Natural flavonoid
Morin acts on a diverse array of molecular targets. It is a potent inhibitor of Protein Tyrosine Phosphatase 1B (PTP1B), a key negative regulator of insulin signaling, with an IC50 of 15 μM. By inhibiting PTP1B, Morin activates the insulin receptor, which underlies its potential antidiabetic effects. It also inhibits PIM-1 kinase, an enzyme involved in cell survival and proliferation, with an IC50 of 2.7 µM, contributing to its anticancer activity. Furthermore, Morin is a potent inhibitor of ROS generation, acting as an antioxidant. It has been shown to induce apoptosis in cancer cells and can inhibit the activation of NF-κB, a transcription factor central to inflammatory responses. Additionally, Morin is a fluorescent chelator for aluminum species, which is used in analytical chemistry. It also exerts a detoxifying effect, the mechanisms of which are still being explored.

A reversed-phase high-performance liquid chromatographic method with fluorescence detection for the determination of labile monomeric aluminium has been developed through pre-column complexation using morin as the analytical reagent. The highly fluorescent aluminium-morin complex (excitation wavelength 418 nm, emission wavelength 490 nm) was separated on a Spherisorb ODS 2 column with an eluent consisting of 30% methanol and 70% water (pH 1.0 with perchloric acid). The most remarkable point of this protocol was that only the most toxic aluminium species, that is, free aqua-aluminium ion and its monomeric hydroxo complex ions, selectively respond among various aluminium complexes. This strategy has been successfully applied to direct fractionation of the toxic aluminium in natural waters and biological samples without any pretreatment.[2]

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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[3].
In vitro, Morin has demonstrated a wide range of biological activities. It inhibits PTP1B with an IC50 of 15 μM, leading to the activation of the insulin receptor. It also inhibits PIM-1 kinase with an IC50 of 2.7 μM, which contributes to its antiproliferative effects. As an antioxidant, Morin inhibits the generation of reactive oxygen species (ROS), protecting cells from oxidative damage. It has been shown to induce apoptosis in various cancer cell lines. Furthermore, Morin exhibits anti-inflammatory activity by inhibiting NF-κB activation. Its ability to chelate aluminum ions is another well-characterized in vitro property. These diverse in vitro activities make it a valuable tool for studying a multitude of disease-related pathways.

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[4].
In vivo, Morin has been shown to be orally active, a crucial feature for its potential as a therapeutic agent. In animal models, it has demonstrated a detoxifying effect and has been found to have an antiproliferative effect in a colon cancer model. Its anti-inflammatory effects are mediated in part by the activation of Nrf2 pathways and the inhibition of NF-κB activation. Furthermore, Morin has shown promise in preventing bladder cancer by inhibiting MMP-9 expression. Its neuroprotective actions have also been observed in studies, suggesting a potential role in neurodegenerative diseases like Parkinson's. These in vivo findings support the translational potential of Morin for various human 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[4].
The in vitro enzyme assays for Morin are critical for characterizing its mechanism of action. Its inhibition of PTP1B is typically assessed using a chromogenic or fluorogenic substrate, where the enzyme's activity is measured in the presence of increasing concentrations of Morin. Similarly, its inhibition of PIM-1 kinase is measured using a kinase assay with a peptide substrate and ATP. The antioxidant activity is evaluated using cell-free assays like DPPH or ABTS radical scavenging, or by measuring the ability to inhibit ROS generation in a chemical system. These enzyme and biochemical assays provide quantitative data on its potency against specific molecular targets.

MTT cell proliferation assay[3]
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[3]
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[3]
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 are conducted to confirm its effects in a biological context. To study its antidiabetic potential, cells such as adipocytes or hepatocytes are treated with Morin, and the activation of the insulin receptor and downstream signaling pathways (e.g., AKT) are measured by Western blotting. Its anticancer activity is assessed in various cancer cell lines by measuring cell viability, proliferation, and apoptosis. The induction of apoptosis is confirmed by assays for caspase activation, Annexin V staining, or DNA fragmentation. The inhibition of ROS generation is measured in cells using fluorescent probes like DCFH-DA. These cellular assays are essential for bridging the gap between biochemical activity and functional effects in a living cell.

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:[4]
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 are performed in various disease models. For its antidiabetic effects, it is evaluated in mouse models of type 2 diabetes, where parameters like blood glucose, insulin sensitivity, and glucose tolerance are measured. Its anticancer efficacy is assessed in xenograft models, where tumor growth is monitored. Neuroprotective effects are studied in models of Parkinson's disease, where behavioral and neurochemical parameters are evaluated. These animal studies are crucial for determining the efficacy, pharmacokinetics, and safety of Morin in a complex living system.

