The natural anthraquinones from Rheum palmatum induced the metabolic disorder of melatonin by inhibiting human CYP and SULT enzymes.

Published on Nov 16, 2016in Toxicology Letters3.569
· DOI :10.1016/J.TOXLET.2016.09.004
Weiru Jiang2
Estimated H-index: 2
(Dalian Medical University),
Xiangge Tian18
Estimated H-index: 18
(Dalian Medical University)
+ 9 AuthorsXiaochi Ma26
Estimated H-index: 26
(Dalian Medical University)
Abstract Melatonin (Mel) as an endogenous hormone, has been widely used in clinic for multiple therapeutic purposes. Further, the natural anthraquinones were widespread in various plants including herbs, foods, and some flavoring agents. The present work aims to evaluate the metabolic disorder of Mel caused by various common herbs and further identify their underlying mechanism. More importantly, the relationships between inhibitory activity and their structures were also investigated. Our results demonstrate that some herbs containing anthraquinone derivatives exhibited strong inhibition on Mel metabolism. Additionally, five anthraquinones from R. palmatum could inhibit phase I and II metabolism of Mel with a mixed inhibition kinetic model based on the mechanism of inhibiting human CYP1A1, 1A2, and SULT1A1. At last, the influence of R. palmatum and its five major components on the Mel metabolism were verified in human primary hepatocytes. In conclusion, our studies elucidated that herbs or foods containing abundant anthraquinones such as R. palmatum will cause a metabolic disorder of Mel, and should be avoided to combined application with Mel in clinic .
📖 Papers frequently viewed together
24 Citations
10 Citations
#1Maryam Bazrgar (Damghan University)H-Index: 1
#2Iran Goudarzi (Damghan University)H-Index: 12
Last. Mahmoud Elahdadi Salmani (Damghan University)H-Index: 12
view all 4 authors...
Abstract During the particular period of cerebellum development, exposure to lead (Pb) decreases cerebellum growth and can result in selective loss of neurons. The detection and prevention of Pb toxicity is a major international public health priorities. This research study was conducted to evaluate the effects of melatonin, an effective antioxidant and free radical scavenger, on Pb induced neurotoxicity and oxidative stress in the cerebellum. Pb exposure was initiated on gestation day 5 with th...
24 CitationsSource
#1Dennis Zetner (UCPH: University of Copenhagen)H-Index: 5
#2Lars Peter Holst Andersen (UCPH: University of Copenhagen)H-Index: 14
Last. Jacob Rosenberg (UCPH: University of Copenhagen)H-Index: 22
view all 3 authors...
Background: Melatonin is traditionally administered orally but has a poor and variable bioavailability. This study aims to present an overview of studies investigating the pharmacokinetics of alternative administration routes of melatonin. Methods: A systematic literature search was performed and included experimental or clinical studies, investigating pharmacokinetics of alternative administration routes of melatonin in vivo. Alternative administration routes were defined as all administration ...
35 CitationsSource
#1Dun Xian Tan (UTSA: University of Texas at San Antonio)H-Index: 127
#2Lucien C. Manchester (UTSA: University of Texas at San Antonio)H-Index: 68
Last. Russel J. Reiter (UTSA: University of Texas at San Antonio)H-Index: 195
view all 5 authors...
Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is speculated that the melatonin synthetic machinery in eukaryotes was inherited from bacteria as a result of endosymbiosis. However, melatonin’s synthetic mechanisms in microorganisms are currently unknown. Melatonin metabolism ...
244 CitationsSource
#1Hang Sun (Tongji University)H-Index: 6
#2Fang-fang Huang (Tongji University)H-Index: 1
Last. Shen Qu (Tongji University)H-Index: 27
view all 3 authors...
Melatonin (N-acetyl-5-methoxytryptamine, MLT) is a neuroendocrine hormone, which is primarily synthesized by the pineal gland in vertebrates. Melatonin is a remarkable molecule with diverse biological and physiological actions and is involved in the regulation of various important functions such as circadian rhythm, energy metabolism, the reproductive system, the cardiovascular system, and the neuropsychiatric system. It also plays a role in disease by having anti-neoplastic and anti-osteoarthri...
31 CitationsSource
#1Yan-Xi Zhou (CDUTCM: Chengdu University of Traditional Chinese Medicine)H-Index: 5
#2Wei XiaH-Index: 9
Last. Hong Zhang ('SMMU': Second Military Medical University)H-Index: 51
view all 6 authors...
