Frontiers in Pharmacology (Sep 2019)

Betulinic Acid Enhances the Viability of Random-Pattern Skin Flaps by Activating Autophagy

  • Jiafeng Li,
  • Jiafeng Li,
  • Jiafeng Li,
  • Guodong Bao,
  • Guodong Bao,
  • Guodong Bao,
  • Eman ALyafeai,
  • Jian Ding,
  • Jian Ding,
  • Jian Ding,
  • Shihen Li,
  • Shihen Li,
  • Shihen Li,
  • Shimin Sheng,
  • Zitong Shen,
  • Zhenyu Jia,
  • Chen Lin,
  • Chen Lin,
  • Chen Lin,
  • Chenxi Zhang,
  • Chenxi Zhang,
  • Chenxi Zhang,
  • Zhiling Lou,
  • Zhiling Lou,
  • Zhiling Lou,
  • Huazi Xu,
  • Huazi Xu,
  • Huazi Xu,
  • Weiyang Gao,
  • Weiyang Gao,
  • Weiyang Gao,
  • Kailiang Zhou,
  • Kailiang Zhou,
  • Kailiang Zhou

DOI
https://doi.org/10.3389/fphar.2019.01017
Journal volume & issue
Vol. 10

Abstract

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Random-pattern skin flap replantation is commonly used to repair skin defects during plastic and reconstructive surgery. However, flap necrosis due to ischemia and ischemia–reperfusion injury limits clinical applications. Betulinic acid, a plant-derived pentacyclic triterpene, may facilitate flap survival. In the present study, the effects of betulinic acid on flap survival and the underlying mechanisms were assessed. Fifty-four mice with a dorsal random flap model were randomly divided into the control, betulinic acid group, and the betulinic acid + 3-methyladenine group. These groups were treated with dimethyl sulfoxide, betulinic acid, and betulinic acid plus 3-methyladenine, respectively. Flap tissues were acquired on postoperative day 7 to assess angiogenesis, apoptosis, oxidative stress, and autophagy. Betulinic acid promoted survival of the skin flap area, reduced tissue edema, and enhanced the number of microvessels. It also enhanced angiogenesis, attenuated apoptosis, alleviated oxidative stress, and activated autophagy. However, its effects on flap viability and angiogenesis, apoptosis, and oxidative stress were reversed by the autophagy inhibitor 3-methyladenine. Our findings reveal that betulinic acid improves survival of random-pattern skin flaps by promoting angiogenesis, dampening apoptosis, and alleviating oxidative stress, which mediates activation of autophagy.

Keywords