Synergistic enhancement and hepatoprotective effect of combination of total phenolic extracts of Citrus aurantium L. and methotrexate for treatment of rheumatoid arthritis

Dan He, Zhenli Liu*, Menglei Wang, Yisong Shu, Siyu Zhao, Zhiqian Song, Hui Li, Linlin Liu, Wei Liang, Wen Li, Zhiwen Cao, Cheng Lu, Aiping LYU, Yuanyan Liu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder characterized by joint destruction and bone damage. Methotrexate (MTX) is recommended as the first-line disease-modifying agent for the treatment of RA. However, the clinical efficacy of MTX is limited due to its low response and side effects, especially hepatotoxicity. Total phenolic extracts of Citrus aurantium L. (TPE-CA) are rich in dietary bioactive flavonoids, which show beneficial effects on liver health and are regarded as therapeutic tools against inflammatory diseases. In this study, the efficacy of MTX, alone or in combination with TPE-CA, for the treatment of collagen-induced arthritis and protection against hepatic injury in rats was investigated. TPE-CA and MTX combination effectively reduced the inflammatory symptoms and joint damage by inhibiting the NF-κB pathway. Moreover, TPE-CA significantly ameliorated MTX-induced chronic hepatic injury by enhancing antioxidant enzymes activities, suppressing hepatic cytochrome P450 2E1 expression, and modulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway. This combination regimen not only provided synergistic enhancement but also exhibited hepatoprotective effect against chemically induced chronic hepatotoxicity. This could be an alternative strategy to improve the low response of MTX in RA treatment.

Original languageEnglish
Pages (from-to)1122-1133
Number of pages12
JournalPhytotherapy Research
Volume33
Issue number4
DOIs
Publication statusPublished - Apr 2019

Scopus Subject Areas

  • Pharmacology

User-Defined Keywords

  • antiinflammation
  • hepatotoxicity
  • methotrexate
  • rheumatoid arthritis
  • total phenolic extracts of Citrus aurantium L

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