Diacerein is an orally active anthraquinone with anti-inflammatory, anti-catabolic, and pro-anabolic properties on cartilage and synovial membrane [1]. Diacerein can decrease the activation of IL-1β via a reduced production of IL-1 converting enzyme, as well as affect the sensitivity to IL-1 by decreasing IL-1 receptor levels on the cell surface of chondrocytes [2]. Diacerein has been widely used to alleviate osteoarthritis and inhibit SARS-CoV virus infection [3].
In vitro, Diacerein treatment for 48 hours significantly inhibited the production of TNF-α, IL-6 and IL-1β in RAW264.7 cells, with IC50 values of 126.77, 106.90, and 65.41µM, respectively[4]. Diacerein treatment for 48 hours significantly inhibited HCT116 cells, RKO cells, and SW80 cells, with IC50 values of 46.56µM, 29.93µM, and 33.47µM, respectively[5]. Treatment with 100µM Diacerein for 48 hours resulted in G2/M phase arrest of SW-1353 cells and a decrease in the mRNA levels of Cyclin B1, CDK1, and CDK2[6].
In vivo, Diacerein treatment via intravenous tail vein injection at a dose of 40 mg/kg every other day for 4 weeks significantly inhibited tumor growth in the MDA-MB-231 xenograft mouse model and led to reduced phosphorylation levels of STAT3, MAPK, and Akt in the tumors [7]. Oral administration of 100mg/kg/day Diacerein for 21 days significantly prevented bone loss, reduced the serum alkaline phosphatase, and decreased the excretion of urinary hydroxyproline in the ovariectomized rats[8].
References:
[1] Pavelka K, Bruyere O, Cooper C, et al. Diacerein: benefits, risks and place in the management of osteoarthritis. An opinion-based report from the ESCEO[J]. Drugs & aging, 2016, 33(2): 75-85.
[2] Almezgagi M, Zhang Y, Hezam K, et al. Diacerein: Recent insight into pharmacological activities and molecular pathways[J]. Biomedicine & Pharmacotherapy, 2020, 131: 110594.
[3] de Oliveira P G, Termini L, Durigon E L, et al. Diacerein: A potential multi-target therapeutic drug for COVID-19[J]. Medical hypotheses, 2020, 144: 109920.
[4] Wang J, Wei W, Zhang X, et al. Synthesis and biological evaluation of C-17-amino-substituted pyrazole-fused betulinic acid derivatives as novel agents for osteoarthritis treatment[J]. Journal of Medicinal Chemistry, 2021, 64(18): 13676-13692.
[5] Qiaobei Y E, Yu Z H U, Meng S H I, et al. Repurposing diacerein to suppress colorectal cancer growth by inhibiting the DCLK1/STAT3 signaling pathway[J]. Chinese Journal of Natural Medicines, 2024, 22(4): 318-328.
[6] Lohberger B, Leithner A, Stuendl N, et al. Diacerein retards cell growth of chondrosarcoma cells at the G2/M cell cycle checkpoint via cyclin B1/CDK1 and CDK2 downregulation[J]. BMC cancer, 2015, 15(1): 891.
[7] Bharti R, Dey G, Ojha P K, et al. Diacerein-mediated inhibition of IL-6/IL-6R signaling induces apoptotic effects on breast cancer[J]. Oncogene, 2016, 35(30): 3965-3975.
[8] Tamura T, Shirai T, Kosaka N, et al. Pharmacological studies of diacerein in animal models of inflammation, arthritis and bone resorption[J]. European journal of pharmacology, 2002, 448(1): 81-87.
Diacerein是一种口服有效的蒽醌类化合物，对软骨和滑膜具有抗炎、抗分解代谢和促合成代谢的特性[1]。Diacerein可通过减少IL-1转化酶的产生来降低IL-1β的激活，并通过降低软骨细胞表面IL-1受体的水平来影响细胞对IL-1的敏感性[2]。Diacerein已被广泛用于缓解骨关节炎和抑制SARS-CoV病毒感染[3]。
在体外，Diacerein处理RAW264.7细胞48小时，显著抑制了TNF-α、IL-6和IL-1β的产生，IC50值分别为126.77、106.90和65.41µM[4]。Diacerein处理HCT116细胞、RKO细胞和SW80细胞48小时，显著抑制了细胞增殖，IC50值分别为46.56µM、29.93µM和33.47µM[5]。100µM的Diacerein处理SW-1353细胞48小时，导致细胞周期阻滞在G2/M期，并降低了Cyclin B1、CDK1和CDK2的mRNA水平[6]。
在体内，隔日尾静脉注射40mg/kg剂量的Diacerein，持续4周，显著抑制了MDA-MB-231异种移植小鼠模型中的肿瘤生长，并导致肿瘤中STAT3、MAPK和Akt的磷酸化水平降低[7]。每日口服100mg/kg剂量的Diacerein，持续21天，显著预防了去卵巢大鼠的骨丢失，降低了血清碱性磷酸酶水平，并减少了尿羟脯氨酸的排泄[8]。