Betulinic Acid Enhances the Viability of Random-Pattern Skin Flaps by Activating Autophagy
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 su...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.01017/full |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 Betulinic Acid Enhances the Viability of Random-Pattern Skin Flaps by Activating Autophagy Frontiers in Pharmacology betulinic acid random-pattern skin flaps autophagy angiogenesis apoptosis oxidative stress |
| author_facet |
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 |
| author_sort |
Jiafeng Li |
| title |
Betulinic Acid Enhances the Viability of Random-Pattern Skin Flaps by Activating Autophagy |
| title_short |
Betulinic Acid Enhances the Viability of Random-Pattern Skin Flaps by Activating Autophagy |
| title_full |
Betulinic Acid Enhances the Viability of Random-Pattern Skin Flaps by Activating Autophagy |
| title_fullStr |
Betulinic Acid Enhances the Viability of Random-Pattern Skin Flaps by Activating Autophagy |
| title_full_unstemmed |
Betulinic Acid Enhances the Viability of Random-Pattern Skin Flaps by Activating Autophagy |
| title_sort |
betulinic acid enhances the viability of random-pattern skin flaps by activating autophagy |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Pharmacology |
| issn |
1663-9812 |
| publishDate |
2019-09-01 |
| description |
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. |
| topic |
betulinic acid random-pattern skin flaps autophagy angiogenesis apoptosis oxidative stress |
| url |
https://www.frontiersin.org/article/10.3389/fphar.2019.01017/full |
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doaj-0cba963eeb91499eaa685ac80755e0d32020-11-25T02:41:15ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-09-011010.3389/fphar.2019.01017474208Betulinic Acid Enhances the Viability of Random-Pattern Skin Flaps by Activating AutophagyJiafeng Li0Jiafeng Li1Jiafeng Li2Guodong Bao3Guodong Bao4Guodong Bao5Eman ALyafeai6Jian Ding7Jian Ding8Jian Ding9Shihen Li10Shihen Li11Shihen Li12Shimin Sheng13Zitong Shen14Zhenyu Jia15Chen Lin16Chen Lin17Chen Lin18Chenxi Zhang19Chenxi Zhang20Chenxi Zhang21Zhiling Lou22Zhiling Lou23Zhiling Lou24Huazi Xu25Huazi Xu26Huazi Xu27Weiyang Gao28Weiyang Gao29Weiyang Gao30Kailiang Zhou31Kailiang Zhou32Kailiang Zhou33Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaZhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, ChinaThe Second Clinical Medical College of Wenzhou Medical University, Wenzhou, ChinaDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaZhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, ChinaThe Second Clinical Medical College of Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, ChinaDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaZhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, ChinaThe Second Clinical Medical College of Wenzhou Medical University, Wenzhou, ChinaDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaZhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, ChinaThe Second Clinical Medical College of Wenzhou Medical University, Wenzhou, ChinaThe Second Clinical Medical College of Wenzhou Medical University, Wenzhou, ChinaRenji College of Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, ChinaDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaZhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, ChinaThe Second Clinical Medical College of Wenzhou Medical University, Wenzhou, ChinaDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaZhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, ChinaThe Second Clinical Medical College of Wenzhou Medical University, Wenzhou, ChinaDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaZhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, ChinaThe Second Clinical Medical College of Wenzhou Medical University, Wenzhou, ChinaDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaZhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, ChinaThe Second Clinical Medical College of Wenzhou Medical University, Wenzhou, ChinaDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaZhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, ChinaThe Second Clinical Medical College of Wenzhou Medical University, Wenzhou, ChinaDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaZhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, ChinaThe Second Clinical Medical College of Wenzhou Medical University, Wenzhou, ChinaRandom-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.https://www.frontiersin.org/article/10.3389/fphar.2019.01017/fullbetulinic acidrandom-pattern skin flapsautophagyangiogenesisapoptosisoxidative stress |