Loggenberg Samantha Rae, Twilley Danielle, De Canha Marco Nuno, Meyer Debra, Mabena Ephraim Cebisa, Lall Namrita
Department of Plant and Soil Sciences, University of Pretoria, Pretoria, South Africa.
Department of Biochemistry, Faculty of Science, University of Johannesburg, Johannesburg, South Africa.
Front Pharmacol. 2022 Apr 11;13:806285. doi: 10.3389/fphar.2022.806285. eCollection 2022.
Angiogenesis is an essential mechanism in both physiological and pathological functions, such as wound healing and cancer metastasis. Several growth factors mediate angiogenesis, including vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF). This study evaluated the potential wound healing activity of Szyszyl (GR) and its effect on growth factors regulating angiogenesis. The ethanolic leaf extract of GR was evaluated for antibacterial activity against wound associated bacteria; and . It exhibited antibacterial activity against two strains of (ATCC 25293 and ATCC 6538) displaying a minimum inhibitory concentration (MIC) at 250 and 500 μg/ml, respectively. The antioxidant activity of the extract was investigated for nitric oxide (NO) scavenging activity and showed a fifty percent inhibitory concentration (IC) of 1266.5 ± 243.95 μg/ml. The extract was further investigated to determine its effect on the proliferation and modulation of growth factors secreted by human keratinocytes (HaCaT). Its effect on wound closure was evaluated using the scratch assay, where non-toxic concentrations were tested, as determined by the antiproliferative assay against HaCat cells (IC > 400 μg/ml). Results showed that the extract significantly inhibited wound closure, with a percentage closure of 60.15 ± 1.41% ( < 0.05) and 49.52 ± 1.43% ( < 0.01) at a concentration of 50 and 100 μg/ml, respectively, when compared to the 0.25% Dimethyl sulfoxide vehicle control (65.86 ± 1.12%). Quantification of secreted growth factors from cell-free supernatant, collected from the scratch assay, revealed that the extract significantly decreased the concentration of platelet-derived growth factor (PDGF-AA) at both 50 ( < 0.05) and 100 μg/ml ( < 0.001) (443.08 ± 77.36 and 178.98 ± 36.60 pg/ml) when compared to the 0.25% DMSO vehicle control (538.33 ± 12.64 pg/ml). Therefore, whilst the extract showed antibacterial activity against wound associated bacteria, it did not induce wound healing but rather showed a significant inhibition of wound closure, which was confirmed by the inhibition of PDGF-AA, a major growth factor involved in angiogenesis. Therefore, the GR extract, should be considered for further investigation of anti-angiogenic and anti-metastatic properties against cancer cells.
血管生成是生理和病理功能中的一种重要机制，如伤口愈合和癌症转移。几种生长因子介导血管生成，包括血管内皮生长因子（VEGF）和血小板衍生生长因子（PDGF）。本研究评估了Szyszyl（GR）潜在的伤口愈合活性及其对调节血管生成的生长因子的影响。对GR的乙醇叶提取物进行了针对伤口相关细菌的抗菌活性评估；并且。它对两种菌株（ATCC 25293和ATCC 6538）表现出抗菌活性，最低抑菌浓度（MIC）分别为250和500μg/ml。研究了该提取物的抗氧化活性以评估其对一氧化氮（NO）的清除活性，其半数抑制浓度（IC）为1266.5±243.95μg/ml。进一步研究该提取物以确定其对人角质形成细胞（HaCaT）分泌的生长因子的增殖和调节作用。使用划痕试验评估其对伤口闭合的影响，在该试验中测试了无毒浓度，这是通过针对HaCaT细胞的抗增殖试验确定的（IC>400μg/ml）。结果表明，与0.25%二甲基亚砜载体对照（65.86±1.12%）相比，该提取物在浓度为50和100μg/ml时分别显著抑制伤口闭合，闭合百分比分别为60.15±1.41%（P<0.05）和49.52±1.43%（P<0.01）。对划痕试验收集的无细胞上清液中分泌的生长因子进行定量分析，结果显示，与0.25%二甲基亚砜载体对照（538.33±12.64pg/ml）相比，该提取物在50（P<0.05）和100μg/ml（P<0.001）时均显著降低了血小板衍生生长因子（PDGF-AA）的浓度（分别为443.08±77.36和178.98±36.60pg/ml）。因此，虽然该提取物对伤口相关细菌表现出抗菌活性，但它并未促进伤口愈合，反而显著抑制了伤口闭合，这一点通过对参与血管生成的主要生长因子PDGF-AA的抑制得到证实。因此，GR提取物应考虑进一步研究其对癌细胞的抗血管生成和抗转移特性。
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