Natural flavone
The molecular targets and mechanisms of action of Morin Hydrate are identical to those of its anhydrous form, Morin. As a flavonoid, it exerts its effects through multiple pathways. It is a potent antioxidant, effectively scavenging free radicals and reducing oxidative stress. This is a key mechanism underlying its protective effects in various diseases. It is also a well-known inhibitor of Protein Tyrosine Phosphatase 1B (PTP1B), a negative regulator of insulin signaling, with an IC50 of 15 μM. This inhibition leads to the activation of the insulin receptor, contributing to its antidiabetic potential. Furthermore, Morin Hydrate has been shown to inhibit platelet activation, which is a major factor in cardiovascular diseases. It also prevents inflammation and apoptosis of cells and has been found to inhibit the activity of xanthine oxidase, a free-radical generating enzyme from the ischemic endothelium. Its ability to inhibit protein aggregation is another key property relevant to neurodegenerative diseases.

Over the last few decades, the number of people diagnosed with cancer has increased dramatically every year, making it a major cause of mortality today. Colon cancer is the third most common cancer worldwide, and the second in mortality rate. Current cancer treatment fails to treat colon cancer completely due to the remains of Cancer Stem Cells (CSCs). Morin flavonoid present in figs (Ficus carica) and other plant sources, was found to have an anti-proliferative effect on the colon cancer model and cell line, but it is not studied for its effect on the colon CSCs. In this study, we have tested the potency of morin to inhibit CSCs. We found that morin has significantly reduced colon cancer cell proliferation, colony formation, migration, and colonospheroid formation in a dose-dependent manner. Pumilio-1 (PUM1) has been shown to play an important role in colon CSCs maintenance. We found that morin has a good binding affinity with PUM1 protein with one hydrophobic and two hydrogen bond interactions. Further, the immunofluorescence results have also shown a reduction in PUM1 expression in colon cancer cell lines after morin treatment. CD133 is overexpressed in colon CSCs and morin treatment has reduced the CD133 expression in HCT116 and CT26 colon cancer cell lines. Our research outcome has explored the anti-cancer stem cell potency of morin via targeting the PUM1 protein and further reducing the colon spheroids formation and reducing the CD133 expression in colon cancer cells[1].
In vitro studies on Morin Hydrate have confirmed its broad pharmacological activities. It has been proven to prevent inflammation and apoptosis in various cell types. It effectively inhibits platelet activation, which is a critical step in thrombosis and cardiovascular disease. Its ability to scavenge oxyradicals has been demonstrated in cell culture, where it prolonged the survival of three types of human circulatory system cells. These studies have established its potent antioxidant and cytoprotective properties at the cellular level, providing a strong foundation for its observed in vivo effects. The compound's ability to inhibit protein aggregation is also studied in cell models of neurodegenerative diseases.

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].
In vivo, Morin Hydrate has demonstrated significant protective effects in various animal models. It has been studied in a rat model of Huntington's disease (induced by 3-nitropropionic acid), showing neuroprotective effects. Its ability to prevent arterial thrombosis has been investigated in vivo. Furthermore, it has shown efficacy in models of cardiovascular, liver, and renal disorders. These studies confirm that its in vitro activities translate to meaningful therapeutic effects in living organisms, highlighting its potential for the prevention and treatment of a wide range of diseases.

Mindray Perfect Plus 400 was used to measure the activities of aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) in the serum. The results were given in units of U/L[2].
The in vitro assays for Morin Hydrate are the same as those used for Morin. Its antioxidant activity is typically measured using cell-free assays such as DPPH or ABTS radical scavenging, or by measuring its ability to inhibit ROS generation in a chemical system. Its inhibition of PTP1B is assessed using an enzyme activity assay with a chromogenic or fluorogenic substrate. The inhibition of platelet activation is studied in platelet-rich plasma by measuring aggregation in response to agonists. These biochemical and functional assays are crucial for quantifying its potency and understanding its primary mechanisms of action.

MTT cell proliferation assay[1]
Morin’s effect on the proliferation of HCT116 and CT26 was determined using 3-(4,5-Dimethylthiazol-2-YI)-2,5-Diphenyltetrazolium Bromide (MTT) based colorimetric assay. Wells were seeded with 5000 cells/well and allowed to grow overnight. Cells were treated with different concentrations of morin (50 μM,100 μM,150 μM, 200 μM, and 400 μM) and incubated for 48 h. After the incubation time, MTT reagent was added and incubated in the incubator for 4 h. Later DMSO is added to dissolve the formazan crystals and incubated in dark for 30 min, absorbance at 570 nm is measured.

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Colony formation assay[1]
HCT116 and CT26 cells (500 cells/well) were seeded on a 6-well plate and allowed to grow overnight. The next day the plates were treated with IC50 concentration of morin for respective cell lines. After 48 h of incubation, the medium was changed and incubated for 10 days. Colonies were fixed with 10% formalin and stained with 1% crystal violet in 10% ethanol. Images were documented and colonies were counted using ImageJ software and graphs were plotted using GraphPad Prism.

