Sulfated oligosaccharides having anti-inflammatory activity
Provided herein are small molecule compounds, including non-anticoagulant heparan sulfate oligosaccharide molecules, having anti-inflammatory properties and capable of interacting with high mobility group box 1 (HMGB1) proteins in a manner sufficient to affect an interaction between the HMGB1 protein and a receptor for advanced glycation end products (RAGE). Also provided herein are methods of treating Paracetamol (APAP) overdose in subjects.
1. A method of treating a subject, the method comprising:
providing a subject to be treated, wherein the subject is suffering from inflammation; and
administering to the subject a small molecule compound having an anti-inflammatory property, the small molecule compound comprising a non-anticoagulant heparan sulfate oligosaccharide molecule comprising one of the following structural formulas:
wherein R 3 is H or a detectable tag.
2. The method of claim 1 , wherein the subject suffers from any injury resulting in increased inflammation.
3. The method of claim 1 , wherein the subject suffers from liver injury.
4. The method of claim 1 , wherein the subject in need of treatment is a subject suffering from an overdose of Paracetamol (APAP).
5. The method of claim 1 , wherein the subject in need of treatment is a human subject.
6. The method of claim 1 , wherein the small molecule compound comprises a disaccharide structure unit as shown:
wherein R=—H or —SO 3 H.
7. The method of claim 6 , wherein the small molecule compound comprising a disaccharide structure unit is selected from the group consisting of non-anticoagulant heparin, non-anticoagulant low-molecular weight heparin, and O-desulfated heparin (ODSH).
8. The method of claim 1 , wherein the oligosaccharide molecule comprises about 10 to about 20 saccharide units, or about 12 to about 18 saccharide units.
9. The method of claim 1 , wherein the oligosaccharide molecule comprises about 18 saccharide units.
10. The method of claim 1 , wherein the oligosaccharide molecule comprises one of the following structures:
11. The method of claim 1 , wherein administration of the oligosaccharide molecule decreases neutrophil infiltration in the subject.
12. The method claim 1 , wherein administration of the oligosaccharide molecule decreases inflammation in the subject.
13. The method claim 1 , wherein administration of the oligosaccharide molecule protects against liver damage and multi-organ system failure in the subject.
14. The method claim 1 , wherein the subject to be treated suffers from drug-induced inflammation.
15. A method of treating Paracetamol (APAP) overdose in a subject, the method comprising:
providing a subject in need of treatment for APAP overdose;
administering to the subject a small molecule compound having an anti-inflammatory property, the small molecule compound comprising a non-anticoagulant heparan sulfate oligosaccharide molecule comprising one of the following structural formulas:
wherein R 3 is H or a detectable tag and wherein damage from the APAP overdose in the subject is mitigated.
16. The method of claim 15 , wherein the treatment for the APAP overdose in the subject is effective between 0 hours and 24 hours after the overdose, or at least within 12 hours after the overdose.
17. The method of claim 15 , wherein the treatment for the APAP overdose in the subject comprises protection against liver injury and/or multi-organ system failure.
18. The method of claim 15 , wherein the treatment for the APAP overdose in the subject comprises a decrease in neutrophil infiltration in the subject.
19. The method of claim 15 , wherein the treatment for the APAP overdose in the subject comprises blocking an interaction between a high mobility group box 1 (HMGB1) protein and a receptor for advanced glycation endproducts (RAGE).
20. The method of claim 15 , wherein the small molecule compound comprises a disaccharide structure unit as shown:
wherein R=—H or —SO 3 H.
21. The method of claim 20 , wherein the small molecule compound comprising a disaccharide structure unit is selected from the group consisting of non-anticoagulant heparin, non-anticoagulant low-molecular weight heparin, and O-desulfated heparin (ODSH).
22. The method of claim 15 , wherein the oligosaccharide molecule comprises about 10 to about 20 saccharide units, or about 12 to about 18 saccharide units.
23. The method claim 15 , wherein the oligosaccharide molecule comprises about 18 saccharide units.
24. A method of treating Paracetamol (APAP) overdose in a subject, the method comprising:
providing a subject in need of treatment for APAP overdose;
administering to the subject a non-anticoagulant heparan sulfate oligosaccharide molecule having an anti-inflammatory property,
wherein damage from the APAP overdose in the subject is mitigated, and wherein the oligosaccharide molecule comprises one of the following: