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Neuroinflammation is often associated with a localized oxidative stress at the level of the morphofunctional unit. The latter comprises the venous microcirculation, the nervous perivascular system and mast cells, and normally regulates cross-talk between nerve cells and the vascular endothelium. This neuroinflammation is sustained by mast cell hyperreactivity, and leads to a markedly altered neuro-vascular homeostatic balance. Factors of neurogenic, immunogenic, psychogenic, hormonal, microbial and thermal origin contribute to onset of mast cell hyper-reactivity, leading to impaired micro-vascular permeability and local neoinnervation and neoangiogenesis, and resultant increased microvascular district, tissue fibroblasts activation and proliferation.
The above are cellular features of Chronic Venous Insufficiency (CVI), a disease with high incidence, especially in females. It is usually manifested by signs such as varicose veins, edema, venous eczema, hyperpigmentation of the leg skin, atrophie blanche and lipodermatosclerosis with venous ulcers, fibrosis and subcutaneous fat accumulation. Symptoms more frequently related to CVI include pain, heaviness, a swollen feeling in legs, muscle cramps, itching/tingling of the lower limbs and restless leg syndrome.
Under these conditions, it has been shown that the regulatory action exerted by micron-size Palmitoylethanolamide on the mast cell, through a completely physiological mechanism (ALIA mechanism), in sinergy with the effect on the localized oxidative stress performed by the Polydatin, contributes to the normalization of neuroinflammation favoring the neuro-vasal homeostasis (NEVA homeostasis).

Bibliografia

Aloe L. and Levi-Montalcini R. A proposed autacoid mechanism controlling mastocyte behaviour. Agents Actions. 1993
Esposito E. et al. A new co-micronized composite containing palmitoylethanolamide and polydatin shows superior oral efficacy compared to their association in a rat paw model of carrageenan-induced inflammation. Eur J Pharmacol. 2016.
Gugliandolo E. et al. Palmitoylethanolamide and Polydatin combination reduces inflammation and oxidative stress in vascular injury. Pharmacological research. 2016
Rinne P. Palmitoylethanolamide promotes antiinflammatory phenotype of macrophages and attenuates plaque formation in ApoE/mice. Cardiovascular Research Supplements. 2016
Wang HL. Comparative studies of polydatin and resveratrol on mutual transformation and antioxidative effect in vivo. Phytomedicine. 2015