Abstract Exogenous melatonin (Mel) is widely used in clinic for multiple therapeutic purposes. In metabolism pathways of Mel, 6-hydroxymelatonin-sulfate (S-O-Mel) and N-acetylserotonin sulfate (S-NAS) are the most abundant metabolites account for over 90% of total Mel metabolites in humans, indicating that sulfation plays an important role in reflecting the functions and clearance of Mel in vivo. In the present study, we characterized Mel sulfation using various human organ cytosols (liver, lung, kidney, small intestine and brain), liver cytosols from five different animal species, and cDNA-expressed human sulfotransferase (SULT) for the first time. Our results demonstrated that liver, lung, kidney and small intestine of humans had high catalytic efficiency for Mel sulfation, however, brain contained a very low reaction rate. Interestingly, organ cytosols prepared from females exhibited higher sulfation activity than those of males. SULT isoforms 1A1, 1A2, 1A3, 1B1 and 1E1 exhibited metabolic activities toward Mel. According to kinetic parameters (Km and Vmax), chemical inhibition, correlation analysis, molecular docking and sulfation assays with recombinant human SULTs isoforms, SULT1A1 was determined as the major enzyme responsible for Mel sulfation. Furthermore, considerable species differences in Mel sulfation were observed, and the total intrinsic clearance rate of Mel sulfation was as follows: monkey > rat > dog > human > pig > mouse. Additionally, the anti-inflammatory effects of Mel and its sulfated metabolites were evaluated by inhibiting nitric oxide (NO) production in RAW264.7 cells, and S-O-Mel as a bioactive form, exhibited potent bioactivity. Our investigation provided a global view of the enzyme-dependent sulfation of Mel that can guide biomedical research on Mel.
#1Xiangge Tian(Dalian Medical University)H-Index: 18
#2Si-Cheng Liang(CAS: Chinese Academy of Sciences)H-Index: 13
Last. Xiaochi Ma(CAS: Chinese Academy of Sciences)H-Index: 26
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Andrographolide (AND) and two of its derivatives, deoxyandrographolide (DEO) and dehydroandrographolide (DEH), are widely used in clinical practice as anti-inflammatory agents. However, UDP-glucuronosyltransferase (UGT)-mediated phase II metabolism of these compounds is not fully understood. In this study, glucuronidation of AND, DEO, and DEH was characterized using liver microsomes and recombinant UGT enzymes. We isolated six glucuronides and identified them using 1D and 2D nuclear magnetic res...
Last. I. Gögenur(UCPH: University of Copenhagen)H-Index: 9
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Circadian- and sleep disturbances may be central for understanding the pathophysiology and treatment of depression. The effect of melatonin on depression/depressive symptoms has been investigated previously. This systematic review assesses the current evidence of a therapeuticand prophylactic effect of melatonin in adult patients against depression or depressive symptoms. A search was performed in The Cochrane Library, PubMed, EMBASE and PsycINFO for published trials on November 14th 2013. Inclu...
#1Yang Yang(Fourth Military Medical University)H-Index: 53
#2Yang Sun(Fourth Military Medical University)H-Index: 8
Last. Dinghua Yi(Fourth Military Medical University)H-Index: 31
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Cardiac tissue loss is one of the most important factors leading to the unsatisfactory recovery even after treatment of ischemic heart disease. Melatonin, a circadian molecule with marked antioxidant properties, protects against ischemia–reperfusion (IR) injury. In particular, the myocardial protection of melatonin is substantial. We initially focus on the cardioprotective effects of melatonin in myocardial IR. These studies showed how melatonin preserves the microstructure of the cardiomyocyte ...
Last. Ming-Cheh Liu(UT: University of Toledo)H-Index: 21
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The current study was designed to examine the sulfation of eight opioid drugs, morphine, hydromorphone, oxymorphone, butorphanol, nalbuphine, levorphanol, nalorphine, and naltrexone, in HepG2 human hepatoma cells and human organ samples (lung, liver, kidney, and small intestine) and to identify the human SULT(s) responsible for their sulfation. Analysis of the spent media of HepG2 cells, metabolically labeled with [35S]sulfate in the presence of each of the eight opioid drugs, showed the generat...
This study describes the anti-inflammatory activities of two semisynthesized melatonin (MT) derivatives, benzoyl-melatonin (BMT) and acetyl-melatonin (AMT), on the production of pro- inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophage cells (RAW 264.7) and their antinociceptive effects in mice. The MT derivatives inhibited production of nitric oxide NO and prosta- glandin E2 in LPS-stimulated RAW264.7 cells in a dose-dependent manner with IC50 values lower than those of MT. ...
