Modulation of oxidative stress, apoptosis, and calcium entry in leukocytes of patients with multiple sclerosis by Hypericum perforatum

Abstract

Objectives

Hypericum perfortarum (HP, St John's wort) is a modulator of Ca²⁺ entry in neutrophils and it may modulate intracellular free Ca²⁺ ([Ca²⁺]_i) entry in leukocytes of patients with multiple sclerosis (MS). We investigated effects of HP on oxidative stress, apoptosis, and [Ca²⁺]_i concentrations in serum and leukocytes of patients with MS.

Methods

Neutrophils of nine newly diagnosed MS patients and nine healthy subjects within four subgroups were used in the study. The first group was a control; the second group was patients with MS. The neutrophils from patient group were incubated non-specific TRPM2 channel blocker (2-APB), voltage-gated calcium channel blockers, verapamil and diltiazem (V + D) with HP before N-formyl-L-methionyl-L-leucyl-L-phenylalanine stimulation, respectively.

Results

Neutrophil and serum lipid peroxidation, neutrophil apoptosis and [Ca²⁺]_i levels in patients with MS were higher than in control although their levels were decreased by HP, 2-APB, and V + D incubations. The modulator role of V + D in MS and MS + HP groups was higher than in the 2-APB group. Neutrophilic glutathione peroxidase (GSH-Px) and serum vitamin A and E concentrations were lower in the MS group than in control. However, the neutrophil GSH-Px activity was increased by HP incubation. The neutrophil reduced glutathione, serum vitamin C and β-carotene concentrations did not change in control and patients.

Discussion

We observed that HP-induced protective effects on oxidative stress and [Ca²⁺]_i concentrations by modulating transient receptor potential and voltage gated calcium channel in the patients with MS. Thus, it may provide useful treatment of neutrophil activity in the patients.

Keywords:

• Multiple sclerosis
• Inflammation
• Intracellular Ca²⁺ concentration
• Oxidative stress
• Neutrophils
• TRP Channels

Acknowledgement

The study was supported by Scientific Research Unit of Suleyman Demirel University (Protocol Number: 2529-M-10). Abstract of the study as poster presentation was submitted in 4th International Congress on Cell Membranes and Oxidative Stress Focus on: Calcium Signaling and TRP Channels, 26–29 June 2012, Isparta, Turkey (http://www.cmos.org.tr). The authors declare that there are no conflicts of interest. Authors' Roles: M.N. formulated the present hypothesis and was responsible for writing the report. B.Ç. and M.A. were responsible analyses the data. S.K. and V.A.Y. made diagnosis and blood collection of the patients. The authors wish to thank Dr Peter J Butterworth (London, UK) for polishing English of the manuscript.