A perfect couple: Masquelier's OPCs and Zinc

Masquelier's OPCs can act as zinc-ionophores. In terms of vascular health, this means that OPCs and zinc now form a wonderful couple that support the microvasculature's dynamic and constantly active urge to maintain its optimum structure and function and, as such, perform its essential role in overall human health.
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The health benefits of the essential trace mineral zinc are numerous and undisputed. To name a few: zinc protects cells, DNA, proteins and fats against oxidative damage; plays a role in the process of cell division; helps digest sugars and starches; contributes to fertility and reproduction; supports hair, nail and bone growth; contributes to a healthy skin, normal eyesight and cognitive function. Zinc is also known to reduce viral replication and boost immune responses. This is why a deficiency in Zinc leads to the detoriation of many bodily structures and functions, but also to increased severity of COVID-19 and other viral infections. That zinc is such a crucial factor in so many seemingly unrelated biological systems and pathways mainly stems from the fact that it is involved in the synthesis and activation of various proteins and enzymes that facilitate vital extra- and intracellular functions. And that's precisely where Masquelier's OPCs come in.

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The interplay between Masquelier's OPCs and Zinc can best be understood when we focus on the dynamic processes that take place at the level of the microvasculature, which is the thinnest and most fragile "capillary" trajectory of the vascular system. The capillaries or "hair vessels" form the wall of separation between the blood and the tissues. This wall consists of nothing but cells embedded in a matrix of collagen and elastin. These – "endothelial" – cells have the unique function of regulating the transport of oxygen and nutrients from the blood to the tissues and, vice versa, carbon dioxide and waste materials from the tissues to the blood. Moreover, the "endothelium" also plays a role in the regulation of blood clotting, inflammation and blood pressure.

The extracellular matrix (ECM) that surrounds and supports the endothelial cells is not a rigid "concrete" structure. It is a plastic living tissue that is constantly being broken down and rebuilt to keep it in optimum shape. In this continuous remodelling of the ECM, enzymes that go by the name of "Matrix MetalloProteinases" ("MMPs") are the "cutters" that break down the matrix's worn out or damaged structures of collagen and elastin. To prevent a "runaway" breakdown of the ECM that would lead to leakage and edema, these "cutters" are controlled by proteins that inhibit and modulate their "cutting" activity. They go by the name of "TIMPs". The TIMPs fine-tune when and where the "cutting" occurs thus allowing the "re-modelling" to take place in an orderly way. Excessive MMP activity drives uncontrolled degradation, inflammation, or metastasis, whereas excess TIMP activity impairs remodelling and leads to scarring and clustering of the ECM's constituents ("fibrosis"). 

This interplay between MMPs and TIMPs depends on the relationship that each of these substances entertains with zinc. In turn, these relationships depend in great measure on the state of oxidation in the extracellular the environment. Oxidative stress can activate precursors of MMPs and turn them into active ones by disrupting their bond with zinc. Anti-oxidative conditions and interactions between TIMPs and zinc restore the latters' capacity to inhibite the MMPs. This is how, under the influence of the state of oxidation, the zinc-dependent MMP–TIMP system continuously oscillates between controlled degradation and reconstruction, sustaining ECM integrity and physiological renewal. Zinc functions as the on-off switch in this delicate interplay. Oxidative stress flips the switch on while the antioxidant state flips it off again.

New data presented recently by a Spanish group of researchers show that Masquelier's OPCs are capable of transporting zinc into and throughout the extracellular matrix. [I] As zinc-carriers, OPCs thus modulate the trace-element's availability, but they do so without directly disturbing or interfering with the remodelling functions of MMP's and TIMPs. At the same time, OPCs' main action remains their well-known protection of the ECM's collagen & elastin structures against oxidative stress and enzymatic degradation. In addition to this, OPCs also mitigate inflammatory signals that drive excessive MMP expression. This is how OPCs contribute to keeping the ECM in optimum shape without compromising the enzymes’ physiological remodelling activity. The new "ionophore" findings now open the possibility of clarifying how this extracellular balance might connect with intracellular regulation of oxidative stress through zinc. 

The new study not only shows that OPCs can bind zinc and deliver it in the extracellular matrix, but that, as versatile "ionophores", OPCs are also capable of facilitating zinc's passage into the endothelial cells across the membranes that envelop them. At the inner side of the cell's membrane, OPCs release the zinc so that it can be picked up by intracellular carriers which deliver it to zinc-dependent antioxidant enzymes such as superoxide dismutase (SOD) and glutathione-related systems. In addition, zinc is now made available for modulating a specific protein-complex that is involved in cellular responses to stimuli such as stress, free radicals, heavy metals, ultraviolet irradiation and oxidized cholesterol (LDL). An incorrect or disturbed regulation of this protein-complex has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. 

There is hardly any physological process that can function without the beneficial involvement of zinc. The human body cannot store zinc reserves, so we need carriers to pick it up and bring it to where it is needed. The Spanish team of researchers has now conclusively demonstrated that Masquelier's OPCs deserve their place in the family of "ionophores" that shuttle zinc across the cells' mebrane and that OPCs complement the body's zinc-transport system. In the field of vascular health, this means that OPCs and zinc now form a wonderful couple that supports the microvasculature's dynamic and constantly active urge to maintain its optimum structure and function and, as such, perform its essential role in overall human health.

[I] Assessing the interaction of Masquelier’s oligomeric proanthocyanidin (OPC) botanical extracts with zinc; Teresa Mairal-Lerga, Vasso Skouridou, Mayreli Ortiz, Ciara K. O’Sullivan; Interfibio Research Group, Departament d´Enginyeria Química, Universitat Rovira i Virgili, 43007 Tarragona, Spain; Institució Català de Recerca i Estudis Avençats (ICREA), 08010 Barcelona, Spain. Pre-publication paper; 2025.