6-Shogaol, an active substance from ginger, has anti-inflammatory, anti-tumor, and anti-oxidative effects [1]. 6-shogaol inhibits AKT kinase activity by binding to the variable configuration site of Akt, thereby inducing cleavage of the apoptosis markers Caspase-3 and Caspase-7 [2]. 6-Shogaol has been widely used in different cell and animal models to inhibit tumor progression and to develop novel combination therapies to eliminate tumor drug resistance[3].
In vitro, 6-Shogaol treatment for 72 hours significantly inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) with an IC50 value of 8µM[4]. Treatment with 50µM 6-Shogaol for 24h induced apoptosis in HepG2 and Huh-7 cells, accompanied by nuclear volume reduction, chromatin condensation, and aggregation at the edge of the nuclear membrane, and totally fragmented nuclear bodies[5]. Treatment with 10μg/ml 6-Shogaol for 24 hours blocked the G2/M phase progression of NCI-H226 cells and promoted caspase cascade to induce apoptosis[6].
In vivo, 6-Shogaol via intraperitoneal administration at a daily dose of 50mg/kg for 12 weeks significantly reduced body weight, reduced fasting blood glucose and serum insulin levels, and alleviated kidney pathological damage in C57BL/KsJ db/db obese mice[7]. Oral administration of 6-Shogaol at 1mg/kg/day for 8 weeks significantly reduced pressure overload-induced cardiac hypertrophy and systolic dysfunction in mice[8].
References:
[1] Li F, Nitteranon V, Tang X, et al. In vitro antioxidant and anti-inflammatory activities of 1-dehydro-[6]-gingerdione, 6-shogaol, 6-dehydroshogaol and hexahydrocurcumin[J]. Food chemistry, 2012, 135(2): 332-337.
[2] Kim M O, Lee M H, Oi N, et al. [6]-Shogaol inhibits growth and induces apoptosis of non-small cell lung cancer cells by directly regulating Akt1/2[J]. Carcinogenesis, 2014, 35(3): 683-691.
[3] Jia Y, Li X, Meng X, et al. Anticancer perspective of 6-shogaol: anticancer properties, mechanism of action, synergism and delivery system[J]. Chinese Medicine, 2023, 18(1): 138.
[4] Bischoff-Kont I, Primke T, Niebergall L S, et al. Ginger constituent 6-shogaol inhibits inflammation-and angiogenesis-related cell functions in primary human endothelial cells[J]. Frontiers in pharmacology, 2022, 13: 844767.
[5] Wu J J, Omar H A, Lee Y R, et al. 6-Shogaol induces cell cycle arrest and apoptosis in human hepatoma cells through pleiotropic mechanisms[J]. European journal of pharmacology, 2015, 762: 449-458.
[6] Itharat A, Rattarom R, Hansakul P, et al. The effects of Benjakul extract and its isolated compounds on cell cycle arrest and apoptosis in human non-small cell lung cancer cell line NCI-H226[J]. Research in Pharmaceutical Sciences, 2021, 16(2): 129-140.
[7] Xu Y, Bai L, Chen X, et al. 6-Shogaol ameliorates diabetic nephropathy through anti-inflammatory, hyperlipidemic, anti-oxidative activity in db/db mice[J]. Biomedicine & Pharmacotherapy, 2018, 97: 633-641.
[8] Kawase Y, Sunagawa Y, Shimizu K, et al. 6-shogaol, an active component of ginger, inhibits P300 histone acetyltransferase activity and attenuates the development of pressure-overload-induced heart failure[J]. Nutrients, 2023, 15(9): 2232.
6-Shogaol是生姜中的一种活性物质，具有抗炎、抗肿瘤和抗氧化作用[1]。6-Shogaol通过与Akt的构象可变位点结合来抑制AKT激酶活性，从而诱导凋亡标志物Caspase-3和Caspase-7的裂解[2]。6-Shogaol已被广泛用于不同的细胞和动物模型，以抑制肿瘤进展并开发消除肿瘤耐药性的新型联合疗法[3]。
在体外，6-Shogaol处理72小时显著抑制了人脐静脉内皮细胞（HUVECs）的增殖，IC50值为8µM[4]。使用50µM的6-Shogaol处理24小时，诱导了HepG2和Huh-7细胞凋亡，伴随细胞核体积缩小、染色质浓缩并聚集于核膜边缘，以及核体完全碎裂[5]。使用10μg/ml的6-Shogaol处理24小时，阻断了NCI-H226细胞的G2/M期进程，并通过促进caspase级联反应诱导细胞凋亡 [6]。
在体内，每日腹腔注射50mg/kg剂量的6-Shogaol，持续12周，显著降低了C57BL/KsJ db/db肥胖小鼠的体重，减少了空腹血糖和血清胰岛素水平，并减轻了肾脏病理损伤[7]。每日口服1mg/kg剂量的6-Shogaol，持续8周，显著减轻了压力超负荷诱导的小鼠心脏肥大和收缩功能障碍[8]。