2. Autophagy Apoptosis Neuronal Signaling
  3. Autophagy α-synuclein Monoamine Oxidase Apoptosis
  4. Harmol hydrochloride

Harmol hydrochloride 是一种具有口服活性的 β-carboline 生物碱。Harmol hydrochloride 是 TFEB 激活剂和单胺氧化酶抑制剂。Harmol hydrochloride 可诱导细胞有丝分裂，自噬 (Autophagy) 和凋亡 (Apoptosis)。Harmol hydrochloride 通过调节自噬-溶酶体通路，促进 α-突触核蛋白 (α-synuclein) 降解。Harmol hydrochloride 有抗肿瘤，抗抑郁，延缓衰老的活性。Harmol hydrochloride 改善小鼠帕金森模型运动损伤。

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Harmol hydrochloride

Harmol hydrochloride Chemical Structure

CAS No. : 40580-83-4

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Harmol hydrochloride 相关抗体

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MCE 顾客使用本产品发表的 1 篇科研文献

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  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

Harmol hydrochloride is an orally active β-carboline alkaloid. Harmol hydrochloride is a TFEB activator and monoamine oxidase inhibitor. Harmol hydrochloride can induce cell mitosis, Autophagy and Apoptosis. Harmol hydrochloride promotes the degradation of α-synuclein by regulating the autophagy-lysosomal pathway. Harmol hydrochloride has anti-tumor, anti-depressant and anti-aging activities. Harmol hydrochloride improves motor impairment in a mouse Parkinson's disease model[1][2][3][4].

体外研究
(In Vitro)

Harmol (3-30 μM，6-24 h) hydrochloride 在 PC12 细胞中，以剂量和时间依赖的方式降低 α-syn[1]。
Harmol (30 μM，24 h) hydrochloride 在 Hela 细胞中促进外源性 TFEB (转录因子 EB) 的核易位，在 N2a 促进内源性 TFEB 的核易位，并伴随自噬通量和溶酶体生物发生的恢复[1]。
Harmol (0-100 μM，24 和 48 h) hydrochloride 呈时间依赖性与剂量依赖性抑制 U251MG 细胞增殖，诱导细胞死亡[2]。
Harmol (0-100 μM，0-48 h) hydrochloride 在 U251MG 细胞中抑制 survivin 的表达，促进 LC3-Ⅰ 和 LC3-Ⅱ 蛋白的表达，抑制 Akt/mTOR 通路，诱导细胞自噬和细胞凋亡[2]。
Harmol (0-100 μM，0-24 h) 在 A549 和 H226 细胞中具有轻微细胞毒性，在 H596 中表现出很强的细胞毒性，抑制肿瘤增殖[3]。
Harmol (60 μM，3-6 h) hydrochloride 提高了 caspase-3，caspase-6，caspase-8，caspase-9 活性，增加了 RAPA (caspase-3 内源性底物) 裂解，诱导 H596 细胞凋亡[3]。
Harmol (1.3 μg/mL，1-3 h) hydrochloride 在 C2C12 细胞中激活了细胞自噬[4]。
Harmol (1.3 μg/mL，45-60 min) hydrochloride 在 C2C12 细胞中是线粒体特异性自噬，且仅发生在无活性的 TMRM 阴性线粒体中[4]。
Harmol (1.3 μg/mL，16 h) hydrochloride 在 C2C12 细胞中代表线粒体功能的标志物表达上调[4]。
Harmol (1.3 μg/mL，0-20 h) hydrochloride 对 MAO-B 有特异性抑制作用[4]。
Harmol hydrochloride 减少 GABA 能神经传递，但不能完全抑制 GABA 与 GABAAR 的结合，GABAAR 活性对 Harmol 介导的线粒体去极化至关重要，并依靠线粒体功能发挥作用[4]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Harmol hydrochloride 相关抗体:

Western Blot Analysis[1][4]

