Unveiling the Unexplored Multifactorial Potential of 5-Aminosalicylic Acid in Diabetic Wound Therapy
Abstract
:1. Introduction
2. Hypothesis
3. Evaluation of the Hypothesis
3.1. 5-ASA and Inflammation
3.2. 5-ASA and Oxidation
3.3. 5-ASA and TGF-β1 Activation
3.4. 5-ASA and PPAR-γ Activation
3.5. 5-ASA and Re-Epithelialization
4. Implications
5. Conclusions
6. Future Directions and Technical Roadmap
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
List of Abbreviations
Abbreviation | Full Form |
DM | Diabetes mellitus |
DW | Diabetic wound |
DFU | Diabetic foot ulcers |
5-ASA | 5-aminosalicylic acid |
PPAR-γ | Peroxisome proliferator-activated receptor gamma |
TGF-β | Transforming growth factor beta |
ECM | Extracellular matrix |
MMP | Matrix metalloproteinase |
NF-κB | Nuclear factor-kappa B |
TNF-α | Tumor necrosis factor-alpha |
HO-1 | Heme oxygenase-1 |
TREG | Regulatory T cell |
MPO | Myeloperoxidase |
CAS | Clinical activity score |
PC | Phosphatidylcholine |
ALP | Alkaline phosphatase |
COMP | Cartilage oligomeric matrix protein |
MDA | Malondialdehyde |
SOD | Superoxide dismutase |
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Drug/ Formulation | Pharmacological Effect | Biomarkers | Type of Study Conducted | References |
---|---|---|---|---|
5-ASA-bound nanoparticles | Inflammation | Clinical activity score (CAS), colon weight/length index, myeloperoxidase (MPO) | Preexistent colitis model in mice | [39] |
5-ASA and chitosan combination | Inflammation | Clinical activity score (CAS), colon weight/length index, myeloperoxidase (MPO), alkaline phosphatase (ALP), TNF-α, IL-6, and NF-κB, p65 | Colitis model in male Swiss/CD-1 mice | [40] |
5-ASA in combination with acacia and guar gum | Inflammation | Disease activity index, colon weight/length ratio, IL-1β, NF-κB, p65, TNF-α, and IL-6 | Colitis model in male Swiss/CD-1 mice | [41] |
5-ASA and hyaluronic acid combination | Inflammation | Clinical activity index, MPO, TNF-α, IL-6, and IL-1β | Colitis model in male Swiss/CD-1 mice | [42] |
5-ASA and chitosan microspheres | Inflammation | Cell viability and expression of mRNA levels | Caco-2 cell lines | [43] |
5-ASA | Inflammation | IL-6, IL-8, COX-2, nitric oxide, glycosaminoglycan, and anabolic genes (aggrecan (ACAN), alpha-1 chain of type II collagen (COL2A1), proteoglycan 4 (PRG4), cartilage oligomeric matrix protein (COMP)) | In vitro (chondrocyte pellets) and ex vivo (osteochondral explants) human inflammatory osteoarthritis models | [44] |
5-ASA | Inflammation | NO, IL-6, induced nitric oxide synthase (iNOS), c-Jun N-terminal kinases (JNKs), p38, and NF-κB | LPS-induced murine macrophages | [45] |
5-ASA–silicon oxide nanoparticles | Inflammation | MPO, IL-6, and TNF-α | BALB/c colitis model | [46] |
5-ASA in combination with hyaluronic acid | Inflammation | MPO, COX-2, TNF-α, IL-1β, and IL-6 | TNBS-induced colitis rat model | [47] |
5-ASA gelatin-coated nanoparticles | Inflammation | TNF-α, IL-1β, COX-2, and iNOS | Dextran sodium sulfate-induced colitis murine model | [48] |
5-ASA | Oxidation | Free radicals such as hydroxyl, haloperoxyl, one-electron oxidizing, lipid peroxyl, glutathiyl, superoxide, tryptophany | Nanosecond pulse radiolysis technique coupled with transient spectrophotometry has been used for in situ generation of free radicals and to follow their reaction pathways | [49] |
