Fuziline
(Synonyms: 附子灵; 15α-Hydroxyneoline) 目录号 : GC38023
A diterpene alkaloid with cardioprotective activity
Cas No.:80665-72-1
Sample solution is provided at 25 µL, 10mM.
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- Purity: >98.00%
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Fuziline is a diterpene alkaloid that has been found in A. lateralis and has cardioprotective activity.1 It reduces sodium pentobarbital-induced cell death in primary neonatal rat cardiomyocytes when used at concentrations ranging from 0.1 to 10 ?M. Fuziline (0.5 ?M) reduces the production of reactive oxygen species (ROS) and apoptosis induced by isoproterenol in H9c2 rat cardiomyocytes.2 In vivo, fuziline (3 and 10 mg/kg) reduces isoproterenol-induced myocardial necrosis and fibrosis in rats.
1.Xiong, L., Peng, C., Xie, X.-F., et al.Alkaloids isolated from the lateral root of Aconitum carmichaeliiMolecules17(8)9939-9946(2012) 2.Fan, C.-L., Yao, Z.-H., Ye, M.-N., et al.Fuziline alleviates isoproterenol-induced myocardial injury by inhibiting ROS-triggered endoplasmic reticulum stress via PERK/eIF2α/ATF4/Chop pathwayJ. Cell Mol. Med.24(2)1332-1344(2020)
| Cas No. | 80665-72-1 | SDF | |
| 别名 | 附子灵; 15α-Hydroxyneoline | ||
| Canonical SMILES | O[C@@H]1C(C(N(CC)C2)C3[C@@H]4OC)([C@@](C[C@@]5([H])[C@@H]6O)([H])[C@@]6([H])[C@@]3([C@@H](O)[C@@H]5OC)O)[C@@]4([H])[C@@]2(COC)CC1 | ||
| 分子式 | C24H39NO7 | 分子量 | 453.57 |
| 溶解度 | Chloroform: soluble,DMSO: soluble | 储存条件 | Store at -20°C,protect from light |
| 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 | 2.2047 mL | 11.0237 mL | 22.0473 mL |
| 5 mM | 0.4409 mL | 2.2047 mL | 4.4095 mL |
| 10 mM | 0.2205 mL | 1.1024 mL | 2.2047 mL |
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| 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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。
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Fuziline alleviates isoproterenol-induced myocardial injury by inhibiting ROS-triggered endoplasmic reticulum stress via PERK/eIF2α/ATF4/Chop pathway
J Cell Mol Med 2020 Jan;24(2):1332-1344.PMID:31811750DOI:10.1111/jcmm.14803.
Fuziline, an aminoalcohol-diterpenoid alkaloid derived from Aconiti lateralis radix preparata, has been reported to have a cardioprotective activity in vitro. However, the potential mechanism of Fuziline on myocardial protection remains unknown. In this study, we aimed to explore the efficacy and mechanism of Fuziline on isoproterenol (ISO)-induced myocardial injury in vitro and in vivo. As a result, Fuziline effectively increased cell viability and alleviated ISO-induced apoptosis. Meanwhile, Fuziline significantly decreased the production of ROS, maintained mitochondrial membrane potential (MMP) and blocked the release of cytochrome C, suggesting that Fuziline could play the cardioprotective role through restoring the mitochondrial function. Fuziline also could suppress ISO-induced endoplasmic reticulum (ER) stress via the PERK/eIF2α/ATF4/Chop pathway. In addition, using ROS scavenger NAC could decrease ISO-induced apoptosis and block ISO-induced ER stress, while PERK inhibitor GSK2606414 did not reduce the production of ROS, indicating that excess production of ROS induced by ISO triggered ER stress. And Fuziline protected against ISO-induced myocardial injury by inhibiting ROS-triggered ER stress. Furthermore, Fuziline effectively improved cardiac function on ISO-induced myocardial injury in rats. Western blot analysis also showed that Fuziline reduced ER stress-induced apoptosis in vivo. Above these results demonstrated that Fuziline could reduce ISO-induced myocardial injury in vitro and in vivo by inhibiting ROS-triggered ER stress via the PERK/eIF2α/ATF4/Chop pathway.
