Maresin 1
(Synonyms: 7(R)MaR1, 7(R)Maresin 1) 目录号 : GC40979A specialized pro-resolving mediator
Cas No.:1268720-28-0
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Docosahexaenoic acid (DHA) is an ω-3 fatty acid that is abundant in the brain and the retina and is known to be important in early development.[1],[2] Maresin 1 (7(R)-MaR1) is a 7,14-dihydroxy DHA formed from 14(S)-hydroperoxy DHA supplied exogenously to resident peritoneal mouse macrophages activated with zymosan A. It potently reduces infiltration of neutrophils into the mouse peritoneum in zymosan A-induced peritonitis when given intravenously (0.2 ng) and significantly increases phagocytosis of FITC-labeled zymosan A by isolated mouse macrophages (0.1-100 nM).[3] Analytical and biological comparisons of synthetic 7(R)-MaR1 with endogenously derived 7(R)-MaR1 have confirmed its identity as matching the natural product.[4]
Reference:
[1]. Su, H.-M. Mechanisms of n-3 fatty acid-mediated development and maintenance of learning memory performance. J. Nutr. Biochem. 21(5), 364-373 (2010).
[2]. Wu, T.C., and Chen, P.H. Health consequences of nutrition in childhood and early infancy. Pediatr. Neonatol. 50(4), 135-142 (2009).
[3]. Serhan, C.N., Yang, R., Martinod, K., et al. Maresins: Novel macrophage mediators with potent antiinflammatory and proresolving actions. J. Exp. Med. 206(1), 15-23 (2009).
[4]. Serhan, C. . (2007).
| Cas No. | 1268720-28-0 | SDF | |
| 别名 | 7(R)MaR1, 7(R)Maresin 1 | ||
| 化学名 | 7R,14S-dihydroxy-4Z,8E,10E,12Z,16Z,19Z-docosahexaenoic acid | ||
| Canonical SMILES | O[C@@H](/C=C/C=C/C=C\[C@@H](O)C/C=C\C/C=C\CC)C/C=C\CCC(O)=O | ||
| 分子式 | C22H32O4 | 分子量 | 360.5 |
| 溶解度 | 50mg/mL in Ethanol; 50mg/mL in DMSO; 50mg/mL in DMF; PBS (pH 7.2): 0.05 mg/ml | 储存条件 | Store at -80°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7739 mL | 13.8696 mL | 27.7393 mL |
| 5 mM | 0.5548 mL | 2.7739 mL | 5.5479 mL |
| 10 mM | 0.2774 mL | 1.387 mL | 2.7739 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Maresin 1 protects against lipopolysaccharide/d-galactosamine-induced acute liver injury by inhibiting macrophage pyroptosis and inflammatory response
Biochem Pharmacol 2022 Jan;195:114863.PMID:34861244DOI:10.1016/j.bcp.2021.114863.
Background: Acute liver injury (ALI) caused by sepsis is a fearful disease with high mortality and poor prognosis. This study aimed to explore the roles and mechanism of Maresin 1 (MaR1) in lipopolysaccharide/d-galactosamine (LPS/D-GalN)-induced ALI. Methods: We established an ALI mouse model induced by LPS/D-GalN. Each group was treated with or without LPS/D-GalN or MaR1. For the vitro experiments, RAW264.7, NCTC1469 cells, and bone marrow-derived macrophages (BMDMs) were stimulated with LPS. The effects of MaR1 on the reactive oxygen species (ROS), pyroptosis and inflammatory response in macrophages were investigated. Results: MaR1 significantly inhibited an excessive inflammatory response and proinflammatory markers during LPS/D-GalN-induced ALI. MaR1 markedly decreased the levels of ROS, tumor necrosis factor-α, and interleukin-1β (IL-1β) in macrophages, and limited hepatocyte apoptosis in vitro. Upon exploring the mechanisms underlying the protective role of MaR1, we found MaR1 markedly upregulated the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), and considerably reduced the phosphorylation of p38, ERK, and nuclear factor-kappa B (NF-κB)-p65. Knocking down Nrf2 decreased the effect of MaR1. Furthermore, we observed that MaR1 reduced inflammatory injury by inhibiting M1 macrophages and promoting M2 macrophage polarization. Finally, we observed that MaR1 could inhibit the production of gasdermin D N-terminus (GSDMD-N) in vivo. In vitro, MaR1 could significantly suppressed the expression of NLR family pyrin domain containing 3 (NLRP3) inflammasome, GSDMD-N, and IL-1β caused by LPS and nigericin stimulation in BMDMs. Conclusion: MaR1 could ameliorate inflammation during LPS/D-GalN induced ALI by suppressing mitogen-activated protein kinase /NF-κB signaling and NLRP3 inflammasome-induced pyroptosis, activating macrophage M1/M2 polarization and Nrf2/HO-1 signaling. This provides new evidence for the potential of developing MaR1 for ALI treatment.
