Atorvastatin
(Synonyms: 阿托伐他汀) 目录号 : GC35419
阿托伐他汀（Atorvastatin）是一种口服活性HMG-CoA还原酶抑制剂，可以有效降低血脂
Cas No.:134523-00-5
Sample solution is provided at 25 µL, 10mM.
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- Purity: >98.00%
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- Datasheet
| Cell experiment [1]: | |
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Cell lines |
Differentiated THP-1 human monocytes |
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Preparation Method |
Following differentiation, cells were treated with either vehicle control or one of the six statins (atorvastatin;0-100 µM) and incubated at 37 ¡栩n 5% CO2 for 60 minutes. |
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Reaction Conditions |
0-100uM atorvastatin at 37 ¡栦or 60 minutes |
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Applications |
Pretreatment with atorvastatin was able to significantly reduce LPS-induced interleukin (IL)-1β and tumour necrosis factor (TNF)-α release, as well as decrease LPS-induced prostaglandin E2 (PGE2). Similarly, global reactive oxygen species (ROS) and nitric oxide (NO) production were decreased following pretreatment with atorvastatin. |
| Animal experiment [2]: | |
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Animal models |
Male adult Swiss albino mice (30-50 g) |
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Preparation Method |
Animals were pretreated with 10 mg/kg/day of atorvastatin, orally or vehicle (saline, 0.9%) once a day for 7 days before preparing hippocampal slices for ex vivo OGD induction and measurement of cellular viability, oxidative stress and glutamatergic transmission parameters. |
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Dosage form |
10 mg/kg atorvastatin, orally once a day for 7 days |
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Applications |
Atorvastatin pretreatment promoted increased cell viability after OGD and reoxygenation of hippocampal slices. Atorvastatin-induced neuroprotection may be related to diminished oxidative stress, since it prevented OGD-induced decrement of non-proteic thiols (NPSH) levels and increase in the production of reactive oxygen species (ROS). |
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References: [1]. McFarland AJ, Davey AK, et,al. Statins Reduce Lipopolysaccharide-Induced Cytokine and Inflammatory Mediator Release in an In Vitro Model of Microglial-Like Cells. Mediators Inflamm. 2017;2017:2582745. doi: 10.1155/2017/2582745. Epub 2017 May 4. PMID: 28546657; PMCID: PMC5435995. |
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Atorvastatin is an orally active HMG-CoA reductase inhibitor, has the ability to effectively decrease blood lipids[1]. Atorvastatin inhibits human SV-SMC proliferation and invasion with IC50s of 0.39 µM and 2.39 mM.
PMA-differentiated THP-1 cells were used as surrogate microglial cells, and LPS was used to induce inflammatory conditions. Pretreatment with atorvastatin was able to significantly reduce LPS-induced interleukin (IL)-1β and tumour necrosis factor (TNF)-α release, as well as decrease LPS-induced prostaglandin E2 (PGE2). Similarly, global reactive oxygen species (ROS) and nitric oxide (NO) production were decreased following pretreatment with atorvastatin[5]. In rat NP cells, Atorvastatin might suppress matrix degradation induced by TNF-α by suppressing NLRP3 inflammasome activity and inducing autophagic flux. Moreover, atorvastatin suppressed NF-κB signaling induced by TNF-α. NF-κB signaling inhibition suppressed NLRP3 inflammasome activity, and NLRP3 inhibition suppressed NF-κB signaling activation induced by TNF-α. NLRP3 inhibition or NLRP3 knockdown induced autophagic flux in the presence of TNF-α[7].
In mice, Atorvastatin pretreatment promoted increased cell viability after OGD and reoxygenation of hippocampal slices. Atorvastatin-induced neuroprotection may be related to diminished oxidative stress, since it prevented OGD-induced decrement of non-proteic thiols (NPSH) levels and increase in the production of reactive oxygen species (ROS)[3]. The oral treatment with atorvastatin (10mg/kg/day)was able to prevent short-term memory impairments and depressive-like behavior of rats assessed in the social recognition and forced swimming tests at 7 and 14 days, respectively, after a single intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1mg/nostril)[4].The effects of atorvastatin antidepressants are related to the regulation of serotonergic transmission, the inhibition of NMDA receptor and NO-CGMP synthesis, and the activation of receptor γ dependent on peroxisome proliferators[6]. Atorvastatin treatment exerted neuroprotective effects against LPS-induced depressive-like behaviour which may be related to reduction of TNF-α release, oxidative stress and modulation of BDNF expression[2].
References:
[1]: Taciak PP, Lysenko N, et,al. Drugs which influence serotonin transporter and serotonergic receptors: Pharmacological and clinical properties in the treatment of depression. Pharmacol Rep. 2018 Feb;70(1):37-46. doi: 10.1016/j.pharep.2017.07.011. Epub 2017 Jul 16. PMID: 29309998.
