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Front. Pharmacol. | doi: 10.3389/fphar.2019.01017

Betulinic acid Enhances the Vitality of Random-Pattern Skin Flaps by Activation of Autophagy

 Kailiang Zhou1*, Jiafeng Li1, Guodong Bao1, Eman ALyafeai2, Jian Ding1, Shihen Li1, Shimin Sheng3, Zitong Shen4, Zhenyu Jia2,  Chen Lin1,  Chenxi Zhang1, Zhiling Lou1, Huazi Xu1 and Weiyang Gao1*
  • 1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, China
  • 2School of Pharmaceutical Sciences, Wenzhou Medical University, China
  • 3School of Second Clinical Medical, Wenzhou Medical University, China
  • 4Wenzhou Medical University, China

In plastic and reconstructive surgery, random-skin flaps replantation have been commonly used to repair skin defects. However, flap necrosis due to ischemia and IR injury, limit clinical applications. Betulinic acid (BA), a pentacyclic triterpene of plant origin, may facilitate the survival of flaps. In the present study, the effects of BA on flap survival and the underlying mechanisms were assessed.Forty-eight mice with “McFarlane flap” model were randomly divided into Control, BA groups and BA+3MA groups, which were administrated with vehicle Control, BA, 3MA and BA. On a postoperative day 7, flap tissues were acquired to assess angiogenesis, apoptosis, oxidative stress, and autophagy. Our results showed that BA promoted the random skin flaps survival area, reduced tissue edema, and enhanced the number of microvessels. Besides, enhanced angiogenesis, attenuated apoptosis, alleviated oxidative stress and activated autophagy. However, the effects of BA on flap vitality and angiogenesis, apoptosis and oxidative stress were reversed by the inhibition of autophagy. Our finding revealed that BA improves the survival of random skin flaps, via promoting angiogenesis, dampening apoptosis and alleviating oxidative stress, which is mediated by activation of autophagy.

Keywords: Betulinic acid, Random-pattern skin flaps, Autophagy, Angiogenesis, Apoptosis, Oxidative Stress

Received: 24 May 2019; Accepted: 09 Aug 2019.

Edited by:

Salvatore Salomone, University of Catania, Italy

Reviewed by:

Codruta Soica, university of medicine and pharmacy victor babes
İRFAN ÖZYAZGAN, Faculty of Medicine, Erciyes University, Turkey  

Copyright: © 2019 Zhou, Li, Bao, ALyafeai, Ding, Li, Sheng, Shen, Jia, Lin, Zhang, Lou, Xu and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Kailiang Zhou, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China, zhoukailiang@wmu.edu.cn
Mx. Weiyang Gao, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China, weiyanggaoi@126.com