Natural flavone

在过去的几十年里，被诊断为癌症的人数每年都在急剧增加，这使其成为当今死亡的主要原因。癌症是全球第三大癌症，死亡率第二。由于癌症干细胞（CSCs）的残留，目前癌症治疗无法完全治疗癌症。在无花果（Ficus carica）和其他植物来源中存在的Morin类黄酮被发现对结肠癌癌症模型和细胞系具有抗增殖作用，但其对结肠癌CSCs的作用尚未研究。在这项研究中，我们测试了桑色素抑制CSC的效力。我们发现morin以剂量依赖的方式显著降低了结肠癌细胞增殖、集落形成、迁移和类结肠激素的形成。Pumilio-1（PUM1）已被证明在结肠CSC的维持中起着重要作用。我们发现桑色素与PUM1蛋白具有良好的结合亲和力，具有一种疏水性和两种氢键相互作用。此外，免疫荧光结果还显示了桑色素处理后结肠癌癌症细胞系中PUM1表达的降低。CD133在结肠癌CSCs中过表达，桑色素治疗降低了HCT116和CT26结肠癌癌症细胞系中CD133的表达。我们的研究结果通过靶向PUM1蛋白，进一步减少结肠癌癌症细胞中结肠球状体的形成和减少CD133的表达，探索了桑色素的抗癌干细胞效力[1]。

大鼠口服桑色素（50和100mg/kg体重）10天。第5天，通过单次腹腔注射MTX（20mg/kg体重）诱导肝毒性。MTX相关肝损伤与MDA增加有关，而GSH水平、内源性抗氧化剂（谷胱甘肽过氧化物酶、超氧化物歧化酶和过氧化氢酶）的活性以及肝组织中HO-1和Nrf2的mRNA水平降低有关。MTX治疗还通过增加Bax、caspase-3、Apaf-1的mRNA转录水平和下调Bcl-2导致肝组织凋亡。相反，不同剂量（50和100mg/kg）的桑色素治疗显著减轻了MTX诱导的肝组织氧化应激和凋亡。桑色素还减轻了MTX诱导的ALT、ALP和AST水平的升高，下调了基质金属蛋白酶（MMP-2和MMP-9）、MAPK14和MAPK15、JNK、Akt2和FOXO1基因的mRNA表达[2]。

迈瑞Perfect Plus 400用于测量血清中天冬氨酸转氨酶（AST）、碱性磷酸酶（ALP）和丙氨酸转氨酶（ALT）的活性。结果以U/L[2]为单位给出。

MTT细胞增殖试验[1]
使用基于3-（4,5-二甲基噻唑-2-YI）-2,5-二苯基四唑溴化物（MTT）的比色法测定桑色素对HCT116和CT26增殖的影响。用5000个细胞/孔接种孔，并让其生长过夜。用不同浓度的桑色素（50μM、100μM、150μM、200μM和400μM）处理细胞并孵育48小时。孵育时间结束后，加入MTT试剂并在培养箱中孵育4小时。然后加入DMSO溶解甲酰胺晶体并在黑暗中孵育30分钟，测量570 nm处的吸光度。

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菌落形成试验[1]
将HCT116和CT26细胞（500个细胞/孔）接种在6孔板上，并使其生长过夜。第二天，用IC50浓度的桑色素处理各细胞系的平板。孵育48小时后，更换培养基并孵育10天。用10%福尔马林固定菌落，用10%乙醇中的1%结晶紫染色。使用ImageJ软件记录图像并计数菌落，使用GraphPad Prism绘制图表。

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伤口愈合试验[1]
对于伤口愈合试验，将1×105个细胞接种在6孔板的每个孔中，并培养至融合率达到75-80%。使用100μl移液管尖端制作伤口，用PBS洗涤分离的细胞，并用还原血清培养基覆盖细胞。在0小时、24小时和48小时拍摄图像，使用ImageJ软件定量测量伤口面积。