Development and Validation of an UPLC-Q-TOF-MS Method for Quantification of Fuziline in Beagle Dog After Intragastric and Intravenous Administration
J Chromatogr Sci 2016 Mar;54(3):405-12.PMID:26564737DOI:10.1093/chromsci/bmv156.
A specific and sensitive UPLC-Q-TOF-MS method operated in the positive ion mode was developed and validated for the quantification of Fuziline in Beagle dog plasma. Fuziline and Neoline internal standard were separated on an Acquity UPLC BEH C18 column with the total running time of 4 min using gradient elution at the flow rate of 0.25 mL/min. The calibration curves for Fuziline showed good linearity in the concentrations ranging from 2 to 400 ng/mL with correlation coefficients (r) greater than 0.9971. The lower limit of quantification was 0.8 ng/mL. Intra- and interbatch relative standard deviations ranged from 2.11 to 3.11% and 3.12 to 3.81%, respectively. Fuziline was stable under different sample storage and processing conditions. The developed method was successfully applied to the comparative pharmacokinetic study of Fuziline in Beagle dog after intravenous and oral administration. Low absolute bioavailability of Fuziline (1.45 ± 0.76%) suggested a significant metabolism transformation extent in Beagle dog.
Neuropharmacological effects of Aconiti Lateralis Radix Praeparata
Clin Exp Pharmacol Physiol 2020 Apr;47(4):531-542.PMID:31837236DOI:10.1111/1440-1681.13228.
Aconiti Lateralis Radix Praeparata (Fuzi in Chinese), which are the lateral roots of Aconitum Carmichaelii Debx, is widely used in China to treat many neurological diseases. Fuzi, in its various forms, has many neuropharmacological effects. It can act as an analgesic and help with depression, epilepsy, and dementia. However, the neuropharmacological effects of Aconiti Lateralis Radix Praeparata are seldom comprehensively reviewed. In this review, the neuropharmacological activities of some components contained in Aconiti Lateralis Radix Praeparata are considered. These include aconitine, mesaconitine, hypaconitine, total alkaloid, polysaccharide-1, benzoylmesaconine, Fuziline, songorine, and napelline. We also specifically discuss the antidepressant effects of total alkaloids and polysaccharide-1. This review may provide a theoretical basis for further utilization of Aconiti Lateralis Radix Praeparata for diseases that affect the central nervous system.
Quantitative determination of diterpenoid alkaloid Fuziline by hydrophilic interaction liquid chromatography (HILIC)-electrospray ionization mass spectrometry and its application to pharmacokinetic study in rats
J Chromatogr B Analyt Technol Biomed Life Sci 2013 Jan 15;913-914:55-60.PMID:23270939DOI:10.1016/j.jchromb.2012.11.017.
A rapid, sensitive and specific hydrophilic interaction liquid chromatography coupled to electrospray ionization mass spectrometric (HILIC-MS) method for the quantification of Fuziline (15α-Hydroxyneoline) in rat plasma was developed and validated. After liquid-liquid extraction with ethyl acetate, Fuziline and Guanfu base A (internal standard) were separated with HILIC Chrom Matrix HP amide column (5μm, 10cm×3.0mm I.D.) with isocratic elution at a flow-rate of 0.2mL/min. The analytes were detected by using an electrospray positive ionization mass spectrometry in the selected ion monitoring (SIM) mode. A good linear relationship was obtained in the concentration ranging from 1 to 1000ng/mL (R(2)=0.999) with the lower limit of quantification (LLOQ) at 1ng/mL and limit of detection (LOD) at 0.5ng/mL. The average recoveries of Fuziline in plasma at the concentrations of 2, 50, 1000ng/mL ranged from 68.2 to 69.9%. Intra- and inter-batch relative standard deviations ranged from 1.5 to 3.3% and 2.6 to 8.3%, respectively. Fuziline was stable under different sample storage and processing conditions except three-cycle freeze-thaw treatment at 2ng/mL. This method was successfully applied to the pharmacokinetic studies in Sprague-Dawley rats. The absolute bioavailability of Fuziline after oral administration 4mg/kg Fuziline in rats was 21.1±7.0%, with clearance rate at 1745.6±818.1mL/kg/h, and half-life at about 6.3±2.6h.