Maresin 1 intervention reverses experimental pulmonary arterial hypertension in mice
Br J Pharmacol 2022 Nov;179(22):5132-5147.PMID:35764296DOI:10.1111/bph.15906.
Background and purpose: Pulmonary arterial hypertension (PAH) is a pulmonary vasculature obstructive disease that leads to right heart failure and death. Maresin 1 is an endogenous lipid mediator known to promote inflammation resolution. However, the effect of Maresin 1 on PAH remains unclear. Experimental approach: The serum Maresin 1 concentration was assessed using UPLC. A mouse model of PAH was established by combining the Sugen 5416 injection and hypoxia exposure. After treatment with Maresin 1, the right ventricular systolic pressure (RVSP) and right ventricular function were measured by haemodynamic measurement and echocardiography, respectively. Vascular remodelling was evaluated by histological staining. Confocal microscopy and western blot were used to test related protein expression. In vitro cell migration, proliferation and apoptosis assays were performed in primary rat pulmonary artery smooth muscle cells (PASMCs). Western blotting and siRNA transfection were used to clarify the mechanism of Maresin 1. Key results: Endogenous serum Maresin 1 was decreased in PAH patients and mice. Maresin 1 treatment decreased RVSP and attenuated right ventricular dysfunction (RVD) in the murine PAH model. Maresin 1 reversed abnormal changes in pulmonary vascular remodelling, attenuating endothelial to mesenchymal transformation and enhancing apoptosis of α-SMA positive cells. Furthermore, Maresin 1 inhibited PASMC proliferation and promoted apoptosis by inhibiting STAT, AKT, ERK, and FoxO1 phosphorylation via LGR6. Conclusion and implications: Maresin 1 improved abnormal pulmonary vascular remodelling and right ventricular dysfunction in PAH mice, targeting aberrant PASMC proliferation. This suggests Maresin 1 may have a potent therapeutic effect in vascular disease.
Maresin 1 Attenuates Lipopolysaccharide-Induced Acute Kidney Injury via Inhibiting NOX4/ROS/NF-κB Pathway
Front Pharmacol 2021 Dec 10;12:782660.PMID:34955852DOI:10.3389/fphar.2021.782660.
Sepsis-associated acute kidney injury (S-AKI) is a common complication in hospitalized and critically ill patients, which increases the risk of multiple comorbidities and is associated with extremely high mortality. Maresin 1 (MaR1), a lipid mediator derived from the omega-3 fatty acid docosahexaenoic acid has been reported to protect against inflammation and promote the regression of acute inflammation. This study proposed to systematically investigate the renoprotective effects and potential molecular mechanism of MaR1 in septic acute kidney injury. We established a S-AKI animal model by a single intraperitoneal injection of lipopolysaccharide (LPS), 10 mg/kg, on male C57BL/6J mice. LPS-stimulated (100 μg/ml) mouse kidney tubular epithelium cells (TCMK-1) were used to simulate septic AKI in vitro. The results showed that pretreatment with MaR1 significantly reduced serum creatinine and blood urea nitrogen levels as well as tubular damage scores and injury marker neutrophil gelatinase-associated lipocalin in septic AKI mice. Meanwhile, MaR1 administration obviously diminished pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, and MCP-1), downregulated BAX and cleaved caspase-3 expression, and upregulated BCL-2 expression in the injured kidney tissues and TCMK-1 cells. In addition, MaR1 reduced malondialdehyde production and improved the superoxide dismutase activity of renal tissues while inhibiting reactive oxygen species (ROS) production and protecting the mitochondria. Mechanistically, LPS stimulated the expression of the NOX4/ROS/NF-κB p65 signaling pathway in S-AKI kidneys, while MaR1 effectively suppressed the activation of the corresponding pathway. In conclusion, MaR1 attenuated kidney inflammation, apoptosis, oxidative stress, and mitochondrial dysfunction to protect against LPS-induced septic AKI via inhibiting the NOX4/ROS/NF-κB p65 signaling pathway.
