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柚皮苷、二十烷和二十八烷的抗氧化、伤口愈合潜力及计算机评估。

Antioxidant, Wound Healing Potential and In Silico Assessment of Naringin, Eicosane and Octacosane.

机构信息

Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Cheras 56000, Kuala Lumpur, Malaysia.

Faculty of Pharmaceutical Sciences, Department of Organic Chemistry, Medical University of Sílesia, Jagiellonska, Str. 4, 41-200 Sosnowiec, Poland.

出版信息

Molecules. 2023 Jan 20;28(3):1043. doi: 10.3390/molecules28031043.

Abstract
  1. Diabetic chronic wounds, mainly foot ulcers, constitute one of the most common complications of poorly managed diabetes mellitus. The most typical reasons are insufficient glycemic management, latent neuropathy, peripheral vascular disease, and neglected foot care. In addition, it is a common cause of foot osteomyelitis and amputation of the lower extremities. Patients are admitted in larger numbers attributable to chronic wounds compared to any other diabetic disease. In the United States, diabetes is currently the most common cause of non-traumatic amputations. Approximately five percent of diabetics develop foot ulcers, and one percent require amputation. Therefore, it is necessary to identify sources of lead with wound-healing properties. Redox imbalance due to excessive oxidative stress is one of the causes for the development of diabetic wounds. Antioxidants have been shown to decrease the progression of diabetic neuropathy by scavenging ROS, regenerating endogenous and exogenous antioxidants, and reversing redox imbalance. Matrix metalloproteinases (MMPs) play vital roles in numerous phases of the wound healing process. Antioxidant and fibroblast cell migration activity of (MP) crude extract has previously been reported. Through their antioxidant, epithelialization, collagen synthesis, and fibroblast migration activities, the authors hypothesise that naringin, eicosane and octacosane identified in the MP extract may have wound-healing properties. 2. The present study aims to identify the bioactive components present in the dichloromethane (DCM) extract of and evaluate their antioxidant and wound healing activity. Bioactive components were identified using LCMS, HPTLC and GCMS. Excision wound on STZ-induced diabetic rat model, human dermal fibroblast (HDF) cell line and colorimetric antioxidant assays were used to evaluate wound healing and antioxidant activities, respectively. Molecular docking and pkCMS software would be utilised to predict binding energy and affinity, as well as ADME parameters. 3. Naringin (NAR), eicosane (EIC), and octacosane (OCT) present in MP displayed antioxidant action and wound excision closure. Histological examination HDF cell line demonstrates epithelialization, collagen production, fibroblast migration, polymorphonuclear leukocyte migration (PNML), and fibroblast movement. The results of molecular docking indicate a substantial attraction and contact between MMPs. pkCMS prediction indicates inadequate blood-brain barrier permeability, low toxicity, and absence of hepatotoxicity. 4. Wound healing properties of (NEO) naringin, eicosane and octacosane may be the result of their antioxidant properties and possible interactions with MMP.
摘要
  1. 糖尿病慢性创面,主要是足部溃疡,是糖尿病患者血糖控制不佳的最常见并发症之一。最典型的原因是血糖控制不足、潜在的神经病变、周围血管疾病和足部护理不当。此外,它也是足部骨髓炎和下肢截肢的常见原因。与任何其他糖尿病疾病相比,因慢性创面而住院的患者更多。在美国,糖尿病目前是最常见的非创伤性截肢原因。大约 5%的糖尿病患者会出现足部溃疡,1%的患者需要截肢。因此,有必要确定具有愈合作用的潜在来源。由于氧化应激导致的氧化还原失衡是糖尿病创面发展的原因之一。抗氧化剂通过清除 ROS、再生内源性和外源性抗氧化剂以及逆转氧化还原失衡,已被证明可以减缓糖尿病神经病变的进展。基质金属蛋白酶(MMPs)在创面愈合过程的多个阶段发挥重要作用。先前已经报道了(MP)粗提物的抗氧化和成纤维细胞迁移活性。作者假设,从 MP 提取物中鉴定出的柚皮苷、二十烷和二十八烷具有愈合作用,因为它们具有抗氧化、上皮化、胶原合成和成纤维细胞迁移活性。

  2. 本研究旨在鉴定 中二氯甲烷(DCM)提取物中的生物活性成分,并评估其抗氧化和创面愈合活性。使用 LCMS、HPTLC 和 GCMS 鉴定生物活性成分。使用 STZ 诱导的糖尿病大鼠模型的切口创面、人真皮成纤维细胞(HDF)细胞系和比色抗氧化测定法分别评估创面愈合和抗氧化活性。将使用分子对接和 pkCMS 软件预测结合能和亲和力以及 ADME 参数。

  3. MP 中的柚皮苷(NAR)、二十烷(EIC)和二十八烷(OCT)具有抗氧化和创面切除闭合作用。HDF 细胞系的组织学检查显示上皮化、胶原生成、成纤维细胞迁移、多形核白细胞迁移(PNML)和成纤维细胞运动。分子对接结果表明 MMP 之间存在显著的吸引力和接触。pkCMS 预测表明血脑屏障通透性不足、毒性低且无肝毒性。

  4. (NEO)柚皮苷、二十烷和二十八烷的创面愈合特性可能是由于其抗氧化特性以及与 MMP 的可能相互作用所致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9251/9919607/0a1be555dffa/molecules-28-01043-g001.jpg

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