Oral colon-specific drug delivery system reduces the nephrotoxicity of rhubarb anthraquinones when they produce purgative efficacy

Liu, Pei; Wei, Hongwei; Chang, Jinhua; Miao, Guowang; Liu, Xigang; Li, Zhongsi; Liu, Liyan; Zhang, Xiangrong; Cui-zhe, Liu

doi:10.3892/etm.2017.4959

Cited by 10 publications

(5 citation statements)

References 20 publications

(23 reference statements)

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“…Metabolomics is a discipline that has grown up after proteomics and genomics. 11 , 12 The metabolic network of biological systems can be derived by observing the dynamic changes in metabolites before and after stimulation or perturbation of organism systems on the basis of various analytical tools. 13 , 14 Metabolomics is widely used in various scientific fields due to its high pathway integrity, high sensitivity, and high selectivity.…”

Section: Introductionmentioning

confidence: 99%

Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology

Li¹,

Wang²,

Li³

et al. 2021

DDDT

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Background Rhubarb, as a traditional Chinese medicine, is the preferred drug for the treatment of stagnation and constipation in clinical practice. It has been reported that rhubarb possesses hepatotoxicity, but its mechanism in vivo is still unclear. Methods In this study, the chemical components in rhubarb were identified based on UPLC-Q-TOF/MS combined with data postprocessing technology. The metabolic biomarkers obtained through metabolomics technology were related to rhubarb-induced hepatotoxicity. Furthermore, the potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology involving the above components and metabolites. Meanwhile, GO gene enrichment analysis and KEGG pathway analysis were performed on the common targets. Results Twenty-eight components in rhubarb were identified based on UPLC-Q-TOF/MS, and 242 targets related to rhubarb ingredients were predicted. Nine metabolic biomarkers obtained through metabolomics technology were closely related to rhubarb-induced hepatotoxicity, and 282 targets of metabolites were predicted. Among them, the levels of 4 metabolites, namely dynorphin B (10–13), cervonoyl ethanolamide, lysoPE (18:2), and 3-hydroxyphenyl 2-hydroxybenzoate, significantly increased, while the levels of 5 metabolites, namely dopamine, biopterin, choline, coenzyme Q9 and P1, P4-bis (5ʹ-uridyl) tetraphosphate significantly decreased. In addition, 166 potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology. The KEGG pathway analysis was performed on the common targets to obtain 46 associated signaling pathways. Conclusion These data suggested that rhubarb may cause liver toxicity due to its action on dopamine D1 receptor (DRD1), dopamine D2 receptor (DRD2), phosphodiesterase 4B (PDE4B), vanilloid receptor (TRPV1); transient receptor potential cation channel subfamily M member 8 (TRPM8), prostanoid EP2 receptor (PTGER2), acetylcholinesterase (ACHE), muscarinic acetylcholine receptor M3 (CHRM3) through the cAMP signaling pathway, cholinergic synapses, and inflammatory mediators to regulate TRP channels. Metabolomics technology and network pharmacology were integrated to explore rhubarb hepatotoxicity to promote the reasonable clinical application of rhubarb.

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Section: Introductionmentioning

confidence: 99%

Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology

Li¹,

Wang²,

Li³

et al. 2021

DDDT

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“…It contains Anthraquinones (AQs) in Rheum australe . An increasing number of studies have reported that AQs induce nephrotoxicity [ 66 ]. The young leaves of Phytolacca acinosa are used as wild vegetables, but the red roots of it are poisonous and inedible [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

An ethnobotanical study on wild plants used by Tibetan people in Gyirong Valley, Tibet, China

