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7α,15-Dihydroxydehydroabietic acid from Pinus koraiensis inhibits the promotion of angiogenesis through downregulation of VEGF, p-Akt and p-ERK in HUVECs
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2018-02-09 , DOI: 10.1016/j.bmcl.2018.02.014
Tae Kyoung Lee , Jun Yeon Park , Jae Sik Yu , Tae Su Jang , Seong Taek Oh , Changhyun Pang , Yoon-Joo Ko , Ki Sung Kang , Ki Hyun Kim

Pinus koraiensis pinecones are considered an undesired waste by-product of the processing of seeds. However, recent studies of the potential anti-tumor effects of the pinecones have led to increasing interest in their chemical constituents. The present study examined the potential antiangiogenic effects of the constituents of pinecones and further characterized their underlying mechanisms of action. Chemical investigation of a water extract of P. koraiensis pinecones led to the isolation and identification of the eight main components including five diterpenoids (15), two monoterpenes (6,7) and a phenolic acid (8). The structure of the compounds was determined by spectroscopic analysis of NMR spectra and LC/MS analysis. Of the isolated compounds, 7α,15-dihydroxydehydroabietic acid (5) significantly inhibited the promotion of angiogenesis in human umbilical vein endothelial cells (HUVECs). Compound 5 inhibited angiogenesis through downregulation of the VEGF, p-Akt and p-ERK signaling pathways. These results provide experimental evidence of a novel biological activity of 7α,15-dihydroxydehydroabietic acid (5) as a potential antiangiogenic substance. This study also suggests that compound 5 could potentially be a useful adjuvant therapeutic substance for cancer prevention and treatment.



中文翻译:

红松中的7α,15-二羟基脱氢松香酸通过下调HUVECs中的VEGF,p-Akt和p-ERK抑制血管生成的促进

红松松果被认为是种子加工过程中不希望的废物副产品。然而,最近对松果的潜在抗肿瘤作用的研究已引起人们对其化学成分的日益增长的兴趣。本研究检查了松果成分的潜在抗血管生成作用,并进一步表征了其潜在的作用机理。的水提取物的化学调查红松松果导致包括五二萜类化合物(八个主要成分的分离和鉴定1 - 5),两个单萜(67)和酚酸(8)。通过NMR光谱的光谱分析和LC / MS分析确定化合物的结构。在分离出的化合物中,7α,15-二羟基脱氢松香酸(5)显着抑制人脐静脉内皮细胞(HUVEC)中血管生成的促进。化合物5通过下调VEGF,p-Akt和p-ERK信号传导途径抑制血管生成。这些结果提供了7α,15-二羟基脱氢松香酸(5)作为潜在的抗血管生成物质的新型生物活性的实验证据。这项研究还表明,化合物5可能是预防和治疗癌症的有用辅助治疗物质。

更新日期:2018-02-09
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