Abstract
Plicosepalus acacia (Fam. Loranthaceae) has been reported to possess hypoglycemic, antioxidant, antimicrobial, and anti-inflammatory effects. Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) analysis revealed the presence of a high content of polyphenolic compounds that are attributed to the therapeutic effects of the crude extract. In addition, methyl gallate and quercetin were detected as major phytomedicinal agents at concentrations of 1.7% and 0.062 g%, respectively, using high-performance thin layer chromatography (HPTLC). The present study investigated the effect of the P. acacia extract and its isolated compounds, methyl gallate and quercetin, on hind limb ischemia induced in type 1 diabetic rats. Histopathological examination revealed that treatment with P. acacia extract, methyl gallate, and quercetin decreased degenerative changes and inflammation in the ischemic muscle. Further biochemical assessment of the hind limb tissue showed decreased oxidative stress, increased levels of nitric oxide and endothelial nitric oxide synthase (eNOS), and enhancement of the levels of heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) in the groups treated with methyl gallate and quercetin. Expression levels of hypoxia inducible factor-1 alpha (HIF-1α), VEGF, fibroblast growth factor-2 (FGF-2), and miR-146a were upregulated in the muscle tissue of methyl gallate- and quercetin-treated groups along with downregulation of nuclear factor kappa B (NF-κB). In conclusion, P. acacia extract and its isolated compounds, methyl gallate and quercetin, mediated therapeutic angiogenesis in diabetic hind limb ischemia.
Highlights
Diabetes mellitus increases the risk of developing ischemic vascular disease, especially peripheral artery disease (PAD)
Levels of heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) were determined in the hind limb tissue lysate of the studied groups by a Rat Heme Oxygenase 1 ELISA Kit (MyBioSource, San Diego, CA, USA, Catalog No MBS764989) and a Rat Vascular Endothelial Growth Factor ELISA Kit (CUSABIO, Houston, TA, USA, Catalog No MBS724516), respectively
Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) is a modern tool for the detection of natural metabolites that may have beneficial therapeutic effects
Summary
Diabetes mellitus increases the risk of developing ischemic vascular disease, especially peripheral artery disease (PAD). Therapeutic angiogenesis was applied using cytokines to stimulate angiogenesis or transplanting cells such as endothelial progenitor cells in bone marrow to differentiate into endothelial cells and yield proangiogenic cytokines [7], but angiogenic cytokines may generate pathological vessels and cause some complications [8]. The family Loranthaceae represents the largest family of the order Santalales with about 70 genera and 800 species of semi-parasitic plants commonly known as mistletoes They tend to parasitize a broad range of gymnosperms and angiosperms causing serious damage to their hosts [13,14,15]. The current work investigated the effect of the P. acacia extract and its isolated compounds, methyl gallate and quercetin, on therapeutic angiogenesis in experimentally induced diabetic hind limb ischemia and the possible underlying mechanisms of this effect through the assessment of ischemia-induced, antioxidant, and angiogenic markers
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