35 male Wistar albino rats (weighing between 280 and 300 g, 11–12 weeks old) were separated into five groups of 7 male rats each at random:[2]
Control group: The animals received 0.9% saline via oral gavage for 10 days and a single intraperitoneal injection of saline on day 5 only.
Morin group: The animals were given 100 mg/kg morin hydrate orally for 10 days and intraperitoneal saline injection was given on the 5th day of the experiment.
MTX group: The animals were administered saline orally for 10 days and on the 5th day of the experiment, a single dose of 20 mg/kg MTX was injected intraperitoneally.
MTX + Morin 50 group: Rats were given 50 mg/kg morin hydrate orally for 10 days and a single dose of 20 mg/kg MTX was injected intraperitoneally on the 5th day of the experiment.
MTX + Morin 100 group: Rats were given 100 mg/kg morin hydrate orally for 10 days and a single dose of 20 mg/kg MTX was injected intraperitoneally on the 5th day of the experiment.
Following day, the rats were sacrificed under mild sevoflurane anesthesia. Blood serum was separated by centrifugation at 3000×g for 10 min, and the serum samples were then tested for liver function analysis. Livers were immediately removed and washed with ice-cold physiological saline solution for biochemical and molecular analysis and then stored at -20 °C.

Metabolism / Metabolites
Morin has known human metabolites that include (2S,3S,4S,5R)-6-[2-(2,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxochromen-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid.

mouse LD50 intraperitoneal 555 mg/kg BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY); BEHAVIORAL: MUSCLE WEAKNESS; LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION Archives Internationales de Pharmacodynamie et de Therapie., 123(395), 1960 [PMID:13796312]

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Adverse Effects
Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

[1]. Morin inhibits colon cancer stem cells by inhibiting PUM1 expression in vitro. Med Oncol . 2022 Oct 12;39(12):251.
[2]. Morin ameliorates methotrexate-induced hepatotoxicity via targeting Nrf2/HO-1 and Bax/Bcl2/Caspase-3 signaling pathways. Mol Biol Rep . 2023 Apr;50(4):3479-3488.

Background: Organ toxicity limits the therapeutic efficacy of methotrexate (MTX), an anti-metabolite therapeutic that is frequently used as an anti-cancer and immunosuppressive medicine. Hepatocellular toxicity is among the most severe side effects of long-term MTX use. The present study unveils new confirmations as regards the remedial effects of morin on MTX-induced hepatocellular injury through regulation of oxidative stress, apoptosis and MAPK signaling.[2]
Methods and results: Rats were subjected to oral treatment of morin (50 and 100 mg/kg body weight) for 10 days. Hepatotoxicity was induced by single intraperitoneal injection of MTX (20 mg/kg body weight) on the 5th day. MTX related hepatic injury was associated with increased MDA while decreased GSH levels, the activities of endogen antioxidants (glutathione peroxidase, superoxide dismutase and catalase) and mRNA levels of HO-1 and Nrf2 in the hepatic tissue. MTX treatment also resulted in apoptosis in the liver tissue via increasing mRNA transcript levels of Bax, caspase-3, Apaf-1 and downregulation of Bcl-2. Conversely, treatment with morin at different doses (50 and 100 mg/kg) considerably mitigated MTX-induced oxidative stress and apoptosis in the liver tissue. Morin also mitigated MTX-induced increases of ALT, ALP and AST levels, downregulated mRNA expressions of matrix metalloproteinases (MMP-2 and MMP-9), MAPK14 and MAPK15, JNK, Akt2 and FOXO1 genes.2]
Conclusion: According to the findings of this study, morin may be a potential way to shield the liver tissue from the oxidative damage and apoptosis.

C15H12O8

320.253

320.053

C, 56.26; H, 3.78; O, 39.97

654055-01-3

654055-01-3 (hydrate);480-16-0; 6202-27-3

18542136

Typically exists as solid at room temperature

299-300 °C (dec.)(lit.)

128Ų

7

9

1

24

488

0

O1C(=C(C(C2=C(C([H])=C(C([H])=C12)O[H])O[H])=O)O[H])C1C([H])=C([H])C(=C([H])C=1O[H])O[H].O([H])[H]

MYUBTSPIIFYCIU-UHFFFAOYSA-N

InChI=1S/C15H10O7.H2O/c16-6-1-2-8(9(18)3-6)15-14(21)13(20)12-10(19)4-7(17)5-11(12)22-15;/h1-5,16-19,21H;1H2

2',3,4',5,7-Pentahydroxyflavone Hydrate

AI3 38057; NSC19801; AI3-38057; NSC-19801; Morin hydrate; 654055-01-3; 6202-27-3; Morin (monohydrate); 2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one hydrate; MFCD00217054; Morin Hydrate (>85% purity); 2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one;hydrate; Morin Hydrate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。