Protective effect of luteolin on skin ischemia-reperfusion injury through an AKT-dependent mechanism

Chen,Gang; Shen,Hugang; Zang,Linlin; Su,Zhonglan; Huang,Jilong; Sun,Yong; Wang,Hongwei

doi:10.3892/ijmm.2018.3915

Protective effect of luteolin on skin ischemia-reperfusion injury through an AKT-dependent mechanism

Authors:
- Gang Chen
- Hugang Shen
- Linlin Zang
- Zhonglan Su
- Jilong Huang
- Yong Sun
- Hongwei Wang
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Affiliations: Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China, Department of Esthetic Plastic Surgery, The First Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu 210029, P.R. China, Medical Laboratory, Qingdao HaiCi Medical Group, Qingdao, Shandong 266000, P.R. China, Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: October 2, 2018 https://doi.org/10.3892/ijmm.2018.3915
Pages: 3073-3082
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cutaneous ischemia‑reperfusion (I/R) injury is one of the most crucial problems in flap surgery, which affects the survival of the skin flap and patient prognosis, luteolin, a plant derived flavonoid, has previously been shown to exert a variety of beneficial effects for reducing I/R injury in several organs. The aim of the present study was to evaluate the anti‑inflammatory and anti‑oxidative stress effects of luteolin on cutaneous I/R injury. The in vitro study were performed using a permanent human immortalized epidermal keratinocyte cell line (HaCaT), cells were cultured in the presence of luteolin and were then treated with hydrogen peroxide, the cell viability, mitochondrial membrane potential and the cell survival/apoptosis related signaling pathway activation were assessed to investigate the cytoprotective effects of luteolin. For in vivo experiments, skin flap I/R injury animal model was established in Sprague‑Dawley rats, by measuring the area of flap survival, analyzing the expression of pro‑inflammatory cytokine and evaluation of the histological changes in the skin tissue, the protective effects of luteolin on skin I/R injury were investigated. The function of protein kinase B (AKT) and heme oxygenase‑1 (HO‑1) activation on luteolin mediated I/R injury protection was assessed by administration of phosphoinositide‑3‑kinase/AKT inhibitor LY294002 and HO‑1 inhibitor ZNPP. The results showed that luteolin treatment significantly increased the viability of HaCaT cells upon exposure to hydrogen peroxide, and the administration of luteolin in vivo significantly improved skin flap survival in the I/R injury rat model. The mechanisms underlying these beneficial effects included increased phosphoinositide‑3‑kinase/protein kinase B activation, improved expression of antioxidant enzyme, and scavenging the cytotoxic effects of reactive oxygen species (ROS). Taken together, the results suggested that luteolin preconditioning yielded significant protection against cutaneous I/R injury by protecting skin keratinocytes from ROS‑induced damage.

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