Demethyleneberberine
(Synonyms: 去亚甲基小檗碱) 目录号 : GC38101
Demethyleneberberine (DMB), as a natural active component of medicinal plant Cortex phellodendri chinensis, has favorable bioactivity.
Cas No.:25459-91-0
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
| Cell experiment [1]: | |
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Cell lines |
RAW264.7 |
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Preparation Method |
DMB (Demethyleneberberine)(10, 20, 40 µM) and N-acetyl cysteine (NAC, 5 mM) were co-cultured with RAW264.7 for 2 h prior to lipopolysaccharide (LPS) stimulation, and splenocytes from the mice were cultured ex vivo for 48 h for immune response test. |
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Reaction Conditions |
10, 20, 40 µM; 2h |
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Applications |
In vitro, ROS production and pro-inflammation cytokines were markedly inhibited by DMB in RAW264.7 cell. |
| Animal experiment [2]: | |
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Animal models |
Male ICR mice (24-26 g) |
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Preparation Method |
Mice were injected with TAA (250 mg/kg, IP) to induce fulminant hepatic failure. DMB (10 mg/kg, IP) and BBR (10 mg/kg, IP) were administered to mice for five days after TAA challenge. |
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Dosage form |
10 mg/kg, i.p. |
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Applications |
All mice in the model group showed activity reduction; 50% mice in BBR(Berberine)-treated group and 20% mice in DMB(Demethyleneberberine)-treated group showed activity reduction. All animals died from fulminant hepatic failure during the four days after TAA(thioacetamide) injection. These data show that DMB is able to improve the survival rate of mice with TAA-induced fulminant hepatic failure as compared to BBR. |
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References: [1] Chen YY, et al. Demethyleneberberine alleviates inflammatory bowel disease in mice through regulating NF-κB signaling and T-helper cell homeostasis. Inflamm Res. 2017 Feb;66(2):187-196. | |
Demethyleneberberine (DMB), as a natural active component of medicinal plant Cortex phellodendri chinensis, has favorable bioactivity[1]. Demethyleneberberine also, as a natural mitochondria-targeted antioxidant, can inhibit oxidative stress, mitochondrial dysfunction, and steatosis in an alcoholic hepatic disease model[2].
In vitro experiment it shown that with 0, 10, 20, 40, 80, and 160 μmol/L DMB (Demethyleneberberine) obviously inhibit proliferation of HSCs in a concentration dependent manner. The IC50 of DMB(Demethyleneberberine) for HSC-T6 cells at 48 h was 36.7 μmol/L[3]. In vitro, Demethyleneberberine has the inhibition of monoamine oxidase B (MAO-B) with IC50 of 9.06 μM[4].
In vivo efficacy test it demonstrated that mice were administrated 50 mg/kg/d orally Demethyleneberberine for 98 days markedly improved colon atrophy, colonic tissue mass score, neutrophil infiltration and histological damage, which was mainly attributed to the anti-inflammatory effect of Demethyleneberberine[5]. In vivo, methionine and choline deficient (MCD) high-fat diet feeding mice and db/db mice were injected with 20 or 40 mg/kg intraperitoneally can reduce hepatic lipid accumulation. In addition, DMB treatmentthe can obviously attenuate oxidative damage and inflammation induced by NAFLD(Non-alcoholic fatty liver disease)[6]. In vivo, inflammatory colitis mice were administrated with 150 and 300 mg/kg orally Demethyleneberberine caused the reduction of weight loss and myeloperoxidase (MPO) activity, while significantly decrease the production of pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), and inhibited the activation of NF-κB signaling pathway[7].
References:
[1] Liu J, et al. Demethyleneberberine induces cell cycle arrest and cellular senescence of NSCLC cells via c-Myc/HIF-1α pathway. Phytomedicine. 2021 Oct;91:153678.
[2] Zhang P., et al. Demethyleneberberine, a natural mitochondria-targeted antioxidant, inhibits mitochondrial dysfunction, oxidative stress, and steatosis in alcoholic liver disease mouse model. J. Pharmacol. Exp. Ther. 2015;352:139–147.
[3] Wang Y, et al. Demethyleneberberine Protects against Hepatic Fibrosis in Mice by Modulating NF-κB Signaling. Int J Mol Sci. 2016 Jun 30;17(7):1036.
[4] Tao C, et al. Highly efficient synthesis and monoamine oxidase B inhibitory profile of demethyleneberberine, columbamine and palmatine. Neurochem Int. 2020 Oct;139:104807.
[5] Zhao Y, et al. Demethyleneberberine blocked the maturation of IL-1β in inflammation by inhibiting TLR4-mitochondria signaling. Int Immunopharmacol. 2022 Dec;113(Pt A):109319.
[6] Qiang X, et al. Demethyleneberberine attenuates non-alcoholic fatty liver disease with activation of AMPK and inhibition of oxidative stress. Biochem Biophys Res Commun. 2016 Apr 15;472(4):603-9.
[7] Chen YY, et al. Demethyleneberberine alleviates inflammatory bowel disease in mice through regulating NF-κB signaling and T-helper cell homeostasis. Inflamm Res. 2017 Feb;66(2):187-196.
