Hyperforin (dicyclohexylammonium salt)
(Synonyms: 贯叶金丝桃素二环己基铵盐,Hyp-DCHA, Hyperforin-DCHA) 目录号 : GC43884
A natural compound with diverse actions
Cas No.:238074-03-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Hyperforin is a natural activator of the steroid X receptor (active at 0.1 to 0.5 µg/ml) and inhibitor of several cytochrome P450 (CYP) isoforms (IC50 = 10 µg/ml for CYP2D6).[1],[2] It can also inhibit microsomal prostaglandin E2 synthase-1 (mPGES-1; IC50 = 1 µM), 5-lipoxygenase activating protein, and sirtuins.[3],[4],[5]
Reference：
[1]. Wentworth, J.M., Agostini, M., Love, J., et al. St. John’s wort, a herbal antidepressant, activates the steroid X receptor. Journal of Endocrinology 166, R11-R16 (2000).
[2]. Obach, R.S. Inhibition of human cytochrome P450 enzymes by constituents of St. John’s wort, an herbal preparation used in the treatment of depression. Journal of Pharmacology and Experimental Therapeutics 294(1), 88-95 (2000).
[3]. Chang, H.H., and Meuillet, E.J. Identification and development of mPGES-1 inhibitors: Where we are at? Future Med.Chem. 3(15), 1909-1934 (2011).
[4]. Greiner, C., Hörnig, C., Rossi, A., et al. 2-(4-(Biphenyl-4-ylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (HZ52) - a novel type 5-lipoxygenase inhibitor with favorable molecular pharmacology and efficacy in vivo. British Journal of Pharmacology 164(2b), 781-793 (2011).
[5]. Milne, J.C., and Denu, J.M. The sirtuin family:Therapeutic targets to treat diseases of aging. Current Opinion in Chemical Biology 12, 11-17 (2008).
| Cas No. | 238074-03-8 | SDF | |
| 别名 | 贯叶金丝桃素二环己基铵盐,Hyp-DCHA, Hyperforin-DCHA | ||
| 化学名 | (1R,5S,6R,7S)-4-hydroxy-6-methyl-1,3,7-tris(3-methyl-2-buten-1-yl)-5-(2-methyl-1-oxopropyl)-6-(4-methyl-3-penten-1-yl)-bicyclo[3.3.1]non-3-ene-2,9-dione, N-cyclohexylcyclohexanamine (1:1) | ||
| Canonical SMILES | O=C1C(C/C=C(C)/C)=C(O)[C@]2(C(C(C)C)=O)[C@@](CC/C=C(C)/C)(C)[C@@H](C/C=C(C)/C)C[C@@]1(C/C=C(C)/C)C2=O.C3(NC4CCCCC4)CCCCC3 | ||
| 分子式 | C35H52O4 • C12H23N | 分子量 | 718.1 |
| 溶解度 | DMF: 20 mg/ml,DMSO: 20 mg/ml,Ethanol: 20 mg/ml,Ethanol:PBS(pH 7.2) (1:1): 0.5 mg/ml | 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 | 1.3926 mL | 6.9628 mL | 13.9256 mL |
| 5 mM | 0.2785 mL | 1.3926 mL | 2.7851 mL |
| 10 mM | 0.1393 mL | 0.6963 mL | 1.3926 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。
Stabilization of Hyperforin dicyclohexylammonium salt with dissolved albumin and albumin nanoparticles for studying Hyperforin effects on 2D cultivation of keratinocytes in vitro
Eur J Pharm Biopharm 2018 May;126:115-122.PMID:28870756DOI:10.1016/j.ejpb.2017.08.009.
