Periplocymarin
(Synonyms: 杠柳次苷) 目录号 : GC39059
Periplocymarin 是从 Periploca sepium 和 Periploca graeca 中分离得到的一种强心苷，是一种潜在的抗癌化合物。
Cas No.:32476-67-8
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Periplocymarin, a cardiac glycoside isolated from Periploca sepium and Periploca graeca, is a potential anti-cancer compound[1][2].
[1]. Martey ON, et al. Periplocymarin is a potential natural compound for drug development: highly permeable with absence of P-glycoprotein efflux and cytochrome P450 inhibitions. Biopharm Drug Dispos. 2014 May;35(4):195-206. [2]. Redox-responsive PEGylated self-assembled prodrug-nanoparticles formed by single disulfidebond bridge periplocymarin-vitamin E conjugate for liver cancer chemotherapy. Drug Deliv. 2017 Nov;24(1):1170-1178.
| Cas No. | 32476-67-8 | SDF | |
| 别名 | 杠柳次苷 | ||
| Canonical SMILES | O[C@@]12[C@@]3([H])[C@@](CC[C@@]1([C@@H](C4=CC(OC4)=O)CC2)C)([H])[C@@]5([C@@](O)(C[C@@H](O[C@@]6([H])C[C@@H]([C@H](O)[C@@H](C)O6)OC)CC5)CC3)C | ||
| 分子式 | C30H46O8 | 分子量 | 534.68 |
| 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.8703 mL | 9.3514 mL | 18.7028 mL |
| 5 mM | 0.3741 mL | 1.8703 mL | 3.7406 mL |
| 10 mM | 0.187 mL | 0.9351 mL | 1.8703 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。
Periplocymarin Alleviates Doxorubicin-Induced Heart Failure and Excessive Accumulation of Ceramides
Front Cardiovasc Med 2021 Nov 19;8:732554.PMID:34869633DOI:10.3389/fcvm.2021.732554.
Doxorubicin-driven cardiotoxicity could result in dilated cardiomyopathy and heart failure (HF). Previously, we showed that Periplocymarin exerted a cardiotonic role by promoting calcium influx and attenuating myocardial fibrosis induced by isoproterenol (ISO) by improving the metabolism of cardiomyocytes. However, the impact of Periplocymarin on doxorubicin (DOX)-triggered cardiomyopathy has not been investigated. In the current study, C57BL/6 mice were randomly divided into three groups, namely, the control, DOX, and DOX+Periplocymarin groups. The cardiac function and apoptosis were measured. Our results revealed that Periplocymarin administration greatly improved the DOX-induced cardiac dysfunction manifested by the ejection fraction (EF%), fractional shortening (FS%), left ventricular posterior wall thickness (LVPW), left ventricular anterior wall thickness (LVAW), left ventricular (LV) mass, and attenuated DOX-induced cardiomyocyte apoptosis assessed by hematoxylin and eosin (H&E) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and western blotting. Further study using H9c2 cells revealed that the pretreatment of Periplocymarin suppressed DOX-induced apoptosis evidenced by annexin V staining. Moreover, liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis demonstrated that DOX lead to an accumulation in serum ceramide, and the pre-treatment of Periplocymarin could reverse this phenomenon. Network pharmacology also demonstrated that ceramide metabolism was involved in the process. Consistently, real-time PCR showed that Periplocymarin significantly abolished the induction of the genes involved in the de novo synthesis of ceramide, i.e., CerS2, CerS4, CerS5, and CerS6, and the induction was attributed to the treatment of DOX. Collectively, these results suggested that Periplocymarin reduced cardiomyocyte apoptosis to protect hearts from DOX-induced cardiotoxicity and the de novo synthesis of ceramides was involved in this process.
Periplocymarin protects against myocardial fibrosis induced by β-adrenergic activation in mice
Biomed Pharmacother 2021 Jul;139:111562.PMID:33839492DOI:10.1016/j.biopha.2021.111562.
