Hassan Nevine H, El-Hawary Seham S, Emam Mahmoud, Rabeh Mohamed A, Tantawy Mohamed A, Seif Mohamed, Abd-Elal Radwa M A, Bringmann Gerhard, Abdelmohsen Usama Ramadan, Selim Nabil M
Pharmacognosy Department, Faculty of Pharmacy, Modern University for Technology and Information, Cairo 11571, Egypt.
Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Giza 11562, Egypt.
Pharmaceuticals (Basel). 2023 Jul 3;16(7):957. doi: 10.3390/ph16070957.
This study shed light for the first time on the diabetic wound healing potential activity of natural marine soft coral polymeric nanoparticle gel using an excision wound model. A sp. methanol-methylene chloride extract loaded with pectin nanoparticles (LPNs) was created. For the preparation of gel, ion-gelation techniques, the entrapment efficiency, the particle size, the polydispersity index, the zeta potential, the drug release, and a transmission electron microscope were used and the best formula was selected. Using (UPLC-Q/TOF-MS), 27 secondary metabolites responsible for extract biological activity were identified. Isolation and identification of arachidic acid, oleic acid, nervonic acid, and bis-(2-ethylhexyl)-phthalate (DEHP) of sp. was firstly reported here using NMR and mass spectral analyses. Moreover, LPN gel has the best effects on regulating the proinflammatory cytokines (NF-κB, TNF-α, IL-6, and IL-1β) that were detected on days 7 and 15. The results were confirmed with an enzymatic inhibitory effect of the extract against glycogen synthase kinase (GSK-3) and matrix metalloproteinase-1 (MMP-1), with IC values of 0.178 ± 0.009 and 0.258 ± 0.011 µg/mL, respectively. The molecular docking study showed a free binding energy of -9.6 kcal/mol for chabrolosteroid E, with the highest binding affinity for the enzyme (GSK-3), while isogosterone B had -7.8 kcal/mol for the enzyme (MMP-1). A pharmacokinetics study for chabrolohydroxybenzoquinone F and isogosterone B was performed, and it predicted the mode of action of wound healing activity.
本研究首次利用切除伤口模型，揭示了天然海洋软珊瑚聚合物纳米颗粒凝胶对糖尿病伤口愈合的潜在活性。制备了负载果胶纳米颗粒（LPNs）的一种软珊瑚甲醇 - 二氯甲烷提取物。为制备凝胶，采用了离子凝胶技术、包封率、粒径、多分散指数、zeta电位、药物释放以及透射电子显微镜，并选择了最佳配方。利用超高效液相色谱 - 四极杆飞行时间质谱联用仪（UPLC - Q/TOF - MS），鉴定出27种具有提取物生物活性的次生代谢产物。本研究首次使用核磁共振和质谱分析报告了该软珊瑚中花生酸、油酸、神经酸和邻苯二甲酸二（2 - 乙基己基）酯（DEHP）的分离与鉴定。此外，LPN凝胶对在第7天和第15天检测到的促炎细胞因子（NF - κB、TNF - α、IL - 6和IL - 1β）具有最佳调节作用。提取物对糖原合酶激酶（GSK - 3）和基质金属蛋白酶 - 1（MMP - 1）的酶抑制作用证实了这些结果，其IC值分别为0.178±0.009和0.258±0.011μg/mL。分子对接研究表明，查布罗甾醇E与酶（GSK - 3）的自由结合能为 - 9.6 kcal/mol，具有最高的结合亲和力，而异睾酮B与酶（MMP - 1）的结合能为 - 7.8 kcal/mol。对查布罗羟基苯醌F和异睾酮B进行了药代动力学研究，并预测了伤口愈合活性的作用模式。
