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Review
. 2022 Dec;395(12):1463-1475.
doi: 10.1007/s00210-022-02284-6. Epub 2022 Sep 5.

Citicoline and COVID-19: vis-à-vis conjectured

Hayder M Al-Kuraishy  1 , Ali K Al-Buhadily  1 , Ali I Al-Gareeb  1 , Mohammed Alorabi  2 , Nasser A Hadi Al-Harcan  3 , Maisra M El-Bouseary  4 , Gaber El-Saber Batiha  5
Affiliations
Review

Citicoline and COVID-19: vis-à-vis conjectured

Hayder M Al-Kuraishy et al. Naunyn Schmiedebergs Arch Pharmacol. 2022 Dec.

Abstract

Coronavirus disease 2019 (COVID-19) is a current pandemic disease caused by a novel severe acute respiratory syndrome coronavirus virus respiratory type 2 (SARS-CoV-2). SARS-CoV-2 infection is linked with various neurological manifestations due to cytokine-induced disruption of the blood brain barrier (BBB), neuroinflammation, and peripheral neuronal injury, or due to direct SARS-CoV-2 neurotropism. Of note, many repurposed agents were included in different therapeutic protocols in the management of COVID-19. These agents did not produce an effective therapeutic eradication of SARS-CoV-2, and continuing searching for novel anti-SARS-CoV-2 agents is a type of challenge nowadays. Therefore, this study aimed to review the potential anti-inflammatory and antioxidant effects of citicoline in the management of COVID-19.

Keywords: COVID-19; Citicoline; Neuroinflammation; SARS-CoV-2.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Chemical structure of citicoline
Fig. 2
Fig. 2
Neuroprotective effect of citicoline (CTN): CTN, through its anti-inflammatory and antioxidant effects as well as through induction of neurogenesis and neuronal energy, attenuates neurodegeneration and neuroinflammation, respectively. CTN induces expression of silent information regulator 1 (SIRT1), which inhibits neuroinflammation and produces a direct neuroprotective effect. The final effect of CTN is neuroprotection
Fig. 3
Fig. 3
Citicoline reduces SARS-CoV-2-induced neuroinflammation through a silent information regulator 1 (SIRT1)-dependent pathway: citicoline (CTN) increases expression of forkhead box O (Foxo) and adenosine monophosphate protein kinase (AMPK) with inhibition expression of disintegrin and metalloproteinase 17 (ADAM17) and p53 with subsequent inhibition of SARS-CoV-2-induced oxidative stress, neuroinflammation, and release of pro-inflammatory cytokines leads to inhibition of SARS-CoV-2-induced neuroinflammation
Fig. 4
Fig. 4
The possible role of citicoline in SARS-CoV-2-induced neuroinflammation: citicoline (CTN) activates the hypothalamic pituitary axis (HPA), acetylcholine (Ach), dopamine (DPM), silent information regulator 1 (SIRT1) and inhibits inflammation, oxidative stress, and glutamine release (Glu), leading to attenuation of SARS-CoV-2-induced neuroinflammation
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