去亚甲基小檗碱(DMB)作为药用植物黄柏的天然活性成分，具有良好的生物活性[1]。去亚甲基小檗碱作为一种天然的靶向线粒体的抗氧化剂，还可以抑制酒精性肝病模型中的氧化应激、线粒体功能障碍和脂肪变性[2]。
体外实验表明，0、10、20、40、80、160 μmol/L DMB（Demethyleneberberine）浓度依赖性明显抑制HSCs增殖。 DMB(Demethyleneberberine)对HSC-T6细胞48 h的IC50为36.7 μmol/L[3]。在体外，Demethyleneberberine 对单胺氧化酶 B (MAO-B) 具有抑制作用，IC50 为 9.06 μM[4]。
体内药效试验表明，小鼠口服去亚甲基小檗碱50 mg/kg/d，持续98天，显着改善结肠萎缩、结肠组织质量评分、中性粒细胞浸润和组织学损伤，这主要归因于抗炎作用去亚甲基小檗碱[5]。在体内，蛋氨酸和胆碱缺乏症 (MCD) 高脂肪饮食喂养小鼠和 db/db 小鼠腹腔注射 20 或 40 mg/kg 可减少肝脏脂质积累。此外，DMB治疗可明显减轻NAFLD（非酒精性脂肪性肝病）引起的氧化损伤和炎症[6]。在体内，给炎性结肠炎小鼠口服 150 和 300 mg/kg 的去亚甲基小檗碱，导致体重减轻和髓过氧化物酶 (MPO) 活性降低，同时显着降低促炎细胞因子的产生，例如白细胞介素 (IL)-6 和肿瘤坏死因子-α（TNF-α），抑制NF-κB信号通路的激活[7]。
| Cas No. | 25459-91-0 | SDF | |
| 别名 | 去亚甲基小檗碱 | ||
| Canonical SMILES | COC1=C(OC)C2=C[N+]3=C(C4=CC(O)=C(O)C=C4CC3)C=C2C=C1 | ||
| 分子式 | C19H18NO4+ | 分子量 | 324.35 |
| 溶解度 | DMSO: 33.33 mg/mL (102.76 mM) | 储存条件 | 4°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 | 3.0831 mL | 15.4154 mL | 30.8309 mL |
| 5 mM | 0.6166 mL | 3.0831 mL | 6.1662 mL |
| 10 mM | 0.3083 mL | 1.5415 mL | 3.0831 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。
Demethyleneberberine, a potential therapeutic agent in neurodegenerative disorders: a proposed mechanistic insight
Mol Biol Rep 2022 Oct;49(10):10101-10113.PMID:35657450DOI:10.1007/s11033-022-07594-9.
Introduction: Neurodegenerative disorders are a diverse variety of diseases that can be distinguished from developing degeneration of neurons in the CNS. Several alkaloids have shown mounting effects in neurodegenerative disorders, and berberine is one of them. Demethyleneberberine is a metabolite of berberine that has better blood-brain barrier crossing capacity. Demethyleneberberine possesses anti-inflammatory, anti-oxidant, and mitochondrial targeting properties. However, neither the pharmacological action nor the molecular mechanism of action of Demethyleneberberine on neurodegenerative disorders has been explored yet. Materials and methods: A systematic literature review of PubMed, Medline, Bentham, Scopus, and EMBASE (Elseveier) databases was carried out with the help of keywords like "Demethyleneberberine; neuroinflammation; oxidative stress; Neuroprotective; Neurodegenerative disorders" till date. Conclusion: This review focus on the neuroprotective potential of Demethyleneberberine in neurodegenerative disorders by attenuating different pathways, i.e., NF-κB, MAPK, and AMPK signalling.
The metabolism of berberine and its contribution to the pharmacological effects
Drug Metab Rev 2017 May;49(2):139-157.PMID:28290706DOI:10.1080/03602532.2017.1306544.
Berberine, a bioactive alkaloid isolated from several herbal substances, possesses multiple pharmacological effects, including antimicrobial, antidiabetic, anticancer activities. Meanwhile, berberine undergoes extensive metabolism after oral administration which results in its extremely low plasma exposure. Therefore, it is believed that the metabolites of berberine also contribute a lot to its pharmacological effects. Along these lines, this review covers the metabolism studies of berberine in terms of its metabolic pathways and metabolic organs based on the identified metabolites, and it also covers the pharmacological activities of its active metabolites. In brief, the predominant metabolic pathways of berberine are demethylation, demethylenation, reduction, hydroxylation and subsequent conjugation in vivo. Active metabolites such as columbamine, berberrubine and Demethyleneberberine also exhibit similar pharmacological effects by comparison with berberine, such as antioxidant, anti-inflammatory, antitumor, antimicrobial, hepatoprotective, neuroprotective, hypolipidemic and hypoglycemic effects. Overall, berberine together with its metabolites formed the material basis of berberine in vivo.
Demethyleneberberine induces cell cycle arrest and cellular senescence of NSCLC cells via c-Myc/HIF-1α pathway
Phytomedicine 2021 Oct;91:153678.PMID:34385092DOI:10.1016/j.phymed.2021.153678.
