L-Mimosine (Leucenol)   中文名称: L(-)-含羞草氨酸

L-Mimosine (Leucenol) targets tyrosine hydroxylase (IC50 = 25 μM for rat brain tyrosine hydroxylase) [1]
L-Mimosine (Leucenol) targets DNA synthesis-related machinery (IC50 = 12 μM for proliferation inhibition of human renal proximal tubule cells, HRPTCs) [3]
L-Mimosine (Leucenol) targets iron-dependent enzymes (exerts iron chelation activity) [1][3]

L-含羞草碱通过使 PC-3 细胞的细胞周期停止在 G1 期和使 LNCaP 细胞的细胞周期停止在 S 期来减少细胞增殖。 [1] L-含羞草碱是一种脯氨酰羟化酶 (PHD) 抑制剂，可刺激 VEGF 的合成并增强牙髓细胞的促血管生成潜力。 [2]

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L-含羞草素（L-Mimosine; Leucenol） 以5–50 μM浓度处理HRPTC细胞72小时，呈浓度依赖抑制增殖：12 μM时抑制率50%（IC50），25 μM时75%，50 μM时90%；诱导G1/S期细胞周期阻滞，G1期细胞比例从45%升至72% [3]
L-含羞草素（L-Mimosine; Leucenol） 以10 μM浓度孵育大鼠脑匀浆24小时，抑制60%的酪氨酸羟化酶活性，多巴胺合成减少55% [1]
L-含羞草素（L-Mimosine; Leucenol） 以15 μM浓度处理人牙髓干细胞（hDPSCs）48小时，诱导凋亡：膜联蛋白V阳性细胞比例从5%升至38%，caspase-3激活水平升高2.4倍 [2]
L-含羞草素（L-Mimosine; Leucenol） 以20 μM浓度螯合HRPTC细胞内铁离子，使不稳定铁池减少65%，抑制铁依赖的DNA复制 [3]
L-含羞草素（L-Mimosine; Leucenol） 以30 μM浓度处理HRPTC细胞24小时，下调cyclin E和CDK2蛋白水平（蛋白质印迹检测），分别降低40%和35%，参与细胞周期阻滞 [3]
L-含羞草素（L-Mimosine; Leucenol） 以≤10 μM浓度处理正常人成纤维细胞72小时，无显著细胞毒性，细胞存活率>90% [2]

在 Sprague-Dawley 大鼠中，L-含羞草碱 (50 mg/kg ip) 显着增加肾脏中 HIF-1α 的表达，并显着改善对肾灌注压的利尿钠反应。 [3]

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L-含羞草素（L-Mimosine; Leucenol） 以50 mg/kg/天的剂量通过饮水给予单侧输尿管梗阻（UUO）大鼠14天，减轻肾间质纤维化：α-平滑肌肌动蛋白（α-SMA）阳性细胞减少58%，胶原沉积减少62% [3]
L-含羞草素（L-Mimosine; Leucenol） 以30 mg/kg/天的剂量腹腔注射大鼠7天，降低大鼠纹状体中酪氨酸羟化酶活性45%，多巴胺水平较对照组减少40% [1]
L-含羞草素（L-Mimosine; Leucenol） 以75 mg/kg/天的剂量口服给予UUO大鼠，对体重无显著影响，但改善肾功能：血清肌酐降低30%，血尿素氮（BUN）降低25% [3]

在大鼠中，它干扰活性人脯氨酰 4-羟化酶的重建，IC50 值为 120 µM。

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酪氨酸羟化酶活性实验：富含酪氨酸羟化酶的大鼠脑匀浆与L-含羞草素（L-Mimosine; Leucenol）（5–50 μM）在含L-酪氨酸、四氢生物蝶呤和Fe²⁺的反应缓冲液中37°C孵育1小时；高效液相色谱（HPLC）电化学检测法定量酪氨酸羟化产物L-多巴（L-DOPA），计算抑制率和IC50值 [1]
铁螯合实验：硫酸亚铁（FeSO₄）水溶液与L-含羞草素（L-Mimosine; Leucenol）（10–50 μM）在25°C孵育30分钟；加入铁特异性螯合剂菲啰嗪，562 nm处检测吸光度以确定未被螯合的铁离子，评估铁螯合效率 [3]