Uridine diphosphate (UDP)-glucuronosyl-transferases (UGTs) are enzymes involved in the biotransformation of important endogenous compounds such as steroids, bile acids, and hormones as well as exogenous substances including drugs, environmental toxicants, and carcinogens. Here, a novel fluorescent probe BDMP was developed based on boron-dipyrromethene (BODIPY) with high sensitivity for the detection of UGT1A8. The glucuronidation of BDMP not only exhibited a redemission wavelength (λex/λem = 500...
Melatonin is a neuroendocrine hormone which regulates circadian rhythm and is also an antioxidant. The role of melatonin in pregnancy is emerging. The enzymes needed for endogenous synthesis of melatonin have been identified in the placenta, although the contribution to circulating maternal melatonin in normal pregnancy is unclear. This work aimed to determine serum levels of melatonin and its major metabolite 6-hydroxymelatonin sulfate (6-OHMS) in normal pregnant women during each trimester of ...
Last. Dafang Zhong(CAS: Chinese Academy of Sciences)H-Index: 28
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Forsythin extracted from Forsythiae Fructus is widely used to treat fever caused by the common cold or influenza in China, Japan and Korea. The present study aimed to analyze the pharmacokinetics, metabolism and excretion routes of forsythin in humans and determine the major enzymes and transporters involved in these processes. After a single oral administration, forsythin underwent extensive metabolism via hydrolysis and further sulfation. In total, 3 of the 13 metabolites were confirmed by com...
Melatonin is a multifunctional antioxidant neurohormone found in plant foods such as lentil sprouts. We aim to evaluate the effect of lentil sprout intake on the plasmatic levels of melatonin and metabolically related compounds (plasmatic serotonin and urinary 6-sulfatoxymelatonin), total phenolic compounds, and plasmatic antioxidant status, and compare it with synthetic melatonin. The germination of lentils increases the content of melatonin. However, the phenolic content diminished due to the ...
Last. Zatollah Asemi(KAUMS: Kashan University of Medical Sciences)H-Index: 50
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Skin cancer, particularly melanoma, is a leading cause of death worldwide. The therapeutic methods for this malignancy are not effective, and due to the side effects of these treatments, applying an appropriate alternative or complementary treatment is important. According to available data, melatonin as the main product of the pineal gland has oncostatic and antitumoral properties. Also, melatonin acts as an anti-inflammatory and reactive oxygen species inducer agent which suppresses the growth...
AbstractObjective:The Kronos Early Estrogen Prevention Study (KEEPS) was designed to address gaps in understanding the effects of timely menopausal hormone treatments (HT) on cardiovascular health and other effects of menopause after the premature termination of the Women's Health Initiative.Method:
AbstractSulfotransferase (SULT) has been found in the brain; however, the details of its function remain unclear. The present study aimed to elucidate the regional differences in the expression of SULT1 and SULT2 mRNA and SULT activities in the eight functional regions of the rat brain (cerebellum, cortex, hippocampus, medulla oblongata, midbrain, olfactory bulb, striatum, and thalamus).All SULT1 isoforms were detected in the medulla oblongata and thalamus. SULT2A1 mRNA was not observed in any o...
Last. Xiaochi Ma(Dalian Medical University)H-Index: 26
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As is well-known, fungi are an important biocatalysis model of glucosylation and have been widely applied for bioactive compounds glucosylation mediated by the intracellular glucosytransferases (GTs). However, there is no efficient method for the real-time detection of GTs and the rapid isolation of the target fungi strains with the high expression of GTs. In the present work, we first developed a two-photon ratiometric fluorescent probe N-(n-butyl)-4-hydroxy-1,8-naphthalimide (NHN) for detectin...
#1Zhenlong Yu(Dalian Medical University)H-Index: 18
#2Xiangge Tian(Dalian Medical University)H-Index: 18
Last. Xiaochi Ma(Dalian Medical University)H-Index: 26
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: Melatonin is an endogenous indoleamine with a wide range of biological functions in the various organisms from bacteria to mammals. Evidence indicates that melatonin facilitates apoptosis in cancer cells and enhances the antitumor activity of chemotherapy in animals and clinical studies. However, the melatonin metabolism and the key metabolic targets in cancer cells still remain unknown. In this study, U118 and SH-SY5Y tumor cell lines were used to investigate the metabolic pathways of melaton...
Last. Xiaochi Ma(HMU: Hainan Medical University)H-Index: 26
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Abstract Human cytosolic sulfotransferase 2A1 (SULT2A1) is an important phase II metabolic enzyme. The detection of SULT2A1 is helpful for the functional characterization of SULT2A1 and diagnosis of its related diseases. However, due to the overlapping substrate specificity among members of the sulfotransferase family, it is difficult to develop a probe substrate for selective detection of SULT2A1. In the present study, through characterization of the sulfation of series of bufadienolides, areno...
