Palmatine hydroxide
目录号 : GC68133Palmatine hydroxide 是一种具有口服活性的、不可逆的 IDO-1 抑制剂，对 HEK 293-hIDO-1 和 rhIDO-1 的 IC50 分别为 3 μM 和 157 μM。Palmatine hydroxide 也能非竞争性抑制西尼罗病毒 (WNV) NS2B-NS3 蛋白酶，IC50 为 96 μM。Palmatine hydroxide 具有抗癌、抗炎、神经保护、抗细菌、抗病毒活性。
Cas No.:131-04-4
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
Palmatine hydroxide is an orally active and irreversible indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor with IC50s of 3 μM and 157μM against HEK 293-hIDO-1 and rhIDO-1, respectively. Palmatine hydroxide can also inhibit West Nile virus (WNV) NS2B-NS3 protease in an uncompetitive manner with an IC50 of 96 μM. Palmatine hydroxide shows anti-cancer, anti-oxidation, anti-inflammatory, neuroprotection, antibacterial, anti-viral activities[1][2][3][4][5].
Palmatine (0-100 μM; 42 h) suppresses WNV with an EC50 value of 3.6 μM, and reduce the viral titers of DENV-2 and YFV with EC50 values of 26.4 μM and 7.3 μM, respectively[3].
Palmatine (0-1128 μM; 24-72 h) inhibits colon cancer cell proliferation[5].
Palmatine (0-704 μM; 24 h) reduces AURKA protein levels, induces G2/M phase arrest, and induces apoptosis in colon cancer cells via the mitochondrial associated pathway[5].
Cell Proliferation Assay[5]
| Cell Line: | HCT-116, SW480, HT-29 |
| Concentration: | 0, 88, 176, 352, and 704 μM (HCT-116, SW480); 0, 141, 282, 564, and 1128 μM (HT-29) |
| Incubation Time: | 24, 48 and 72 h |
| Result: | Decreased cell viability in a dose-dependent manner. |
Western Blot Analysis[5]
| Cell Line: | HCT-116, SW480, HT-29 |
| Concentration: | 100 nM for HCT-116, 500 nM for SW480 and HT-29 |
| Incubation Time: | 24, 48 and 72 h |
| Result: | Promoted the expression of apoptosis markers such as P53 / P73, Caspase3, and Caspase9. Reduced AURKA protein levels. Increased cyt. c in the cytoplasm while reduced Bcl2 and Bcl-xl in a dose-dependent manner. |
Cell Cycle Analysis[5]
| Cell Line: | HCT-116, SW480 |
| Concentration: | 88, 176, 352 and 704 μM |
| Incubation Time: | 24, 48 and 72 h |
| Result: | Induced G2/M phase arrest in a dose-dependent manner. |
Apoptosis Analysis[5]
| Cell Line: | HCT-116, SW480 |
| Concentration: | 88, 176, 352 and 704 μM |
| Incubation Time: | 24, 48 and 72 h |
| Result: | Induced apoptosis in a dose-dependent manner. |
Palmatine (50 or 100 mg/kg; p.o.; daily for 7 days) ameliorates DSS (dextran sulfate sodium)-induced colitis and prevents infiltration of inflammatory cells[1].
Palmatine (0-200 mg/kg; i.p.; once) attenuates D-galactosamine/Lipopolysaccharides -induced fulminant hepatic failure in mice[2].
Palmatine (0-1 mg/kg; i.p.; 10 days) shows memory-enhancing activity in mice[4].