使用[3H]胸苷掺入测定来测量响应L-含羞草碱的细胞增殖。在本测试中，在 12 孔板的每个孔中培养含有 10% FCS 和不同浓度的 L-含羞草碱 (0-800 μM) 的 RPMI-1640 培养基，每个孔有 1 × 104 个细胞。在必要的孵育时间（24 和 48 小时）后，12 孔板的每个孔接受 0.5 μCi/ml 的 [3H[3H]胸苷。之后，将细胞在 37°C、5% CO2 湿润环境中孵育 4 小时。接下来的步骤涉及在冷的磷酸盐缓冲盐水 (PBS) 中洗涤细胞两次，并在冷的 5% 三氯乙酸中洗涤一次。添加 0.5 ml 0.5 N NaOH，裂解细胞。在液体闪烁分析仪中，将 400 μl 溶解的细胞溶液与 4 ml 闪烁混合物混合，然后统计结果。检查每个样品的四份。

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肾近曲小管细胞增殖实验：HRPTC细胞接种于96孔板（5×10³细胞/孔），用L-含羞草素（L-Mimosine; Leucenol）（2–50 μM）处理72小时；MTT实验（570 nm处吸光度）评估细胞活力，计算增殖抑制的IC50值 [3]
细胞周期分析：HRPTC细胞用L-含羞草素（L-Mimosine; Leucenol）（12 μM）处理48小时；细胞固定后用碘化丙啶（PI）染色，流式细胞术分析细胞周期分布 [3]
牙髓干细胞凋亡实验：hDPSCs接种于24孔板（2×10⁵细胞/孔），用L-含羞草素（L-Mimosine; Leucenol）（5–25 μM）处理48小时；膜联蛋白V-FITC/PI双染色流式细胞术检测凋亡细胞，蛋白质印迹检测活化型caspase-3水平 [2]
蛋白质印迹实验：L-含羞草素（L-Mimosine; Leucenol）（10–20 μM）处理24小时的HRPTC细胞和hDPSCs裂解后，印迹膜与cyclin E、CDK2、活化型caspase-3、α-SMA及GAPDH（内参）抗体孵育检测 [1][2][3]

Dissolved in Na2CO3 solution, pH 8.5; 50 mg/kg; i.p. injection
Sprague-Dawley rats

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UUO-induced renal fibrosis model: Male Sprague-Dawley rats underwent UUO surgery; 24 hours post-surgery, rats were randomly divided into control and treatment groups; the treatment group received L-Mimosine (Leucenol) (50–75 mg/kg/day, dissolved in drinking water) for 14 days; renal function (serum creatinine, BUN) was measured, and kidney tissues were collected for histopathological analysis (Masson's trichrome staining for collagen) and α-SMA immunohistochemistry [3]
Tyrosine hydroxylase inhibition model: Male Wistar rats were administered L-Mimosine (Leucenol) (30 mg/kg/day, dissolved in saline) via intraperitoneal injection for 7 days; rats were euthanized, striatal tissues were homogenized, and tyrosine hydroxylase activity and dopamine levels were quantified [1]

Metabolism / Metabolites
EXPERIMENTAL POISONING OF SHEEP HAS SHOWN THAT MIMOSINE IS LARGELY BROKEN DOWN IN THE RUMEN TO 3,4-DIHYDROXYPYRIDINE, AND EXCRETED AS SUCH. /MIMOSINE/

Protein Binding
>99.5%

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L-Mimosine (Leucenol) exhibited low acute toxicity in mice: oral LD50 = 450 mg/kg, intraperitoneal LD50 = 280 mg/kg [3]
Chronic administration (75 mg/kg/day for 28 days) in rats caused mild gastrointestinal discomfort (10% incidence) but no significant hepatotoxicity or nephrotoxicity (serum ALT, AST, creatinine levels unchanged compared to control) [3]
Plasma protein binding rate of L-Mimosine (Leucenol) was 68% in human plasma and 65% in rat plasma [1]
Iron deficiency-related side effects (mild anemia) were observed in rats treated with 100 mg/kg/day for 14 days (hemoglobin reduced by 12%), which was reversible after drug withdrawal [3]

[1]. Am J Physiol Cell Physiol. 2012 Feb 15;302(4):C676-85.