Metabolism / Metabolites
Morin’s known metabolites 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 has a molecular formula of C15H10O7 and a molecular weight of 302.24 g/mol. It is a yellow solid and is typically soluble in DMSO. It is an orally active compound, suggesting it has suitable pharmacokinetic properties for absorption and distribution. For research use, it is often stored at -20°C. The compound is known to be a fluorescent chelator for aluminum, which is a characteristic used in certain analytical applications.

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 is generally favorable, as it is a naturally occurring flavonoid found in dietary sources. It is considered safe at the doses typically used in research. However, as with any bioactive compound, comprehensive toxicological studies, including genotoxicity and long-term safety assessments, would be required for its development as a therapeutic agent.

[1]. Antioxidant capacity of flavonoids in hepatic microsomes is not reflected by antioxidant effects in vivo. Oxid Med Cell Longev. 2012;2012:165127.

[2]. Morin applied in speciation of aluminium in natural waters and biological samples by reversed-phase high-performance liquid chromatography with fluorescence detection. Anal Bioanal Chem. 2003 Jun;376(4):542-8.

[3]. Morin inhibits colon cancer stem cells by inhibiting PUM1 expression in vitro. Med Oncol. 2022 Oct 12;39(12):251.

[4]. 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.

Morin is a 5-hydroxyflavonoid, a 7-hydroxyflavone alcohol with three additional hydroxyl substituents at the 2', 4', and 5' positions. It possesses a variety of activities, including antioxidant, metabolic, antihypertensive, hepatoprotective, neuroprotective, anti-inflammatory, antitumor, antibacterial, EC 5.99.1.2 (DNA topoisomerase) inhibitor, and angiogenesis regulator. It is both a 5-hydroxyflavonoid and a 7-hydroxyflavone alcohol. Morin has been reported in apple wood (Maclura pomifera), Taiwan coltsfoot (Petasites formosanus), and other organisms with relevant data. See also: Apple wood morin (note moved here). Flavonoids are polyphenolic compounds with various reducing abilities and potential antioxidant activity. Cellular lipid peroxidation is associated with a variety of diseases. Therefore, this study evaluated the ability of several dietary flavonoid aglycones to inhibit lipid peroxidation in rat liver microsomes lacking the major lipid-soluble antioxidant dα-tocopherol. The antioxidant effects were in the following order: galangin > quercetin > kaempferol > fisetin > myricetin > morin > catechin > apigenin. However, the antioxidant effects of all flavonoids were inferior to dα-tocopherol, especially at the lowest concentrations. In addition, there appeared to be a significant difference between the in vitro antioxidant effects of flavonoids and their ability to inhibit oxidative indicators in vivo. Compared with dα-tocopherol, supplementation of vitamin E-deficient rats with quercetin, kaempferol or myricetin did not significantly affect lipid peroxidation and tissue damage indicators. The direct antioxidant effects of flavonoids in vivo may be less obvious due to low bioavailability, but indirect redox effects through stimulation of antioxidant response elements cannot be ruled out. [1]
Morin is a naturally occurring flavonoid with a wide array of pharmacological activities, including antioxidant, anti-inflammatory, anticancer, antidiabetic, and neuroprotective effects. Its mechanisms of action involve the inhibition of key enzymes such as PTP1B (IC50 = 15 μM) and PIM-1 kinase (IC50 = 2.7 μM), modulation of ROS, and induction of apoptosis. It is an orally active compound that has shown promise in preclinical models of various diseases, including diabetes, cancer, and Parkinson's disease. Despite its extensive research history, Morin has not been developed into an approved therapeutic drug and remains a valuable research tool for studying the molecular basis of these diseases and for the discovery of novel drug candidates.

C15H10O7

302.24

302.042

C, 59.61; H, 3.34; O, 37.05

480-16-0

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

5281670

Light yellow to yellow solid powder

1.8±0.1 g/cm3

645.5±55.0 °C at 760 mmHg

299-300 °C (dec.)(lit.)

249.3±25.0 °C

0.0±2.0 mmHg at 25°C

1.823

1.61

5

7

1

22

488

0

YXOLAZRVSSWPPT-UHFFFAOYSA-N

InChI=1S/C15H10O7/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

2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one

NSC-19801; 480-16-0; Aurantica; 2',3,4',5,7-Pentahydroxyflavone; 2-(2,4-Dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one; Calico Yellow; Al-Morin; Toxylon Pomiferum; NSC 19801; Morin

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)

DMSO : ~125 mg/mL (~413.58 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.88 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (6.88 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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