2. Academic Validation
  3. Betulinic Acid Enhances the Viability of Random-Pattern Skin Flaps by Activating Autophagy

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

  • Front Pharmacol. 2019 Sep 13;10:1017. doi: 10.3389/fphar.2019.01017.
Jiafeng Li 1 2 3,  Guodong Bao 1 2 3,  Eman ALyafeai 4,  Jian Ding 1 2 3,  Shihen Li 1 2 3,  Shimin Sheng 3,  Zitong Shen 5,  Zhenyu Jia 4,  Chen Lin 1 2 3,  Chenxi Zhang 1 2 3,  Zhiling Lou 1 2 3,  Huazi Xu 1 2 3,  Weiyang Gao 1 2 3,  Kailiang Zhou 1 2 3
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 2 Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China.
  • 3 The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, China.
  • 4 School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
  • 5 Renji College of Wenzhou Medical University, Wenzhou, China.
PMID: 31572190 DOI: 10.3389/fphar.2019.01017
Abstract

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

angiogenesis; apoptosis; autophagy; betulinic acid; oxidative stress; random-pattern skin flaps.

Figures
Products