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Global Translational Medicine Impact of flavonoids on vascular health

factor kappa-light-chain-enhancer of activated B cells minimize the size of the injury and reduce blood loss,
(NF-κB). Activation of NF-κB leads to the upregulation resulting in vascular spasms. Collagen, found in the vessel
of pro-inflammatory mediators such as inducible NO walls, becomes exposed to the blood when vessels are
synthase (iNOS), COX-2, TNF-α, and interleukin-6 (IL-6). damaged, promoting platelet adhesion at the injury site
Moreover, NF-κB activation is intricately associated with where collagen fibers are exposed. On contact with this
the mitogen-activated protein kinases (MAPKs), pivotal collagen, platelets release cytoplasmic granules containing
components in the propagation of pro-inflammatory serotonin, ADP, and thromboxane A (TXA ), leading
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responses correlated with endothelial dysfunction. to vasoconstriction. To address the remaining issue,
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A plethora of investigations substantiate the inhibitory platelets activate each other and simultaneously initiate
effects of flavonoids on the redox-sensitive NF-κB/MAPK the coagulation cascade to form a blood clot. Platelet
signaling pathway, thereby demonstrating their anti- activation plays a central role in both protective hemostasis
inflammatory properties. 79-81 and pathological thrombosis through various physiological
Flavonoids exhibit the capacity to impede the pathways. Excessive platelet aggregation is closely linked to
proliferation, migration, and tube formation of endothelial several chronic diseases, including diabetes, hypertension,
cells, potentially facilitating their antiangiogenic and various CVDs. 68
properties. This effect often correlates with a reduction in High concentrations of adhesion proteins, resulting
the expression of vascular endothelial growth factor. 83,84 from excessive platelet activation, lead to the generation
Additionally, flavonoids have demonstrated the ability of thrombi, contributing to the development of various
to inhibit proliferation, mitigate hypertrophy, or induce thrombotic diseases. This development is primarily due to
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apoptosis in VSMCs in culture, thereby potentially limiting thrombi clogging narrow blood vessels, causing blockages
vascular remodeling. These inhibitory effects on VSMC in or near the affected areas. TXA , released during platelet
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hypertrophy and DNA synthesis are believed to be linked activation, acts as a potent vasoconstrictor and platelet
to reduced MAPK activity. 85,86 activator. Synthesized in platelets by the cytoplasmic
Despite the potential of flavonoid-rich foods to increase COX enzyme from arachidonic acid sourced from platelet
NO bioavailability and combat vascular disorders, their membranes, it undergoes conversion into TXA through
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low in vivo bioavailability remains a significant hurdle either the TXA or PGI pathways. This conversion process,
in clinical applications. This limitation is attributed to facilitated by COX-1, is crucial for platelet activation.
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poor absorption, rapid metabolism, and degradation. Given TXA ’s role in platelet recruitment and activation,
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Clinical studies have reported significantly lower plasma blocking COX can potentially reduce platelet activation
concentrations of orally administered flavonoids compared and aggregation at or near the injury site. Flavonoids
to those used in in vitro and in vivo experiments, potentially demonstrate several beneficial effects, including improved
insufficient to achieve protective effects on endothelial endothelial functioning, reduced platelet adhesion, and
function. 63,87 Overcoming this challenge hinges on interference in lipid metabolism. 71
addressing the factors contributing to low bioavailability,
including extensive metabolism and the impact of gut Flavonoids function as antagonists of TXA receptors
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microbiota on absorption. 88-90 located on the platelet membrane, influencing TXA2
receptor levels that regulate COX expression. The presence
4. Flavonoids-induced effects in relation to of flavonoids indirectly inhibits COX-1 activity, resulting
vasodilation in platelet inactivation. Structural features of flavonoids,
such as double bonds at C2 – C3 and a keto group at
4.1. Antiplatelet effects C4, enable tight stearic binding to TXA receptors. Non-
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Platelets, smaller blood corpuscles, are pivotal in the glucuronidated flavonoids such as genistein and daidzein
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coagulation process for hemostasis, preventing bleeding. hinder platelet aggregation by binding to TXA surface
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Intact blood vessels inhibit clotting, while any injury receptors. Collagen, a key initiator of platelet aggregation,
activates them. The regulation of this process occurs is influenced by flavonoids, which not only intervene in
through the endothelial lining, which secretes inhibitors arachidonic acid metabolism but also impact collagen
of coagulation and platelet aggregation when undamaged. metabolism, reducing platelet aggregation. Flavonoids
However, on rupture, this endothelial lining releases von minimize oxidative stress, a trigger for collagen-
Willebrand factor (vWF), a crucial molecule maintaining induced platelet aggregation, by acting as NADPH
hemostasis in humans. On injury to blood vessels, local oxidase inhibitors. Plant extracts containing flavonoids
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sympathetic pain receptors trigger an immediate reflex exert antiplatelet effects through various mechanisms,
response. The damaged vessels undergo constriction to including the inhibition of intracellular Ca to prevent
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Volume 3 Issue 2 (2024) 6 doi: 10.36922/gtm.2458