[2]: Taniguti EH, Ferreira YS, et,al. Atorvastatin prevents lipopolysaccharide-induced depressive-like behaviour in mice. Brain Res Bull. 2019 Mar;146:279-286. doi: 10.1016/j.brainresbull.2019.01.018. Epub 2019 Jan 25. PMID: 30690060.
[3]: Vandresen-Filho S, Martins WC, et,al. Atorvastatin prevents cell damage via modulation of oxidative stress, glutamate uptake and glutamine synthetase activity in hippocampal slices subjected to oxygen/glucose deprivation. Neurochem Int. 2013 Jun;62(7):948-55. doi: 10.1016/j.neuint.2013.03.002. Epub 2013 Mar 14. PMID: 23500607.
[4]: Castro AA, Wiemes BP, et,al. Atorvastatin improves cognitive, emotional and motor impairments induced by intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in rats, an experimental model of Parkinson's disease. Brain Res. 2013 Jun 4;1513:103-16. doi: 10.1016/j.brainres.2013.03.029. Epub 2013 Mar 30. PMID: 23548600.
[5]: McFarland AJ, Davey AK, et,al. Statins Reduce Lipopolysaccharide-Induced Cytokine and Inflammatory Mediator Release in an In Vitro Model of Microglial-Like Cells. Mediators Inflamm. 2017;2017:2582745. doi: 10.1155/2017/2582745. Epub 2017 May 4. PMID: 28546657; PMCID: PMC5435995.
[6]: Ludka FK, Constantino LC, et,al. Atorvastatin evokes a serotonergic system-dependent antidepressant-like effect in mice. Pharmacol Biochem Behav. 2014 Jul;122:253-60. doi: 10.1016/j.pbb.2014.04.005. Epub 2014 Apr 21. PMID: 24769309.
[7]: Chen J, Yan J, et,al.Atorvastatin inhibited TNF-α induced matrix degradation in rat nucleus pulposus cells by suppressing NLRP3 inflammasome activity and inducing autophagy through NF-κB signaling. Cell Cycle. 2021 Oct;20(20):2160-2173. doi: 10.1080/15384101.2021.1973707. Epub 2021 Sep 8. PMID: 34494933; PMCID: PMC8565837.
阿托伐他汀是一种具有口服活性的 HMG-CoA 还原酶抑制剂，具有有效降低血脂的能力[1]。阿托伐他汀抑制人 SV-SMC 增殖和侵袭，IC50 分别为 0.39 µM 和 2.39 mM。
PMA 分化的 THP-1 细胞用作替代小胶质细胞，LPS 用于诱导炎症条件。阿托伐他汀预处理能够显着降低 LPS 诱导的白细胞介素 (IL)-1β；和肿瘤坏死因子（TNF）-α；释放，以及减少 LPS 诱导的前列腺素 E2 (PGE2)。类似地，在用阿托伐他汀[5] 预处理后，总体活性氧 (ROS) 和一氧化氮 (NO) 的产生减少。在大鼠 NP 细胞中，阿托伐他汀可能抑制 TNF-α 诱导的基质降解；通过抑制 NLRP3 炎性体活性和诱导自噬通量。此外，阿托伐他汀抑制 NF-κB 信号由 TNF-α 诱导。 NF-κB 信号抑制抑制 NLRP3 炎性体活性，NLRP3 抑制抑制 NF-κTNF-α 诱导的 B 信号激活;。在 TNF-α 存在的情况下，NLRP3 抑制或 NLRP3 敲低诱导自噬通量；[7]。
在小鼠中，阿托伐他汀预处理促进 OGD 后细胞活力增加和海马切片复氧.阿托伐他汀诱导的神经保护作用可能与氧化应激减弱有关，因为它阻止了 OGD 诱导的非蛋白硫醇 (NPSH) 水平下降和活性氧 (ROS) 产生的增加[3] .口服阿托伐他汀（10mg/kg/天）能够预防大鼠在单次鼻内给药后分别在第 7 天和第 14 天的社会认知和强迫游泳测试中评估的短期记忆障碍和抑郁样行为1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP)（1 毫克/鼻孔）[4]。阿托伐他汀抗抑郁药的作用与血清素能传递的调节有关, NMDA受体和NO-CGMP合成的抑制，以及受体γ的激活；依赖于过氧化物酶体增殖物[6]。阿托伐他汀治疗对 LPS 诱导的抑郁样行为具有神经保护作用，这可能与 TNF-α 的减少有关； BDNF表达的释放、氧化应激和调控[2].
