Hesperidin mitigates inflammation and modulates ectoenzymes activity and some cellular processes in complete Freund's adjuvant-induced arthritic rats

J Pharm Pharmacol. 2021 Oct 7;73(11):1547-1561. doi: 10.1093/jpp/rgab100.

Abstract

Objectives: This study was aimed at assessing the anti-arthritic effects of hesperidin on the inflammatory markers in serum/plasma, ectoenzymes activity in platelet, reactive oxygen species (ROS), apoptosis and cell cycle in bone marrow cells of a rat model of arthritis.

Methods: Fifty-six adult female Wistar rats (245-274 g) were grouped into eight of seven rats each: control rats given normal saline or 40 mg/kg of hesperidin or 80 mg/kg of hesperidin, 0.2 mg/kg of dexamethasone, arthritic rats given normal saline, or 40 mg/kg of hesperidin or 80 mg/kg of hesperidin, and 0.2 mg/kg of dexamethasone. Myeloperoxidase and nitrate plus nitrite levels were evaluated in the plasma and serum, respectively. The ecto-nucleoside triphosphate diphosphohydrolases, ecto-5'-nucleotidase and ecto-adenosine deaminase activities were assessed in platelets. Subsequently, the cells of the bone marrow were obtained, and the assays for ROS, apoptosis and cell cycle were evaluated using flow cytometry.

Key findings: The results showed that hesperidin mitigated inflammation, modulated adenosine nucleotides and nucleoside hydrolysing enzymes and levels, minimized ROS intracellularly, attenuated apoptotic process and activated cell cycle arrest in arthritic rat.

Conclusion: This study suggests that hesperidin could be a natural and promising anti-inflammatory compound for the management of arthritis.

Keywords: apoptosis; cell cycle; ectoenzymes; flow cytometry; hesperidin; reactive oxygen species.

MeSH terms

  • 5'-Nucleotidase / metabolism
  • Adenosine Deaminase / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Apoptosis
  • Arthritis, Experimental* / drug therapy
  • Arthritis, Experimental* / metabolism
  • Arthritis, Experimental* / pathology
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Cell Cycle Checkpoints / drug effects*
  • Citrus / chemistry*
  • Female
  • Freund's Adjuvant
  • Hesperidin / pharmacology*
  • Hesperidin / therapeutic use
  • Hydrolases / metabolism*
  • Inflammation* / metabolism
  • Inflammation* / prevention & control
  • Membrane Proteins / metabolism
  • Nucleoside-Triphosphatase / metabolism
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Pyrophosphatases
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism

Substances

  • Anti-Inflammatory Agents
  • Membrane Proteins
  • Plant Extracts
  • Reactive Oxygen Species
  • Freund's Adjuvant
  • Hesperidin
  • Hydrolases
  • 5'-Nucleotidase
  • Ada protein, rat
  • Adenosine Deaminase
  • Pyrophosphatases
  • Nucleoside-Triphosphatase