Phellodendrine
(Synonyms: 黄柏碱) 目录号 : GC38170
An alkaloid with diverse biological activities
Cas No.:6873-13-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Phellodendrine is an alkaloid that has been found in P. amurense and has diverse biological activities.1,2,3 It inhibits acetylcholinesterase (AChE) activity (IC50 = 36.51 ?M) and scavenges ABTS radicals in cell-free assays when used at concentrations ranging from 12.5 to 100 ?M.2 Phellodendrine induces apoptosis in PANC-1 pancreatic cancer cells and reduces tumor growth in a PANC-1 mouse xenograft model.1 It inhibits the local graft versus host (GVH) reaction in irradiated mice receiving splenocyte grafts, indicating immunosuppressant activity, when administered at a dose of 20 mg/kg.3
1.Thu, P.M., Zheng, Z.-G., Zhou, Y.-P., et al.Phellodendrine chloride suppresses proliferation of KRAS mutated pancreatic cancer cells through inhibition of nutrients uptake via macropinocytosisEur. J. Pharmacol.85023-34(2019) 2.Kim, Y.J., Lim, H.-Y., Kim, Y., et al.Phytochemical quantification and the in vitro acetylcholinesterase inhibitory activity of Phellodendron chinense and its componentsMolecules22(6)925(2017) 3.Mori, H., Fuchigami, M., Inoue, N., et al.Principle of the bark of Phellodendron amurense to suppress the cellular immune response: effect of phellodendrine on cellular and humoral immune responsesPlanta Med.61(1)45-49(1995)
| Cas No. | 6873-13-8 | SDF | |
| 别名 | 黄柏碱 | ||
| Canonical SMILES | OC1=C(OC)C=C2CC[N@@+]3(C)CC4=CC(OC)=C(O)C=C4C[C@@]3([H])C2=C1 | ||
| 分子式 | C20H24NO4 | 分子量 | 342.41 |
| 溶解度 | DMSO: 5 mg/mL (14.60 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 | 2.9205 mL | 14.6024 mL | 29.2048 mL |
| 5 mM | 0.5841 mL | 2.9205 mL | 5.841 mL |
| 10 mM | 0.292 mL | 1.4602 mL | 2.9205 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。
Phellodendrine promotes autophagy by regulating the AMPK/mTOR pathway and treats ulcerative colitis
J Cell Mol Med 2021 Jun;25(12):5707-5720.PMID:34002930DOI:10.1111/jcmm.16587.
To investigate the therapeutic effects of Phellodendrine in ulcerative colitis (UC) through the AMPK/mTOR pathway. Volunteers were recruited to observe the therapeutic effects of Compound Cortex Phellodendri Liquid (Huangbai liniment). The main components of Compound Cortex Phellodendri Liquid were analysed via network pharmacology. The target of Phellodendrine was further analysed. Caco-2 cells were cultured, and H2 O2 was used to stimulate in vitro cell model. Expression levels of LC3, AMPK, p-AMPK, mTOR and p-mTOR were detected via Western blotting and through immunofluorescence experiments. The therapeutic effects of Phellodendrine were analysed via expression spectrum chip sequencing. The sequencing of intestinal flora further elucidated the therapeutic effects of Phellodendrine. Compared with the control group, Compound Cortex Phellodendri Liquid could substantially improve the healing of intestinal mucosa. Network pharmacology analysis revealed that Phellodendrine is the main component of Compound Cortex Phellodendri Liquid. Moreover, this alkaloid targets the AMPK signalling pathway. Results of animal experiments showed that Phellodendrine could reduce the intestinal damage of UC compared with the model group. Findings of cell experiments indicated that Phellodendrine treatment could activate the p-AMPK /mTOR signalling pathway, as well as autophagy. Expression spectrum chip sequencing showed that treatment with Phellodendrine could promote mucosal healing and reduce inflammatory responses. Results of intestinal flora detection demonstrated that treatment with Phellodendrine could increase the abundance of flora and the content of beneficial bacteria. Phellodendrine may promote autophagy by regulating the AMPK-mTOR signalling pathway, thereby reducing intestinal injury due to UC.
In vitro inhibitory effects of Phellodendrine on human liver cytochrome P450 enzymes
Xenobiotica 2020 Feb;50(2):231-236.PMID:31020909DOI:10.1080/00498254.2019.1610584.
1. Phellodendrine possesses numerous pharmacological activities. However, whether Phellodendrine affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear.2. In this study, the inhibitory effects of Phellodendrine on eight human liver CYP isoforms (i.e. 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs).3. The results showed that Phellodendrine inhibited the activity of CYP1A2, 3A4 and 2C9, with IC50 values of 20.56, 14.98 and 16.30 μM, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that Phellodendrine was not only a non-competitive inhibitor of CYP3A4, but also a competitive inhibitor of CYP1A2 and 2C9, with Ki values of 7.15, 10.52 and 7.98 μM, respectively. In addition, Phellodendrine is a time-dependent inhibitor for CYP3A4 with Kinact/KI value of 0.046/11.57 μM-1 min-1.4. The in vitro studies of Phellodendrine with CYP isoforms indicate that Phellodendrine could inhibit the activities of CYP1A2, 3A4 and 2C9. Further clinical studies are needed to evaluate the significance of this interaction.
Utilizing network pharmacology and experimental validation to investigate the underlying mechanism of Phellodendrine on inflammation
PeerJ 2022 Sep 23;10:e13852.PMID:36172495DOI:10.7717/peerj.13852.