| Cas No. | 134523-00-5 | SDF | |
| 别名 | 阿托伐他汀 | ||
| Canonical SMILES | O=C(C(C(C1=CC=CC=C1)=C(C2=CC=C(F)C=C2)N3CC[C@@H](O)C[C@@H](O)CC(O)=O)=C3C(C)C)NC4=CC=CC=C4 | ||
| 分子式 | C33H35FN2O5 | 分子量 | 558.64 |
| 溶解度 | DMSO: 100 mg/mL (179.01 mM) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7901 mL | 8.9503 mL | 17.9006 mL |
| 5 mM | 0.358 mL | 1.7901 mL | 3.5801 mL |
| 10 mM | 0.179 mL | 0.895 mL | 1.7901 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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Atorvastatin prevents lipopolysaccharide-induced depressive-like behaviour in mice
Brain Res Bull 2019 Mar;146:279-286.PMID:30690060DOI:10.1016/j.brainresbull.2019.01.018.
Clinical and pre-clinical evidences indicate an association between inflammation and depression since increased levels of pro-inflammatory cytokines are associated with depression-related symptoms. Atorvastatin is a cholesterol-lowering statin that possesses pleiotropic effects including neuroprotective and antidepressant actions. However, the putative neuroprotective effect of Atorvastatin treatment in the acute inflammation mice model of depressive-like behaviour has not been investigated. In the present study, we aimed to investigate the effect of Atorvastatin treatment on lipopolysaccharide (LPS) induced depressive-like behaviour in mice. Mice were treated with Atorvastatin (1 or 10 mg/kg, v.o.) or fluoxetine (30 mg/kg, positive control, v.o.) for 7 days before LPS (0.5 mg/kg, i.p.) injection. Twenty four hours after LPS infusion, mice were submitted to the forced swim test, tail suspension test or open field test. After the behavioural tests, mice were sacrificed and the levels of tumour necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF), glutathione and malondialdehyde were measured. Atorvastatin (1 or 10 mg/kg/day) or fluoxetine treatment prevented LPS-induced increase in the immobility time in the forced swim and tail suspension tests with no alterations in the locomotor activity evaluated in the open field test. Atorvastatin (1 or 10 mg/kg/day) or fluoxetine treatment also prevented LPS-induced increase in TNF-α and reduction of BDNF levels in the hippocampus and prefrontal cortex. Treatment with Atorvastatin (1 or 10 mg/kg/day) or fluoxetine prevented LPS-induced increase in lipid peroxidation and the reduction of glutathione levels in the hippocampus and prefrontal cortex. The present study suggests that Atorvastatin treatment exerted neuroprotective effects against LPS-induced depressive-like behaviour which may be related to reduction of TNF-α release, oxidative stress and modulation of BDNF expression.
Atorvastatin: A Review of Analytical Methods for Pharmaceutical Quality Control and Monitoring
J AOAC Int 2019 May 1;102(3):801-809.PMID:30563586DOI:10.5740/jaoacint.18-0200.
Background: Atorvastatin, a lipid-regulating drug, was the best-selling drug in the world in the early 2000s. Thus, monitoring of this drug is important because it is accessible to a large portion of the population. In addition, its quality control is fundamental to provide quality medicines. Method of analysis can be the first step in the rational use of pharmaceuticals. Objective/Methods: In this context, a critical review of analytical methods present in the literature and official compendia for the pharmaceutical quality control of Atorvastatin was made. Results: Among the analytical methods most used in the evaluation of Atorvastatin, HPLC is highlighted, followed by HPLC coupled to MS, and spectrophotometry in UV. Tablets are the most studied pharmaceutical samples, and plasma is the most studied biological matrix. In the literature, studies with atorvastatin-based pharmaceutical products are more common than biological materials. Acetonitrile is the organic solvent most commonly used in the methods surveyed to evaluate Atorvastatin. Conclusions: Currently, awareness of the impact that the analytical choice has on the health of the operator and the environment is growing. Therefore, the suitability of existing methods for the determination of Atorvastatin can be made to adhere to the current analytical chemistry. In this way, the analytical, environmental, and human consciousness will remain united. Highlights: Although the literature shows interesting methods from an economic and environmental point of view, such as UV, Vis miniaturized, and TLC, they can still be improved to meet the requirements of the current sustainable analytical chemistry.
Effects of Atorvastatin on chronic subdural hematoma: A systematic review
Medicine (Baltimore) 2017 Jun;96(26):e7290.PMID:28658127DOI:10.1097/MD.0000000000007290.
