HPA2 as a new arylalkylamine N-acetyltransferase in S. cerevisiae. This is the first report that clearly proves the involvement of this enzyme in AANAT activity. Full article

Hazelnuts have recently gathered tremendous attention due to the expansion of the confectionary industry. However, the sourced cultivars fail to perform in initial phase of cultivation as they enter bare survival mode due to changes in climatic zones, for example, Southern Ontario, where the climate is continental, as opposed to the milder climate in Europe and Turkey. Indoleamines have been shown to counter abiotic stress and modulate vegetative and reproductive development of plants. Here, we examined the effect of indoleamines on the flowering response of the dormant stem cuttings of sourced hazelnut cultivars in controlled environment chambers. The stem cuttings were exposed to sudden summer-like conditions (abiotic stress) and the female flower development was assessed in relation to endogenous indoleamine titers. The sourced cultivars responded well to serotonin treatment by producing more flowers compared to the controls or other treatments. The probability of buds resulting in female flowers was highest in the middle region of the stem cuttings. It is interesting to note that the tryptamine titers of the locally adapted, and N-acetyl serotonin titers of native hazelnut cultivars, provided the best explanation for adaptation to the stress environment. Titers of both compounds were compromised in the sourced cultivars which resorted mostly to serotonin concentrations to counter the stress. The indoleamines tool kit identified in this study could be deployed in assessing cultivars for stress adaptation attributes. Full article

A series of 15 new derivatives of 6-acetyl-7-hydroxy-4-methylcoumarin containing a piperazine group were designed with the help of computational methods and were synthesized to study their affinity for the serotonin 5-HT_1A and 5-HT_2A receptors. Among them, 6-acetyl-7-{4-[4-(3-bromophenyl)piperazin-1-yl]butoxy}-4-methylchromen-2-one (4) and 6-acetyl-7-{4-[4-(2-chlorophenyl)piperazin-1-yl]butoxy}-4-methylchromen-2-one (7) exhibited excellent activity for 5-HT_1A receptors with Ki values 0.78 (0.4–1.4) nM and 0.57 (0.2–1.3) nM, respectively, comparable to the Ki values of 8-OH-DPAT (0.25 (0.097–0.66) nM). The equilibrium dissociation constant values of the tested compounds showed differential intrinsic activities of the agonist and antagonist modes. Full article

Melatonin, a widely known indoleamine molecule that mediates various animal and plant physiological processes, is formed from N-acetyl serotonin via N-acetylserotonin methyltransferase (ASMT). ASMT is an enzyme that catalyzes melatonin synthesis in plants in the rate-determining step and is homologous to hydroxyindole-O-methyltransferase (HIOMT) melatonin synthase in animals. To date, little is known about the effect of HIOMT on salinity in apple plants. Here, we explored the melatonin physiological function in the salinity condition response by heterologous expressing the homologous human HIOMT gene in apple plants. We discovered that the expression of melatonin-related gene (MdASMT) in apple plants was induced by salinity. Most notably, compared with the wild type, three transgenic lines indicated higher melatonin levels, and the heterologous expression of HIOMT enhanced the expression of melatonin synthesis genes. The transgenic lines showed reduced salt damage symptoms, lower relative electrolyte leakage, and less total chlorophyll loss from leaves under salt stress. Meanwhile, through enhanced activity of antioxidant enzymes, transgenic lines decreased the reactive oxygen species accumulation, downregulated the expression of the abscisic acid synthesis gene (MdNCED3), accordingly reducing the accumulation of abscisic acid under salt stress. Both mechanisms regulated morphological changes in the stomata synergistically, thereby mitigating damage to the plants’ photosynthetic ability. In addition, transgenic plants also effectively stabilized their ion balance, raised the expression of salt stress–related genes, as well as alleviated osmotic stress through changes in amino acid metabolism. In summary, heterologous expression of HIOMT improved the adaptation of apple leaves to salt stress, primarily by increasing melatonin concentration, maintaining a high photosynthetic capacity, reducing reactive oxygen species accumulation, and maintaining normal ion homeostasis. Full article

