Cepharanthine, a bisbenzylisoquinoline alkaloid, has potent antiviral activity with the EC50 values of 0.15µM and 0.026µM for SARS-CoV-2 and HIV-1, respectively[1]. Cepharanthine effectively reversed most of the dysregulated genes and pathways in virus-infected cells, including endoplasmic reticulum (ER) stress/unfolded protein response and heat shock factor 1 (HSF1)-mediated heat shock response[2]. Cepharanthine has been widely used as an anti-inflammatory agent to reduce the levels of TNF-α, IL-1β and IL-6 in cellular and animal models[3].
In vitro, Cepharanthine treatment for 48 hours significantly inhibited the proliferation of Eca109 cells with an IC50 value of 6.20 ± 0.17μM[4]. Treatment with 20μM Cepharanthine for 24 hours significantly inhibited the viability of HT1376 cells, reduced the migration and invasion of cells, and activated the Rap1 signaling pathway in the cells[5]. Pretreatment with 10μM Cepharanthine for 1h significantly inhibited lipopolysaccharide-induced NO production and iNOS and COX-2 expression in RAW264.7 cells[6].
In vivo, Cepharanthine (20mg/kg) administered intraperitoneally once every two days for 24 days significantly suppressed tumor weight and volume in a mouse model of hepatocellular carcinoma and reduced Ki67 expression in tumor tissues[7]. Cepharanthine treatment at a dose of 15mg/kg once weekly via intraperitoneal injection for 12 weeks significantly ameliorated cartilage degeneration and prevented osteoarthritis (OA) in a mouse OA model[8].
References:
[1] Liu K, Hong B, Wang S, et al. Pharmacological activity of cepharanthine[J]. Molecules, 2023, 28(13): 5019.
[2] Shi L, Wang S, Zhang S, et al. Research progress on pharmacological effects and mechanisms of cepharanthine and its derivatives[J]. Naunyn-Schmiedeberg's Archives of Pharmacology, 2023, 396(11): 2843-2860.
[3] Liang D, Li Q, Du L, et al. Pharmacological effects and clinical prospects of cepharanthine[J]. Molecules, 2022, 27(24): 8933.
[4] Zhou P, Zhang R, Wang Y, et al. Cepharanthine hydrochloride reverses the mdr1 (P-glycoprotein)-mediated esophageal squamous cell carcinoma cell cisplatin resistance through JNK and p53 signals[J]. Oncotarget, 2017, 8(67): 111144.
[5] Chen B, Chen L, Yang J, et al. Cepharanthine inhibits migration, invasion, and EMT of bladder cancer cells by activating the Rap1 signaling pathway in vitro[J]. American journal of translational research, 2024, 16(5): 1602.
[6] Paudel K R, Karki R, Kim D W. Cepharanthine inhibits in vitro VSMC proliferation and migration and vascular inflammatory responses mediated by RAW264. 7[J]. Toxicology in vitro, 2016, 34: 16-25.
[7] Feng F, Pan L, Wu J, et al. Cepharanthine inhibits hepatocellular carcinoma cell growth and proliferation by regulating amino acid metabolism and suppresses tumorigenesis in vivo[J]. International journal of biological sciences, 2021, 17(15): 4340.
[8] Yao M, Zhang C, Ni L, et al. Cepharanthine ameliorates chondrocytic inflammation and osteoarthritis via regulating the MAPK/NF-κB-Autophagy pathway[J]. Frontiers in Pharmacology, 2022, 13: 854239.
Cepharanthine是一种双苄基异喹啉生物碱，具有强效抗病毒活性，对SARS-CoV-2和HIV-1的EC50值分别为0.15µM和0.026µM[1]。Cepharanthine能有效逆转病毒感染的细胞中大多数失调基因和通路，包括内质网（ER）应激/未折叠蛋白反应和热休克因子1（HSF1）介导的热休克反应[2]。Cepharanthine作为抗炎剂广泛被应用于细胞和动物模型，可降低TNF-α、IL-1β和IL-6水平[3]。
在体外，Cepharanthine处理48小时可显著抑制Eca109细胞增殖，IC50值为6.20 ± 0.17μM[4]。20μM的Cepharanthine处理HT1376细胞24小时能显著抑制细胞活力，减少细胞的迁移和侵袭，并激活Rap1信号通路[5]。10μM的Cepharanthine预处理RAW264.7细胞1小时可显著抑制脂多糖诱导的NO产生及iNOS和COX-2表达[5]。
在体内，肝细胞癌小鼠模型每两天腹腔注射Cepharanthine（20mg/kg；持续24天）能显著抑制肿瘤重量和体积，并降低肿瘤组织中Ki67表达[7]。骨关节炎小鼠模型每周腹腔注射15mg/kg剂量的Cepharanthine（持续12周）可显著改善软骨退化并预防骨关节炎进展[8]。