Hirsutine
(Synonyms: 毛钩藤碱) 目录号 : GC36229
Hirsutine，一种 Uncaria rhynchophylla 的吲哚生物碱，具有抗癌活性。Hirsutine 诱导细胞凋亡，并且是一种有效的 Dengue virus 抑制剂，具有低毒性。
Cas No.:7729-23-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Hirsutine, an indole alkaloid of Uncaria rhynchophylla, exhibits anti-cancer activity. Hirsutine induces apoptosis and is a potent Dengue virus inhibitor exhibiting low cytotoxicity[1][2][3].
Hirsutine remarkably reduces the viability of MCF-7 and MDA-MB-231 cells in a time- and dose-dependent manner with IC50 values of 447.79 and 179.06 μM, respectively. In the MDA-MB-231 cells, Hirsutine induces apoptosis and depolarization of MMP, releases Cyt C from mitochondria, and activates caspase 9 and caspase 3[2].
Hirsutine induces mPTP-dependent apoptosis through ROCK1/PTEN/PI3K/GSK3β pathway in human lung cancer cells[3].
[1]. Hishiki T, et al. Hirsutine, an Indole Alkaloid of Uncaria rhynchophylla, Inhibits Late Step in Dengue Virus Lifecycle. Front Microbiol. 2017 Aug 30;8:1674. [2]. Huang QW, et al. [Hirsutine induces apoptosis of human breast cancer MDA-MB-231 cells through mitochondrial pathway]. Sheng Li Xue Bao. 2018 Feb 25;70(1):40-46. [3]. Zhang R, et al. Hirsutine induces mPTP-dependent apoptosis through ROCK1/PTEN/PI3K/GSK3β pathway in human lung cancer cells. Cell Death Dis. 2018 May 22;9(6):598.
| Cas No. | 7729-23-9 | SDF | |
| 别名 | 毛钩藤碱 | ||
| Canonical SMILES | O=C(OC)/C([C@H]([C@H](CN1CC2)CC)C[C@]1([H])C3=C2C(C=CC=C4)=C4N3)=C/OC | ||
| 分子式 | C22H28N2O3 | 分子量 | 368.47 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| 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 | 2.7139 mL | 13.5696 mL | 27.1393 mL |
| 5 mM | 0.5428 mL | 2.7139 mL | 5.4279 mL |
| 10 mM | 0.2714 mL | 1.357 mL | 2.7139 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。
Hirsutine ameliorates hepatic and cardiac insulin resistance in high-fat diet-induced diabetic mice and in vitro models
Pharmacol Res 2022 Mar;177:105917.PMID:34597809DOI:10.1016/j.phrs.2021.105917.
Closely associated with type 2 diabetes mellitus (T2DM), hepatic steatosis and cardiac hypertrophy resulting from chronic excess intake can exacerbate insulin resistance (IR). The current study aims to investigate the pharmacological effects of Hirsutine, one indole alkaloid isolated from Uncaria rhynchophylla, on improving hepatic and cardiac IR, and elucidate the underlying mechanism. T2DM and IR in vivo were established by high-fat diet (HFD) feeding for 3 months in C57BL/6 J mice. In vitro IR models were induced by high-glucose and high-insulin (HGHI) incubation in HepG2 and H9c2 cells. Hirsutine administration for 8 weeks improved HFD-induced peripheral hyperglycemia, glucose tolerance and IR by OGTT and ITT assays, and simultaneously attenuated hepatic steatosis and cardiac hypertrophy by pathological observation. The impaired p-Akt expression was activated by Hirsutine in liver and heart tissues of HFD mice, and also in the models in vitro. Hirsutine exhibited the effects on enhancing glucose consumption and uptake in IR cell models via activating phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which was blocked by PI3K inhibitor LY294002. Moreover, the effect of Hirsutine on promoting glucose uptake and GLUT4 expression in HGHI H9c2 cells was also prevented by Compound C, an inhibitor of AMP-activated protein kinase (AMPK). Enhancement of glycolysis might be another factor of Hirsutine showing its effects on glycemic control. Collectively, it was uncovered that Hirsutine might exert beneficial effects on regulating glucose homeostasis, thus improving hepatic and cardiac IR, and could be a promising compound for treating diet-induced T2DM.