Serotonin (Ser) and melatonin (Mel) serve as master regulators of plant growth and development by influencing diverse cellular processes. The enzymes namely, tryptophan decarboxylase (TDC) and tryptamine 5-hydroxylase (T5H) catalyse the formation of Ser from tryptophan. Subsequently, serotonin N-acetyl transferase (SNAT) and acetyl-serotonin methyltransferase (ASMT) form Mel from Ser. Plant genomes harbour multiple genes for each of these four enzymes, all of which have not been identified. Therefore, to delineate information regarding these four gene families, we carried out a genome-wide analysis of the genes involved in Ser and Mel biosynthesis in Arabidopsis, tomato, rice and sorghum. Phylogenetic analysis unravelled distinct evolutionary relationships among these genes from different plants. Interestingly, no gene family except ASMTs showed monocot- or dicot-specific clustering of respective proteins. Further, we observed tissue-specific, developmental and stress/hormone-mediated variations in the expression of the four gene families. The light/dark cycle also affected their expression in agreement with our quantitative reverse transcriptase-PCR (qRT-PCR) analysis. Importantly, we found that miRNAs (miR6249a and miR-1846e) regulated the expression of Ser and Mel biosynthesis under light and stress by influencing the expression of OsTDC5 and OsASMT18, respectively. Thus, this study may provide opportunities for functional characterization of suitable target genes of the Ser and Mel pathway to decipher their exact roles in plant physiology. Full article

Melatonin (N-acetyl-5-methoxytryptamine), a well-known animal hormone, is involved in several biological processes including circadian rhythm and the regulation of abiotic stress. A systematic understanding of the circadian regulation of melatonin biosynthesis-related genes has not been achieved in rice. In this study, key genes for all of the enzymes in the melatonin biosynthetic pathway that showed a peak of expression at night were identified by microarray data analysis and confirmed by qRT–PCR analysis. We further examined the expression patterns of the four genes under drought, salt, and cold stresses. The results showed that abiotic stresses, such as drought, salt, and cold, affected the expression patterns of melatonin biosynthetic genes. In addition, the circadian expression patterns of tryptophan decarboxylase (TDC), tryptamine 5-hydroxylase (T5H), and serotonin N-acetyltransferase (SNAT) genes in wild-type (WT) plants was damaged by the drought treatment under light and dark conditions. Conversely, N-acetylserotonin O-methyltransferase (ASMT) retained the circadian rhythm. The expression of ASMT was down-regulated by the rice gigantea (OsGI) mutation, suggesting the involvement of the melatonin biosynthetic pathway in the OsGI-mediated circadian regulation pathway. Taken together, our results provide clues to explain the relationship between circadian rhythms and abiotic stresses in the process of melatonin biosynthesis in rice. Full article

L-5-hydroxytryptophan (5-HTP) is both a drug and a natural component of some dietary supplements. 5-HTP is produced from tryptophan by tryptophan hydroxylase (TPH), which is present in two isoforms (TPH1 and TPH2). Decarboxylation of 5-HTP yields serotonin (5-hydroxytryptamine, 5-HT) that is further transformed to melatonin (N-acetyl-5-methoxytryptamine). 5-HTP plays a major role both in neurologic and metabolic diseases and its synthesis from tryptophan represents the limiting step in serotonin and melatonin biosynthesis. In this review, after an look at the main natural sources of 5-HTP, the chemical analysis and synthesis, biosynthesis and microbial production of 5-HTP by molecular engineering will be described. The physiological effects of 5-HTP are discussed in both animal studies and human clinical trials. The physiological role of 5-HTP in the treatment of depression, anxiety, panic, sleep disorders, obesity, myoclonus and serotonin syndrome are also discussed. 5-HTP toxicity and the occurrence of toxic impurities present in tryptophan and 5-HTP preparations are also discussed. Full article

