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  1. Diabetes-associated macrovasculopathy: pathophysiology and pathogenesis
    Rahman S, Rahman T, Ismail AA, Rashid AR
    Diabetes Obes Metab, 2007 Nov;9(6):767-80.
    PMID: 17924861 DOI: 10.1111/j.1463-1326.2006.00655.x
    The complications associated with diabetic vasculopathy are commonly grouped into two categories: microvascular and macrovascular complications. In diabetes, macrovascular disease is the commonest cause of mortality and morbidity and is responsible for high incidence of vascular diseases such as stroke, myocardial infarction and peripheral vascular diseases. Macrovascular diseases are traditionally thought of as due to underlying obstructive atherosclerotic diseases affecting major arteries. Pathological changes of major blood vessels leading to functional and structural abnormalities in diabetic vessels include endothelial dysfunction, reduced vascular compliance and atherosclerosis. Besides, advanced glycation end product formation interacts with specific receptors that lead to overexpression of a range of cytokines. Haemodynamic pathways are activated in diabetes and are possibly amplified by concomitant systemic hypertension. Apart from these, hyperglycaemia, non-enzymatic glycosylation, lipid modulation, alteration of vasculature and growth factors activation contribute to development of diabetic vasculopathy. This review focuses on pathophysiology and pathogenesis of diabetes-associated macrovasculopathy.
    Matched MeSH terms: Diabetic Angiopathies/pathology
  2. Dual l-Carnosine/Aloe vera Nanophytosomes with Synergistically Enhanced Protective Effects against Methylglyoxal-Induced Angiogenesis Impairment
    Darvishi B, Dinarvand R, Mohammadpour H, Kamarul T, Sharifi AM
    Mol Pharm, 2021 09 06;18(9):3302-3325.
    PMID: 34297586 DOI: 10.1021/acs.molpharmaceut.1c00248
    Microvascular complications are among the major outcomes of patients with type II diabetes mellitus, which are the consequences of impaired physiological functioning of small blood vessels and angiogenic responses in these patients. Overproduction and accumulation of methylglyoxal (MGO), a highly reactive dicarbonyl byproduct of glycolysis pathway, has been acclaimed as the main inducer of impaired angiogenic responses and microvascular dysfunction in diabetic patients with uncontrolled hyperglycemia. Hence, an effective approach to overcome diabetes-associated microvascular complications is to neutralize the deleterious activity of enhanced the concentration of MGO in the body. Owing to the glycation inhibitory activity of Aloe vera whole extract, and capability of l-carnosine, an endogenous dipeptide, in attenuating MGO's destructive activity, we examined whether application of a combination of l-carnosine and A. vera could be an effective way of synergistically weakening this reactive dicarbonyl's impaired angiogenic effects. Additionally, overcoming the poor cellular uptake and internalization of l-carnosine and A. vera, a nanophytosomal formulation of the physical mixture of two compounds was also established. Although l-carnosine and A. vera at whole studied combination ratios could synergistically enhance viability of human umbilical vein endothelial cells (HUVECs) treated with MGO, the 25:1 w/w ratio was the most effective one among the others (27 ± 0.5% compared to 12 ± 0.3 to 18 ± 0.4%; F (4, 15) = 183.9, P < 0.0001). Developing dual nanophytosomes of l-carnosine/A. vera (25:1) combination ratio, we demonstrated superiority of the nanophytosomal formulation in protecting HUVECs against MGO-induced toxicity following a 24-72 h incubation period (17.3, 15.8, and 12.4% respectively). Moreover, 500 μg/mL concentration of dual l-carnosine/A. vera nanophytosomes exhibited a superior free radical scavenging potency (63 ± 4 RFU vs 83 ± 5 RFU; F (5, 12) = 54.81, P < 0.0001) and nitric oxide synthesizing capacity (26.11 ± 0.19 vs 5.1 ± 0.33; F (5, 12) = 2537, P < 0.0001) compared to their physical combination counterpart. Similarly, 500 μg/mL dual l-carnosine/A. vera nanophytosome-treated HUVECs demonstrated a superior tube formation capacity (15 ± 3 vs 2 ± 0.3; F (5, 12) = 30.87, P < 0.001), wound scratch healing capability (4.92 ± 0.3 vs 3.07 ± 0.3 mm/h; F (5, 12) = 39.21, P < 0.0001), and transwell migration (586 ± 32 vs 394 ± 18; F (5, 12) = 231.8, P < 0.001) and invasion (172 ± 9 vs 115 ± 5; F (5, 12) = 581.1, P < 0.0001) activities compared to the physical combination treated ones. Further confirming the proangiogenic activity of the dual l-carnosine/A. vera nanophytosomes, a significant shift toward expression of proangiogenic genes including HIF-1α, VEGFA, bFGF, KDR, and Ang II was reported in treated HUVECs. Overall, dual l-carnosine/A. vera nanophytosomes could be a potential candidate for attenuating type II DM-associated microvascular complications with an impaired angiogenesis background.
    Matched MeSH terms: Diabetic Angiopathies/pathology
  3. Treatment for diabetic ulcer wounds using a fern tannin optimized hydrogel formulation with antibacterial and antioxidative properties
    Lai JC, Lai HY, Nalamolu KR, Ng SF
    J Ethnopharmacol, 2016 08 02;189:277-89.
    PMID: 27208868 DOI: 10.1016/j.jep.2016.05.032
    ETHNOPHARMACOLOGICAL RELEVANCE: Blechnum orientale Linn. (B. orientale) is a fern traditionally used by the natives as a poultice to treat wounds, boils, ulcers, blisters, abscesses, and sores on the skin.

    AIM OF THE STUDY: To investigate the wound healing ability of a concentrated extract of B. orientale in a hydrogel formulation in healing diabetic ulcer wounds.

    MATERIALS AND METHODS: The water extract from the leaves of B. orientale was separated from the crude methanolic extract and subjected to flash column chromatography techniques to produce concentrated fractions. These fractions were tested for phytochemical composition, tannin content, antioxidative and antibacterial activity. The bioactive fraction was formulated into a sodium carboxymethylcellulose hydrogel. The extract-loaded hydrogels were then characterized and tested on excision ulcer wounds of streptozotocin-induced diabetic rats. Wound size was measured for 14 days. Histopathological studies were conducted on the healed wound tissues to observe for epithelisation, fibroblast proliferation and angiogenesis. All possible mean values were subjected to statistical analysis using One-way ANOVA and post-hoc with Tukey's T-test (P<0.05).

    RESULTS: One fraction exhibited strong antioxidative and antibacterial activity. The fraction was also highly saturated with tannins, particularly condensed tannins. Fraction W5-1 exhibited stronger antioxidant activity compared to three standards (α-Tocopherol, BHT and Trolox-C). Antibacterial activity was also present, and notably bactericidal towards Methicillin-resistant Staphylococcus aureus (MRSA) at 0.25mg/ml. The extract-loaded hydrogels exhibited shear-thinning properties, with high moisture retention ability. The bioactive fraction at 4% w/w was shown to be able to close diabetic wounds by Day 12 on average. Other groups, including controls, only exhibited wound closure by Day 14 (or not at all). Histopathological studies had also shown that extract-treated wounds exhibited re-epithelisation, higher fibroblast proliferation, collagen synthesis, and angiogenesis.

    CONCLUSION: The ethnopharmacological effects of using B. orientale as a topical treatment for external wounds was validated and was also significantly effective in treating diabetic ulcer wounds. Thus, B. orientale extract hydrogel may be presented as a potential treatment for diabetic ulcer wounds.

    Matched MeSH terms: Diabetic Angiopathies/pathology
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