Silibinin

Silibinin is an orally active flavonoid with hepatoprotective and anticancer effects^[1]. Silibinin can treat a variety of cancers by regulating cancer cell growth, proliferation, apoptosis, angiogenesis and many other mechanisms^[2]. Silibinin can improve blood glucose homeostasis by improving the activity of pancreatic β cells, increasing insulin sensitivity in liver and muscle cells, and reducing lipid deposition in adipocytes^[3].

In vitro, pretreatment of colorectal cancer SW480, LoVo and HT29 cells with Silibinin (50-200μM) for 2h significantly inhibited TNFα-induced NF-κB activation and decreased nuclear levels of p65 and p50 subunits, and significantly increased IκBα levels^[4]. Silibinin (5-50μM) treatment of human breast cancer cell lines MCF7 and MDA-MB-231 cells for 24 and 48h reduced cell viability in both cell lines in a dose-dependent manner, induced apoptosis, and induced downregulation of extracellular signal-regulated kinase (ERK) and Akt expression^[5]. Treatment of HT29 cells with Silibinin (0-100μM) for 24h caused cell shrinkage, blistering, and detachment from the culture dish, and induced the cleavage of the DNA repair enzyme PARP in a dose-dependent and time-dependent manner^[6].

In vivo, oral treatment of streptozotocin (STZ)-induced diabetic rats with Silibinin (100, 200mg/kg) for 21 days prevented STZ-induced insulin reduction, reduced serum alanine aminotransferase (ALT), and improved anxiety-like behavior^[7]. Oral treatment of chronic inflammatory rats with Silibinin (300mg/kg) significantly reduced the formation of exudate and granulation tissue^[8].

 References:
[1] Wing Ying Cheung C, Gibbons N, Wayne Johnson D, et al. Silibinin-a promising new treatment for cancer[J]. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 2010, 10(3): 186-195.
[2] Zhu X X, Ding Y H, Wu Y, et al. Silibinin: a potential old drug for cancer therapy[J]. Expert review of clinical pharmacology, 2016, 9(10): 1323-1330.
[3] Chu C, Li D, Zhang S, et al. Role of silibinin in the management of diabetes mellitus and its complications[J]. Archives of pharmacal research, 2018, 41: 785-796.
[4] Raina K, Agarwal C, Agarwal R. Effect of silibinin in human colorectal cancer cells: targeting the activation of NF‐κB signaling[J]. Molecular carcinogenesis, 2013, 52(3): 195-206.
[5] Kim T H, Woo J S, Kim Y K, et al. Silibinin induces cell death through reactive oxygen species–dependent downregulation of notch-1/ERK/Akt signaling in human breast cancer cells[J]. Journal of Pharmacology and Experimental Therapeutics, 2014, 349(2): 268-278.
[6] Woo S M, Min K, Kim S, et al. Silibinin induces apoptosis of HT29 colon carcinoma cells through early growth response-1 (EGR-1)-mediated non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) up-regulation[J]. Chemico-biological interactions, 2014, 211: 36-43.
[7] Dagli Gul A S, Boyuk Ozcan G, Arihan O. Silibinin as a promising treatment for diabetes: Insights into behavioral and metabolic changes in an animal model[J]. Food Science & Nutrition, 2024, 12(5): 3336-3345.
[8] Aziz T A, Marouf B H, Ahmed Z A, et al. Anti-inflammatory activity of silibinin in animal models of chronic inflammation[J]. Am J Pharmacol Sci, 2014, 2(1): 7-11.

Silibinin是一种具有口服活性的类黄酮，具有保肝和抗癌作用^[1]。Silibinin能够通过调节癌细胞生长、增殖、细胞凋亡、血管生成和许多其他机制，治疗多种癌症^[2]。Silibinin能够通过改善胰腺β细胞的活性、增加肝脏和肌肉细胞的胰岛素敏感性以及减少脂肪细胞中的脂质沉积来改善血糖稳态^[3]。

在体外，Silibinin（50-200μM）预处理结直肠癌SW480、LoVo和HT29细胞2h，显著抑制了TNFα诱导的NF-κB活化以及p65和p50亚基的核水平降低，显著增加了IκBα水平^[4]。Silibinin（5-50μM）处理人乳腺癌细胞系MCF7和MDA-MB-231细胞24和48h，以剂量依赖性方式降低了两种细胞系的细胞活力，诱导了细胞凋亡，诱导了细胞外信号调节激酶（ERK）和Akt表达下调^[5]。Silibinin（0-100μM）处理HT29细胞24h，引起了细胞收缩、起泡以及脱离培养皿，以剂量依赖性和时间依赖性方式诱导了DNA修复酶PARP的裂解^[6]。

在体内，Silibinin（100，200mg/kg）通过口服治疗链脲佐菌素（STZ）诱导的糖尿病模型大鼠21天，阻止了STZ引起的胰岛素减少，降低了血清谷丙转氨酶（ALT）的升高，改善了焦虑样行为^[7]。Silibinin（300mg/kg）通过口服治疗慢性炎症大鼠，显著减少了渗出液和肉芽组织的形成^[8]。