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Wound healing assay[1]
For wound healing assay, 1 × 105 cells were seeded in each well of a 6-well plate and cultured until it reaches 75–80% confluency. A wound was made using a 100 μl pipette tip, washed the detached cells with PBS, and cells were overlayed with reduced serum medium. Images were captured at 0 h, 24 h, and 48 h, the wound area was quantitatively measured using ImageJ software.
Cellular assays for Morin Hydrate are conducted in a variety of cell lines to evaluate its protective effects. For example, its anti-apoptotic and anti-inflammatory effects are studied in cells exposed to oxidative stress or inflammatory stimuli. Its effect on platelet activation is assessed in cultured platelets. The inhibition of xanthine oxidase, a source of free radicals, can be studied in endothelial cells. These cell-based experiments are essential for confirming its mechanisms and determining its efficacy in a physiologically relevant context.

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.
In vivo animal experiments for Morin Hydrate are performed in various disease models. Its neuroprotective effects have been evaluated in a rat model of Huntington's disease. Its cardioprotective and anti-thrombotic effects have been studied in models of arterial thrombosis. Its efficacy in metabolic disorders, such as diabetes, and in renal and liver diseases has also been investigated in animal models. These experiments are critical for demonstrating its therapeutic potential and for understanding its pharmacokinetics and safety in a whole organism.

Metabolites/Metabolites
Known metabolites of Morin include (2S,3S,4S,5R)-6-[2-(2,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxochromen-3-yl]oxy-3,4,5-trihydroxyoxacyclohexane-2-carboxylic acid.
Morin Hydrate has a molecular formula of C15H10O7·xH2O and a molecular weight of 302.24 g/mol on an anhydrous basis. It is a yellow powder. The compound is a naturally occurring and bioactive flavonoid. Its physicochemical properties, such as solubility, are similar to those of morin. It is typically stored as a powder at room temperature. Detailed pharmacokinetic parameters for the hydrate form are not distinguished from those of morin in the literature.

The intraperitoneal LD50 in mice was 555 mg/kg. Behavior: somnolence (overall activity inhibition); Behavior: muscle weakness; Lung, pleural, or respiratory: respiratory depression. Archives of Pharmacodynamics and Therapeutics, 123(395), 1960 [PMID:13796312]

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Adverse Reactions
Occupational Hepatotoxicity - Secondary Hepatotoxicity: Potential toxic effects in occupational settings based on cases of human ingestion or animal experimental poisoning.
The toxicity profile of Morin Hydrate is considered to be favorable, as it is a dietary flavonoid found in various foods. It is generally recognized as safe at the concentrations found in the diet and used in research. However, as with any concentrated bioactive compound, comprehensive toxicological studies would be necessary for its development as a therapeutic agent.

[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: Methotrexate (MTX) is a commonly used antimetabolite drug, often used as an anticancer and immunosuppressant, but its organ toxicity limits its therapeutic effect. Hepatotoxicity is one of the most serious side effects of long-term MTX use. This study reveals the repair effect of morin on MTX-induced hepatocellular damage by regulating oxidative stress, apoptosis and MAPK signaling pathways. [2] Methods and Results: Rats were orally administered morin (50 and 100 mg/kg body weight) for 10 consecutive days. On day 5, hepatotoxicity was induced by a single intraperitoneal injection of MTX (20 mg/kg body weight). MTX-related liver injury was associated with increased MDA levels, decreased GSH levels, decreased activity of endogenous antioxidants (glutathione peroxidase, superoxide dismutase and catalase) and decreased HO-1 and Nrf2 mRNA levels in liver tissue. MTX treatment also led to apoptosis of liver tissue cells by increasing the mRNA transcription levels of Bax, caspase-3 and Apaf-1 and downregulating Bcl-2 expression. Conversely, different doses (50 and 100 mg/kg) of morin significantly reduced MTX-induced oxidative stress and apoptosis in liver tissue. Morin also reduced MTX-induced elevations in ALT, ALP, and AST levels and downregulated the mRNA expression of matrix metalloproteinases (MMP-2 and MMP-9), MAPK14 and MAPK15, JNK, Akt2, and FOXO1 genes. [2] Conclusion: Based on the results of this study, morin may be a potential method for protecting liver tissue from oxidative damage and apoptosis.
Morin Hydrate is a bioactive flavonoid with an exceptionally broad spectrum of pharmacological activities. It is a potent antioxidant, anti-inflammatory, anti-apoptotic, and anti-protein aggregation agent. It has shown protective effects in preclinical models of cancer, cardiovascular disease, diabetes, and neurodegenerative disorders like Huntington's disease. Its mechanisms involve the inhibition of PTP1B, modulation of oxidative stress, and inhibition of platelet activation. Despite its remarkable preclinical profile and its status as a natural dietary compound with substantial health benefits, Morin Hydrate has not been developed into an approved therapeutic drug and remains a valuable research compound for studying the molecular basis of chronic diseases.

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.)

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

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)