Periplocymarin is an effective component of Periplocae Cortex, which was wildly used as an ingredient in Traditional Chinese Medicine. Our group previously reported that Periplocymarin exerted cardiotonic role via promoting calcium influx. However, its exact role in the pathogenesis of myocardial fibrosis has not been elucidated yet. The present study was aimed at determining the potential effect and underlying mechanism of Periplocymarin in isoproterenol (ISO)-induced myocardial fibrosis. C57BL/6 mice were subcutaneously injected with ISO (5 mg/kg/day) or saline for 1 week. The early-to-atrial wave ratio (E/A ratio) measured by echocardiography revealed that ISO-induced heart stiffness was remarkably reversed by administration of Periplocymarin (5 mg/kg/day). Masson trichrome staining exhibited that treatment of Periplocymarin reduced the excessive deposition of extracellular matrix (ECM). Further investigations employing real-time PCR and western blot demonstrated that Periplocymarin suppressed the expression of fibrosis related genes (Col1a1, Col3a1, Acta2 and Tgfb1) and proteins (Collagen I, Collagen III, α-SMA and TGF-β1) induced by ISO. Metabolomics analysis demonstrated that Periplocymarin ameliorated the disorders triggered by ISO and many of the differential metabolic substances were involved in amino acid, glucose and lipid metabolism. Further analysis using network pharmacology revealed that three key genes, namely NOS2, NOS3 and Ptgs2, may be the potential targets of Periplocymarin and responsible for the disorders. Validation using heart tissues showed that the mRNA expression of NOS3 was decreased while Ptgs2 was increased upon ISO treatment, which were reversed by Periplocymarin. Moreover, the expression of COX-2 (Ptgs2 encoded protein) was consistent with the aspect of Ptgs2 mRNA, while eNOS (NOS3 encoded protein) expression was unchanged. In vitro studies exhibited that Periplocymarin exerts anti-fibrotic function via regulating at least eNOS and COX-2 in cardiomyocyte. Taken together, Periplocymarin protects against myocardial fibrosis induced by β-adrenergic activation, the potential mechanism was that Periplocymarin targeted on, at least eNOS and COX-2, to improve the metabolic processes of cardiomyocyte and thus attenuated the myocardial fibrosis. Our study highlighted that Periplocymarin is a potential therapeutic agent for the prevention of myocardial fibrosis.
Periplocymarin Plays an Efficacious Cardiotonic Role via Promoting Calcium Influx
Front Pharmacol 2020 Aug 19;11:1292.PMID:32973521DOI:10.3389/fphar.2020.01292.
Periplocymarin, which belongs to cardiac glycosides, is an effective component extracted from Periplocae Cortex. However, its cardiovascular effects remain unidentified. In the present study, injection of Periplocymarin (5 mg/kg) through external jugular vein immediately increased the mean arterial pressure (MAP) in anesthetized C57BL/6 mice. Ex vivo experiments using mouse mesenteric artery rings were conducted to validate the role of Periplocymarin on blood vessels. However, Periplocymarin failed to induce vasoconstriction directly, and had no effects on vasoconstriction induced by phenylephrine (Phe) and angiotensin II (Ang II). In addition, vasodilatation induced by acetylcholine (Ach) was insusceptible to Periplocymarin. Echocardiography was used to evaluate the effects of Periplocymarin on cardiac function. The results showed that the injection of Periplocymarin significantly increase the ejection fraction (EF) in mice without changing the heart rate. In vitro studies using isolated neonatal rat ventricular myocytes (NRVMs) revealed that Periplocymarin transiently increased the intracellular Ca2+ concentration observed by confocal microscope. But in Ca2+-free buffer, this phenomenon vanished. Besides, inhibition of sodium potassium-activated adenosine triphosphatase (Na+-K+-ATPase) by digoxin significantly suppressed the increase of MAP and EF in mice, and the influx of Ca2+ in cardiomyocytes, mediated by Periplocymarin. Collectively, these findings demonstrated that Periplocymarin increased the contractility of myocardium by promoting the Ca2+ influx of cardiomyocytes via targeting on Na+-K+-ATPase, which indirectly led to the instantaneous rise of blood pressure.
Periplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway
Front Oncol 2021 Nov 25;11:753598.PMID:34900704DOI:10.3389/fonc.2021.753598.
Colorectal cancer (CRC) is one of the most common cancers worldwide, and approximately one-third of CRC patients present with metastatic disease. Periplocymarin (PPM), a cardiac glycoside isolated from Periploca sepium, is a latent anticancer compound. The purpose of this study was to explore the effect of PPM on CRC cells. CRC cells were treated with PPM and cell viability was evaluated by CCK-8 assay. Flow cytometry and TUNEL staining were performed to assess cell cycle and apoptosis. Quantitative proteomics has been used to check the proteins differentially expressed by using tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry. Bioinformatic analysis was undertaken to identify the biological processes that these differentially expressed proteins are involved in. Gene expression was analyzed by western blotting. The effect of PPM in vivo was primarily checked in a subcutaneous xenograft mouse model of CRC, and the gene expression of tumor was checked by histochemistry staining. PPM could inhibit the proliferation of CRC cells in a dose-dependent manner, induce cell apoptosis and promote G0/G1 cell cycle arrest. A total of 539 proteins were identified differentially expressed following PPM treatment, where among those there were 286 genes upregulated and 293 downregulated. PPM treatment caused a pro-apoptosis gene expression profile both in vivo and in vitro, and impaired PI3K/AKT signaling pathway might be involved. In addition, PPM treatment caused less detrimental effects on blood cell, hepatic and renal function in mice, and the anti-cancer effect was found exaggerated by PPM+5-FU combination treatment. PPM may perform anti-CRC effects by promoting cell apoptosis and this might be achieved by targeting PI3K/AKT pathway. PPM might be a safe and promising anti-cancer drug that needs to be further studied.
Periplocymarin alleviates pathological cardiac hypertrophy via inhibiting the JAK2/STAT3 signalling pathway
J Cell Mol Med 2022 May;26(9):2607-2619.PMID:35365949DOI:10.1111/jcmm.17267.
Pathological cardiac hypertrophy is the most important risk factor for developing chronic heart failure. Therefore, the discovery of novel agents for treating pathological cardiac hypertrophy remains urgent. In the present study, we examined the therapeutic effect and mechanism of Periplocymarin (PM)-mediated protection against pathological cardiac hypertrophy using angiotensinII (AngII)-stimulated cardiac hypertrophy in H9c2 cells and transverse aortic constriction (TAC)-induced cardiac hypertrophy in mice. In vitro, PM treatment significantly reduced the surface area of H9c2 cells and expressions of hypertrophy-related proteins. Meanwhile, PM markedly down-regulated AngII-induced translocation of p-STAT3 into the nuclei and enhanced the phosphorylation levels of JAK2 and STAT3 proteins. The STAT3 specific inhibitor S3I-201 or siRNA-mediated depleted expression could alleviate AngII-induced cardiac hypertrophy in H9c2 cells following PM treatment; however, PM failed to reduce the expressions of hypertrophy-related proteins and phosphorylated STAT3 in STAT3-overexpressing cells, indicating that PM protected against AngII-induced cardiac hypertrophy by modulating STAT3 signalling. In vivo, PM reversed TAC-induced cardiac hypertrophy, as determined by down-regulating ratios of heart weight to body weight (HW/BW), heart weight to tibial length (HW/TL) and expressions of hypertrophy-related proteins accompanied by the inhibition of the JAK2/STAT3 pathway. These results revealed that PM could effectively protect the cardiac structure and function in experimental models of pathological cardiac hypertrophy by inhibiting the JAK2/STAT3 signalling pathway. PM is expected to be a potential lead compound of the novel agents for treating pathological cardiac hypertrophy.