Guo

Ding

et al. 2022

J Ethnobiology Ethnomedicine

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Background Gyirong Valley known as the “Back Garden of the Himalayas” is located in the core area of the Everest National Nature Reserve. It is also one of the important ports from ancient Tibet to Kathmandu, Nepal, since ancient times. Over the years, the Tibetans of Gyirong had accumulated sufficient traditional knowledge about local plant resources. However, there is almost no comprehensive report available on ethnobotanical knowledge about the local people. The purposes of this study were to (1) conduct a comprehensive study of wild plants used by Tibetan people in Gyirong Valley and record the traditional knowledge associated with wild useful plants, (2) explore the influence of Tibetan traditional culture and economic development on the use of wild plants by local people, and (3) explore the characteristics of traditional knowledge about wild plants of Tibetans in Gyirong. Methods Ethnobotanical data were documented through free listings, key informant interviews and semi-structured interviews during fieldwork. The culture importance index and the informant consensus factor index were used as quantitative indices. Results In total, 120 informants (61 women and 59 men) and 3333 use reports and 111 wild plant species belonging to 39 families and 81 genera were included. These use reports were then classified into 27 categories belonging to three major categories. The use category that contained the most plant species was edible plants (62), followed by medicinal plants (32) and economic plants (22), and other uses (71). Plants with high CI included Allium prattii, Neopicrorhiza scrophulariiflora, Gymnadenia orchidis, Rhododendron anthopogon and Fritillaria cirrhosa. Thirty-six species of plants in the catalog of Gyirong and Yadong were the same, but only 17 species were the same in Gyirong and Burang. There were only 11 overlapping species between all the three regions. Conclusion Tibetans of Gyirong have rich and unique knowledge about plant use, and wild edible and medicinal plants play an important role in the nutrition and health protection of local people. However, traditional knowledge is slowly being lost and is being hit by modern tourism. In the future, more attention needs to be paid to the important role of traditional knowledge in biodiversity conservation.

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“…The presence of the β-type glycoside bonds in conjugates prevents their hydrolysis by α-glucosidase in the upper gastrointestinal tract and, as a consequence, they are hydrolysed to free anthraquinones by bacterial β-glucosidases in the colon. Recently, a Chinese research group designed oral colon-specific drug delivery granules, containing the total free anthraquinones to improve their purgative effect and to reduce anthraquinone nephrotoxicity [ 131 , 132 ]. The postprandial hyperlipidemia-lowering effect and improvement in gastrointestinal transit in diabetic rats was reported for aqueous extract from the rhizome of R. palmatum , administered at doses of 150 and 300 mg/kg b.w.…”

Section: Molecular Targets For Rhubarb-derived Substancesmentioning

confidence: 99%

A Review on Rhubarb-Derived Substances as Modulators of Cardiovascular Risk Factors—A Special Emphasis on Anti-Obesity Action

Liudvytska

Kołodziejczyk-Czepas

2022

Nutrients

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The currently available anti-obesity therapies encounter many associated risks and side effects often causing the ineffectiveness of treatment. Therefore, various plant-derived substances have been extensively studied as a promising support or even an alternative for existing anti-obesity therapies. This review is dealing with the anti-obesity potential of edible and ethnomedicinal rhubarb species and emerging possible role of the rhubarb-derived extracts or individual compounds in the prevention of obesity and perspectives for their use in an anti-obesity treatment. A special emphasis is put on the most popular edible specimens, i.e., Rheum rhabarbarum L. (garden rhubarb) and Rheum rhaponticum L. (rhapontic rhubarb, Siberian rhubarb); however, the anti-obesity potential of other rhubarb species (e.g., R. officinale, R. palmatum, and R. emodi) is presented as well. The significance of rhubarb-derived extracts and low-molecular specialized rhubarb metabolites of diversified chemical background, e.g., anthraquinones and stilbenes, as potential modulators of human metabolism is highlighted, including the context of cardiovascular disease prevention. The available reports present multiple encouraging rhubarb properties starting from the anti-lipidemic action of rhubarb fibre or its use as purgative medicines, through various actions of rhubarb-derived extracts and their individual compounds: inhibition of enzymes of cholesterol and lipid metabolism, targeting of key molecular regulators of adipogenesis, regulators of cell energy metabolism, the ability to inhibit pro-inflammatory signalling pathways and to regulate glucose and lipid homeostasis contributing to overall in vivo and clinical anti-obesity effects.

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Oral colon-specific drug delivery system reduces the nephrotoxicity of rhubarb anthraquinones when they produce purgative efficacy

Cited by 10 publications

References 20 publications

Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology

Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology

An ethnobotanical study on wild plants used by Tibetan people in Gyirong Valley, Tibet, China

A Review on Rhubarb-Derived Substances as Modulators of Cardiovascular Risk Factors—A Special Emphasis on Anti-Obesity Action

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