Cell Line: Tet-on inducible PC12 cells[1]; Hela, N2a[1]; C2C12[4]
Concentration: 3, 10, 30 μM; 30 μM; 1.3 μg/mL; 1.3 μg/mL
Incubation Time: 6, 12, 24 h; 24 h; 16 h; 24 h
Result: Reduced the phosphorylation (p-) and total α-syn levels in PC12 cells in a dose-dependent and time-dependent manner, showing pro-degradation activity between 6 and 24 hours.
Enhanced the LC3B-Ⅱ/LC3B-Ⅰ ratio in PC12 cells, promoted TFEB expression, and increased AMPK phosphorylation at the THr172 site. It facilitated the nuclear translocation of exogenous TFEB in HeLa cells and the translocation of endogenous TFEB to the nucleus in N2a cells. This also increased the expression of the lysosomal marker LAMP1 (lysosomal-associated membrane protein 1) precursor and the mature form of CTSD (cathepsin D).
Showed in C2C12, the protein expression of the mitochondrial transcription and replication factor TFAM and components of complex III (UQCRC2) and complex V (ATP5a) was significantly elevated, along with an increase in polyamine spermidine levels, while DYRK1A phosphorylation remained unchanged.

Immunofluorescence[1]

Cell Line: Hela, PC12
Concentration: 30 μM
Incubation Time: 24 h
Result: Caused 60% of Flag-TFEB to undergo nuclear translocation and significantly increased the lysosomal content.

Cell Autophagy Assay[1][4]

Cell Line: PC12[1]; C2C12[4]
Concentration: 3, 10, 30 μM; 1.3 μg/mL
Incubation Time: 24 h; 45, 60 min
Result: Promoted the autophagic degradation of p62 in PC12 induced cells.
Showed strong co-localization of lysosomes and mitochondria in C2C12 cells.
体内研究
(In Vivo)

Harmol (10-40 mg/kg，i.g.，一天两次，一个月) hydrochloride 在 α-syn 转基因小鼠模型中，可改善运动缺陷，包括运动和协调。下调黑质和前额皮质 α-syn 水平，增强自噬介导的蛋白质聚集体降解[1]。
Harmol (100 mg/kg，灌胃，每日一次，三周) hydrochloride 在小鼠中有轻微的抗焦虑作用[4]。
Harmol (100 mg/kg，口服，三个月) hydrochloride 改善肥胖小鼠胰岛素，葡萄糖稳态和代谢适应性，且对肾功能无影响[4]。
Harmol (15 μg/kg，口服，0-50 天) hydrochloride 延长无脊椎动物的寿命[4]。
Harmol (100 mg/kg，口服，两个月) hydrochloride 在老年小鼠延缓衰弱[4]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: A53T α-syn mice[1]
Dosage: 10, 20, 40 mg/kg; twice a day; one month
Administration: i.g.
Result: Made mice climb the rod faster, spent more time on the spinning rod, travelled farther in open areas, increased their step frequency and standing posture, reduced posture width, stride, step length, swing, and showed recovery of autonomous movement behavior.
Reduced the expression of α-syn and p62 in the brain’s substantia nigra and prefrontal cortex.
Increased the phosphorylation levels of AMPK Thr172 and TFEB in the substantia nigra, while decreasing the phosphorylation level of mTOR Ser2448.Increased the expression of LC3B-II/LC3B-I, LAMP1, pro-CTSD, and mature ctsd in the substantia nigra, while reducing the expression of p62 and p-ULK1(Ser757)/ULK1.
Animal Model: Male mice[4]
Dosage: 100 mg/kg, single dose; 100 mg/kg, daily, 3 weeks
Administration: i.g.
Result: Showed no change in blood glucose levels, with no change in fasting-mediated ketone body increase, and low permeability of the blood-brain barrier. High levels in the liver and plasma, but low levels in the brain. The mitochondrial autophagy marker PINK1 was elevated, while the phosphorylation levels of AMPK target ACC1 or the autophagy marker LC3-II/LC3-I were unaffected.
Showed no change in the time mice spent in the aversive area (center) versus the non-aversive area (border), with no differences in elevated plus maze tests, and significantly less time spent in the dark/light box.
Increased phosphorylation of ACC2 in the liver and BAT, and levels of the mitochondrial autophagy marker PINK1 were also significantly elevated in the liver, BAT, and soleus.
分子量

234.68

Formula

C12H11ClN2O
CAS 号
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
纯度 & 产品资料
参考文献

Harmol hydrochloride 相关分类

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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

Harmol40580-83-4Autophagyα-synucleinMonoamine OxidaseApoptosisα-SynMAONeurological DiseaseAlkaloidβ-carbolineInhibitorinhibitorinhibit

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