The combined use of thymoquinone and metformin provides more effective neuroprotection in a mouse model of MPTPinduced Parkinson’s disease

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Kavrık O., Gümral N., Özmen Ö., Aslankoç R., Saygın M., Yalçın A.

JOURNAL OF RECEPTOR AND SIGNAL TRANSDUCTION RESEARCH, cilt.6, ss.1-13, 2024 (SCI-Expanded, Scopus)

Özet

Thymoquinone (TQ) is known for its antioxidant properties, and although metformin (MM) is known as

an antidiabetic drug, it is suggested that it reduces neurodegeneration. The study aimed to investigate

the neuroprotective effects of TQ and MM, particularly when used together, in relation to Parkinson’s

disease (PD). In the study, sixty-eight male C57BL/6 mice weighing 25–30 g were divided into five

groups as follows: control, MPTP, MPTPþTQ, MPTPþMM, and MPTPþTQþMM. MM (500 mg/kg, orally)

and TQ (5 mg/kg, i.p.) were administered for 21 days. Motor coordination and locomotor activities

were evaluated by the pole test. TOS and TAS analyses were conducted to determine oxidative stress

levels in the substantia nigra. Dopaminergic degeneration in the substantia nigra was evaluated by

analyzing Tyrosine hydroxylase (TH). To evaluate the apoptotic pathway, the expression levels of iNOS,

BDNF, Complex 1, Bax, Bcl-2, Cytochrome C, AIF, and Caspase-3 were examined immunohistochemically.

Compared to the MPTP-treated group, TQ, MM and MMþTQ treatment provided significant

improvement in locomotor activity in mice, significantly increased antioxidant activity, significantly

reduced the expression levels of iNOS, Bax, Cytochrome C, Caspase-3, and AIF, significantly increased

BDNF, Bcl-2, and Complex 1 expressions, and significantly increased the number of TH positive cells.

The separate use of TQ and MM exhibits neuroprotective activity, however, we showed that using TQ

and MM in combination may be more effective. This may provide preclinical evidence supporting the

therapeutic potential of their combined use for treating PD.