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树脂中两种呋喃倍半萜的细胞毒性评价及抗血管生成作用

Cytotoxic Evaluation and Anti-Angiogenic Effects of Two Furano-Sesquiterpenoids from Resin.

机构信息

Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

出版信息

Molecules. 2020 Mar 13;25(6):1318. doi: 10.3390/molecules25061318.

Abstract

resin (Myrrh) has been used in traditional Arabic medicine to treat various inflammatory diseases. Two furano-sesquiterpenoids, 2-methoxyfuranodiene (CM1) and 2-acetoxyfuranodiene (CM2), were isolated from the chloroform fraction of the ethanolic extract of Arabic resin. The cytotoxicity of the compounds was evaluated using human liver carcinoma, breast cancer cells (HepG2 and MCF-7, respectively) and normal human umbilical vein endothelial cells (HUVECs) cell lines. The development toxicity and anti-angiogenic activity of both compounds were also evaluated using zebrafish embryos. Cell survival assays demonstrated that both compounds were highly cytotoxic in HepG2 and MCF7 cells, with IC values of 3.6 and 4.4 µM, respectively. Both compounds induced apoptosis and caused cell cycle arrest in treated HepG2 cells, which was observed using flow cytometric analysis. The development toxicity in zebrafish embryos showed the chronic toxicity of both compounds. The toxicity was only seen when the embryos remained exposed to the compounds for more than three days. The compound CM2 showed a significant level of anti-angiogenic activity in transgenic zebrafish embryos at sublethal doses. Thus, we demonstrated the cytotoxic properties of both compounds, suggesting that the molecular mechanism of these compounds should be further assessed.

摘要

乳香(Myrrh)在传统的阿拉伯医学中被用于治疗各种炎症性疾病。两种呋喃倍半萜类化合物,2-甲氧基呋喃二烯(CM1)和 2-乙酰氧基呋喃二烯(CM2),从阿拉伯乳香的乙醇提取物的氯仿部分中分离得到。使用人肝癌、乳腺癌细胞(HepG2 和 MCF-7,分别)和正常的人脐静脉内皮细胞(HUVECs)细胞系评估了化合物的细胞毒性。还使用斑马鱼胚胎评估了两种化合物的发育毒性和抗血管生成活性。细胞存活测定表明,两种化合物在 HepG2 和 MCF7 细胞中均具有高度的细胞毒性,IC 值分别为 3.6 和 4.4 µM。两种化合物均诱导处理的 HepG2 细胞凋亡并导致细胞周期停滞,这可通过流式细胞术分析观察到。斑马鱼胚胎的发育毒性显示了两种化合物的慢性毒性。只有当胚胎持续暴露于化合物超过三天时,才会出现毒性。在亚致死剂量下,化合物 CM2 在转基因斑马鱼胚胎中表现出显著的抗血管生成活性。因此,我们证明了这两种化合物的细胞毒性特性,表明这些化合物的分子机制应进一步评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e49/7144466/9cb9fbbe1540/molecules-25-01318-g001.jpg

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