Background: Demethyleneberberine (DMB) is a natural active component of medicinal plant Cortex phellodendri chinensis with favorable bioactivity. However, the role of DMB in suppressing non-small cell lung cancer (NSCLC) remains unknown. Purpose: In this study, we aimed to examine the effect and underlying mechanism of DMB in suppressing NSCLC. Methods: CCK8 assay and colony formation assay were utilized to assess the efficiency of DMB on the viability and colony formation capacity of NSCLC cells. Flow cytometry and β-Galactosidase Staining Kit were utilized to determine the efficiency of DMB on the cell cycle and cellular senescence of NSCLC cells. RT-qPCR and Western blot were used to detect the effect of DMB on cell cycle and cellular senescence related gene and protein expression of NSCLC cells. In vivo tumor model was established to evaluate the anti NSCLC effect of DMB. In addition, RNA-seq analysis was performed to detect the differential gene expression after DMB treatments. Results: In this study, we revealed that DMB exhibits efficient inhibitory effect on NSCLC cell proliferation and tumor xenografts growth in vivo. We also demonstrated that DMB could inhibit cell migration by suppressing epithelial-mesenchymal transition (EMT) and trigger cell cycle arrest by down-regulating the expression of cell cycle related genes in NSCLC cells. In addition, DMB treatment efficiently induces cellular senescence of NSCLC cells. From the RNA-seq analysis, we found that DMB accelerates senescence through suppressing HIF-1α expression, which was further elucidated by overexpressing HIF-1α in NSCLC to reduce the inhibitory effect of DMB. Furthermore, we also revealed that DMB decreases the expression of c-Myc, an up-stream protein of HIF-1α. Conclusions: Taken together, we first report that DMB inhibits NSCLC progress through inducing cell cycle arrest and triggering cellular senescence by downregulating c-Myc/HIF-1α pathway.
Demethyleneberberine: A possible treatment for Huntington's disease
Med Hypotheses 2021 Aug;153:110639.PMID:34229236DOI:10.1016/j.mehy.2021.110639.
Huntington disease (HD) is a type of neurodegenerative disease that is characterized by presence of multiple repeats (more than 36) of cytosine-adenine-guanine (CAG) trinucleotides and mutated huntingtin (mHtt). This can further lead to oxidative stress, enhancement in level of ROS/RNS, mitochondrial dysfunction and neuroinflammations. Many clinical and preclinical trials have been conducted so far for the effective treatment of HD however, none of the drugs has shown complete relief. The regeneration of neurons is a very complicated process and associated with multiple pathological pathways. Hence, finding a unique solution using single drug that could act on multiple pathological pathways is really cumbersome. In the proposed hypothesis the use of Demethyleneberberine (DMB) as a potential anti-HD agent has been explained. It is a metabolite of berberine and reported to act on multiple mechanistic pathways that are responsible for HD. Present article highlights new mechanistic insights through which DMB inhibits ROS/RNS, oxidative stress, mitochondrial dysfunctions and neuroinflammation such as NFκB, TNF-α, IL-6 and IL-8, cytokinin. Further its action on cellular apoptosis and neuronal cell death are also reported.
Demethyleneberberine blocked the maturation of IL-1β in inflammation by inhibiting TLR4-mitochondria signaling
Int Immunopharmacol 2022 Dec;113(Pt A):109319.PMID:36252484DOI:10.1016/j.intimp.2022.109319.
Demethyleneberberine (DMB) is a natural product from traditional Chinese medicinal herb the rhizome of Coptis chinensis Franch., which has been reported to possess multiple pharmacological activities, especially anti-inflammation and immunoregulation. However, the potential mechanism of DMB in inflammation is still a mystery. In this study, a mouse model of ulcerative colitis (UC) was induced by Dextran sulfate sodium salt (DSS), and in vitro experiments were performed in RAW264.7 macrophages and the primary intestinal macrophages which obtained from Toll-Like receptor 4 (TLR4) and NOD-Like receptor protein 3 (NLRP3) knockout fetal mouse. Mitochondrial was increased by overexpression of peroxlsome proliferator-activated receptor-γ coactlvator-1α (PGC-1α) and exhausted by adding Ethidium Bromide (EtBr) in RAW264.7 to evaluate the function of mitochondria in the maturation of IL-1β. Additionally, the safety of DMB (50 mg/kg/d) in mice was assessed by orally administrating for 98 days. DMB siginificantly improved colon atrophy, colonic tissue mass score, neutrophil infiltration and histological damage, which was mainly attributed to the anti-inflammatory effect of DMB. Further in vitro analysis showed that DMB blocked the excessive mitochondrial biosynthesis and maintained the homeostasis of mitochondria in inflammatory response. Moreover, the maturation of IL-1β was suppressed by DMB in a mitochondria dependent manner. Crucially, DMB was a candidate agent for UC with free of toxicity and side effects. These findings demonstrated that DMB ameliorated inflammatory response by inhibiting TLR4-mitochondria signaling, and revealed the effectiveness and mechanism of DMB for alleviation of UC and provided an additional strategy for UC intervention.