Chrysosplenetin
(Synonyms: 猫眼草黄素) 目录号 : GC35692
A flavonoid with diverse biological activities
Cas No.:603-56-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Chrysosplenetin is a flavonoid that has been found in A. annua and has diverse biological activities.1,2,3 It is active against P. falciparum in vitro (IC50 = 23 ?M).1 Chrysosplenetin inhibits the cytopathic effect of enterovirus 71 (EV71) in Vero cells (EC50 = 0.68 ?M) and increases survival in a neonatal mouse model of EV71 infection when administered at doses of 1 and 5 mg/kg.2 It also increases proliferation and osteogenic differentiation of isolated human bone marrow stromal cells (BMSCs) and prevents estrogen deficiency-induced bone loss in ovariectomized mice.3
1.Liu, K.C., Yang, S.L., Roberts, M.F., et al.Antimalarial activity of Artemisia annua flavonoids from whole plants and cell culturesPlant Cell Rep.11(12)637-640(1992) 2.Dai, W., Bi, J., Li, F., et al.Antiviral efficacy of flavonoids against enterovirus 71 infection in vitro and in newborn miceViruses11(7)625(2019) 3.Hong, G., He, X., Shen, Y., et al.Chrysosplenetin promotes osteoblastogenesis of bone marrow stromal cells via Wnt/β-catenin pathway and enhances osteogenesis in estrogen deficiency-induced bone lossStem Cell Res. Ther.10(1)277(2019)
| Cas No. | 603-56-5 | SDF | |
| 别名 | 猫眼草黄素 | ||
| Canonical SMILES | O=C1C(OC)=C(C2=CC=C(O)C(OC)=C2)OC3=CC(OC)=C(OC)C(O)=C13 | ||
| 分子式 | C19H18O8 | 分子量 | 374.34 |
| 溶解度 | DMSO : 100 mg/mL (267.14 mM; Need ultrasonic) | 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 | 2.6714 mL | 13.3568 mL | 26.7137 mL |
| 5 mM | 0.5343 mL | 2.6714 mL | 5.3427 mL |
| 10 mM | 0.2671 mL | 1.3357 mL | 2.6714 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。
Chrysosplenetin promotes osteoblastogenesis of bone marrow stromal cells via Wnt/β-catenin pathway and enhances osteogenesis in estrogen deficiency-induced bone loss
Stem Cell Res Ther 2019 Aug 29;10(1):277.PMID:31464653DOI:10.1186/s13287-019-1375-x.
Background: Chrysosplenetin is an O-methylated flavonol compound isolated from the plant Chamomilla recutita and Laggera pterodonta. The aim of our research is to evaluate the function of Chrysosplenetin on osteogenesis of human-derived bone marrow stromal cells (hBMSCs) and inhibition of estrogen deficiency-induced osteoporosis via the Wnt/β-catenin signaling pathway. Method: hBMSCs are cultured and treated by Chrysosplenetin in the absence or presence of Wnt inhibitor dickkopf-related protein 1 (DKK1) or bone morphogenetic protein 2 (BMP2) antagonist Noggin. RT-qPCR is taken to identify the genetic expression of target genes of Wnt/β-catenin pathway and osteoblast-specific markers. The situation of β-catenin is measured by western blot and immunofluorescence staining. An ovariectomized (OVX) mouse model is set up to detect the bone loss suppression by injecting Chrysosplenetin. Micro-CT and histological assay are performed to evaluate the protection of bone matrix and osteoblast number. Serum markers related with osteogenesis are detected by ELISA. Results: In the present study, it is found that Chrysosplenetin time-dependently promoted proliferation and osteoblastogenesis of hBMSCs reaching its maximal effects at a concentration of 10 μM. The expressions of target genes of Wnt/β-catenin pathway and osteoblast-specific marker genes are enhanced by Chrysosplenetin treatment. Furthermore, the phosphorylation of β-catenin is decreased, and nuclear translocation of β-catenin is promoted by Chrysosplenetin. Osteogenesis effects mentioned above are founded to be blocked by DKK1 or BMP2 antagonist Noggin. In vivo study reveals that Chrysosplenetin prevents estrogen deficiency-induced bone loss in OVX mice detected by Micro-CT, histological analysis, and ELISA. Conclusions: Our study demonstrates that Chrysosplenetin improves osteoblastogenesis of hBMSCs and osteogenesis in estrogen deficiency-induced bone loss by regulating Wnt/β-catenin pathway.
