Neoline
(Synonyms: 雪上一枝蒿乙素; Bullatine B) 目录号 : GC39009
A diterpene alkaloid with diverse biological activities
Cas No.:466-26-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Bullatine B is a diterpene alkaloid that has been found in Aconitum and has diverse biological activities.1,2 It inhibits voltage-gated sodium channel 1.7 (Nav1.7) in HEK293 cells expressing the human channel (IC50 = 25.8 nM) and scavenges DPPH radicals by 65.3% at 1 mM. Bullatine B (10 mg/kg) increases the mechanical pain threshold in the von Frey test in streptozotocin-induced diabetic, but not non-diabetic, mice.1
1.Nakatani, Y., Negoro, K., Yamauchi, M., et al.Neoline, an active ingredient of the processed aconite root in Goshajinkigan formulation, targets Nav1.7 to ameliorate mechanical hyperalgesia in diabetic miceJ. Ethnopharmacol.259112963(2020) 2.Begum, S., Ali, A., Ahman, W., et al.Pharmacologically active C-19 diterpenoid alkaloids from the aerial parts of Aconitum laeve royleRec. Nat. Prod.8(2)83-92(2014)
| Cas No. | 466-26-2 | SDF | |
| 别名 | 雪上一枝蒿乙素; Bullatine B | ||
| Canonical SMILES | O[C@@H]1C23[C@@]4([H])[C@](COC)(CN(CC)C2C([C@]5(O)[C@]6([H])[C@@]3([H])C[C@@]([C@@H](OC)C5)([H])[C@@H]6O)[C@@H]4OC)CC1 | ||
| 分子式 | C24H39NO6 | 分子量 | 437.57 |
| 溶解度 | DMSO: 250 mg/mL (571.34 mM) | 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 | 2.2853 mL | 11.4267 mL | 22.8535 mL |
| 5 mM | 0.4571 mL | 2.2853 mL | 4.5707 mL |
| 10 mM | 0.2285 mL | 1.1427 mL | 2.2853 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。
Neoline Improves Memory Impairment and Reduces Amyloid-β Level and Tau Phosphorylation Through AMPK Activation in the Mouse Alzheimer's Disease Model
J Alzheimers Dis 2021;81(2):507-516.PMID:33814448DOI:10.3233/JAD-201614.
Background: Alzheimer's disease (AD) is the most general, chronic, and progressive neurodegenerative senile disorder characterized clinically by progressive cognitive deterioration and memory impairment. Neoline is effective against neuropathic pain models, but the effects of Neoline against AD-like phenotypes have not been investigated. Objective: We offer the investigation of the effects of Neoline in AD. Methods: In this study, a Tg-APPswe/PS1dE9 AD mouse model was treated orally with Neoline at a concentration of 0.5 mg/kg or 0.1 mg/kg starting at 7.5 months and administered for three months, and its anti-AD effects were evaluated. Results: Neoline improved memory and cognition impairments and reduced the number of amyloid-beta plaque and the amount of amyloid-β in the brain of AD mice. Furthermore, Neoline reduced the anxiety behavior in the AD mouse model. The chronic administration of Neoline also induced AMPK phosphorylation and decreased tau, amyloid-β, and BACE1 expression in the hippocampus. These findings indicate that chronic administration of Neoline has therapeutic effects via AMPK activation, and BACE1 downregulation resulted in a decrease in the amyloid-β levels in the brain of Tg-APPswe/PS1dE9 AD mice. Conclusion: Our results suggest that Neoline is a therapeutic agent for the cure of neurodegenerative diseases like AD.
Neoline, an active ingredient of the processed aconite root in Goshajinkigan formulation, targets Nav1.7 to ameliorate mechanical hyperalgesia in diabetic mice
J Ethnopharmacol 2020 Sep 15;259:112963.PMID:32439405DOI:10.1016/j.jep.2020.112963.
Ethnopharmacological relevance: Goshajinkigan (GJG), a traditional Japanese Kampo formula, has been shown to exhibit several pharmacological actions, including antinociceptive effects. Processed aconite root (PA), which is considered to be an active ingredient of GJG, has also been demonstrated to have an ameliorative effect on pain, such as diabetic peripheral neuropathic pain. We recently identified Neoline as the active ingredient of both GJG and PA that is responsible for its effects against oxaliplatin-induced neuropathic pain in mice. Aim of the study: In the present study, we investigated whether GJG, PA, and Neoline could inhibit Nav1.7 voltage-gated sodium channel (VGSC) current and whether Neoline could ameliorate mechanical hyperalgesia in diabetic mice. Materials and methods: To assess the electrophysiological properties of GJG extract formulation, powdered PA, and Neoline on Nav1.7 VGSCs, whole-cell patch clamp recording was performed using human HEK293 cells expressing Nav1.7 VGSCs. In addition, the ameliorative effects of Neoline on diabetic peripheral neuropathic pain were evaluated using the von Frey test in streptozotocin (STZ)-induced diabetic model mice. Results: GJG extract formulation significantly inhibited Nav1.7 VGSC peak current. Powdered PA also inhibited Nav1.7 VGSC peak current. Like GJG and PA, Neoline could inhibit Nav1.7 VGSC current. When diabetic mice were treated with Neoline by intraperitoneal acute administration, the mechanical threshold was increased in diabetic mice, but not in non-diabetic mice, in a behavioral study. Conclusion: These results suggest that Neoline might be a novel active ingredient of GJG and PA that is one of responsible ingredients for ameliorating mechanical hyperalgesia in diabetes via the inhibition of Nav1.7 VGSC current at least.
