Minocycline HCl is an orally effective, blood-brain barrier-permeable semisynthetic tetracycline antibiotic[1]. Minocycline HCl is a hypoxia-inducible factor (HIF-1α) inhibitor with anticancer, anti-inflammatory and glutamate antagonist effects, as well as neuroprotective and antidepressant properties[2]. Minocycline HCl inhibits bacterial protein synthesis by binding to the bacterial ribosome 30S subunit, thereby exerting an antibacterial effect[3].
In vitro, treatment of SH-SY5Y cells with Minocycline HCl (10μM) for 24 h significantly inhibited 6-hydroxydopamine (6-OHDA)-induced cell death, and inhibited cell DNA fragmentation and chromatin condensation[4]. Minocycline HCl (0-100μM) treatment of ovarian cancer cell lines (OVCAR-3, SKOV-3 and A2780 cells) for 24-72 h inhibited cell proliferation and colony formation, downregulated the expression of cyclins A, B and E, inhibited DNA synthesis, and also led to DNA laddering, caspase-3 activation and PARP-1 cleavage[5].
In vivo, Minocycline HCl (25, 50mg/kg) was treated by intraperitoneal injection in spinal cord injury model mice for 28 days, which significantly protected axonal integrity, prevented tissue loss and improved motor behavior[6]. Minocycline HCl (3, 10mg/kg) was injected into the jugular vein in rats with transient middle cerebral artery occlusion (TMCAO) model, which effectively reduced the infarct area and significantly improved neurological deficits[7].
References:
[1] Zhou J, Yang J, Dai M, et al. A combination of inhibiting microglia activity and remodeling gut microenvironment suppresses the development and progression of experimental autoimmune uveitis[J]. Biochemical Pharmacology, 2020, 180: 114108.
[2] Pajarillo E, Nyarko-Danquah I, Digman A, et al. Mechanisms of manganese-induced neurotoxicity and the pursuit of neurotherapeutic strategies[J]. Frontiers in Pharmacology, 2022, 13: 1011947.
[3] Singh S, Khanna D, Kalra S. Minocycline and doxycycline: more than antibiotics[J]. Current Molecular Pharmacology, 2021, 14(6): 1046-1065.
[4] Ossola B, Lantto T A, Puttonen K A, et al. Minocycline protects SH‐SY5Y cells from 6‐hydroxydopamine by inhibiting both caspase‐dependent and‐independent programmed cell death[J]. Journal of neuroscience research, 2012, 90(3): 682-690.
[5] Pourgholami M H, Mekkawy A H, Badar S, et al. Minocycline inhibits growth of epithelial ovarian cancer[J]. Gynecologic oncology, 2012, 125(2): 433-440.
[6] Wells J E A, Hurlbert R J, Fehlings M G, et al. Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice[J]. Brain, 2003, 126(7): 1628-1637.
[7] Xu L, Fagan S C, Waller J L, et al. Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats[J]. BMC neurology, 2004, 4: 1-7.
盐酸米诺环素（Minocycline HCl）是一种口服有效、能透过血脑屏障的半合成四环素类抗生素[1]。Minocycline HCl是一种缺氧诱导因子（HIF-1α）抑制剂，具有抗癌、抗炎和谷氨酸拮抗作用，还具有神经保护特性和抗抑郁作用[2]。Minocycline HCl通过与细菌核糖体30S亚基结合，抑制细菌蛋白的合成，从而产生抑菌作用[3]。
在体外，Minocycline HCl（10μM）处理SH-SY5Y细胞24h，显著抑制了6-羟基多巴胺（6-OHDA）诱导的细胞死亡，抑制了细胞DNA断裂和染色质浓缩[4]。Minocycline HCl（0-100μM）处理卵巢癌细胞系 （OVCAR-3、SKOV-3和A2780细胞）24-72h，抑制了细胞增殖和集落形成，下调了细胞周期蛋白A、B和E的表达，抑制了DNA合成，还导致了DNA梯状化、caspase-3活化和PARP-1裂解[5]。
在体内，Minocycline HCl（25、50mg/kg）通过腹腔注射治疗脊髓损伤模型小鼠28天，显著保护了轴突完整性、防止了组织损失并改善了运动行为[6]。Minocycline HCl（3、10mg/kg）通过颈静脉注射暂时性大脑中动脉闭塞（TMCAO）模型大鼠，可有效减少梗死面积，显著改善神经功能缺损[7]。