Juglone, a phenolic compound found in walnuts, inhibits cystathionine γ-synthase (HpCGS), malonyl-CoA:acylcarrier protein transacylase (HpFabD), and β-hydroxyacylACP dehydratase (HpFabZ) with IC50 values of 7.0±0.7, 20±1, and 30±4µM, respectively[1]. Juglone contains an intramolecular hydrogen bond between hydroxyl and keto groups and is active in donating the hydrogen-atom, which combats oxidative stress[2]. Juglone, a potent urease inactivator, produces irreversible inhibition by covalent modification of protein thiol, which is widely used in antibacterial and antifungal research[3].
In vitro, Juglone treatment for 24h inhibited cell viability of BxPC-3 cells and PANC-1 cells with IC50 values of 21.05 and 21.25μM, respectively[4]. Juglone treatment for 24 hours inhibited the viability of A549 cells with an IC50 value of 9.47μM, arrested the cell cycle and induced apoptosis[5]. Treatment of human fibroblasts with 5μM Juglone for 30min rapidly induced DNA damage, which triggered a stress response leading to H2AX phosphorylation[6].
In vivo, Intraperitoneal injection of Juglone (4mg/kg) to mice every other day for 20 days significantly inhibited the growth of transplanted tumors, resulting in partial degeneration and necrosis of tumor cells [7]. Intraperitoneal injection of Juglone (1mg/kg) every 3 days for 40 days delayed the growth of glioma in mice and prolonged the survival time of glioma-bearing mice [8].
References:
[1] Kong YunHua K Y H, Zhang Liang Z L, Yang ZhengYi Y Z Y, et al. Natural product juglone targets three key enzymes from Helicobacter pylori: inhibition assay with crystal structure characterization[J]. 2008.
[2] Ahmad T, Suzuki Y J. Juglone in oxidative stress and cell signaling[J]. Antioxidants, 2019, 8(4): 91.
[3] Islam A K M M, Widhalm J R. Agricultural uses of juglone: Opportunities and challenges[J]. Agronomy, 2020, 10(10): 1500.
[4] Avcı E, Arıkoğlu H, Kaya D E. Investigation of juglone effects on metastasis and angiogenesis in pancreatic cancer cells[J]. Gene, 2016, 588(1): 74-78.
[5] Zhong J, Hua Y, Zou S, et al. Juglone triggers apoptosis of non-small cell lung cancer through the reactive oxygen species-mediated PI3K/Akt pathway[J]. Plos one, 2024, 19(5): e0299921.
[6] Paulsen M T, Ljungman M. The natural toxin juglone causes degradation of p53 and induces rapid H2AX phosphorylation and cell death in human fibroblasts[J]. Toxicology and applied pharmacology, 2005, 209(1): 1-9.
[7] Wang P, Zhang S D, Jiao J, et al. ROS-mediated p53 activation by juglone enhances apoptosis and autophagy in vivo and in vitro[J]. Toxicology and Applied Pharmacology, 2019, 379: 114647.
[8] Wu J, Zhang H, Xu Y, et al. Juglone induces apoptosis of tumor stem-like cells through ROS-p38 pathway in glioblastoma[J]. BMC neurology, 2017, 17(1): 70.
Juglone是一种存在于核桃中的酚类化合物，可抑制胱硫醚γ-合成酶（HpCGS）、丙二酰辅酶A：酰基载体蛋白转酰基酶（HpFabD）和β-羟基酰基ACP脱水酶（HpFabZ），IC50值分别为7.0±0.7µM、20±1µM和30±4µM[1]。Juglone通过羟基与酮基形成分子内氢键，具有提供氢原子抵抗氧化应激的活性[2]。作为强效脲酶灭活剂，Juglone通过共价修饰蛋白巯基产生不可逆抑制，被广泛用于抗菌和抗真菌研究[3]。
在体外，Juglone处理24小时可抑制BxPC-3和PANC-1细胞活力，IC50值分别为21.05μM和21.25μM[4]。Juglone处理A549细胞24小时的IC50值为9.47μM，可诱导细胞周期阻滞和凋亡[5]。5μM的Juglone处理人成纤维细胞30分钟能快速诱导DNA损伤，触发应激反应导致H2AX磷酸化[6]。
在体内，小鼠隔日腹腔注射Juglone（4mg/kg；持续20天）可显著抑制移植瘤生长，导致肿瘤细胞部分变性和坏死[7]。每3天腹腔注射1mg/kg剂量的Juglone（持续40天）能延缓小鼠神经胶质瘤生长并延长荷瘤鼠生存时间[8]。