Due to the limited chemical stability of the natural Hyperforin molecule, a more stable form of Hyperforin, i.e., the Hyperforin dicyclohexylammonium salt (HYP-DCHA) has been used for ex vivo and in vitro experiments in recent years, but its actual stability under typical cell culture conditions has never been studied before. In this contribution the stability of HYP-DCHA was examined under typical cell culture conditions. Different cell culture media with and without fetal calf serum (FCS) supplementation were studied with regard to further stabilization of HYP-DCHA determined with HPLC analysis. Furthermore, albumin nanoparticles were examined as a stabilizing carrier system for HYP-DCHA. In this context, the interaction between HYP-DCHA and albumin nanoparticles (ANP) was examined with regard to size and loading with HYP . The effects of HYP-DCHA either supplied in cell culture medium or loaded on ANP on viability and cytotoxicity were studied in vitro on HaCaT monolayers (human keratinocyte cell line). HYP-DCHA supplied in FCS-containing medium was recovered completely after 24h of incubation. However, a lack of FCS caused a total loss of HYP-DCHA after less than 24h incubation time. Supplying HYP-DCHA loaded on ANP in an FCS-free medium resulted in a recovery of about 60% after 24h incubation. HYP-DCHA supplied in medium along with FCS showed a slow dose-dependent decrease in viability of HaCaT cells without any cytotoxic effects (antiproliferative effect). Treatment with HYP-DCHA with a lack of FCS resulted in a significantly faster decrease in viability which was mainly due to cytotoxicity. The latter was true for HYP-DHCA-loaded ANP where increased cytotoxicity was observed despite the presence of FCS. The results show that the stability of the widely used HYP-DCHA is rather limited under cell culture conditions. Especially a lack of FCS leads to degradation and/or oxidation of HYP-DCHA probably causing an increased cytotoxicity. In contrast, FCS supplementation fairly stabilizes HYP-DCHA under cell culture conditions while albumin nanoparticles may serve the same stabilization purpose despite increasing cytotoxic effects onto the cells themselves.
Induction of apoptosis in K562 cells by dicyclohexylammonium salt of Hyperforin through a mitochondrial-related pathway
Chem Biol Interact 2011 Apr 25;190(2-3):91-101.PMID:21376709DOI:10.1016/j.cbi.2011.02.026.
Hyperforin is an abundant phloroglucinol-type constituent isolated from the extract of the flowering upper portion of the plant Hypericum perforatum L. The dicyclohexylammonium salt of Hyperforin (DCHA-HF) has exhibited antitumor and antiangiogenic activities in various cancer cells. Here, the antitumor effects of DCHA-HF on the chronic myeloid leukemia K562 cell line were investigated for the first time. DCHA-HF exhibited dose- and time-dependent inhibitory activities against K562 cells, with IC(50) values of 8.6 and 3.2 μM for 48 h and 72 h of treatment, respectively, which was more effective than that of the Hyperforin. In contrast, little cytotoxic activity was observed with DCHA-HF on HUVECs. DCHA-HF treatment resulted in induction of apoptosis as evidenced from DNA fragmentation, nuclear condensation and increase of early apoptotic cells by DAPI staining analysis, TUNEL assay and Annexin V-FITC/PI double-labeled staining analysis, respectively. Moreover, DCHA-HF elicited dissipation of mitochondrial transmembrane potential that commenced with the release of cytochrome c through down-regulation of expression of anti-apoptotic proteins and up-regulation of expression of pro-apoptotic proteins. DCHA-HF treatment induced activation of the caspase 3, 8, and 9 cascade and subsequent PARP cleavage, and DCHA-HF-induced apoptosis was significantly inhibited by caspase inhibitors. Treated cells were arrested at the G1 phase of the cell cycle and the expression of p53 and p27(Kip1), two key regulators related to cell cycle and apoptosis, was up-regulated. These results suggest that DCHA-HF inhibits K562 cell growth by inducing caspase-dependent apoptosis mediated by a mitochondrial pathway and arresting the cell cycle at the G1 phase. Therefore, DCHA-HF is a potential chemotherapeutic antitumor drug for chronic myeloid leukemia therapy.
Role of Hyperforin in the antidepressant-like activity of Hypericum perforatum extracts
Psychopharmacology (Berl) 2002 Dec;164(4):423-8.PMID:12457273DOI:10.1007/s00213-002-1229-5.
