The Potential of Vinpocetine in the Treatment of Cardiovascular Diseases

Vinpocetine

Vinpocetine is a synthetic derivative of vincamine, an alkaloid derived from the periwinkle plant (Vinca minor). In Asia and Europe, it has been used for many years in the prevention and treatment of neurological disorders such as dementia, memory impairments, and ischemic stroke (iCMP). In the USA, it is sold as a dietary supplement and memory enhancer.

It is typically taken 3 times a day at a dose of 5–10 mg (15–30 mg/day) due to its short biological half-life (1–2 hours). It is rapidly absorbed from the gastrointestinal tract and readily crosses the blood-brain barrier. To date, no significant or severe adverse effects have been reported, and at therapeutic doses, it has no contraindications apart from hypersensitivity to the active substance.

Mechanism of Action

Vinpocetine acts on several targets within the body. These include Ca²⁺/calmodulin-stimulated phosphodiesterase 1 (PDE1), voltage-gated Na⁺ channels, and IκB kinase (IKK). It is presumed that by inhibiting PDE1, vinpocetine acts against pathological remodeling of the heart and blood vessels. Through the inhibition of voltage-gated Na⁺ channels, it functions neuroprotectively, and as an IKK inhibitor, it suppresses NF-κB-dependent inflammation. The anti-inflammatory effects of vinpocetine have been described in various types of cells—epithelial and endothelial cells, vascular smooth muscle cells, monocytes/macrophages, neutrophils, dendritic cells, microglia, and astrocytes.

Described Effects

Preclinical and clinical studies with vinpocetine suggest multiple effects, including vasodilation, antioxidant and anti-inflammatory action, prevention of pathological remodeling of the heart and blood vessels, and suppression of lipid uptake, achieved through the synergy of its effects on various pharmacological targets. Given that the development of CV diseases results from a complex process involving multiple cells and intercellular interactions, vinpocetine could be beneficial due to its multiple effects.

In animal models, its inhibitory effect on the development of atherosclerosis has been described. This effect may be achieved through its actions against lipid uptake by macrophages, osteoblast differentiation of vascular smooth muscle cells, oxidative stress, and inflammation. Vinpocetine also demonstrated a reduction in platelet aggregability, and its administration led to a decreased risk of thrombosis and hemorrhage into atherosclerotic plaques in a murine model of atherosclerosis. Another effect is the suppression of pathological vascular remodeling by inhibiting the proliferation of vascular smooth muscle cells. Vinpocetine also has a documented vasodilation effect, probably mediated by the inhibition of PDE1A.

A recent study revealed cardioprotective effects of vinpocetine in a mouse model of myocardial infarction. Vinpocetine increased the activity and amount of antioxidant enzymes in animals. Its effect against pathological myocardial remodeling in a mouse model of cardiomyopathy where it suppressed angiotensin II-stimulated cardiomyocyte hypertrophy and cardiac fibroblast activation was also observed.

Several works have shown the protective effect of vinpocetine against brain damage associated with ischemia. In an animal model of cerebral ischemia, it reduced mortality induced by hypoxia, hippocampal neuron damage, infarct volume, and improved the recovery of motor functions. In clinical studies, treatment with vinpocetine in iCMP patients was associated with increased cerebral blood flow, better glucose uptake and oxygen utilization in the brain, better recovery of neurological functions, slower growth of the infarct lesion, and better cognitive outcomes in the acute phase and several months after iCMP. These effects could be achieved by vinpocetine acting against inflammation, thrombosis, and neuronal damage and death.

Conclusion

Although not all molecular mechanisms of these newly observed effects of vinpocetine are precisely elucidated, these findings, along with previous knowledge, could lead to broader utilization of vinpocetine in the prevention and treatment of CV diseases in humans. However, the results achieved in experimental studies need to be verified in clinical evaluations.

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Sources:
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