Network Pharmacology Study and Experimental Confirmation Revealing the Ameliorative Effects of Decursin on Chemotherapy-Induced Alopecia

医学 MAPK/ERK通路 药理学 蛋白激酶B PI3K/AKT/mTOR通路 p38丝裂原活化蛋白激酶 细胞凋亡 信号转导 癌症研究 化学 生物化学
作者
Mi Hye Kim,Sang Jun Park,Woong Mo Yang
出处
期刊:Pharmaceuticals [MDPI AG]
卷期号:14 (11): 1150-1150 被引量:3
标识
DOI:10.3390/ph14111150
摘要

Decursin, a pyranocoumarin compound from the root of Angelica gigas Nakai as a main constituent, has been reported to have various biological activities, including anti-inflammatory, anticancer, and antioxidant effects. This study aimed to predict and confirm the pharmacological relevance of Decursin on chemotherapy-induced alopecia (CIA) with the underlying molecular mechanisms. Decursin-targeted genes were compared with the gene set of alopecia and investigated through functional enrichment analysis. CIA was induced in C57BL/6J mice by injection of cyclophosphamide, and 1, 10, and 100 μM of Decursin were topically treated to depilated dorsal skin. KGF+ expression was detected in the dorsal skin tissues. Based on the predicted results, caspase, PIK3/AKT, and MAPKs protein expressions by Decursin were analyzed in the TNF-α-induced keratinocytes. The Decursin network had 60.20% overlapped genes with the network of alopecia. Biological processes, such as cellular response to chemical stimulus, apoptosis, PI3K-AKT signaling pathway, and MAPK signaling pathway, were derived from the Decursin network. In the Decursin-treated skin, there was morphological hair growth and histological restoration of hair follicles in the CIA mice. The KGF+ fluorescence and protein expressions were significantly increased by Decursin treatment. In addition, caspase-3, -7, and -8 expressions, induced by TNF-α, were dose-dependently decreased along with the inhibition of PI3K, AKT, ERK, and p38 expressions in Decursin-treated keratinocytes. These findings indicated that Decursin would be a potent therapeutic option for hair loss, in response to chemotherapy.
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