Bullatine A
(Synonyms: 雪上一枝蒿甲素) 目录号 : GC35567
Bullatine A (BLA) 雪上一枝蒿甲素是乌头属 genus Aconitum 的二萜类生物碱，具有抗风湿，抗炎和抗伤害感受作用。 Bullatine A 是一种有效的 P2X7 拮抗剂，可抑制 ATP 诱导的细胞凋亡和 P2X 受体介导的炎症反应。Bullatine A 能缓解过敏反应。
Cas No.:1354-84-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
Bullatine A (BLA), a diterpenoid alkaloid of the genus Aconitum, possesses anti-rheumatic, anti-inflammatory and anti-nociceptive effects. Bullatine A (BLA) is a potent P2X7 antagonist, inhibits ATP-induced cell death/apoptosis and P2X receptor-mediated inflammatory responses[1].Bullatine A attenuates pain hypersensitivity, regardless of the pain models employed[2].
[1]. Li J, et al. Bullatine A, a diterpenoid alkaloid of the genus Aconitum, could attenuate ATP-induced BV-2 microglia death/apoptosis via P2X receptor pathways. Brain Res Bull. 2013 Aug;97:81-5. [2]. Huang Q, et al. Bullatine A stimulates spinal microglial dynorphin A expression to produce anti-hypersensitivity in a variety of rat pain models. J Neuroinflammation. 2016 Aug 30;13(1):214.
| Cas No. | 1354-84-3 | SDF | |
| 别名 | 雪上一枝蒿甲素 | ||
| Canonical SMILES | [Bullatine A] | ||
| 分子式 | C22H33NO2 | 分子量 | 343.5 |
| 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 | 2.9112 mL | 14.556 mL | 29.1121 mL |
| 5 mM | 0.5822 mL | 2.9112 mL | 5.8224 mL |
| 10 mM | 0.2911 mL | 1.4556 mL | 2.9112 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 | ||||||||||
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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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Bullatine A exerts anti-inflammatory effects by inhibiting the ROS/JNK/NF-κB pathway and attenuating systemic inflammatory responses in mice
Pharm Biol 2022 Dec;60(1):1840-1849.PMID:36200648DOI:10.1080/13880209.2022.2121410.
Context: Aconiti brachypodi Radix (Xue-shang-yi-zhi-hao) is a traditional Chinese herbal medicine that is capable of anti-analgesic and anti-inflammatory effects. Bullatine A (BA) is one of the major active ingredients of this plant, and most of the previous studies reported that it has anti-analgesic effects. However, the mechanism of BA anti-inflammatory remains unclear. Objective: This study investigates the anti-inflammatory activities of BA, both in vitro and in vivo, and elucidates its mechanism. Materials and methods: In vitro, BA (10, 20, 40 and 80 μM) was added to 1 µg/mL of lipopolysaccharide (LPS)-activated microglia BV2 cells and immortalized murine bone marrow-derived macrophages, respectively. After 6 h, the mRNA and protein levels of inflammatory factors were determined by real-time quantitative PCR and western blotting. In vivo, C57BL/6 mice were randomly divided into control, model (5 mg/kg dose of LPS) and treated groups (LPS with 5, 10 or 20 mg/kg dose of BA) to evaluate the anti-inflammatory efficacy of BA. Results: BA significantly inhibited LPS-induced expression of inflammatory factors, such as IL-1β, IL-6, TNF-α, inducible nitric oxide synthase (iNOS) and COX-2. Further investigations showed that BA reduced the translocation of NF-κB p65 (38.5%, p < 0.01). BA also reduced the phosphorylation of c-Jun N-terminal kinase (JNK) (11.2%, p < 0.05) and reactive oxygen species (ROS) generation (24.2%, p < 0.01). Furthermore, BA treatment attenuated the LPS-primed inflammatory response and liver and lung damage in vivo. Conclusions: BA can inhibit the inflammatory response in part through the ROS/JNK/NF-κB signalling pathway, providing a theoretical basis for the clinical application of BA in the treatment of periphery inflammatory diseases.
Bullatine A stimulates spinal microglial dynorphin A expression to produce anti-hypersensitivity in a variety of rat pain models
J Neuroinflammation 2016 Aug 30;13(1):214.PMID:27577933DOI:10.1186/s12974-016-0696-2.
Background: Aconiti brachypodi Radix (Xue-shang-yi-zhi-hao) has been prescribed to manage chronic pain, arthritis, and traumatic injuries. Bullatine A, a C20-diterpenoid alkaloid, is one of its principle effective compounds. This study aimed to investigate the anti-hypersensitivity of Bullatine A in a variety of rat pain models and explore its mechanisms of action. Methods: Rat neuropathic pain, inflammatory pain, diabetic neuropathic pain, and bone cancer pain models were used. Dynorphin A and pro-inflammatory cytokines were measured in the spinal cord and cultured primary microglia. Double immunofluorescence staining of dynorphin A and glial and neuronal cellular markers was also measured in the spinal cord. Results: Subcutaneous and intrathecal injection of Bullatine A dose-dependently attenuated spinal nerve ligation-, complete Freud's adjuvant-, diabetes-, and bone cancer-induced mechanical allodynia and thermal hyperalgesia, with the efficacies of 45-70 % inhibition, and half-effective doses of 0.9-1.9 mg/kg for subcutaneous injection. However, Bullatine A was not effective in blocking acute nociceptive response in the normal condition. Bullatine A specifically stimulated dynorphin A expression in microglia in the spinal cord in vivo and cultured primary microglia in vitro; the stimulatory effects were completely inhibited by the microglial inhibitor minocycline. In contrast, Bullatine A did not have an inhibitory effect on peripheral nerve injury- or lipopolysaccharide-induced pro-inflammatory cytokine expression. The spinal anti-allodynic effects of Bullatine A were entirely blocked by intrathecal injection of minocycline, the specific dynorphin A antiserum, and the selective k-opioid receptor antagonist. Conclusions: We, for the first time, demonstrate that Bullatine A specifically attenuates pain hypersensitivity, regardless of the pain models employed. The results also suggest that stimulation of spinal microglial dynorphin A expression mediates Bullatine A anti-nociception in pain hypersensitivity conditions.