Hirsutine, a novel megakaryopoiesis inducer, promotes thrombopoiesis via MEK/ERK/FOG1/TAL1 signaling
Phytomedicine 2022 Jul 20;102:154150.PMID:35569185DOI:10.1016/j.phymed.2022.154150.
Background: Thrombocytopenia (TP) remains a challenge in clinical hematology. TP may have serious consequences, such as recurrent skin and mucosal bleeding and increased risk of intracranial and internal organ hemorrhage. However, effective and safe therapeutic drugs for the long-term management of TP are still lacking. Purpose: This study aimed to identify more effective active compounds for TP therapy. Methods: Liquid chromatography-mass spectrometry-nuclear magnetic resonance analysis was used to confirm the medicinal species and chemical structure of Hirsutine (HS). The proliferation of HS was examined by Cell Counting Kit (CCK-8) assay on cells lines. The effect of HS on megakaryocyte differentiation was analyzed by evaluating the expression of CD41, CD42b, and DNA ploidy via flow cytometry (FCM). The morphology of megakaryocytes and intermediate cells was observed using an optical microscope. K562 cells were then stained with Giemsa and benzidine. qRT-PCR was used to examine the mRNA expression of GATA-1, GATA-2, FOG-1, TAL-1, RUNX-1, NF-E2, and KLF-1 in K562 cells. Protein levels of the transcription factors were analyzed by western blotting. An MEK inhibitor was used to verify the relationship between the MEK/ERK signaling pathway and CD41/CD42b (FCM), FOG-1, and TAL-1. The Kunming thrombocytopenia mouse model was established by X-ray irradiation (4 Gy) and used to test HS activity and related hematopoietic organ index in vivo. Finally, computer simulations of molecular docking were used to predict the binding energies between HS-MEK and HS-ERK. Results: We preliminarily identified HS by screening a plant-sourced compound library for natural compounds with megakaryocytic differentiation and maturation (MKD/MKM)-promoting activity. We found that HS not only enhanced MKD/MKM of K562 and Meg01 cells, but also suppressed the decline of peripheral platelet levels in X-ray-induced myelosuppressive mice. In addition, HS promoted MKD via activation of MEK-ERK-FOG1/TAL1 signaling, which may be the key molecular mechanism of HS action in TP treatment. Molecular docking simulations further verified that HS targets the signaling protein MEK with high-affinity. Conclusion: In this study, we report for the first time that Hirsutine boosts MKD/MKM through the MEK/ERK/FOG1/TAL1 signaling pathway and thus represents a promising treatment option for TP.
Hirsutine induces mPTP-dependent apoptosis through ROCK1/PTEN/PI3K/GSK3β pathway in human lung cancer cells
Cell Death Dis 2018 May 22;9(6):598.PMID:29789524DOI:10.1038/s41419-018-0641-7.
Hirsutine extracted from Uncaria rhynchophylla has been shown to exhibit anti-cancer activity. However, the molecular mechanism by which Hirsutine exhibits anti-lung cancer activity remains unclear. In the present study, we showed that Hirsutine induces apoptosis in human lung cancer cells via loss of mitochondrial membrane potential (∆ψm), adenosine triphosphate (ATP) depletion, ROS production, as well as cytochrome c release. Dephosphorylation of GSK3β is involved in hirsutine-mediated mitochondrial permeability transition pore (mPTP) opening through ANT1/CypD interaction. Mechanistic study revealed that interruption of ROCK1/PTEN/PI3K/Akt signaling pathway plays a critical role in hirsutine-mediated GSK3β dephosphorylation and mitochondrial apoptosis. Our in vivo study also showed that Hirsutine effectively inhibits tumor growth in a A549 xenograft mouse model through ROCK1/PTEN/PI3K/Akt signaling-mediated GSK3β dephosphorylation and apoptosis. Collectively, these findings suggest a hierarchical model in which induction of apoptosis by Hirsutine stems primarily from activation of ROCK1 and PTEN, inactivation of PI3K/Akt, leading in turn to GSK3β dephosphorylation and mPTP opening, and culminating in caspase-3 activation and apoptosis. These findings could provide a novel mechanistic basis for the application of Hirsutine in the treatment of human lung cancer.
