Conophylline
(Synonyms: 长春花碱) 目录号 : GC63379
Conophylline 是一种从热带植物 Ervatamia microphylla 中提取的长春花生物碱。Conophylline 是胰腺细胞分化的诱导剂。Conophylline 能抑制 HSC，诱导其凋亡。
Cas No.:142741-24-0
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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- Datasheet
Conophylline is a vinca alkaloid extracted from leaves of a tropical plant Ervatamia microphylla. Conophylline is a differentiation inducer of for pancreatic cells. Conophylline suppresses HSC and induces apoptosis[1][2].
Conophylline (100 ng/ml; 48 hours) reproduces differentiationinducing activity but not apoptosis-inducing activity of activin[1].Conophylline (100 ng/ml; 72 hours) exhibits the differentiation-inducing activity in AR42J cells and converts these cells to endocrine cells[1].Conophylline increases the expression of neurogenin-3 by activating p38 mitogen-activated protein kinase to induce differentiation of AR42J cells[1].Conophylline reduces the expression of α-SMA and collagen-1 in rat HSC and Lx-2 cells[2].Conophylline inhibits DNA synthesis induced by serum[2].Conophylline also promots activation of caspase-3 and induces apoptosis in Lx-2 Cells[2].
Conophylline (0.9 mg/kg; p.o.; daily; for 12 weeks) attenuates formation of the liver fibrosis induced by TAA in vivo[2].
[1]. Kojima I, et al. Conophylline: a novel differentiation inducer for pancreatic beta cells. Int J Biochem Cell Biol. 2006;38(5-6):923-30.
[2]. Kubo N, et al. Conophylline suppresses hepatic stellate cells and attenuates thioacetamide-induced liver fibrosis in rats. Liver Int. 2014 Aug;34(7):1057-67.
| Cas No. | 142741-24-0 | SDF | |
| 别名 | 长春花碱 | ||
| 分子式 | C44H50N4O10 | 分子量 | 794.89 |
| 溶解度 | 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 | 1.258 mL | 6.2902 mL | 12.5804 mL |
| 5 mM | 0.2516 mL | 1.258 mL | 2.5161 mL |
| 10 mM | 0.1258 mL | 0.629 mL | 1.258 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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DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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Conophylline Suppresses Angiotensin II-Induced Myocardial Fibrosis In Vitro via the BMP4/JNK Pathway
Bull Exp Biol Med 2021 Jul;171(3):305-311.PMID:34302205DOI:10.1007/s10517-021-05217-0.
We studied the effects and mechanisms of action of Conophylline in different concentrations in the original in vitro model of myocardial fibrosis (treatment of cardiac fibroblasts isolated form the hearts of newborn rats with angiotensin II). Viability, collagen content, and expression of related protein in cardiac fibroblasts were assessed using the MTT-test, Sircol assay, and Western blotting, respectively. Conophylline markedly protected the cultured cells against the development of angiotensin II-induced fibrosis, which was seen from reduced viability of fibroblasts, decreased collagen content, and down-regulation of the expression of α-smooth muscle actin (α-SMA). Conophylline did not affect the TGF-β pathway altered by angiotensin II, but markedly decreased the level of bone morphogenetic protein-4 (BMP4) enhanced by angiotensin II and BMP4 itself. Conophylline produced no effect on phosphorylation of α-SMA and Smad homologue-1/5/8, the classic BMP4 downstream pathway elements, but reduced the level of c-Jun N-terminal kinase (JNK) elevated by BMP4. Conophylline did not inhibit the development of myocardial fibrosis in the presence of JNK activator anisomycin. Thus, Conophylline inhibited angiotensin II-provoked myocardial fibrosis via the BMP4/JNK pathway.
Therapeutic activity of plant-derived alkaloid Conophylline on metabolic syndrome and neurodegenerative disease models
Hum Cell 2018 Apr;31(2):95-101.PMID:29249016DOI:10.1007/s13577-017-0196-4.
Increasing metabolic syndromes including type-2 diabetes mellitus, obesity, and steatohepatitis are serious problems in most countries in the world. Neurodegenerative diseases such as Alzheimer, Parkinson's, and Huntington's diseases are increasing in many countries. However, therapy for these diseases is not sufficient yet. Thus, effective chemotherapy for these diseases is being expected. Conophylline is an alkaloid isolated from the leaves of Ervatamia microphylla and related plants. It was found to induce beta-cell differentiation in the precursor pancreatic cells. Oral administration of this compound ameliorated type-2 diabetes mellitus model in mice and rats. Later, fibrosis of the pancreatic islets was found to be greatly reduced by Conophylline in the pancreatic islets. It also inhibited chemically induced liver cirrhosis. Further study indicated that Conophylline inhibited non-alcoholic steatohepatitis in the model mice. On the one hand, loss of autophagy often causes protein aggregation to give neural cell death. Conophylline was found to activate autophagy in cultured neural cells. Activation of autophagy ameliorated cellular models of Parkinson's and Huntington's diseases. Thus, Conophylline is likely to be useful for the development of chemotherapy for metabolic and neurodegenerative diseases.