Chrysosplenetin inhibits artemisinin efflux in P-gp-over-expressing Caco-2 cells and reverses P-gp/MDR1 mRNA up-regulated expression induced by artemisinin in mouse small intestine
Pharm Biol 2017 Dec;55(1):374-380.PMID:27931149DOI:10.1080/13880209.2016.1241810.
Context: CYP3A4 and P-gp together form a highly efficient barrier for orally absorbed drugs and always share the same substrates. Our previous work revealed that Chrysosplenetin (CHR) significantly augmented the rat plasma level and anti-malarial efficacy of artemisinin (ART), partially due to the uncompetitive inhibition effect of CHR on rat CYP3A. But the impact of CHR on P-gp is still unknown. Objective: The present study investigates whether CHR interferes with P-gp-mediated efflux of ART and elucidates the underlying mechanism. Materials and methods: P-gp-over-expressing Caco-2 cells were treated with ART (10 μM) or ART-CHR (1:2, 10:20 μM) in ART bidirectional transport experiment. ART concentration was determined by UHPLC-MS/MS method. Healthy male ICR mice were randomly divided into nine groups (n = 6) including negative control (0.5% CMC-Na solution, 13 mL/kg), ART alone (40 mg/kg), verapamil (positive control, 40 mg/kg), ART-verapamil (1:1, 40:40 mg/kg), CHR alone (80 mg/kg), ART-CHR (1:0.1, 40:4 mg/kg), ART-CHR (1:1, 40:40 mg/kg), ART-CHR (1:2, 40:80 mg/kg) and ART-CHR (1:4, 40:160 mg/kg). The drugs were administrated intragastrically for seven consecutive days. MDR1 and P-gp expression levels in mice small intestine were examined by performing RT-PCR and western blot analysis. ABC coupling ATPase activity was also determined. Results: After combined with CHR (1:2), Papp (AP-BL) and Papp (BL-AP) of ART changed to 4.29 × 10 - 8 (increased 1.79-fold) and 2.85 × 10 - 8 cm/s (decreased 1.24-fold) from 2.40 × 10 - 8 and 3.54 × 10 - 8 cm/s, respectively. Efflux ratio (PBA/PAB) declined 2.21-fold (p < 0.01) versus to ART alone. ART significantly up-regulated both MDR1 mRNA and P-gp levels compared with vehicle, while CHR in combination ratio of 0:1, 0.1:1, 1:1, 2:1 and 4:1 with ART, reversed them to normal levels as well as negative control (p < 0.05). The ATPase activities in ART-CHR 1:4 and CHR alone groups achieved a slight increase (p < 0.05) when compared with ART alone. Discussion and conclusion: These results confirm that CHR inhibited P-gp activity and reverse the up-regulated P-gp and MDR1 levels induced by ART. It suggested that CHR potentially can be used as a P-gp reversal agent to obstruct ART multidrug resistance.
In vitro and in silico assessment of DNA interaction, topoisomerase I and II inhibition properties of Chrysosplenetin
Int J Biol Macromol 2020 Nov 15;163:1053-1059.PMID:32673727DOI:10.1016/j.ijbiomac.2020.07.049.
