Crocin is a water-soluble natural carotenoid derived from the stigma of Crocus sativus [1]. Crocin significantly inhibits the phosphorylation activity of the JAK2/STAT3 and ERK signaling pathways, thereby blocking STAT3 transcriptional activity and reducing the expression of downstream pro-proliferation genes such as cyclin D1, VEGF, and CXCR4. It also upregulates the pro-apoptotic protein Bax and downregulates the anti-apoptotic protein Bcl-2, ultimately inducing cell cycle arrest (usually at the G0/G1 phase) and triggering mitochondria-dependent apoptotic pathways (caspase-9/caspase-3) [2-3]. Crocin is commonly used to treat various tumors, including colon, skin, thyroid, breast, and gastric cancers [4].
In A549 and SPC-A1 cells, Crocin (0-16mg/mL; 24-72h) inhibited the proliferation of cell in a concentration-dependent manner [5]. In HCT-116 cells, Crocin (0.25-3mg/mL; 48h) possesses significant anti-proliferation effects on human colorectal cancer cells [6]. In BV2 mouse microglial cells, Crocin (0-20μM; 30min) effectively inhibits LPS-induced nitric oxide (NO) release in cultured rat brain microglia [7].
In chronic mild stress (CMS) mice model, animals that received Crocin (4.84mg/kg, 9.69mg/kg, 19.38mg/kg; po; 21d) administration during the three CMS sessions had significantly shorter immobility times during the tail suspension test [8]. In dextran sodium sulfate (DSS)-induced UC mice model, Crocin (10mg/kg, 30mg/kg; ip; 3 weeks) prevents ulcerative colitis by inhibiting NF-κB-mediated inflammation [9].
References:
[1]. Zaghloul M S, Said E, Suddek G M, et al. Crocin attenuates lung inflammation and pulmonary vascular dysfunction in a rat model of bleomycin-induced pulmonary fibrosis[J]. Life sciences, 2019, 235: 116794.
[2]. Yang H, Zhang Y, Zhang D, et al. Crocin exerts anti-tumor effect in colon cancer cells via repressing the JaK pathway[J]. European Journal of Histochemistry: EJH, 2023, 67(3): 3697.
[3]. Boozari M, Hosseinzadeh H. Crocin molecular signaling pathways at a glance: A comprehensive review[J]. Phytotherapy Research, 2022, 36(10): 3859-3884.
[4]. Veisi A, Akbari G, Mard S A, et al. Role of crocin in several cancer cell lines: An updated review[J]. Iranian journal of basic medical sciences, 2020, 23(1): 3.
[5]. Chen S, Zhao S, Wang X, et al. Crocin inhibits cell proliferation and enhances cisplatin and pemetrexed chemosensitivity in lung cancer cells[J]. Translational lung cancer research, 2015, 4(6): 775.
[6]. Aung H H, Wang C Z, Ni M, et al. Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells[J]. Experimental oncology, 2007, 29(3): 175.
[7]. Nam K N, Park Y M, Jung H J, et al. Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells[J]. European journal of pharmacology, 2010, 648(1-3): 110-116.
[8]. Alsanie W F, Alamri A S, Abdulaziz O, et al. Antidepressant effect of crocin in mice with chronic mild stress[J]. Molecules, 2022, 27(17): 5462.
[9]. Teng S, Hao J, Bi H, et al. The protection of crocin against ulcerative colitis and colorectal cancer via suppression of NF-κB-mediated inflammation[J]. Frontiers in Pharmacology, 2021, 12: 639458.
Crocin是一种水溶性天然类胡萝卜素，来源于藏红花的柱头 [1]。Crocin能显著抑制JAK2/STAT3和ERK信号通路的磷酸化活性，从而阻断STAT3的转录活性，并降低下游促增殖基因（如细胞周期蛋白D1、VEGF和CXCR4）的表达。它还能上调促凋亡蛋白Bax，下调抗凋亡蛋白Bcl-2，最终诱导细胞周期停滞（通常处于G0/G1期）并启动线粒体依赖性凋亡途径（caspase-9/caspase-3） [2-3]。Crocin常用于治疗多种肿瘤，包括结肠癌、皮肤癌、甲状腺癌、乳腺癌和胃癌 [4]。
在A549和SPC-A1细胞中，Crocin（0-16mg/mL；24-72h）以浓度依赖性方式抑制细胞增殖 [5]。在HCT-116细胞中，Crocin（0.25-3mg/mL；48h）对人结肠直肠癌细胞具有显著的抗增殖作用 [6]。在BV2小鼠小胶质细胞中，Crocin（0-20μM；30min）有效抑制LPS诱导的培养大鼠脑小胶质细胞一氧化氮（NO）释放 [7]。
在慢性轻度应激（CMS）小鼠模型中，在三个CMS周期中分别给予Crocin（4.84mg/kg，9.69mg/kg，19.38mg/kg；po；21d）的小鼠在尾部悬吊实验中的静止时间显著缩短 [8]。在葡聚糖硫酸钠（DSS）诱发的UC小鼠模型中，Crocin（10mg/kg，30mg/kg；ip；3周）通过抑制NF-κB介导的炎症来预防溃疡性结肠炎 [9]。