Conophylline: a novel differentiation inducer for pancreatic beta cells
Int J Biochem Cell Biol 2006;38(5-6):923-30.PMID:16337165DOI:10.1016/j.biocel.2005.09.019.
Reduction of the beta cell mass is critical in the pathogenesis of diabetes mellitus. The discovery of agents, which induce differentiation of pancreatic progenitors to beta cells, would be useful to develop a new therapeutic approach to treat diabetes. To identify a new agent to stimulate differentiation of pancreatic progenitor cells to beta cells, we screened various compounds using pancreatic AR42J cells, a model of pancreatic progenitor cells. Among various compounds and extracts tested, we found that Conophylline, a vinca alkaloid extracted from leaves of a tropical plant Ervatamia microphylla, was effective in converting AR42J into endocrine cells. Conophylline reproduces the differentiation-inducing activity of activin A. Unlike activin A, however, Conophylline does not induce apoptosis. To induce differentiation of AR42J cells, Conophylline increases the expression of neurogenin-3 by activating p38 mitogen-activated protein kinase. Conophylline also induces differentiation in cultured pancreatic progenitor cells obtained from fetal and neonatal rats. More importantly, Conophylline is effective in reversing hyperglycemia in neonatal streptozotocin-treated rats, and both the insulin content and the beta cell mass are increased by Conophylline. Histologically, Conophylline increases the numbers of ductal cells positive for pancreatic-duodenal-homeobox protein-1 and islet-like cell clusters. Conophylline and related compounds are useful in inducing differentiation of pancreatic beta cells both in vivo and in vitro.
The plant alkaloid Conophylline inhibits matrix formation of fibroblasts
J Biol Chem 2018 Dec 28;293(52):20214-20226.PMID:30377255DOI:10.1074/jbc.RA118.005783.
Conophylline is a Vinca alkaloid from leaves of the tropical plant Ervatamia microphylla and has been shown to mimic the effect of the growth and differentiation factor activin A on pancreatic progenitor cells. However, activin A stimulates fibrosis of pancreatic stellate cells, whereas Conophylline inhibits it, suggesting that this compound may serve as an antifibrotic drug. Here we investigated the effects of Conophylline on human foreskin fibroblasts, especially focusing on extracellular matrix (ECM) proteins. A gene microarray analysis revealed that Conophylline remarkably suppressed expression of the gene for hyaluronan synthase 2 (HAS2) and of its antisense RNA, whereas the expression of collagen genes was unaffected. Of note, immunostaining experiments revealed that Conophylline substantially inhibits incorporation of versican and collagens into the ECM in cells treated with transforming growth factor β (TGFβ), which promotes collagen synthesis, but not in cells not treated with TGFβ. Moreover, a protein biosynthesis assay disclosed that Conophylline decreases collagen biosynthesis, concomitant with a decrease in total protein biosynthesis, indicating that conophylline-mediated inhibition of fibrosis is not specific to collagen synthesis. Conophylline affected neither TGFβ-induced nuclear translocation of SMAD family member 2/3 (SMAD2/3) nor phosphorylation of SMAD2. However, Conophylline substantially inhibited phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), suggesting that Conophylline inhibits HAS2 expression via TGFβ-mediated activation of the ERK1/2 pathway. Taken together, our results indicate that Conophylline may be a useful inhibitor of ECM formation in fibrosis.
Direct and Indirect Anticancer Activity of Plant-Derived Alkaloid Conophylline
Crit Rev Oncog 2021;26(2):67-72.PMID:34347973DOI:10.1615/CritRevOncog.2020034129.
K-Ras is one of the most important oncogenes in human oncogenesis. K-Ras transfection of normal rat fibroblasts induces phenotypic change from flat to round morphology. Then, we screened compounds inducing flat morphology in K-Ras transformed fibroblasts from microbial culture filtrates and plant extracts. As a result, the alkaloid Conophylline was isolated from the leaves of Ervatamia microphylla collected in Thailand. Conophylline induced flat morphology and inhibited cellular invasion in K-Ras-transformed normal rat kidney (K-Ras-NRK) cells. It also inhibited the growth of the K-Ras-NRK tumor in mice. Cancer-associated fibroblasts are now considered to activate cancer growth. Conophylline was found to suppress secretions of various inflammatory cytokines by pancreatic cancer-associated fibroblasts. Moreover, when combined with gemcitabine, it inhibited the growth of pancreatic cancer growth in mice. Conophylline is orally active. Thus, the plant-derived alkaloid Conophylline inhibited cancer growth directly and indirectly, and it shows promise as a new anticancer agent.