Background: The high recurrent rate of chronic subdural hematoma (CSDH) has consistently confused the neurosurgeons, and the role of Atorvastatin in the management of CSDH has remained unclear over past decade, and Atorvastatin seems to be a safe and cost-effective treatment to CSDH. Therefore, it is necessary to conduct a systematic review to discuss the effect of Atorvastatin in CSDH. Method: We searched the PubMed, EMBASE, Cochrane Library, and the China Biology Medicine disc, up to March 2017, for published studies on the effects of Atorvastatin in the management of CSDH, and reviewers performed a brief qualitative descriptive analysis of Atorvastatin's efficacy in the management of CSDH. Results: Three eligible studies were included in this systematic review. Results indicated that Atorvastatin accelerated hematoma absorption, decreased recurrence risk, and surgical requirement. Conclusion: Limited evidence suggests that oral Atorvastatin may be beneficial in the management of CSDH. Further high-quality studies focused on dosage, duration, hematoma size are needed to further elucidate the role of Atorvastatin in the management of CSDH.
Impact of Atorvastatin on erectile dysfunction: A meta-analysis and systematic review
Andrologia 2022 Jul;54(6):e14408.PMID:35224753DOI:10.1111/and.14408.
Atorvastatin may be an effective treatment for erectile dysfunction (ED). The purpose of this meta-analysis was to determine whether Atorvastatin therapy is effective in the treatment of ED. All published research on Atorvastatin in the treatment of ED patients in EMBASE, PubMed, Web of Science and Cochrane were investigated till 30 October 2021. A meta-analysis of randomized controlled trials (RCTs) was done to investigate the efficacy of Atorvastatin and placebo in the treatment of ED. Moreover, we also performed a meta-analysis based on single-arm trials (SATs) to explore the Atorvastatin treatment on the efficacy of ED. In a meta-analysis based on RCTs, the weighted mean difference of the change of International Index for Erectile Function-5 (IIEF-5) score in the Atorvastatin treatment group with or without treatment was 4.53 (95 per cent confidence interval [CI] of 3.28-5.79) higher than in the control group. In an SAT-based meta-analysis, the ES of the change in IIEF-5 score in the Atorvastatin treatment group before and after treatment was 3.22 (95 per cent CI of 1.32-5.12). Atorvastatin is an effective therapeutic drug for patients with ED. However, we expect that more multicentre clinical trials will be conducted to support this assertion.
Safety and Efficacy of Atorvastatin for Chronic Subdural Hematoma in Chinese Patients: A Randomized ClinicalTrial
JAMA Neurol 2018 Nov 1;75(11):1338-1346.PMID:30073290DOI:10.1001/jamaneurol.2018.2030.
Importance: Chronic subdural hematoma (CSDH) is a trauma-associated condition commonly found in elderly patients. Surgery is currently the treatment of choice, but it carries a significant risk of recurrence and death. Nonsurgical treatments remain limited and ineffective. Our recent studies suggest that Atorvastatin reduces hematomas and improves the clinical outcomes of patients with CSDH. Objective: To investigate the safety and therapeutic efficacy of Atorvastatin to nonsurgically treat patients with CSDH. Design, setting, and participants: The Effect of Atorvastatin on Chronic Subdural Hematoma (ATOCH) randomized, placebo-controlled, double-blind phase II clinical trial was conducted in multiple centers in China from February 2014 to November 2015. For this trial, we approached 254 patients with CSDH who received a diagnosis via a computed tomography scan; of these, 200 (78.7%) were enrolled because 23 patients (9.1%) refused to participate and 31 (12.2%) were disqualified. Interventions: Patients were randomly assigned to receive either 20 mg of Atorvastatin or placebo daily for 8 weeks and were followed up for an additional 16 weeks. Main outcomes and measures: The primary outcome was change in hematoma volume (HV) by computed tomography after 8 weeks of treatment. The secondary outcomes included HV measured at the 4th, 12th, and 24th weeks and neurological function that was evaluated using the Markwalder grading scale/Glasgow Coma Scale and the Barthel Index at the 8th week. Results: One hundred ninety-six patients received treatment (169 men [86.2%]; median [SD] age, 63.6 [14.2] years). The baseline HV and clinical presentations were similar between patients who were taking Atorvastatin (98 [50%]) and the placebo (98 [50%]). After 8 weeks, the HV reduction in patients who were taking Atorvastatin was 12.55 mL more than those taking the placebo (95% CI, 0.9-23.9 mL; P = .003). Forty-five patients (45.9%) who were taking Atorvastatin significantly improved their neurological function, but only 28 (28.6%) who were taking the placebo did, resulting in an adjusted odds ratio of 1.957 for clinical improvements (95% CI, 1.07-3.58; P = .03). Eleven patients (11.2%) who were taking Atorvastatin and 23 (23.5%) who were taking the placebo underwent surgery during the trial for an enlarging hematoma and/or a deteriorating clinical condition (hazard ratio, 0.47; 95% CI, 0.24-0.92; P = .03). No significant adverse events were reported. Conclusions and relevance: Atorvastatin may be a safe and efficacious nonsurgical alternative for treating patients with CSDH. Trial registration: ClinicalTrials.gov Identifier: NCT02024373.