Neoline, Fuziline, songorine and 10-OH mesaconitine are potential quality markers of Fuzi: In vitro and in vivo explorations as well as pharmacokinetics, efficacy and toxicity evaluations
J Ethnopharmacol 2023 Mar 1;303:115879.PMID:36370966DOI:10.1016/j.jep.2022.115879.
Ethnopharmacological relevance: Fuzi, the lateral roots of Aconitum carmichaelii Debx, plays an irreplaceable role in treating Yang deficiency and cold coagulation syndromes. However, Fuzi has a narrow margin of safety since its pharmacological constituents, Aconitum alkaloids, have potential cardiotoxicity and neurotoxicity. The current quality markers (Q-markers) for the control of Fuzi's efficacy and toxicity are 3 monoester-diterpenoid alkaloids, namely, benzoylaconine (BAC), benzoylhypaconine and benzoylmesaconine (BMA) and 3 diester-diterpenoid alkaloids, namely, aconitine (AC), hypaconitine and mesaconitine (MA). However, mounting evidence indicates that the current 6 Q-markers may not be efficacy- or toxicity-specific enough for Fuzi. Aim of the study: The aim of this study was to explore and evaluate efficacy- or toxicity-specific potential quality markers (PQ-markers) of Fuzi. Materials and methods: PQ-markers were explored by analyzing 30 medicinal samples and alkaloids exposed in mouse. Pharmacokinetics of PQ-markers on C57BL/6J mice were determined. Anti-inflammatory effects of PQ-markers were evaluated by λ-carrageenan-induced paw edema model and lipopolysaccharide-induced RAW264.7 cell inflammatory model, while analgesic effects were assessed by acetic acid-induced pain model and Hargreaves test. Cardiotoxicity and neurotoxicity of PQ-markers were assessed by histological and biochemical analyses, while acute toxicity was evaluated by modified Kirschner method. Results: After in vitro and in vivo explorations, 7 PQ-markers, namely, neoline (NE), Fuziline (FE), songorine (SE), 10-OH mesaconitine (10-OH MA), talatizamine, isotalatizidine and 16β-OH cardiopetalline, were found. In the herbal medicines, NE, FE, SE and 10-OH MA were found in greater abundance than many other alkaloids. Specifically, the amounts of NE, FE and SE in the Fuzi samples were all far higher than that of BAC, and the contents of 10-OH MA in 56.67% of the samples were higher than that of AC. In mouse plasma and tissues, NE, FE, SE, talatizamine, isotalatizidine and 16β-OH cardiopetalline had higher contents than the other alkaloids, including the 6 current Q-markers. The pharmacokinetics, efficacy and toxicity of NE, FE, SE and 10-OH MA were further evaluated. The average oral bioavailabilities of NE (63.82%), FE (18.14%) and SE (49.51%) were higher than that of BMA (3.05%). Additionally, NE, FE and SE produced dose-dependent anti-inflammatory and analgesic effects, and their actions were greater than those of BMA. Concurrently, the toxicities of NE, FE and SE were lower than those of BMA, since no cardiotoxicity or neurotoxicity was found in mice after NE, FE and SE treatment, while BMA treatment notably increased the creatine kinase activity and matrix metalloproteinase 9 level in mice. The average oral bioavailability of 10-OH MA (7.02%) was higher than that of MA (1.88%). The median lethal dose (LD50) of 10-OH MA in mice (0.11 mg/kg) after intravenous injection was close to that of MA (0.13 mg/kg). Moreover, 10-OH MA produced significant cardiotoxicity and neurotoxicity, and notable anti-inflammatory and analgesic effects that were comparable to those of MA. Conclusions: Seven PQ-markers of Fuzi were found after in vitro and in vivo explorations. Among them, NE, FE and SE were found to be more efficacy-specific than BMA, and 10-OH MA was as toxicity-specific as MA.