Rhein (4, 5-dihydroxyanthraquinone-2-carboxylic acid) is a lipophilic anthraquinone extensively found in medicinal herbs, such as Rheum palmatum L., Cassia tora L., Polygonum multiflorum Thunb., and Aloe barbadensis Miller, which have been used medicinally in China for more than 1,000 years. Its biological activities related to human health are being explored actively. Emerging evidence suggests that rhein has many pharmacological effects, including hepatoprotective, nephroprotective, anti-infla...
74 CitationsSource
#1Xiangge Tian (Dalian Medical University)H-Index: 18
#2Xiaokui Huo (Dalian Medical University)H-Index: 22
Last. Xiaochi Ma (Dalian Medical University)H-Index: 26
view all 8 authors...
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...
24 CitationsSource
#1B. Claustrat (French Institute of Health and Medical Research)H-Index: 1
#2J. LestonH-Index: 1
Abstract Melatonin is a methoxyindole synthesized and secreted principally by the pineal gland at night under normal light/dark conditions. The endogenous rhythm of secretion is generated by the suprachiasmatic nuclei and entrained to the light/dark cycle. Light is able to either suppress or synchronize melatonin production according to the light schedule. The nycthohemeral rhythm of this hormone can be evaluated by repeated measurement of plasma or saliva melatonin or urine sulfatoxymelatonin, ...
205 CitationsSource
#1Rüdiger Hardeland (GAU: University of Göttingen)H-Index: 60
#2Daniel P. Cardinali (Pontifical Catholic University of Argentina)H-Index: 81
Last. Seithikurippu R. Pandi-Perumal (NYU: New York University)H-Index: 60
view all 4 authors...
Abstract Melatonin is known to possess several properties of value for healthy aging, as a direct and indirect antioxidant, protectant and modulator of mitochondrial function, antiexcitotoxic agent, enhancer of circadian amplitudes, immune modulator and neuroprotectant. It is levels tend to decrease in the course of senescence and are more strongly reduced in several neurodegenerative disorders, especially Alzheimer's disease, and in diseases related to insulin resistance such as diabetes type 2...
113 CitationsSource
#1Li Yaoguang (DICP: Dalian Institute of Chemical Physics)H-Index: 2
#2Jie Hou (Dalian Medical University)H-Index: 24
Last. Ling Yang (DICP: Dalian Institute of Chemical Physics)H-Index: 53
view all 10 authors...
fructus psoraleae (fp) is an edible chinese herbal which is widely used in asia for the treatment of various diseases including asthma, diarrhea, and osteoporosis. this study aimed to investigate the inhibitory effects of the crude ethanol extract from fp on human carboxylesterase 2 (hce2), as well as to identity and characterize the naturally occurring inhibitors of hce2 in fp. our results demonstrated that the ethanol extract of fp displayed potent inhibitory effects towards hce2, while five m...
52 CitationsSource
#1Elżbieta Miller (Medical University of Łódź)H-Index: 18
#2Agnieszka MorelH-Index: 11
Last. Joanna SalukH-Index: 17
view all 4 authors...
Neurodegeneration is the hallmark of many chronic progressive neurogical disorders characterized by specific clinical, morphological and biochemical features. Central nervous system is very sensitive to oxidative stress, which is considered as a key factor of neurodegenerative disorders. Therefore, many therapeutical strategies are focused on molecules with redox activity to re-establish the equilibrium between pro and antioxidants. Due to the fact that melatonin readily crosses the blood- brain...
58 CitationsSource
Cited By10
#1Wenlong Wei (CAS: Chinese Academy of Sciences)H-Index: 4
#2Zhenwei Li (CAS: Chinese Academy of Sciences)H-Index: 5
Last. De-An Guo (CAS: Chinese Academy of Sciences)H-Index: 68
view all 11 authors...
Abstract Traditional Chinese medicines (TCMs), have been widely used for the prevention, treatment, and cure of various diseases for thousands of years in China and Asian countries. It is usually applied either alone or in combination with synthetic drugs or other herbs to be more effective. However, the evaluation of TCMs against the main phase I metabolic enzyme CYP3A4 in vitro was limited. In the present study, a high throughput method based on an isoform-specific probe was applied to evaluat...
#1Bernadetta Bilska (Jagiellonian University)H-Index: 3
#2F. Schedel (WWU: University of Münster)H-Index: 4
Last. Konrad Kleszczyński (WWU: University of Münster)H-Index: 15
view all 11 authors...
Melanoma is a leading cause of cancer deaths worldwide. Although immunotherapy has revolutionised the treatment for some patients, resistance towards therapy and unwanted side effects remain a problem for numerous individuals. Broad anti-cancer activities of melatonin are recognised, however additional investigations still need to be elucidated. Herein, using various human melanoma cell models, we explore in vitro the new insights into the regulation of melanoma by melatonin and its metabolites ...