5-ASA | Oxidation | ROS (O2•−, H2O2, 1O2, ROO•, and HOCl) and reactive nitrogen species (•NO and ONOO−) | Chemical scavenging validated test | [50] |
5-ASA in combination with cyanidin-3-glucoside (Cy3glc) | Oxidation | ROS and NO | LPS-activated macrophage line | [51] |
5-ASA | Oxidation | ROS species for oxidative DNA damage | Diversion colitis model in experimental Wistar rats | [52] |
5-ASA and ascorbic acid | Oxidation | Vitamin E consumption, oxygen consumption and formation of conjugated dienes | Lipid peroxidation (thermal decomposition of Azo compounds) in phosphatidylcholine (PC) liposomes as a model | [53] |
5-ASA | Oxidation | ROS and catalase | Oxidant-induced cell signaling pathways in HT-29 cells and IECs from mice | [54] |
5-ASA and vitamin E | Oxidation | Change in body weight and lactate dehydrogenase activity | Acrylamide-induced kidney injury in Wistar rat model | [55] |
5-ASA and lycopene | Oxidation and inflammation | Myeloperoxidase (MPO), malondialdehyde (MDA), and superoxide dismutase (SOD) | Colitis model in iodoacetamide rat | [56] |
5-ASA | Inflammation and PPAR-γ activation | Oxygen consumption, E. coli growth | Dextran sulfate sodium (DSS)-induced colitis murine model | [57] |
5-ASA | Inflammation and PPAR-γ activation | PPAR-γ expression, β-actin, and MPO | 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis murine model | [21] |
5-ASA | Inflammation and PPAR-γ activation | IFN-γ, NF-κB, STAT-1 and -3, SOCS-1 and -3 | 10 Gy γ-irradiation (Co source)-induced colitis rat model | [58] |
5-ASA and n-3 ploy unsaturated fatty acids | Inflammation and PPAR-γ activation | NF-κB, COX-2, and leukotriene-B4 | TNBS-induced colitis rat model | [59] |
5-ASA | Inflammation, oxidation, and proliferation | ROS, MTT assay, cell apoptosis assay, caspase-3 activity, SOD2 and wound healing assay | Indomethacin-induced injury in IEC-6 cell line of rats | [60] |
5-ASA in combination with azathioprine | Inflammation, oxidation, and proliferation | ROS and senescence-associated β-galactosidase activity, cell cycle analysis, BrdU incorporation assay, TNF-α | T-84 cell lines and small intestinal large bowel organoids from C57BL/6J wild-type and IL-10−/− (IL-10 KO) mice | [61] |
5-ASA pluronic lecitin organogel | Cell proliferation and migration | MTT assay, cell migration | Full thickness excision wound rat model | [6] |
5-ASA | Cell proliferation and migration | MTT assay, migration assay | IEC-6 in vitro wounding model | [19] |
5-ASA | Angiogenesis | Expression of VEGF, endostatin, angiostatin, TNF-α, and MMP-2 and -9 | Iodoacetamide-induced ulcerative colitis rat model | [62] |
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Sanapalli, B.K.R.; Deshpande, A.; Sanapalli, V.; Sigalapalli, D.K. Unveiling the Unexplored Multifactorial Potential of 5-Aminosalicylic Acid in Diabetic Wound Therapy. Diseases 2024, 12, 172. https://doi.org/10.3390/diseases12080172
Sanapalli BKR, Deshpande A, Sanapalli V, Sigalapalli DK. Unveiling the Unexplored Multifactorial Potential of 5-Aminosalicylic Acid in Diabetic Wound Therapy. Diseases. 2024; 12(8):172. https://doi.org/10.3390/diseases12080172
Chicago/Turabian StyleSanapalli, Bharat Kumar Reddy, Ashwini Deshpande, Vidyasrilekha Sanapalli, and Dilep Kumar Sigalapalli. 2024. "Unveiling the Unexplored Multifactorial Potential of 5-Aminosalicylic Acid in Diabetic Wound Therapy" Diseases 12, no. 8: 172. https://doi.org/10.3390/diseases12080172