Hirsutine ameliorates myocardial ischemia-reperfusion injury through improving mitochondrial function via CaMKII pathway
Clin Exp Hypertens 2023 Dec 31;45(1):2192444.PMID:36951068DOI:10.1080/10641963.2023.2192444.
Acute myocardial infarction (AMI) is the leading cause of death worldwide. Ischemia-reperfusion (I/R) injury is considered the most common contributor to AMI. Hirsutine has been shown to protect cardiomyocytes against hypoxic injury. The present study investigated whether Hirsutine improved AMI induced by I/R injury and the underlying mechanisms. In our study, we used a rat model of myocardial I/R injury. The rats were given Hirsutine daily (5, 10, 20 mg/kg) by gavage for 15 days before the myocardial I/R injury. Detectable changes were observed in myocardial infarct size, mitochondrial function, histological damage, and cardiac cell apoptosis. According to our findings, Hirsutine pre-treatment reduced the myocardial infarct size, enhanced cardiac function, inhibited cell apoptosis, reduced the tissue lactate dehydrogenase (LDH) and reactive oxygen species (ROS) content, as well as enhanced myocardial ATP content and mitochondrial complex activity. In addition, Hirsutine balanced mitochondrial dynamics by increasing Mitofusin2 (Mfn2) expression while decreasing dynamin-related protein 1 phosphorylation (p-Drp1), which was partially regulated by ROS and calmodulin-dependent protein kinase II phosphorylation (p-CaMKII). Mechanistically, Hirsutine inhibited mitochondrial-mediated apoptosis during I/R injury by blocking the AKT/ASK-1/p38 MAPK pathway. This present study provides a promising therapeutic intervention for myocardial I/R injury.
[Hirsutine induces apoptosis of human breast cancer MDA-MB-231 cells through mitochondrial pathway]
Sheng Li Xue Bao 2018 Feb 25;70(1):40-46.PMID:29492513doi
The aim of this study was to investigate the effects of Hirsutine on apoptosis of breast cancer cells and its possible mechanism. The MCF-10A, MCF-7 and MDA-MB-231 cells were treated with Hirsutine at different concentrations for 48 h or incubated with 160 μmol/L Hirsutine for 24, 48, and 72 h. The MCF-10A cell line is a non-tumorigenic epithelial cell line, and the MCF-7 and MDA-MB-231 are human breast adenocarcinoma cell lines. CCK-8 assay was employed to detect the cell viability. Flow cytometry was used to assay the apoptosis and mitochondrial membrane potential (MMP). The protein expressions of Bcl-2, Bax, cleaved-caspase 9, cleaved-caspase 3 and cytochrome C (Cyt C) in the MDA-MB-231 cells were detected by Western blotting. The results showed that Hirsutine remarkably reduced the viability of MCF-7 and MDA-MB-231 cells in a time- and dose-dependent manner (P < 0.05) with IC50 values of 447.79 and 179.06 μmol/L, respectively. In the MDA-MB-231 cells, Hirsutine induced apoptosis and depolarization of MMP (P < 0.05), released Cyt C from mitochondria (P < 0.05), and activated caspase 9 and caspase 3 (P < 0.05). However, these effects induced by Hirsutine were all inhibited by cyclosporin A (CsA) (P < 0.05), a specific inhibitor of mitochondrial permeability transition pore (MPTP). In addition, Hirsutine down-regulated the protein level of Bcl-2 and up-regulated the protein level of Bax (P < 0.05). These results suggest that Hirsutine may induce apoptosis of human breast cancer MDA-MB-231 cells through decreasing the ratio of Bcl-2 to Bax, opening MPTP, releasing Cyt C from mitochondria, and activating caspase 9 and caspase 3.