Affiliation:
1. Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA
70125, USA
2. Department of Chemistry, School of STEM, Dillard University, New Orleans, LA, 70122, USA
Abstract
Background:
Heparins are sulfated glycosaminoglycans that are used as anticoagulants
to treat thrombosis. Heparins exhibit other potential therapeutic effects, such as anti-inflammatory,
anti-viral, and anti-malarial effects. However, the strong anticoagulant activity of heparins poses a
risk of life-threatening bleeding, limiting their therapeutic use for other diseases beyond thrombosis.
To exploit the other effects of heparins and eliminate the bleeding risk, we explored an alternative
polymer called lignosulfonic acid sodium (LSAS), which acts as a sulfonated heparin mimetic.
LSAS targets factor XIa to exert an anticoagulant effect, and thus, unlike heparins, it is unlikely
to cause bleeding.
Methods:
This study investigated the multiple effects of LSAS to identify potential leads for complex
pathologies treatment. A series of chromogenic substrate hydrolysis assays were used to evaluate
the inhibition of three inflammation-related proteases by LSAS. Its chemical antioxidant activity
against the system of ABTS/hydrogen peroxide/metmyoglobin was also determined. Lastly, the
effect of LSAS on TNFα-induced activation of the NF-κB pathway in HEK-293 cells was also tested
to determine its cellular anti-inflammatory activity.
Results:
The results showed that LSAS effectively inhibited human neutrophil elastase, cathepsin
G, and plasmin, with IC50 values ranging from 0.73 to 212.5 μg/mL. Additionally, LSAS demonstrated
a significant chemical antioxidant effect, with an IC50 value of 44.1 μg/mL. Furthermore, at
a concentration of approximately 530 μg/mL, LSAS inhibited the TNFα-induced activation of the
NF-κB pathway in HEK-293 cells, indicating a substantial anti-inflammatory effect. An essential
advantage of LSAS is its high water solubility and virtual non-toxicity, making it a safe and readily
available polymer.
Conclusion:
Based on these findings, LSAS is put forward as a polymeric heparin mimetic with
multiple functions, serving as a potential platform for developing novel therapeutics to treat complex
pathologies.
Funder
NIGMS, National Institute of General Medical Sciences
Publisher
Bentham Science Publishers Ltd.
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