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

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

Front Pharmacol. 2019 Sep 13;10:1017.

PMID: 31572190

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP472151 Betulinic acid Betulinic acid 472-15-1 Price
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