Cordycepin

Cordycepin (3’-deoxyadenosine) is a nucleoside analog that inhibits polyadenylation^[1]. Cordycepin has a wide range of biological activities, including anti-cancer, anti-inflammatory, and antidepressant effects^{[2, 3]}.

In vitro, treatment of NIH3T3 fibroblasts with Cordycepin (5, 10µM) for 72h significantly reduced cell number and inhibited cell division, but did not induce apoptosis, and reduced the length of polyadenylic acid tails of some mRNAs^[4]. Treatment of HepG2 cells with Cordycepin (100µM) for 1h reversibly activated adenylate-activated protein kinase (AMPK) in the cells^[5]. Cordycepin (0-80μg/mL) was used to treat NB-4 and U937 cells for 24h, with IC₅₀ values of 18.4μg/mL (73.2μM) and 22.7μg/mL (90.4μM), respectively^[6].

In vivo, Cordycepin (15, 50mg/kg/day) was intraperitoneally injected into pancreatic cancer cell xenograft mice for 24 days, which reduced tumor volume and weight in a dose-dependent manner, had no significant effect on mouse body weight, upregulated the levels of cleaved caspase-3, caspase-9, PARP, and Bax in tumor tissues, and downregulated the level of Bcl-2^[7]. Cordycepin (10mg/kg) was orally treated into mice with cerebral ischemia for 21 days, which significantly improved the Y-maze learning performance of mice and reduced the neuronal loss caused by ischemia in the CA1 and CA3 regions of the hippocampus^[8].

References:
[1] Qin P, Li X K, Yang H, et al. Therapeutic potential and biological applications of cordycepin and metabolic mechanisms in cordycepin-producing fungi[J]. Molecules, 2019, 24(12): 2231.
[2] Radhi M, Ashraf S, Lawrence S, et al. A systematic review of the biological effects of cordycepin[J]. Molecules, 2021, 26(19): 5886.
[3] Du J, Kan W, Bao H, et al. Interactions between adenosine receptors and cordycepin (3'-deoxyadenosine) from cordyceps militaris: possible pharmacological mechanisms for protection of the brain and the amelioration of covid-19 pneumonia[J]. Journal of Biotechnology and Biomedicine, 2021, 4(2): 26-32.
[4] Wong Y Y, Moon A, Duffin R, et al. Cordycepin inhibits protein synthesis and cell adhesion through effects on signal transduction[J]. Journal of Biological Chemistry, 2010, 285(4): 2610-2621.
[5] Hawley S A, Ross F A, Russell F M, et al. Mechanism of activation of AMPK by cordycepin[J]. Cell chemical biology, 2020, 27(2): 214-222. e4.
[6] Liao Y, Ling J, Zhang G, et al. Cordycepin induces cell cycle arrest and apoptosis by inducing DNA damage and up-regulation of p53 in Leukemia cells[J]. Cell cycle, 2015, 14(5): 761-771.
[7] Zhang Y, Zhang X X, Yuan R Y, et al. Cordycepin induces apoptosis in human pancreatic cancer cells via the mitochondrial-mediated intrinsic pathway and suppresses tumor growth in vivo[J]. OncoTargets and therapy, 2018: 4479-4490.
[8] Cai Z L, Wang C Y, Jiang Z J, et al. Effects of cordycepin on Y-maze learning task in mice[J]. European journal of pharmacology, 2013, 714(1-3): 249-253.

Cordycepin（3’-deoxyadenosine; 虫草素）是一种核苷类似物，抑制聚腺苷酸化^[1]。Cordycepin具有广泛的生物活性，包括抗癌、抗炎、抗抑郁等作用^{[2, 3]}。

在体外，Cordycepin（5, 10µM）处理NIH3T3成纤维细胞72h，显著减少了细胞数量，抑制了细胞分裂，但不诱导细胞凋亡，减少了一部分mRNA的聚腺苷酸尾长度^[4]。Cordycepin（100µM）处理HepG2细胞1h，可逆地激活了细胞中的腺苷酸激活蛋白激酶（AMPK）^[5]。Cordycepin（0-80μg/mL）处理NB-4和U937细胞24h，IC₅₀值分别为18.4μg/mL（73.2μM）和22.7μg/mL（90.4μM）^[6]。

在体内，Cordycepin（15, 50mg/kg/day）通过腹腔注射治疗胰腺癌细胞异种移植小鼠24天，剂量依赖性地减小了肿瘤体积和重量，且对小鼠体重无明显影响，上调了肿瘤组织中裂解的caspase-3、caspase-9、PARP、Bax水平，下调了Bcl-2水平^[7]。Cordycepin（10mg/kg）通过口服治疗脑缺血小鼠21天，显著改善了小鼠的Y迷宫学习表现，减少海马CA1和CA3区缺血引起的神经元损失^[8]。