Maresin 1 promotes nerve regeneration and alleviates neuropathic pain after nerve injury
J Neuroinflammation 2022 Feb 2;19(1):32.PMID:35109876DOI:10.1186/s12974-022-02405-1.
Background: Peripheral nerve injury (PNI) is a public health concern that results in sensory and motor disorders as well as neuropathic pain and secondary lesions. Currently, effective treatments for PNI are still limited. For example, while nerve growth factor (NGF) is widely used in the treatment of PNI to promote nerve regeneration, it also induces pain. Maresin 1 (MaR1) is an anti-inflammatory and proresolving mediator that has the potential to regenerate tissue. We determined whether MaR1 is able to promote nerve regeneration as well as alleviating neuropathic pain, and to be considered as a putative therapeutic agent for treating PNI. Methods: PNI models were constructed with 8-week-old adult male ICR mice and treated with NGF, MaR1 or saline by local application, intrathecal injection or intraplantar injection. Behavioral analysis and muscle atrophy test were assessed after treatment. Immunofluorescence assay was performed to examine the expression of ATF-3, GFAP, IBA1, and NF200. The expression transcript levels of inflammatory factors IL1β, IL-6, and TNF-α were detected by quantitative real-time RT-PCR. AKT, ERK, mTOR, PI3K, phosphorylated AKT, phosphorylated ERK, phosphorylated mTOR, and phosphorylated PI3K levels were examined by western blot analysis. Whole-cell patch-clamp recordings were executed to detect transient receptor potential vanilloid 1 (TRPV1) currents. Results: MaR1 demonstrated a more robust ability to promote sensory and motor function recovery in mice after sciatic nerve crush injury than NGF. Immunohistochemistry analyses showed that the administration of MaR1 to mice with nerve crush injury reduced the number of damaged DRG neurons, promoted injured nerve regeneration and inhibited gastrocnemius muscle atrophy. Western blot analysis of ND7/23 cells cultured with MaR1 or DRG neurons collected from MaR1 treated mice revealed that MaR1 regulated neurite outgrowth through the PI3K-AKT-mTOR signaling pathway. Moreover, MaR1 dose-dependently attenuated the mechanical allodynia and thermal hyperalgesia induced by nerve injury. Consistent with the analgesic effect, MaR1 inhibited capsaicin-elicited TRPV1 currents, repressed the nerve injury-induced activation of spinal microglia and astrocytes and reduced the production of proinflammatory cytokines in the spinal cord dorsal horn in PNI mice. Conclusions: Application of MaR1 to PNI mice significantly promoted nerve regeneration and alleviated neuropathic pain, suggesting that MaR1 is a promising therapeutic agent for PNI.
Maresin 1 improves the Treg/Th17 imbalance in rheumatoid arthritis through miR-21
Ann Rheum Dis 2018 Nov;77(11):1644-1652.PMID:30045854DOI:10.1136/annrheumdis-2018-213511.
Objective: Treg/Th17 imbalance plays an important role in rheumatoid arthritis (RA). Maresin 1 (MaR1) prompts inflammation resolution and regulates immune responses. We explored the effect of MaR1 on RA progression and investigated the correlation between MaR1 and Treg/Th17 balance. Methods: Both patients with RA and healthy controls were recruited into the study. Collagen-induced arthritis (CIA) model was constructed to detect the clinical score, histopathological changes and Treg/Th17 ratio. Purified naive CD4+ T-cells were used to study the effect of MaR1 on its differentiation process and microRNA microarray studies were performed to investigate MaR1 downstream microRNAs in this process. MicroRNA transfection experiments were conducted by lentivirus to verify the mechanism of MaR1 on Treg/Th17 balance. Results: Compared with controls, the MaR1 concentration was higher in the patients with inactive RA and lower in the patients with active RA. Expression of the Treg transcription factor FoxP3 was the highest in inactive RA and the lowest in active RA, while the Th17 transcription factor RORc showed a reverse trend. An inverse correlation was observed between the FoxP3/RORc ratio and Disease Activity Score 28. Intervention of MaR1 in the CIA model reduced joint inflammation and damage, and improved the imbalanced Treg/Th17 ratio. MaR1 increased Treg cells proportion while reduced Th17 cells proportion under specific differentiation conditions. Furthermore, miR-21 was verified as MaR1 downstream microRNA, which was upregulated by MaR1, modulating the Treg/Th17 balance and thus ameliorating the RA progression. Conclusions: MaR1 is a therapeutic target for RA, likely operating through effects on the imbalanced Treg/Th17 ratio found in the disease.