Apoptosis of intestinal epithelial cells following oxidative stress is a major cause of mucosal barrier dysfunction and is associated with the pathogenesis of various gastrointestinal diseases. Although L-tryptophan (Trp) is known to improve intestinal integrity and function, a beneficial effect of N-acetyl serotonin (NAS), a metabolite of Trp, on the apoptosis of enterocytes and the underlying mechanisms remain largely unknown. In the present study, we showed that porcine enterocytes treated with 4-hydroxy-2-nonenal (4-HNE), a metabolite of lipid peroxidation, led to upregulation of apoptotic proteins, including Bax and cleaved caspase-3, and reduction of tight junction proteins. These effects of 4-HNE were significantly abrogated by NAS. In addition, NAS reduced ROS accumulation while increasing the intracellular concentration of glutathione (GSH), and the abundance of the Nrf2 protein in the nucleus and its downstream target proteins. Importantly, these protective effects of NAS were abrogated by Atra, an inhibitor of Nrf2, indicating a dependence on Nrf2 signaling. Taken together, we demonstrated that NAS attenuated oxidative stress-induced cellular injury in porcine enterocytes by regulating Nrf2 signaling. These findings provide new insights into a functional role of NAS in maintaining intestinal homeostasis. Full article

Autism spectrum disorder (ASD) refers to complex neurobehavioral and neurodevelopmental conditions characterized by impaired social interaction and communication, restricted and repetitive patterns of behavior or interests, and altered sensory processing. Environmental, immunological, genetic, and epigenetic factors are implicated in the pathophysiology of autism and provoke the occurrence of neuroanatomical and neurochemical events relatively early in the development of the central nervous system. Many neurochemical pathways are involved in determining ASD; however, how these complex networks interact and cause the onset of the core symptoms of autism remains unclear. Further studies on neurochemical alterations in autism are necessary to clarify the early neurodevelopmental variations behind the enormous heterogeneity of autism spectrum disorder, and therefore lead to new approaches for the treatment and prevention of autism. In this review, we aim to delineate the state-of-the-art main research findings about the neurochemical alterations in autism etiology, and focuses on gamma aminobutyric acid (GABA) and glutamate, serotonin, dopamine, N-acetyl aspartate, oxytocin and arginine-vasopressin, melatonin, vitamin D, orexin, endogenous opioids, and acetylcholine. We also aim to suggest a possible related therapeutic approach that could improve the quality of ASD interventions. Over one hundred references were collected through electronic database searching in Medline and EMBASE (Ovid), Scopus (Elsevier), ERIC (Proquest), PubMed, and the Web of Science (ISI). Full article

The aim of this study was to characterize the embryonic ontogeny of 5-hydroxyindoles and 5-methoxyindoles synthesis pathways in the goose pineal organ. The study was performed on embryos aged 14–28 days, which have been incubated under a 12L:12D cycle. The pineal organs were collected for measurements of indole content by HPLC every 6 h on embryonic day (ED) 14, ED 16, ED 18 and ED 22 or every 2 h on ED 24, ED 26 and ED 28. The level of tryptophan showed no significant changes during development and no day-night variations. The content of 5-hydroxytryptophan increased between ED 14 and ED 26. It was significantly higher during scotophase than during photophase starting from ED 14. The serotonin content was low during the early stages of development (ED 14–ED 18) and prominently increased from ED 20. The serotonin levels also showed day-night differences; however, they were less conspicuous than those of 5-hydroxytryptophan. The changes in the level of 5-hydroxyindole acetic acid were similar to those of serotonin. 5-Hydroxytryptophol was measurable from ED 18. Levels of N-acetylserotonin, which were detectable for the first time on ED 16, prominently increased between ED 22 and ED 28 and showed significant day–night differences from ED 20. Melatonin was detectable from ED 18. Like N-acetylserotonin, its content increased rapidly between ED 22 and ED 28, and from ED 20 showed diurnal variations. 5-Methoxyindole acetic acid and 5-methoxytryptophol occurred at measurable levels from ED 18 and ED 26, respectively. The obtained results showed that embryonic development of indole metabolism in the goose pineal organ starts with the beginning of serotonin synthesis. The processes of serotonin acetylation and 5-hydroxyindoles methylation were turned on later. Diurnal rhythmicity develops very early in the embryonic pineal organ of the goose when the eggs are incubated under a 12 h light: 12 h dark schedule. Two processes are responsible for generation of the diurnal rhythms of 5-hydroxyindoles and 5-methoxyindoles: (i) hydroxylation of tryptophan and (ii) acetylation of serotonin. Full article