Background: Phellodendrine, one of the characteristic and important active components of Cortex phellodendri, has been proven to show anti-inflammatory effects. However, the underlying mechanism of Phellodendrine on inflammation remains largely unclear. Aim of the study: In this study, network pharmacology and experimental validation were used to explore the underlying mechanism of Phellodendrine on inflammation. Materials and methods: PubChem and SwissADME database were used to evaluate the drug-likeness and other characteristics of Phellodendrine. The targets of Phellodendrine for the treatment of inflammation were analyzed with multiple databases. Other extensive analyses including protein-protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were accomplished with the STRING database, Cytoscape software, and DAVID database. Moreover, the effect of Phellodendrine on anti-inflammation was proven in RAW264.7. Results: The network pharmacology results indicated that Phellodendrine had drug potential. Phellodendrine acted directly on 12 targets, including PTGS1, PTGS2, HTR1A, and PIK3CA, and then regulated cAMP, estrogen, TNF, serotonergic synapse, and other signaling pathways to exert anti-inflammatory effects. The experimental results showed that Phellodendrine reduced the levels of IL-6 compared with the LPS group in 24 h and changed the mRNA expression of PTGS1, PTGS2, HSP90ab1, AKT1, HTR1A, PI3CA, and F10. Conclusion: Our research preliminarily uncovered the therapeutic mechanisms of Phellodendrine on inflammation with multiple targets and pathways. Phellodendrine may be a potential treatment for inflammation-related diseases related to the cAMP and TNF signaling pathways.
Characterization of metabolic fate of Phellodendrine and its potential pharmacological mechanism against diabetes mellitus by ultra-high-performance liquid chromatography-coupled time-of-flight mass spectrometry and network pharmacology
Rapid Commun Mass Spectrom 2021 Sep 30;35(18):e9157.PMID:34182613DOI:10.1002/rcm.9157.
Rationale: Characterizing the functional mechanism of quality control marker (Q-marker) was of great importance in revealing the primary pharmacological mechanism of herbs or the other complex system, and drug-related metabolites always contribute to the pharmacological functions. Cortex Phellodendri was used as a core herb in the treatment of diabetes mellitus (DM). As a Q-marker of Cortex Phellodendri, the role of Phellodendrine in DM was still unclear. Thus, the characterization of phellodendrine-related metabolites in vivo and the subsequent induced functional mechanism exerted great importance in elucidating the anti-DM mechanism of Cortex Phellodendri. Methods: An ultra-high-performance liquid chromatography-coupled time-of-flight mass spectrometry (UHPLC/Q-TOF MS) method was developed to profile metabolites of Phellodendrine in rats. The potential pharmacological mechanism against DM was predicted by network pharmacology. Results: A total of 19 phellodendrine-related metabolites were screened out in rats for the first time. Among them, M4, M5, M9, and M12 were regarded as the primary metabolites. Meanwhile, phase I metabolic reactions of hydroxylation, demethylation, and isomerization and phase II reactions of glucuronidation and sulfation occurred to Phellodendrine; glucuronidation and hydroxylation were the two main metabolic reactions. Moreover, the potential targets of Phellodendrine and three main metabolites (M4, M5, and M12) were predicted by a network pharmacological method, and they mainly shared 52 targets, including PDE5A, CHRNA3, SIGMAR1, F3, ESR1, DRD1, DRD2, DRD3, and DRD4. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that calcium signaling pathway, cGMP-PKG signaling pathway, and cAMP signaling pathway were regarded as the core mechanism of Phellodendrine to treat DM. Conclusion: The metabolic feature of Phellodendrine in vivo was revealed for the first time, and its anti-DM mechanism information for further pharmacological validations was also supplied. It also gave a direction to further elucidation of pharmacological mechanism of Cortex Phellodendri in treating DM.
Phellodendrine chloride suppresses proliferation of KRAS mutated pancreatic cancer cells through inhibition of nutrients uptake via macropinocytosis
Eur J Pharmacol 2019 May 5;850:23-34.PMID:30716311DOI:10.1016/j.ejphar.2019.01.060.
Despite the massive efforts to develop the treatment of pancreatic cancers, no effective application exhibits satisfactory clinical outcome. Macropinocytosis plays a critical role for continuous proliferation of pancreatic ductal adenocarcinoma (PDAC). In this study, we generated a screening method and identified Phellodendrine chloride (PC) as a potential macropinocytosis inhibitor. PC significantly inhibited the viability of KRAS mutant pancreatic cancer cells (PANC-1 and MiaPaCa-2) in a dose-dependent manner; however, it did not affect the wild type KRAS pancreatic cancer cells (BxPC-3). Further experiments indicated that PC reduced the growth of PANC-1 cells through inhibition of macropinocytosis and diminishing the intracellular glutamine level. Disruption of glutamine metabolism led to enhance the reactive oxygen species level and induce mitochondrial membrane potential depolarization in PANC-1 cells. PC treatment caused increased Bax and decreased Bcl-2 expression, along with the activation of cleaved caspase-3, 7, 9 and cleaved-PARP, thus induced mitochondrial apoptosis. Moreover, PC inhibited macropinocytosis in vivo and effectively reduced the growth of PANC-1 xenograft tumors. All together, we demonstrated that inhibition of macropinocytosis might be an effective strategy to treat pancreatic cancers. Thus, PC could be a potential compound with improved therapeutic efficacy in patients with pancreatic cancers.