Neoline is the active ingredient of processed aconite root against murine peripheral neuropathic pain model, and its pharmacokinetics in rats
J Ethnopharmacol 2019 Sep 15;241:111859.PMID:30974202DOI:10.1016/j.jep.2019.111859.
Ethnopharmacological relevance: Processed aconite root (PA), the root of Aconitum carmichaeli (Ranunculaceae), is a crude drug used in traditional Chinese or Japanese kampo medicine to treat pain associated with coldness. In our previous study, PA and its active ingredient, Neoline, alleviated oxaliplatin-induced peripheral neuropathy in mice. Aim of the study: The present study investigated the effects of PA on a murine peripheral neuropathy model induced by intraperitoneal injection of paclitaxel and partial ligation of the sciatic nerve (Seltzer model), and identified its active ingredients. Materials and methods: PA powder (1 g/kg/day) was orally administered, and either Neoline or benzoylmesaconine (10 mg/kg/day) was subcutaneously injected into the murine model. Mechanical hyperalgesia was evaluated via the von Frey filament method. PA extract was orally administered to rats; blood samples were chronologically collected, and the plasma concentrations of Aconitum alkaloids were measured. The contents of Aconitum alkaloids in commercial PA products were also measured. Results: PA extract and Neoline significantly attenuated the mechanical hyperalgesia induced by either paclitaxel or partial ligation of the sciatic nerve in mice. In the plasma samples of rats treated with PA extract, higher concentrations of benzoylmesaconine and Neoline were apparent among Aconitum alkaloids. The contents of benzoylmesaconine and Neoline varied among PA products with different processing procedures. Subcutaneous injection of benzoylmesaconine did not attenuate the hyperalgesia induced by each paclitaxel, partial ligation of the sciatic nerve, or oxaliplatin in mice. Conclusions: The present results indicate that PA and its active ingredient, Neoline, are promising agents for the alleviation of neuropathic pain. Neoline can be used as a marker compound to determine the quality of the PA products for the treatment of neuropathic pain.
Neoline from Aconitum flavum Hand
Acta Crystallogr Sect E Struct Rep Online 2011 Jun 1;67(Pt 6):o1435.PMID:21754813DOI:10.1107/S1600536811015170.
The title compound, C(24)H(39)NO(6) [systematic name: (1α,6α,14α,16β)-N-ethyl-6,16-dimeth-oxy-4-meth-oxy-methylaconitane-1,8,14-triol], is a C(19)-diterpenoid alkaloid from the roots of Aconitum flavum Hand. The mol-ecule has an aconitane carbon skeleton with four six-membered rings and two five-membered rings. Both five-membered rings adopt envelope conformations. Two six-membered rings adopt chair conformations, whereas the other two adopt boat conformations. Intra-molecular O-H⋯O and O-H⋯N and inter-molecular O-H⋯O hydrogen bonds are present in the structure. In the crystal, one methyl group is disordered over two sites with an occupancy ratio of 0.70 (3):0.30 (3).
Processed aconite root and its active ingredient Neoline may alleviate oxaliplatin-induced peripheral neuropathic pain
J Ethnopharmacol 2016 Jun 20;186:44-52.PMID:27038579DOI:10.1016/j.jep.2016.03.056.
Ethnopharmacological relevance: Processed aconite root (PA, the root of Aconitum carmichaeli, Ranunculaceae) is a crude drug used in traditional Chinese or Japanese kampo medicine to generate heat in the body and to treat pain associated with coldness. Oxaliplatin (L-OHP) is a platinum-based anticancer drug that frequently causes acute and chronic peripheral neuropathies, including cold and mechanical hyperalgesia. Aim of the study: We investigated the effects of PA on L-OHP-induced peripheral neuropathies and identified the active ingredient within PA extract. Materials and methods: L-OHP was intraperitoneally injected into mice, and PA boiled water extract was orally administered. Cold and mechanical hyperalgesia were evaluated using the acetone test and the von Frey filament method, respectively. Dorsal root ganglion (DRG) neurons were isolated from normal mice and cultured with L-OHP with or without PA extract. Cell viability and neurite elongation were evaluated. Results: PA extract significantly attenuated cold and mechanical hyperalgesia induced by L-OHP in mice. In cultured DRG neurons, L-OHP reduced cell viability and neurite elongation in a dose-dependent manner. Treatment with PA extract significantly alleviated the L-OHP-induced reduction of neurite elongation, while the cytotoxicity of L-OHP was not affected. Using activity-guided fractionation, we isolated Neoline from PA extract as the active ingredient. Neoline significantly alleviated L-OHP-induced reduction of neurite elongation in cultured DRG neurons in a concentration-dependent manner. Moreover, subcutaneous injection of Neoline attenuated cold and mechanical hyperalgesia in L-OHP-treated mice. PA extract and Neoline did not show sedation and motor impairment. Conclusions: The present study indicates that PA and its active ingredient Neoline are promising agents to alleviate L-OHP-induced neuropathic pain.