2 CitationsSource
#1Athar Husain (AcSIR: Academy of Scientific and Innovative Research)H-Index: 5
#2Mohammed Riyazuddin (Central Drug Research Institute)H-Index: 6
Last. Jiaur R. Gayen (AcSIR: Academy of Scientific and Innovative Research)H-Index: 26
view all 9 authors...
Abstract Background Traditionally Cassia occidentalis L. extract is used for the treatment of several diseases including fever, bone diseases, fracture, kidney and digestive diseases. Ethanolic extract of Cassia occidentalis L. (EECO) is being developed as a phytopharmaceutical for corticosteroid-induced osteoporosis. Purpose This study was aimed to investigate the effect of EECO on the pharmacokinetics of acetaminophen (ACET), theophylline (THEO), omeprazole (OMEP), methotrexate (MTX), and meth...
1 CitationsSource
#1Yitong Liu (CFSAN: Center for Food Safety and Applied Nutrition)H-Index: 2
#2Mapa S.T. Mapa (CFSAN: Center for Food Safety and Applied Nutrition)H-Index: 6
Last. Robert L. Sprando (CFSAN: Center for Food Safety and Applied Nutrition)H-Index: 23
view all 3 authors...
Anthraquinones exhibit various pharmacological activities (e.g., antioxidant and laxative) and are commonly found in consumer products including foods, dietary supplements, drugs, and traditional medicines. Despite their widespread use, there are limited data available on their toxicokinetic properties. Cytochrome P450 enzymes (CYPs) in the liver play major roles in metabolizing exogenous chemicals (e.g., pharmaceuticals, food ingredients, and environmental pollutants) and endogenous biomolecule...
#1David J. Kennaway (University of Adelaide)H-Index: 55
Melatonin continues to generate interest in the scientific community and the general public. In recent years, there has been growing interest in the possibility that melatonin present in human foods may have physiological effects. This has led to the promotion of "melatonin-rich" foods and "phyto-melatonin". The night time secretion of endogenous melatonin from the pineal gland provides a daily circadian signal which is detected by receptors in various tissues. In animals the changing circadian ...
1 CitationsSource
#1Mohammad Hossein Pourhanifeh (KAUMS: Kashan University of Medical Sciences)H-Index: 18
#2Mostafa Mahdavinia (Tehran University of Medical Sciences)H-Index: 4
Last. Zatollah Asemi (KAUMS: Kashan University of Medical Sciences)H-Index: 50
view all 4 authors...
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...
18 CitationsSource
#1Md. Moshfekus Saleh-e-In (Bangladesh Council of Scientific and Industrial Research)H-Index: 6
#2Ayan Roy (UKZN: University of KwaZulu-Natal)H-Index: 7
Last. Johannes Van Staden (UKZN: University of KwaZulu-Natal)H-Index: 58
view all 9 authors...
Abstract Anethum sowa L. has been used as a spice herb in the Asian and European culinary systems to add flavour and taste. The studied plant has diverse folkloric medicinal value. Present study was designed to isolate phytochemicals from the hexane, chloroform and ethyl acetate extracts of the roots by various chromatographic techniques. Based on spectral analysis (IR, LC–MS, NMR) the isolated compounds were identified as physcione (1), β-sitosterol (2), stigmasterol (3), 2-oxo-3-propyl-2H-chro...
12 CitationsSource
#1Tao Xu (ZJU: Zhejiang University)H-Index: 1
#2Baiyi Lu (ZJU: Zhejiang University)H-Index: 21
AbstractA circadian rhythm is any biological activity rhythm driven by internal circadian clocks (∼24 h) and entrained by external signals. Its disruption leads to the development of many diseases,...
13 CitationsSource
#1Yannan Li (Dalian Medical University)H-Index: 3
#2Jing Ning (Dalian Medical University)H-Index: 20
Last. Xiaochi Ma (Dalian Medical University)H-Index: 26
view all 11 authors...
Abstract The high risk of herb-drug interactions (HDIs) mediated by the herbal medicines and dietary supplements which containing abundant flavonoids had become more and more frequent in our daily life. In our study, the inhibition activities of 44 different structures of flavonoids toward human CYPs were systemically evaluated for the first time. According to our results, a remarkable structure-dependent inhibition behavior toward CYP3A4 was observed in vitro . Some flavonoids such as licoflavo...
25 CitationsSource
#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
view all 11 authors...
: 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...
25 CitationsSource