Tetramethylpyrazine identified by a network pharmacology approach ameliorates methotrexate-induced oxidative organ injury

Zhang, Bo; Lü, Cheng; Bai, Ming; He, Xiaojuan; Tan, Yong; Bian, Yanqin; Xiao, Cheng; Zhang, Ge; Lü, Aiping; Li, Shao

doi:10.1016/j.jep.2015.09.034

Cited by 19 publications

(13 citation statements)

References 58 publications

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“…Previously, we have suggested that target profiles predicted using computational approaches (eg, drugCIPHER-CS) might also help to solve this problem, as has been demonstrated elsewhere [14,15] . To computationally determine the target-specific effects derived from nuciferine treatment, we mapped the target profile of nuciferine on signaling pathways from the KEGG database and biological processes from gene ontology tools [27] and diseases in OMIM [28] .…”

Section: Resultsmentioning

confidence: 83%

“…Vitexicarpin has been found to specifically target AKT and SRC in the VEGF pathway [14] . Another example is the identification of tetramethylpyrazine from Ligusticum wallichii Franchat as a potent compound for alleviating oxidative organ injury induced by methotrexate [15] . In this study, we utilized a clustering analysis approach based on the target profiles predicted by drugCIPHER-CS to predict several potential antitumor compounds from an herbal compound database.…”

Section: Introductionmentioning

confidence: 99%

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Identification of the anti-tumor activity and mechanisms of nuciferine through a network pharmacology approach

et al. 2016

Acta Pharmacol Sin

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Aim: Nuciferine is an aporphine alkaloid extracted from lotus leaves, which is a raw material in Chinese medicinal herb for weight loss. In this study we used a network pharmacology approach to identify the anti-tumor activity of nuciferine and the underlying mechanisms. Methods: The pharmacological activities and mechanisms of nuciferine were identified through target profile prediction, clustering analysis and functional enrichment analysis using our traditional Chinese medicine (TCM) network pharmacology platform. The antitumor activity of nuciferine was validated by in vitro and in vivo experiments. The anti-tumor mechanisms of nuciferine were predicted through network target analysis and verified by in vitro experiments. Results: The nuciferine target profile was enriched with signaling pathways and biological functions, including "regulation of lipase activity", "response to nicotine" and "regulation of cell proliferation". Target profile clustering results suggested that nuciferine to exert anti-tumor effect. In experimental validation, nuciferine (0.8 mg/mL) markedly inhibited the viability of human neuroblastoma SY5Y cells and mouse colorectal cancer CT26 cells in vitro, and nuciferine (0.05 mg/mL) significantly suppressed the invasion of 6 cancer cell lines in vitro. Intraperitoneal injection of nuciferine (9.5 mg/mL, ip, 3 times a week for 3 weeks) significantly decreased the weight of SY5Y and CT26 tumor xenografts in nude mice. Network target analysis and experimental validation in SY5Y and CT26 cells showed that the anti-tumor effect of nuciferine was mediated through inhibiting the PI3K-AKT signaling pathway and IL-1 levels in SY5Y and CT26 cells. Conclusion: By using a TCM network pharmacology method, nuciferine is identified as an anti-tumor agent against human neuroblastoma and mouse colorectal cancer in vitro and in vivo, through inhibiting the PI3K-AKT signaling pathways and IL-1 levels.

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Section: Resultsmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Identification of the anti-tumor activity and mechanisms of nuciferine through a network pharmacology approach

et al. 2016

Acta Pharmacol Sin

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“…Zhang et al . have found that tetramethylpyrazine, a compound isolated from Ligusticum wallichii Franchat, ameliorates oxidative organ injury associated with methotrexate treatment in patients with rheumatoid arthritis . These examples illustrate the possibility of utilizing herbal compounds in combination therapeutics.…”

Section: Drug Selection For Combination Therapeuticsmentioning

confidence: 96%

Combination therapeutics in complex diseases

Lü

Zheng

et al. 2016

J Cellular Molecular Medi

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The biological redundancies in molecular networks of complex diseases limit the efficacy of many single drug therapies. Combination therapeutics, as a common therapeutic method, involve pharmacological intervention using several drugs that interact with multiple targets in the molecular networks of diseases and may achieve better efficacy and/or less toxicity than monotherapy in practice. The development of combination therapeutics is complicated by several critical issues, including identifying multiple targets, targeting strategies and the drug combination. This review summarizes the current achievements in combination therapeutics, with a particular emphasis on the efforts to develop combination therapeutics for complex diseases.

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“…While the recent MTX study has shown some beneficial effects of resveratrol at a low dose in a cancer‐free treatment model in rats, future studies will be needed to investigate potential treatment effects of resveratrol, optimal dosage, and mechanisms of action in modulating the adverse effects of MTX and other cancer drugs on bone and other tissues in normal animals (or humans) or in cancer‐bearing experimental models (or humans) . Previously, MTX was shown to induce oxidative stress and damage liver, kidney, and bone marrow . However, it remains to be investigated whether MTX can also induce potential oxidative stress in bone and, if so, whether it can be attenuated by resveratrol.…”

Section: Potential Strategies For Preventing Methotrexate‐induced Bonmentioning

confidence: 99%

Childhood cancer chemotherapy–induced bone damage: pathobiology and protective effects of resveratrol and other nutraceuticals

Chen

Hassanshahi

et al. 2017

Annals of the New York Academy of Sciences

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Intensive cancer chemotherapy causes significant bone loss, for which the mechanisms remain unclear and effective treatments are lacking. This is a significant issue particularly for childhood cancers, as the most common ones have a >75% cure rate following chemotherapy; there is an increasing population of survivors who live with chronic bone defects. Studies suggest that these defects are the result of reduced bone from increased marrow fat formation and increased bone resorption following chemotherapy. These changes probably result from altered expression/activation of regulatory molecules or pathways regulating skeletal cell formation and activity. Treatment with methotrexate, an antimetabolite commonly used in childhood oncology, has been shown to increase levels of proinflammatory/pro-osteoclastogenic cytokines (e.g., enhanced NF-κB activation), leading to increased osteoclast formation and bone resorption, as well as to attenuate Wnt signaling, leading to both decreased bone and increased marrow fat formation. In recent years, understanding the mechanisms of action and potential health benefits of selected nutraceuticals, including resveratrol, genistein, icariin, and inflammatory fatty acids, has led to preclinical studies that, in some cases, indicate efficacy in reducing chemotherapy-induced bone defects. We summarize the supporting evidence.

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Tetramethylpyrazine identified by a network pharmacology approach ameliorates methotrexate-induced oxidative organ injury

Cited by 19 publications

References 58 publications

Identification of the anti-tumor activity and mechanisms of nuciferine through a network pharmacology approach

Identification of the anti-tumor activity and mechanisms of nuciferine through a network pharmacology approach

Combination therapeutics in complex diseases

Childhood cancer chemotherapy–induced bone damage: pathobiology and protective effects of resveratrol and other nutraceuticals

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