Bullatine A has an antidepressant effect in chronic social defeat stress mice; Implication of microglial inflammasome
Brain Res Bull 2023 Apr;195:130-140.PMID:36828203DOI:10.1016/j.brainresbull.2023.02.015.
Inflammatory microglia and P2X7R are involved in the development of stress-induced depression. Endoplasmic reticulum (ER) stress and mitochondrial damage play an important role in depression and microglial activation. Bullatine A (BLA) has anti-inflammatory and anti-rheumatic effects, and can be used as a P2X7R antagonist. We found that Bullatine A can effectively inhibit the calcium overload of mitochondria and the increase of ER and mitochondrial colocalization caused by eATP (extracellular ATP) in BV2-cells. Bullatine A can also inhibit the activation of PERK-elF-2α unfolded protein response (UPR), lysosome production and the increase of NLRP3 inflammasome protein expression in BV2-cells Both intragastric administration and intra-hippocampal microinjection of Bullatine A can significantly improve the despair behavior but not anhedonia of Chronic chronic social defeat stress (CSDS) mice. Bullatine A may have a beneficial therapeutic effect in treating diseases related to stress stimulation, such as depression.
Concurrent Bullatine A enhances morphine antinociception and inhibits morphine antinociceptive tolerance by indirect activation of spinal κ-opioid receptors
J Ethnopharmacol 2017 Jan 20;196:151-159.PMID:27989510DOI:10.1016/j.jep.2016.12.027.
Ethnopharmacological relevance: Bullatine A, a C20-diterpenoid alkaloid and one of the major effective ingredients in Aconiti brachypodi Radix (Xue-shang-yi-zhi-hao), can block pain hypersensitivity in a variety of rodent models through expression of spinal microglial dynorphin A. Aim of the study: To assess the interaction between Bullatine A and morphine on antinociception in acute nociception and pain hypersensitivity states, with the exogenous synthetic dynorphin A as a comparison MATERIALS AND METHODS: Spinal nerve ligation-induced neuropathic rats and naïve mice were used for assessing the acute and chronic interactions of Bullatine A/dynorphin A with morphine. Results: Single subcutaneous injection of Bullatine A or dynorphin A(1-17) did not either alter formalin- and thermally (hot-plate and water immersion tests)-induced acute nociception or potentiate morphine antinociception in naïve mice. In contrast, Bullatine A dose-dependently inhibited formalin-induced tonic pain with the efficacy of 54% inhibition and the half-effective dose of 0.9mg/kg. Concurrent Bullatine A additively enhanced morphine antinociception. In neuropathic rats, the antinociceptive effects of multiple bidaily intrathecal injections of Bullatine A and dynorphin A remained consistent over 13 days, whereas morphine produced progressive and complete tolerance to antinociception, which was completely inhibited by concurrent Bullatine A and dynorphin A. A single intrathecal injection of Bullatine A and dynorphin A immediately reversed established morphine tolerance in neuropathic rats, although the blockade was a less degree in the thermally induced mouse acute nociceptive tests. The inhibitory effects of Bullatine A and dynorphin A on morphine tolerance were immediately and completely attenuated by intrathecal dynorphin A antibody and/or selective κ-opioid receptor antagonist GNTI. Conclusion: These results suggest that Bullatine A produces antinociception without induction of tolerance and inhibits morphine antinociceptive tolerance, and provide pharmacological basis for concurrent Bullatine A and morphine treatment for chronic pain and morphine analgesic tolerance.
Bullatine A, a diterpenoid alkaloid of the genus Aconitum, could attenuate ATP-induced BV-2 microglia death/apoptosis via P2X receptor pathways
Brain Res Bull 2013 Aug;97:81-5.PMID:23769848DOI:10.1016/j.brainresbull.2013.05.015.
Bullatine A (BLA), a diterpenoid alkaloid of the genus Aconitum, possesses anti-rheumatic, anti-inflammatory and anti-nociceptive effects. The mechanism underlying the effects was examined in the present study. The effect of BLA on extracellular ATP induced cell death/apoptosis and pro-inflammatory cytokines release were investigated using BV-2 microglia cell line. The mediation/efficacy of inflammatory cytokines and P2X receptors was evaluated by detecting the mRNA levels of iNOS, IL-6, IL-1β and P2X receptors, respectively. The results demonstrated that BV-2 cells could be damaged after incubation with higher dose of ATP, leading to activation of pro-inflammatory cytokines, transcriptional activation of iNOS and overproduction of NO via activation of P2X receptor. The BLA (1-50μM) potently inhibits ATP-induced BV-2 cell death/apoptosis and P2X receptor-mediated inflammatory responses via selectively suppressing the up-regulation of P2X7 receptor mRNA. Since P2X7 receptors have an important role in immune and pain response, inflammation and inflammatory disease, this discovery of BLA as a potent P2X7 antagonist indicated that BLA may be a potential useful candidate for the treatment of neurodegenerative diseases such as arthritis.