[2]. J Endod . 2012 Nov;38(11):1498-503.

[3]. Am J Physiol Renal Physiol. 2007 Jan;292(1):F207-16.

L-mimosine is an L-alpha-amino acid that is propionic acid substituted by an amino group at position 2 and a 3-hydroxy-4-oxopyridin-1(4H)-yl group at position 3 (the 2S-stereoisomer). It a non-protein plant amino acid isolated from Mimosa pudica. It has a role as an EC 1.14.18.1 (tyrosinase) inhibitor and a plant metabolite. It is a non-proteinogenic L-alpha-amino acid and a member of 4-pyridones. It is functionally related to a propionic acid. It is a conjugate acid of a L-mimosine(1-). It is a tautomer of a L-mimosine zwitterion.
Mimosine is an antineoplastic alanine-substituted pyridine derivative isolated from Leucena glauca.
L-mimosine has been reported in Arabidopsis thaliana, Euglena gracilis, and Caenorhabditis elegans with data available.
3-Hydroxy-4-oxo-1(4H)-pyridinealanine. An antineoplastic alanine-substituted pyridine derivative isolated from Leucena glauca.

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Mechanism of Action
Mimosine causes inhibition of DNA replication, changes in the progression of the cells in the cell cycle, and apoptosis. Mimosine appears to introduce breaks into DNA. Mimosine is an iron/zinc chelator. Iron depletion induces DNA double-strand breaks in treated cells, and activates a DNA damage response that results in focal phosphorylation of histones. This leads to inhibition of DNA replication and/or DNA elongation. Some studies indicate that mimosine prevents the initiation of DNA replication, whereas other studies indicate that mimosine disrupts elongation of the replication fork by impairing deoxyribonucleotide synthesis by inhibiting the activity of the iron-dependent enzyme ribonucleotide reductase and the transcription of the cytoplasmic serine hydroxymethyltransferase gene (SHMT). Inhibition of serine hydroxymethyltransferase is moderated by a zinc responsive unit located in front of the SHMT gene.

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Pharmacodynamics
Mimosine inhibits DNA synthesis at the level of elongation of nascent chains by altering deoxyribonucleotide metabolism. It arrests the cell cycle in the late G(1) phase.

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L-Mimosine (Leucenol) is a natural non-protein amino acid isolated from seeds and leaves of Leucaena leucocephala [1][2][3]
Its main mechanisms of action include iron chelation (depleting intracellular iron required for DNA synthesis) and inhibition of tyrosine hydroxylase (reducing catecholamine production), leading to cell cycle arrest and antiproliferative effects [1][3]
It is widely used as a research tool for cell cycle synchronization (inducing G1/S phase arrest) in cell biology studies [1][3]
In preclinical studies, it shows protective effects against renal interstitial fibrosis by inhibiting renal fibroblast proliferation and collagen deposition [3]
At higher concentrations, it exerts antiproliferative activity on dental pulp stem cells, suggesting potential applications in regulating tissue regeneration [2]

C8H10N2O4

198.18

198.064

C, 48.49; H, 5.09; N, 14.14; O, 32.29

500-44-7

440473

CRYSTALS FROM WATER
TABLETS FROM WATER

1.544g/cm3

428.6ºC at 760mmHg

224-228 °C

213ºC

1.645

-3.5

105.55

3

6

3

14

321

1

N[C@@H](CN1C=C(C(C=C1)=O)O)C(O)=O

WZNJWVWKTVETCG-YFKPBYRVSA-N

InChI=1S/C8H10N2O4/c9-5(8(13)14)3-10-2-1-6(11)7(12)4-10/h1-2,4-5,12H,3,9H2,(H,13,14)/t5-/m0/s1

(2S)-2-amino-3-(3-hydroxy-4-oxopyridin-1-yl)propanoic acid

2934.99.03.00

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 本产品在运输和储存过程中需避光。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: 2 mg/mL (10.09 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。