Lovastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that impacts the mevalonate pathway[1], which has an IC50 value of 77nM[2]. Lovastatin can inhibit cholesterol synthesis[3], EC50 value is 0.002mg/kg[2].
Lovastatin can induce apoptosis (10μM , 24h) inspontaneously immortalized rat brain neuroblasts[4]. Lovastatin efficiently inhibited Ras activation,which was associated with a significant decrease in ERK1/2 (extracellular-signalregulated kinase1/2) phosphorylation[4] . Lovastatin can inhibit A549 (human lung adenocarcinoma cells) cell proliferation (50μM , 24h) by regulating the ERK1/2 and COX-2 pathways[5].
Lovastatin (5mg/kg ; 14 days ; Intraperitoneal injection) attenuates hippocampal cell death in Pilocarpine-induced status epilepticus rat model through downregulation of the pro-apoptotic Mst1 gene[6]. Lovastatin (0.5mg/kg ; 10 days ; subcutaneous injection) enhanced ovarian activity throughout follicular development in ICR mice model[7].
Scheme of Low-Density Lipoprotein Receptor（LDLR）activity signaling pathway for follicular development with lovastatin stimulates steroidogenesis in ovaries[7].
References:
[1] AMADASU E, KANG R, USMANI A, et al. Effects of Lovastatin on Brain Cancer Cells [J]. Cell Transplant, 2022, 31(9636897221102903.
[2] H BISCHOFF R A, M BOBERG, D PETZINNA, D SCHMIDT, W STEINKE, G THOMAS. Preclinical review of cerivastatin sodium--a step forward in HMG-CoA reductase inhibition [J]. 1998,
[3] BORUTA T, BIZUKOJC M. Production of lovastatin and itaconic acid by Aspergillus terreus: a comparative perspective [J]. World J Microbiol Biotechnol, 2017, 33(2): 34.
[4] CEREZO-GUISADO M I, GARCIA-ROMAN N, GARCIA-MARIN L J, et al. Lovastatin inhibits the extracellular-signal-regulated kinase pathway in immortalized rat brain neuroblasts [J]. Biochem J, 2007, 401(1): 175-83.
[5] LIU S, YANG P, WANG M, et al. Inhibitory effect of lovastatin on human lung cancer cell proliferation by regulating the ERK1/2 and COX-2 pathways [J]. Transl Cancer Res, 2022, 11(4): 813-22.
[6] ABDANIPOUR A, DEHESHJO F, SOHRABI D, et al. Neuroprotective effect of lovastatin through down-regulation of pro-apoptotic Mst1 gene expression in rat model pilocarpine epilepsy [J]. Neurol Res, 2018, 40(10): 874-82.
[7] KIM Y J, CHO Y I, JANG J, et al. Lovastatin, an Up-Regulator of Low-Density Lipoprotein Receptor, Enhances Follicular Development in Mouse Ovaries [J]. Int J Mol Sci, 2023, 24(8).
Lovastatin是一种3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂，通过影响甲羟戊酸途径来发挥作用[1]，IC50值为77nM[2]。Lovastatin能抑制胆固醇合成[3]，EC50值为0.002mg/kg[2]。
Lovastatin能够在特定条件下诱导细胞凋亡，特别是在自发永生化的鼠脑神经母细胞中（10μM , 24小时）[4]。Lovastatin有效地抑制了Ras的激活，这与ERK1/2（细胞外信号调节激酶1/2）磷酸化的显著减少有关[4]。Lovastatin可以通过调节ERK1/2和COX-2信号通路来抑制A549（人肺腺癌细胞）的增殖（50μM , 24小时）[5]。
Lovastatin能通过下调促凋亡基因Mst1来减轻由Pilocarpine诱导的癫痫持续状态大鼠模型中海马的细胞死亡[6]。Lovastatin(0.5 mg/kg ；10天 ；皮下注射)增强了ICR小鼠在卵泡发育过程中的卵巢活性[7]。
通过激活低密度脂蛋白受体（LDLR）活性信号通路促进卵泡发育，并刺激卵巢中类固醇的生成方案[7]。