Palmatine (33.75-135 mg/kg; p.o.; daily for 26 days) can effectively inhibit the growth of HCT-116 xenografts in mice[5].
| Animal Model: | DSS- induced Colitis BALB/c mice model (8-week-old)[1] |
| Dosage: | 50 or 100 mg/kg |
| Administration: | Orally, daily, for 7 days |
| Result: | Ameliorated DSS-induced colitis and prevented infiltration of inflammatory cells; remarkably extended the colon length; significantly suppressed the colonic MPO activity. Decreased the levels of colonic inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10); Protected mucosal integrity by modulating TJs protein and apoptosis proteins; Restored DSS-induced decreases of TJ protein ZO-1, ZO-2 and claudin-1; Reduced Bax expression and enhanced Bcl-2 expression at the dose of 100 mg/kg, prevented epithelial apoptosis and improved intestinal integrity. Prevented DSS-induced changes of gut microbiota in colitis mice. |
| Animal Model: | Male ICR mice (20-22 g), D-galactosamine/lipopolysaccharide (GalN/LPS)-induced fulminant hepatic failure model[2] |
| Dosage: | 25, 50, 100, or 200 mg/kg |
| Administration: | Intraperitoneal injection, 1 h before the GalN/LPS treatment |
| Result: | Attenuated the mortality and serum aminotransferase activities increased by GalN/LPS. Prevented the increase of serum TNF-α and augmented that of serum IL-10. Decreased the TNF-a mRNA expression and increased the IL-10 mRNA expression. Attenuated the apoptosis of hepatocytes. |
| Animal Model: | Swiss young male albino mice, with Scopolamine - and diazepam-induced amnesia model[4] |
| Dosage: | 0.1, 0.5, 1 mg/kg |
| Administration: | Intraperitoneal injection, 10 days |
| Result: | Significantly improved learning and memory of mice at 0.5 and 1 mg/kg and did not show any significant effect on locomotor activity of the mice. Significantly reversed scopolamine- and diazepam-induced amnesia in mice. Significantly reduced brain acetylcholinesterase activity of mice. |
| Animal Model: | BALB/c-nude mice, HCT-116 xenograft model[5] |
| Dosage: | 33.75, 67.5 and 135 mg/kg |
| Administration: | Oral administration, once a day for 26 days |
| Result: | The tumor volume and weight of the treatment group were significantly reduced. |
[1]. Zhang XJ, et al. Palmatine ameliorated murine colitis by suppressing tryptophan metabolism and regulating gut microbiota.Pharmacol Res. 2018 Nov;137:34-46.
[2]. Lee WC, et al. Palmatine attenuates D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure in mice. Food Chem Toxicol. 2010 Jan;48(1):222-8.
[3]. Jia F, et al. Identification of palmatine as an inhibitor of West Nile virus. Arch Virol. 2010 Aug;155(8):1325-9.
[4]. Dhingra D, et al. Memory-enhancing activity of palmatine in mice using elevated plus maze and morris water maze. Adv Pharmacol Sci. 2012;2012:357368.
[5]. Liu X, et al. Palmatine induces G2/M phase arrest and mitochondrial-associated pathway apoptosis in colon cancer cells by targeting AURKA. Biochem Pharmacol. 2020 May;175:113933.
[6]. Long J, et al. Palmatine: A review of its pharmacology, toxicity and pharmacokinetics. Biochimie. 2019 Jul;162:176-184.
| Cas No. | 131-04-4 | SDF | Download SDF |
| 分子式 | C21H23NO5 | 分子量 | 369.41 |
| 溶解度 | DMSO : 15.62 mg/mL (42.28 mM; ultrasonic and warming and heat to 60°C) | 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 | 2.707 mL | 13.5351 mL | 27.0702 mL |
| 5 mM | 0.5414 mL | 2.707 mL | 5.414 mL |
| 10 mM | 0.2707 mL | 1.3535 mL | 2.707 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，
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1. 首先保证母液是澄清的；
2.
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Palmatine: A review of its pharmacology, toxicity and pharmacokinetics
Biochimie 2019 Jul;162:176-184.PMID:31051209DOI:10.1016/j.biochi.2019.04.008.
