TPPU is a soluble epoxide hydrolase (sEH) inhibitor with IC50 values of 37 and 3.7 nM for monkey and human sEH. TPPU has anti-inflammatory, analgesic, antiatherogenic and antihypertensive effects[1-2].
TPPU(1–10 μM; 48 h) reversed CORT-induced cell death in PC12 cells[3]. TPPU(0.1–10 μM; 24 h) protects tau from H2O2-induced hyperphosphorylation in HEK293/tau cells by regulating PI3K/AKT/GSK-3β pathway[4].
TPPU (i.p.; 10 mg/kg) treatment decreases serum dihydroxyeicosatrienoic acid (DHET) levels and serum IL-6 levels following burn injury, preventing DHET induced neutrophil depression in burn injury mice model [5]. TPPU(0-5 mg/L TPPU; delivered in drinking water; 1 week) increased exercise-induced effects on inhibiting cardiac enlargement and improving cardiac function by increasing EET levels in MI mice[6]. Pre-treatment with TPPU(0.1 mg/kg/d; i.g) attenuated seizures severity during status epilepticus (SE) and depressive behaviours during the period of epileptogenesis[7].
参考文献:
[1]. Ulu A, Appt S, et,al. Pharmacokinetics and in vivo potency of soluble epoxide hydrolase inhibitors in cynomolgus monkeys. Br J Pharmacol. 2012 Mar;165(5):1401-12. doi: 10.1111/j.1476-5381.2011.01641.x. PMID: 21880036; PMCID: PMC3372725.
[2]. Li J, Wen Z, et,al. Soluble epoxide hydrolase inhibitor promotes the healing of oral ulcers. Clinics (Sao Paulo). 2023 May 4;78:100208. doi: 10.1016/j.clinsp.2023.100208. PMID: 37148830; PMCID: PMC10192938.
[3]. Wu Q, Song J, et,al. TPPU, a sEH Inhibitor, Attenuates Corticosterone-Induced PC12 Cell Injury by Modulation of BDNF-TrkB Pathway. J Mol Neurosci. 2019 Mar;67(3):364-372. doi: 10.1007/s12031-018-1230-z. Epub 2019 Jan 14. PMID: 30644034.
[4]. Yao ES, Tang Y, et,al. TPPU protects tau from H2O2-induced hyperphosphorylation in HEK293/tau cells by regulating PI3K/AKT/GSK-3β pathway. J Huazhong Univ Sci Technolog Med Sci. 2016 Dec;36(6):785-790. doi: 10.1007/s11596-016-1662-z. Epub 2016 Dec 7. PMID: 27924507.
[5]. Bergmann CB, Hammock BD, et,al. TPPU treatment of burned mice dampens inflammation and generation of bioactive DHET which impairs neutrophil function. Sci Rep. 2021 Aug 16;11(1):16555. doi: 10.1038/s41598-021-96014-2. PMID: 34400718; PMCID: PMC8368302.
[6]. Guo Y, Luo F, et,al. TPPU enhanced exercise-induced epoxyeicosatrienoic acid concentrations to exert cardioprotection in mice after myocardial infarction. J Cell Mol Med. 2018 Mar;22(3):1489-1500. doi: 10.1111/jcmm.13412. Epub 2017 Dec 19. PMID: 29265525; PMCID: PMC5824362.
[7]. Peng W, Shen Y et,al. TPPU Pre-Treatment Rescues Dendritic Spine Loss and Alleviates Depressive Behaviours during the Latent Period in the Lithium Chloride-Pilocarpine-Induced Status Epilepticus Rat Model. Brain Sci. 2021 Nov 5;11(11):1465. doi: 10.3390/brainsci11111465. PMID: 34827464; PMCID: PMC8615907.
TPPU是一种可溶性环氧化物水解酶(sEH)抑制剂，对猴和人sEH的IC50值分别为37和3.7 nM。TPPU具有抗炎、镇痛、抗动脉粥样硬化、降压等作用[1-2]。
TPPU (1–10 μM; 48 h)逆转CORT诱导的PC12细胞死亡[3]。TPPU (0.1–10 μM; 24 h)通过调节PI3K/AKT/GSK-3β通路，保护HEK293/tau细胞中H2O2诱导的tau过度磷酸化[4]。
TPPU (i.p.; 10 mg/kg) 处理可降低烧伤后小鼠血清dihydroxyeicosatrienoic acid (DHET)水平和血清IL-6水平，预防DHET诱导的烧伤模型小鼠中性粒细胞抑制 [5]。TPPU (0-5 mg/L TPPU; delivered in drinking water; 1 week)通过提高心肌梗死小鼠EET水平，增强运动诱导的抑制心肌扩大和改善心功能的作用[6]。TPPU (0.1 mg/kg/d; i.g)预处理可减轻癫痫持续状态期间癫痫发作的严重程度和癫痫发生期间的抑郁行为[7]。
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Cell experiment [1]: |
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Cell lines |
PC12 cells |
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Preparation method |
PC12 cells were exposed to 200 μM CORT for 48 h and then with 1-10 μM TPPU. |
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Reaction Conditions |
1-10 μM; 48 h |
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Applications |
TPPU reversed CORT-induced cell death in PC12 cells. |
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Animal experiment [2]: |
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Animal models |
C57BL/6 mice |
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Preparation method |
Myocardial infarction(MI) mouse model was established. After 1 week recovery, the surviving mice were randomly divided into four groups: non-myocardial infarction and non-exercise training (NMI NET), non-myocardial infarction with exercise training (NMI ET), myocardial infarction and non-exercise training (MI NET), and myocardial infarction with exercise training (MI ET).Mice in the ET groups underwent 4 weeks of exercise. To test the effect of TPPU on exercised mice, mice in the MI ET group were fed 0, 0.2, 1 or 5 mg/L TPPU for 1 week prior to the MI surgery and subsequent 4-week exercise programme. |
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Dosage form |
0-5 mg/L TPPU; delivered in drinking water; 1 week |
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Applications |
TPPU increased exercise-induced effects on inhibiting cardiac enlargement and improving cardiac function by increasing epoxyeicosatrienoic acid (EET) levels in MI mice. |
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参考文献: [1]. Wu Q, Song J,et,al. TPPU, a sEH Inhibitor, Attenuates Corticosterone-Induced PC12 Cell Injury by Modulation of BDNF-TrkB Pathway. J Mol Neurosci. 2019 Mar;67(3):364-372. doi: 10.1007/s12031-018-1230-z. Epub 2019 Jan 14. PMID: 30644034. [2]. Guo Y, Luo F et,al. TPPU enhanced exercise-induced epoxyeicosatrienoic acid concentrations to exert cardioprotection in mice after myocardial infarction. J Cell Mol Med. 2018 Mar;22(3):1489-1500. doi: 10.1111/jcmm.13412. Epub 2017 Dec 19. PMID: 29265525; PMCID: PMC5824362. |
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