A review on the relationship between Arachidonic acid 15-Lipoxygenase (ALOX15) and diabetes mellitus

Abstract

Arachidonic acid 15-lipoxygenase (ALOX15), as one of the lipoxygenase family, is mainly responsible for catalyzing the oxidation of various fatty acids to produce a variety of lipid components, contributing to the pathophysiological processes of various immune and inflammatory diseases. Studies have shown that ALOX15 and its related products are widely distributed in human tissues and related to multiple diseases such as liver, cardiovascular, cerebrovascular diseases, diabetes mellitus and other diseases. Diabetes mellitus (DM), the disease studied in this article, is a metabolic disease characterized by a chronic increase in blood glucose levels, which is significantly related to inflammation, oxidative stress, ferroptosis and other mechanisms, and it has a high incidence in the population, accompanied by a variety of complications. Figuring out how ALOX15 is involved in DM is critical to understanding its role in diseases. Therefore, ALOX15 inhibitors or combination therapy containing inhibitors may deliver a novel research direction for the treatment of DM and its complications. This article aims to review the biological effect and the possible function of ALOX15 in the pathogenesis of DM.

Anti-diabetic and anti-inflammatory bioactive hits from Coriaria intermedia Matsum. stem and Dracontomelon dao (Blanco) Merr. & Rolfe bark through bioassay-guided fractionation and liquid chromatography-tandem mass spectrometry

“…It has been hypothesized that ALOX15 inhibitors have the potential to be used as treatments for airway inflammatory diseases, including asthma. ALOX15 and its metabolites have also been implicated in the pathology and mechanism of T2DM, which may be related to the effect of ALOX15 on islet cell and macrophage functions, (He et al, 2023), as well as in serious complications that arise from the disease, such as diabetic retinopathy, peripheral neuropathy, and nephropathy (Singh and Rao, 2019). This implies that ALOX15 inhibitors may also be explored as a possible treatment for T2DM and/or its complications.…”

“…In a recent review (Xu et al, 2021), it was mentioned that human arachidonic acid 15-lipoxygenase (ALOX15) inhibitors have the potential to be used as treatments for airway inflammatory diseases, including asthma. ALOX15 and its metabolites have been suggested to also play a role in T2DM and the complications that arise from it (Singh and Rao, 2019;He et al, 2023), implying that ALOX15 inhibitors may be explored as a possible treatment for T2DM and/or its complications. Several compounds and plant extracts that inhibit α-glucosidase or ALOX15 have already been studied (Kumar et al, 2011;Sadeghian and Jabbari, 2015).…”

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“…It has been shown that ALOX15 and its related products are expressed at high levels in many pathological human tissues and organs, which consequently cause in ammation, oxidative stress and iron death [30]. ALOX15 has a proin ammatory effect, and it has been found that ALOX15 metabolites can stimulate the expression of IL-6 and TNF-α in a dose-dependent manner [31], and it promotes the production of in ammatory factors through the activation of mitogen-activated protein kinase, protein kinase C and other pathways [32]. ALOX 15 has also been associated with oxidative stimulation in humans.…”