Palmatine is a natural isoquinoline alkaloid and has been widely used in pharmaceutical field. The purpose of this review is to provide the latest and comprehensive information on the pharmacology, toxicity and pharmacokinetics of Palmatine in the past, to explore the therapeutic potential of this compound and look for ways to reduce toxicity. Information on Palmatine was collected from the internet database PubMed, Elsevier, ResearchGate, Web of Science, Wiley Online Library and Europe PMC using a combination of keywords including "pharmacology", "toxicology", "pharmacokinetics". All studies of this genus were included in this review until March 2019. Palmatine has a wide spectrum of pharmacological effects, including anti-cancer, anti-oxidation, anti-inflammatory, neuroprotection, anti-bacterial, anti-viral and regulating blood lipids. However, Palmatine has obvious DNA toxicity, and has a complex effect on metabolic enzymes in the liver. Pharmacokinetic studies have demonstrated that glucuronidation and sulfation are the main metabolic pathways of Palmatine. Palmatine can be used in many diseases. Future research directions include: how the concentration of Palmatine affects pharmacological effects and toxicity; the mechanism of synergy between Palmatine and other protoberberine alkaloid; Structural modification of Palmatine is one of the key methods to enhance pharmacological activity and reduce activity.
Palmatine attenuated dextran sulfate sodium (DSS)-induced colitis via promoting mitophagy-mediated NLRP3 inflammasome inactivation
Mol Immunol 2019 Jan;105:76-85.PMID:30496979DOI:10.1016/j.molimm.2018.10.015.
Activation of NLRP3 inflammasomes is crucial in the pathological process of Ulcerative colitis (UC), which could be negatively regulated by PINK1/Parkin-driven mitophagy. Palmatine is a herb derived isoquinoline alkaloid with potent anti-inflammatory and anti-bacteria activities. In present study, we evaluated the effect of Palmatine on dextran sulfate sodium (DSS)-induced mice colitis and examined whether its effect is exerted by promoting mitophagy-mediated NLRP3 inflammasome inactivation. The result showed that Palmatine (40, 100 mg/kg) significantly prevented bodyweight loss and colonic shortening in DSS mice, and reduced the disease activity index and histopathologic score. The levels of MPO, IL-1β, TNF-α and the number of F4/80+ cells in colon of DSS mice were remarkably decreased by Palmatine. Moreover, Palmatine suppressed NLRP3 inflammasomes activation, but enhanced the expression of the mitophagy-related proteins involving LC3, PINK1 and Parkin in colonic tissue of DSS mice. These effects was consistent with the in vitro data revealing that Palmatine inhibited the activation of NLRP3 inflammasomes, while promoted the expression and mitochondrial recruitment of PINK1 and Parkin in THP-1 cell differentiated macrophages. Furthermore, the effect of Palmatine on THP-1 cells was neutralized by a mitophagy inhibitor Cyclosporin A (CsA) and PINK1-siRNA. In parallel, CsA significantly attenuated the therapeutic effect of Palmatine in DSS mice, illustrating that the anti-colitis effect of Palmatine is closely related to mitophagy. Taken together, the current results demonstrated that Palmatine protected mice against DSS-induced colitis by facilitating PINK1/Parkin-driven mitophagy and thus inactivating NLRP3 inflammasomes in macrophage.
Palmatine Protects Against MSU-Induced Gouty Arthritis via Regulating the NF-κB/NLRP3 and Nrf2 Pathways
Drug Des Devel Ther 2022 Jul 2;16:2119-2132.PMID:35812134DOI:10.2147/DDDT.S356307.
Purpose: Gouty arthritis could be triggered by the deposition of monosodium uric acid (MSU) crystals. Palmatine (PAL), a protoberberine alkaloid, has been proven to possess compelling health-beneficial activities. In this study, we aimed to explore the effect of PAL on LPS plus MSU crystal-stimulated gouty arthritis in vitro and in vivo. Methods: PMA-differentiated THP-1 macrophages were primed with LPS and then stimulated with MSU crystal in the presence or absence of PAL. The expression of pro-inflammatory cytokines and oxidative stress-related biomarkers and signal pathway key targets were determined by ELISA kit, Western blot, immunohistochemistry and qRT-PCR, respectively. In addition, the anti-inflammatory and antioxidant activities of PAL on MSU-induced arthritis mice were also evaluated. Results: The results indicated that PAL (20, 40 and 80 μM) dose-dependently decreased the mRNA expression and levels of pro-inflammatory cytokines (interleukin-1beta (IL-1β), IL-6, IL-18 and tumor necrosis factor alpha (TNF-α)). The levels of superoxide dismutase (SOD) and glutathione (GSH) were remarkably enhanced, while the level of malondialdehyde (MDA) was reduced. Western blot analysis revealed that PAL appreciably inhibited NF-κB/NLRP3 signaling pathways through inhibiting the phosphorylation of p-65 and IκBα, blocking the expression of NLRP3, ASC, IL-1β and Caspase-1, as well as enhancing the antioxidant protein expression of Nrf2 and HO-1. In vivo, PAL attenuated MSU-induced inflammation in gouty arthritis, as evidenced by mitigating the joint swelling, and decreasing the productions of IL-1β, IL-6, IL-18, TNF-α and MDA, while enhancing the levels of SOD and GSH. Moreover, PAL further attenuated the infiltration of neutrophils into joint synovitis. Conclusion: PAL protected against MSU-induced inflammation and oxidative stress via regulating the NF-κB/NLRP3 and Nrf2 pathways. PAL may represent a potential candidate for the treatment of gouty arthritis.