Rationale: Hyperforin has been identified as an active constituent of Hypericum perforatum but its importance in the antidepressant effect of this plant's extracts is not really known. Objective: To evaluate the antidepressant-like activity of two extracts in relation to the content of Hyperforin and its plasma and whole brain concentrations, compared with a stable salt of Hyperforin (dicyclohexylammonium; DCHA). Methods: The effects of the extracts and Hyperforin were evaluated in the rat forced swimming test. The specificity of the effects was demonstrated evaluating the rats' locomotor activity. Plasma and brain concentrations of Hyperforin were determined by high performance liquid chromatography. Results: The 4.5% extract (but not the 0.5% extract) given as three IP injections in 24 h (3.12-6.25 mg/kg) reduced the total immobility of rats, yielding dose-related plasma concentrations of Hyperforin. These concentrations were of a similar magnitude to those after Hyperforin DCHA which also significantly reduced immobility when given on the basis of the Hyperforin content of the 4.5% extract (0.14 and 0.28 mg/kg). However, Hyperforin was undetectable in rat brain, possibly because of poor passage of the blood-brain barrier. Conclusion: These results support the view that Hyperforin plays a key role in the antidepressant-like activity of Hypericum p. However, brain concentrations after effective doses are probably far from those active in vitro on the neurotransmitter mechanisms so far investigated.
Hyperforin production in Hypericum perforatum root cultures
J Biotechnol 2016 Mar 20;222:47-55.PMID:26876610DOI:10.1016/j.jbiotec.2016.02.016.
Extracts of the medicinal plant Hypericum perforatum are used to treat depression and skin irritation. A major API is Hyperforin, characterized by sensitivity to light, oxygen and temperature. Total synthesis of Hyperforin is challenging and its content in field-grown plants is variable. We have established in vitro cultures of auxin-induced roots, which are capable of producing Hyperforin, as indicated by HPLC-DAD and ESI-MS analyses. The extraction yield and the productivity upon use of petroleum ether after solvent screening were ∼5 mg/g DW and ∼50 mg/L culture after six weeks of cultivation. The root cultures also contained secohyperforin and lupulones, which were not yet detected in intact plants. In contrast, they lacked another class of typical H. perforatum constituents, hypericins, as indicated by the analysis of methanolic extracts. Hyperforins and lupulones were stabilized and enriched as dicyclohexylammonium salts. Upon up-scaling of biomass production and downstream processing, H. perforatum root cultures may provide an alternative platform for the preparation of medicinal extracts and the isolation of APIs.
Potential antidepressant properties of IDN 5491 (hyperforin-trimethoxybenzoate), a semisynthetic ester of Hyperforin
Eur Neuropsychopharmacol 2005 Mar;15(2):211-8.PMID:15695067DOI:10.1016/j.euroneuro.2004.07.004.
Hyperforin is one of the possible active principles mediating the antidepressant activity of Hypericum perforatum L. extracts. The ester derivative IDN 5491 (hyperforin-trimethoxybenzoate) showed antidepressant-like properties in the forced swimming test (FST) in rats, with no effect on open-field activity, when given as three intraperitoneal injections in 24 h at 3.125 and 6.25 mg/kg. The plasma concentrations of IDN 5491 were 30-50 microM, and those of Hyperforin much lower but still close to those after effective doses of hyperforin-dicyclohexylammonium and Hypericum extract. This suggests that Hyperforin plays a role in the antidepressant-like effect of the ester and of Hypericum extract. In vitro binding and uptake data showed that IDN 5491 is inactive on a wide panel of CNS targets at a concentration (14 microM) much higher than that measured in the brain of treated rats (0.3 microM). Like the extract, the antidepressant-like effect of IDN 5491 was blocked by (-)-sulpiride, a selective D2 receptor antagonist and by BD-1047, a selective sigma1 antagonist. Ex-vivo binding studies showed that brain sigma1 receptors are occupied after in vivo treatment with IDN 5491, possibly by an unknown metabolite or by endogenous ligand induced by Hyperforin.