Scholarlink

Background <p>Diabetic foot ulcers (DFUs), a debilitating manifestation of diabetes mellitus, involve persistent inflammation, oxidative stress, and impaired wound healing, largely driven by NF-κB overactivation. Amlexanox (ALX), a synthetic anti-inflammatory and antioxidant agent, was evaluated for its therapeutic potential in DFUs.</p> Methods <p>In-silico molecular docking and pharmacokinetic studies were conducted to predict ALX’s interactions with major DFU targets and to assess its topical suitability. STZ-induced diabetic rats with full-thickness foot ulcers (5&#xa0;mm) received topical ALX (2.5% and 5%) or silver sulfadiazine ointments for 14&#xa0;days. Wound closure, antioxidant enzymes, oxidative stress markers, connective tissue markers, pro-inflammatory markers and NF-κB expression were assessed in the wound tissue.</p> Results <p>ALX demonstrated strong binding to the pathological targets (NF-κB, MMP-9, MPO, and COX-2) and displayed a favourable PK profile. Moreover, ALX topical treatment did not normalise diabetic metabolic alterations, but it dose-dependently promoted wound healing. Indeed, ALX 5% significantly accelerated wound closure (<i>p</i> &lt; 0.0001) and led to marked suppression of NF-κB and MMP-9 expression (<i>p</i> &lt; 0.0001). It also enhanced the levels of connective tissue markers, including hexosamine (<i>p</i> &lt; 0.001), hydroxyproline, and hexuronic acid (<i>p</i> &lt; 0.0001). Robust anti-inflammatory effects were also observed, as ALX reduced IL-1β, IL-6, TNF-α levels and COX-2 activity (<i>p</i> &lt; 0.0001). Furthermore, ALX 5% diminished oxidative stress by lowering LPO, PCO, and MPO levels (<i>p</i> &lt; 0.0001), and restoring GSH levels and SOD and CAT (<i>p</i> &lt; 0.001) activities indicating its anti-oxidant properties.</p> Conclusion <p>Taken together, the present work highlights the mechanisms associated with ALX mediated wound healing in diabetic rats thereby demonstrating its potential as a promising strategy for DFU management.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Repurposing amlexanox as a topical anti-inflammatory and antioxidant intervention for diabetic foot ulcers: insights from in-silico and in-vivo studies

  • 期刊论文

  • 发表日期：

    2025年11月29日

查看全文
  • Nishika Kapoor,
  • Navneet Dhaliwal,
  • Jatinder Dhaliwal,
  • Kanwaljit Chopra

摘要

Background

Diabetic foot ulcers (DFUs), a debilitating manifestation of diabetes mellitus, involve persistent inflammation, oxidative stress, and impaired wound healing, largely driven by NF-κB overactivation. Amlexanox (ALX), a synthetic anti-inflammatory and antioxidant agent, was evaluated for its therapeutic potential in DFUs.

Methods

In-silico molecular docking and pharmacokinetic studies were conducted to predict ALX’s interactions with major DFU targets and to assess its topical suitability. STZ-induced diabetic rats with full-thickness foot ulcers (5 mm) received topical ALX (2.5% and 5%) or silver sulfadiazine ointments for 14 days. Wound closure, antioxidant enzymes, oxidative stress markers, connective tissue markers, pro-inflammatory markers and NF-κB expression were assessed in the wound tissue.

Results

ALX demonstrated strong binding to the pathological targets (NF-κB, MMP-9, MPO, and COX-2) and displayed a favourable PK profile. Moreover, ALX topical treatment did not normalise diabetic metabolic alterations, but it dose-dependently promoted wound healing. Indeed, ALX 5% significantly accelerated wound closure (p < 0.0001) and led to marked suppression of NF-κB and MMP-9 expression (p < 0.0001). It also enhanced the levels of connective tissue markers, including hexosamine (p < 0.001), hydroxyproline, and hexuronic acid (p < 0.0001). Robust anti-inflammatory effects were also observed, as ALX reduced IL-1β, IL-6, TNF-α levels and COX-2 activity (p < 0.0001). Furthermore, ALX 5% diminished oxidative stress by lowering LPO, PCO, and MPO levels (p < 0.0001), and restoring GSH levels and SOD and CAT (p < 0.001) activities indicating its anti-oxidant properties.

Conclusion

Taken together, the present work highlights the mechanisms associated with ALX mediated wound healing in diabetic rats thereby demonstrating its potential as a promising strategy for DFU management.