Palmatine as an Agent Against Metabolic Syndrome and Its Related Complications: A Review
Drug Des Devel Ther 2020 Nov 17;14:4963-4974.PMID:33235437DOI:10.2147/DDDT.S280520.
Palmatine is a naturally occurring isoquinoline alkaloid with various pharmacological properties. Given its antioxidant and anti-inflammatory properties, Palmatine may be able to impede the effects of metabolic syndrome (MetS) and its related diseases triggered by inflammation and oxidative stress. This review summarises the existing literature about the effects of Palmatine supplementation on MetS and its complications. The evidence shows that Palmatine could protect against MetS, and cardiovascular diseases, osteoporosis and osteoarthritis, which might be associated with MetS. These protective effects are mediated by the antioxidant and anti-inflammatory properties of Palmatine. Although preclinical experiments have demonstrated the efficacy of Palmatine against MetS and its related diseases, no human clinical trials have been performed to validate these effects. This research gap should be bridged to validate the efficacy and safety of Palmatine supplementation in protecting humans against MetS and its related diseases.
Palmatine ameliorated murine colitis by suppressing tryptophan metabolism and regulating gut microbiota
Pharmacol Res 2018 Nov;137:34-46.PMID:30243842DOI:10.1016/j.phrs.2018.09.010.
Inflammatory bowel disease (IBD), majorly include Crohn's disease (CD) and ulcerative colitis (UC), is chronic and relapsing inflammatory disorders of the gastrointestinal tract, which treatment options remain limited. Here we examined the therapeutic effects of an isoquinoline alkaloid, Palmatine (Pal), on mice experimental colitis induced by dextran sulfate sodium (DSS) and explored underlying mechanisms. Colitis was induced in BALB/c mice by administering 3% DSS in drinking water for 7 days. Pal (50 and 100 mg kg-1) and the positive drug Sulfasalazine (SASP, 200 mg kg-1) were orally administered for 7 days. Disease activity index (DAI) was evaluated on day 8, and colonic tissues were collected for biochemistry analysis. The fecal microbiota was characterized by high-throughput Illumina MiSeq sequencing. And plasma metabolic changes were detected by UPLC-MS. Our results showed that Pal treatment significantly reduced DAI scores and ameliorated colonic injury in mice with DSS-induced colitis. Mucosal integrity was improved and cell apoptosis was inhibited. Moreover, gut microbiota analysis showed that mice received Pal-treatment have higher relative abundance of Bacteroidetes and Firmicutes, but reduced amount of Proteobacteria. Moreover, Pal not only suppressed tryptophan catabolism in plasma, but also decreased the protein expression of indoleamine 2,3-dioxygenase 1 (IDO-1, the rate-limiting enzyme of tryptophan catabolism) in colon tissue. This is consolidated by molecular docking, which suggested that Pal is a potent IDO-1 inhibitor. Taken together, our findings demonstrate that Pal ameliorated DSS-induced colitis by mitigating colonic injury, preventing gut microbiota dysbiosis, and regulating tryptophan catabolism, which indicated that Pal has great therapeutic potential for colitis.