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Chlorogenic acid (CGA) is a natural organic phenolic compound that is found in many plants, fruits and vegetables. CGA has beneficial bioactivities and strong therapeutic effects in inflammatory processes. CGA-rich fractions have analgesic activity but CGA has not been tested previously in neuropathic pain, which results from tissue damage, inflammation or injury of the nervous system. Chronic constrictive nerve injury (CCI) is a peripheral neuropathic pain model which initiates an inflammatory cascade. We aimed to determine possible antihyperalgesic effects of CGA in neuropathic pain. Our study showed for the first time that CGA [50, 100 and 200 mg/kg; intraperitoneally (i.p.)] produced significant dose- and time-dependent antihyperalgesic activity in CCI-induced neuropathic pain. In addition, chronic administration of CGA (100 mg/kg/day; i.p. for 14 days) prevented the development of mechanical hyperalgesia and attenuated CCI-induced histopathological changes. On the other hand, CGA (200 mg/kg) did not affect falling latencies of rats in the rota rod test. Hence, CGA might represent a novel potential therapeutic option for the management of neuropathic pain.

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.

There has been considerable interest in understanding the effects of antioxidants in flap survival during diabetes. Previous studies showed that chlorogenic acid (CGA) exhibits potent antioxidant effects. We aimed to determine the effects of systemic CGA treatment on skin flap survival in an experimental random-pattern dorsal skin flap model in diabetic rats. Twenty-eight male Wistar rats were divided into four groups: phosphate buffered saline (PBS)-treated or CGA-treated nondiabetic rats, PBS-treated or CGA-treated diabetic rats. Diabetes was induced by streptozotocin (45 mg/kg). Caudally based bipedicled dorsal skin flaps were elevated. CGA (100 mg/kg) or PBS (mL/kg; as vehicle) was administered intraperitoneally once daily. On postoperative day 7, flap survival, regional blood perfusion and microangiography were evaluated. The malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and nitric oxide (NO) levels were evaluated from the flap tissue. Capillary density and vascular endothelial growth factor (VEGF) expression were assessed. Harmful effects of diabetes on flap survival were observed. CGA attenuated these effects and allowed greater survival and blood perfusion. CGA decreased MDA and NO levels and increased GSH and SOD levels. CGA elevated capillary density and VEGF expression. This study showed that peripherally administered CGA significantly improved flap survival in diabetic and nondiabetic rats.Key words antioxidant; chlorogenic acid; diabetes; dorsal skin flap; flap survival; oxidative stress Skin flaps are widely used in the repair of local tissue loss and the reconstruction of several tissue defects. Flap necrosis is frequently observed in flap tissues in the postoperative period and is an unwanted effect of healing. Many factors are known to play a role in this major complication such as ischemia, inadequate blood flow and disturbed venous drainage.

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