Unveiling the Unexplored Multifactorial Potential of 5-Aminosalicylic Acid in Diabetic Wound Therapy.

IF 3 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Diseases (Basel, Switzerland) Pub Date : 2024-08-01 DOI:10.3390/diseases12080172
Bharat Kumar Reddy Sanapalli, Ashwini Deshpande, Vidyasrilekha Sanapalli, Dilep Kumar Sigalapalli
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Abstract

Diabetic wounds (DWs) are considered chronic complications observed in patients suffering from type 2 diabetes mellitus (DM). Usually, DWs originate from the interplay of inflammation, oxidation, impaired tissue re-epithelialization, vasculopathy, nephropathy, and neuropathy, all of which are related to insulin resistance and sensitivity. The conventional approaches available for the treatment of DWs are mainly confined to the relief of wound pressure, debridement of the wound, and management of infection. In this paper, we speculate that treatment of DWs with 5-aminosalicylic acid (5-ASA) and subsequent activation of peroxisome proliferator-activated receptor gamma (PPAR-γ) and transforming growth factor beta (TGF-β) via the AhR pathway might be highly beneficial for DW patients. This estimation is based on several lines of evidence showing that 5-ASA and PPAR-γ activation are involved in the restoration of insulin sensitivity, re-epithelialization, and microcirculation. Additionally, 5-ASA and TGF-β activate inflammation and the production of pro-inflammatory mediators. Suitable stabilized formulations of 5-ASA with high absorption rates are indispensable for scrutinizing its probable pharmacological benefits since 5-ASA is known to possess lower solubility profiles because of its reduced permeability through skin tissue. In vitro and in vivo studies with stabilized formulations and a control (placebo) are mandatory to determine whether 5-ASA indeed holds promise for the curative treatment of DWs.

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揭示 5-氨基水杨酸在糖尿病伤口治疗中尚未开发的多因素潜力
糖尿病伤口(DWs)被认为是 2 型糖尿病(DM)患者的慢性并发症。通常,糖尿病伤口源于炎症、氧化、组织再上皮化受损、血管病变、肾病和神经病变等因素的相互作用,所有这些因素都与胰岛素抵抗和敏感性有关。治疗 DWs 的传统方法主要局限于减轻伤口压力、清创和控制感染。在本文中,我们推测用 5- 氨基水杨酸(5-ASA)治疗 DW,然后通过 AhR 途径激活过氧化物酶体增殖激活受体γ(PPAR-γ)和转化生长因子β(TGF-β),可能对 DW 患者大有裨益。这一估计基于多个证据,这些证据表明 5-ASA 和 PPAR-γ 的激活参与了胰岛素敏感性、上皮重建和微循环的恢复。此外,5-ASA 和 TGF-β 还能激活炎症和促炎介质的产生。众所周知,5-ASA 通过皮肤组织的渗透性较低,因此具有较低的溶解度,因此要仔细研究其可能的药理作用,就必须采用具有高吸收率的合适的 5-ASA 稳定制剂。为了确定 5-ASA 是否确实有望治疗 DWs,必须对稳定制剂和对照组(安慰剂)进行体外和体内研究。
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