Chrysosplenetin is a methoxyflavone with reported anti-cancer effect. We tested its cytotoxic effect on the MCF-7 breast cancer cell line, and determined its effect on DNA intercalation and on the activity of topoisomerases I and II. The compound inhibited proliferation MCF-7 with an IC50 value of 0.29 μM. Chrysosplenetin did not initiate plasmid DNA cleavage but, in a concentration-dependent manner, protected plasmid DNA against damage induced by Fenton reagents. Furthermore, it possessed dual Topoisomerase I and II inhibitory properties. Especially, it inhibited topoisomerase II by 83-96% between the range 12.5-100 μM. In the light of these experimental findings, molecular docking studies were performed to understand binding mode, interactions and affinity of Chrysosplenetin with DNA, and with topoisomerases I and II. These studies showed that of 4-chromone core and the hydroxyl and methoxy groups important for both intercalation with DNA and topoisomerase I and II inhibition.
Antimalarial activity and sensitization of Chrysosplenetin against artemisinin-resistant genotype Plasmodium berghei K173 potentially via dual-mechanism of maintaining host P-glycoprotein homeostasis mediated by NF-κB p52 or PXR/CAR signaling pathways and regulating heme/haemozoin metabolism
Phytother Res 2023 Mar 20.PMID:36938853DOI:10.1002/ptr.7789.
This study investigated antimalarial efficacy and sensitization of Chrysosplenetin against artemisinin-resistant Plasmodium berghei K173 and potential molecular mechanism. Our data indicated a risk of artemisinin resistance because a higher parasitaemia% and lower inhibition% under artemisinin treatment against resistant parasites than those in the sensitive groups were observed. Two non-antimalarial components, verapamil and chrysosplentin, being P-gp inhibitors, possessed a strong efficacy against resistant parasites but it was not the case for Bcrp inhibitor novobiocin. Artemisinin-chrysosplenetin combination improved artemisinin susceptibility of resistant P. berghei. Artemisinin activated intestinal P-gp and Abcb1/Abcg2 expressions and suppressed Bcrp whereas Chrysosplenetin reversed them. Resistant parasite infection led to a decreased haemozoin in organs or an increased heme in peripheral bloods compared with the sensitives; however, that in Abcb1-deficient knockout (KO)-resistant mice reversely got increased or decreased versus wild type (WT)-resistant animals. Chrysosplenetin as well as rifampin (nuclear receptor agonist) increased the transcription levels of PXR/CAR while showed a versatile regulation on hepatic and enternal PXR/CAR in WT- or KO-sensitive or -resistant parasites. Oppositely, hepatic and enteric NF-κB p52 mRNA decreased conformably in WT but increased in KO-resistant mice. NF-κB pathway potentially involved in the mechanism of Chrysosplenetin on inhibiting P-gp expressions while PXR/CAR play a more complicated role in this mechanism.
Inhibition of enterovirus 71 replication by Chrysosplenetin and penduletin
Eur J Pharm Sci 2011 Oct 9;44(3):392-8.PMID:21914477DOI:10.1016/j.ejps.2011.08.030.
In recent years, enterovirus 71 (EV71) infections have caused an increasing epidemic in young children, accompanying with more severe nervous system disease and more deaths. Unfortunately, there is no specific medication for it so far. Here we investigated the anti-EV71 activity of Chrysosplenetin and penduletin, two o-methylated flavonols isolated from the leaves of Laggera pterodonta. These two compounds were found to have strong activity in vitro against EV71 with low cytotoxicity. In the cytopathic effect (CPE) inhibition assays, both plaque reduction assay and virus yield inhibition assay, the compounds showed a similar 50% inhibitory concentration (IC(50)) value of about 0.20 μM. The selectivity indices (SI) of Chrysosplenetin and penduletin were 107.5 and 655.6 in African green monkey kidney (Vero) cells, and 69.5 and 200.5 in human rhabdomyosarcoma (RD) cells, accordingly. The preliminary mechanism analysis indicates that they function not through blocking virus entry or inactivating virus directly but inhibiting viral RNA replication. In the time-of-addition assay, both compounds inhibited progeny virus production and RNA replication by nearly 100% when introduced within 4h post infection. In addition to EV71, both compounds inhibited several other human enteroviruses with similar efficacy. These findings provide a significant lead for the discovery of anti-EV71 drug.