Pharmacologic overview of systemic chlorogenic acid therapy on experimental wound healing
Pharmacologic overview of systemic chlorogenic acid therapy on experimental wound healing
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DOI：
10.1007/s00210-014-1034-9
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发表时间：
2014-11-01
影响因子：
3.6
通讯作者：
Gurun, Mine Sibel
中科院分区：
文献类型：
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作者：
Bagdas, Deniz;Gul, Nihal Yasar;Gurun, Mine Sibel
绿原酸（Chlorogenic acid，CGA）是一种天然抗氧化剂。为了了解CGA通过增强体内抗氧化防御对伤口愈合的影响，本研究试图研究全身CGA治疗对伤口愈合和皮肤氧化应激标志物的潜在作用。我们还旨在了解慢性CGA治疗是否对治疗期间的关键器官或大鼠骨髓有副作用。在大鼠背部造成全层实验伤口。CGA（25、50、100、200 mg/kg）或溶媒腹腔内给药15天。所有大鼠于第16天处死。进行生化、组织病理学和免疫组织化学检查。还研究了可能的副作用。结果表明，CGA以剂量依赖的方式促进伤口愈合。CGA可提高羟脯氨酸含量，降低丙二醛和一氧化氮水平。以及伤口组织中还原型谷胱甘肽、超氧化物歧化酶和过氧化氢酶水平升高。上皮化，血管生成，成纤维细胞增殖，胶原蛋白形成增加CGA，而多形核白细胞浸润减少。CGA调节活检组织中基质金属蛋白酶-9和组织抑制剂-2的表达。另外，高剂量的CGA可增加肝脏和肾脏的脂质过氧化作用，而对心肌和肌肉样品无影响。慢性CGA增加骨髓中的微核形成并诱导细胞毒性。总之，全身CGA在改善伤口修复方面具有有益作用。CGA的抗氧化、自由基清除、血管生成和抗炎作用可改善伤口愈合。大剂量CGA可引起副作用。根据这些观察结果，CGA补充剂或膳食CGA可能对伤口愈合有益。
Chlorogenic acid (CGA) is a well-known natural antioxidant in human diet. To understand the effects of CGA on wound healing by enhancing antioxidant defense in the body, the present study sought to investigate the potential role of systemic CGA therapy on wound healing and oxidative stress markers of the skin. We also aimed to understand whether chronic CGA treatment has side effects on pivotal organs or rat bone marrow during therapy. Full-thickness experimental wounds were created on the backs of rats. CGA (25, 50, 100, 200 mg/kg) or vehicle was administered intraperitoneally for 15 days. All rats were sacrificed on the 16th day. Biochemical, histopathological, and immunohistochemical examinations were performed. Possible side effects were also investigated. The results suggested that CGA accelerated wound healing in a dose-dependent manner. CGA enhanced hydroxyproline content, decreased malondialdehyde and nitric oxide levels. and elevated reduced glutathione, superoxide dismutase, and catalase levels in wound tissues. Epithelialization, angiogenesis, fibroblast proliferation, and collagen formation increased by CGA while polymorph nuclear leukocytes infiltration decreased. CGA modulated matrix metalloproteinase-9 and tissue inhibitor-2 expression in biopsies. Otherwise, high dose of CGA increased lipid peroxidation of liver and kidney without affecting the heart and muscle samples. Chronic CGA increased micronuclei formation and induced cytotoxicity in the bone marrow. In conclusion, systemic CGA has beneficial effects in improving wound repair. Antioxidant, free radical scavenger, angiogenesis, and anti-inflammatory effects of CGA may ameliorate wound healing. High dose of CGA may induce side effects. In light of these observations, CGA supplementation or dietary CGA may have benefit on wound healing.