Lutein targets multiple pathways including Endogenous Metabolite, Apoptosis, and Reactive Oxygen Species. It acts through the Metabolic Enzyme/Protease, Apoptosis, Immunology/Inflammation, and NF-κB pathways. Lutein exerts its anti-inflammatory and antioxidant effects through modulation of ROS, and it reduces A2E photooxidation by protecting against A2-PE photooxidation. It also modulates ICAM-1/Nrf-2 signaling to exert neuroprotective effects.

Lutein (100 or 200 μM) decreases A2E photooxidation and stops A2-PE photooxidation, which is a bis-retinoic acid molecule and the direct precursor of the lipofuscin fluorophore A2E [2].
In vitro, lutein (100 or 200 μM) protects against A2-PE (a bis-retinoid compound that is the immediate precursor of the lipofuscin fluorophore A2E) photooxidation and reduces A2E photooxidation. Lutein demonstrates antioxidant activity by scavenging free radicals and reducing oxidative stress in various cell-based assays. It also exhibits antibacterial and antimutagenic activities in vitro. The compound is soluble in DMSO at 25 mg/mL (43.95 mM) with ultrasonic and warming to 60°C.

Through the anti-inflammatory and antioxidant activities of ICAM-1/Nrf-2, lutein (40–160 mg/kg; in diet for 5 weeks) protects severe traumatic brain injury in rats [3]. In addition to its antioxidant and neuroprotective properties, lutein (0.1–10 mg/kg; orally; once or daily for 7 and 21 days) inhibits the depressive-like behavior that corticosterone induces in mice [4].
In vivo, lutein (40-160 mg/kg; in diet for 5 weeks) protects against severe traumatic brain injury through anti-inflammatory and antioxidative effects via ICAM-1/Nrf-2 in rats. It suppresses IL-1β, IL-6 and MCP-1 expression, reduces serum ROS levels, downregulates NF-κB p65 and COX-2 expression, and upregulates Nrf-2 and endothelin-1 protein levels. Lutein (0.1-10 mg/kg; p.o.; once or daily for 7 and 21 days) prevents corticosterone-induced depressive-like behavior in mice with involvement of antioxidant and neuroprotective activities.

In vitro enzyme/receptor binding assays for lutein involve measuring its antioxidant capacity through ROS scavenging activity. Cell-free assays typically use biochemical methods to assess lutein's ability to quench free radicals and inhibit lipid peroxidation. The compound's interaction with inflammatory mediators such as ICAM-1 and Nrf-2 can be evaluated using purified protein preparations or cell-free systems. Spectrophotometric methods are commonly employed to measure lutein's radical-scavenging activity against DPPH or ABTS radicals.

In vitro cellular experiments are performed using various cell lines treated with lutein at concentrations ranging from 100 to 200 μM. Cells are cultured in appropriate media at 37°C in a humidified atmosphere. After treatment, endpoints such as ROS levels, inflammatory cytokine production, and cell viability are assessed. A2E photooxidation is measured to evaluate lutein's protective effects against retinal pigment epithelium damage. MTT assays are used to assess cell viability and cytotoxicity.

Animal/Disease Models: SD (SD (Sprague-Dawley)) rat, severe traumatic brain injury (STBI) model [3]
Doses: 40, 80 and 160 mg/kg
Route of Administration: Diet for 5 weeks
Experimental Results: Inhibition of interleukin (IL)-1β, IL-6 and monocyte chemoattractant protein-1 expression, diminished serum ROS levels, and diminished superoxide dismutase and glutathione peroxidase activities. Effectively downregulates the expression of NF-κB p65, cyclooxygenase-2, and intercellular adhesion molecule (ICAM)-1 protein, and upregulates nuclear factor erythroid 2-like 2 (Nrf-2) and endothelin-1 protein levels.

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Animal/Disease Models: Male Swiss mouse, chronic corticosterone depression model [4]
Doses: 0.1, 1 and 10 mg/kg
Route of Administration: Oral administration, once or daily for 7 and 21 days
Experimental Results: 10 mg/ Immobility time diminished at kg doses. Counteracts the behavioral changes demonstrated by corticosterone, exhibiting antidepressant-like effects. Exhibits antioxidant effects in mouse hippocampus, prefrontal cortex, and plasma, and exhibits the ability to
In vivo animal studies utilize Sprague-Dawley rats with severe traumatic brain injury (STBI) models, where lutein is administered in diet at 40, 80 and 160 mg/kg for 5 weeks. Male Swiss mice are used for chronic corticosterone-induced depression models with oral administration of lutein at 0.1-10 mg/kg. Endpoints include inflammatory marker expression, ROS levels, antioxidant enzyme activities, and behavioral assessments. Tissue samples are collected for histopathological and biochemical analyses.

Lutein is an orally active compound with good bioavailability. It has a molecular weight of 568.87 and is lipophilic in nature, requiring formulation with lipids or emulsifiers for optimal absorption. Lutein is distributed to various tissues including the brain, where it exerts neuroprotective effects. It is metabolized and excreted through normal carotenoid metabolic pathways. The compound should be stored at -20°C, protected from light, and stored under nitrogen.

Lutein is generally recognized as safe with low toxicity. As a dietary carotenoid, it has been consumed safely in foods for decades. No significant acute or chronic toxicity has been reported at nutritional or supplemental doses. High doses may cause carotenodermia (yellowish skin discoloration), which is benign and reversible. Lutein is not associated with genotoxicity or carcinogenicity. It is well-tolerated in clinical studies at doses up to 20-40 mg daily.

[1]. The Effect of Lutein on Eye and Extra-Eye Health.Nutrients. 2018 Sep 18;10(9). pii: E1321.

[2]. Photooxidation of A2-PE, a photoreceptor outer segment fluorophore, and protection by lutein and zeaxanthin. Exp Eye Res. 2006 May;82(5):828-39.

[3]. Lutein protects against severe traumatic brain injury through anti‑inflammation and antioxidative effects via ICAM‑1/Nrf‑2. Mol Med Rep. 2017 Oct;16(4):4235-4240.

[4]. Lutein prevents corticosterone-induced depressive-like behavior in mice with the involvement of antioxidant and neuroprotective activities. Pharmacol Biochem Behav. 2019 Apr;179:63-72.

Lutein is a carotenoid alcohol. It is both a food coloring and a plant metabolite. It is derived from the hydrogenation of (6'R)-β,ε-carotene. Lutein belongs to the xanthophyll class of compounds and is one of the 600 known natural carotenoids. Lutein can only be synthesized by plants and, like other xanthophyll compounds, is abundant in leafy green vegetables such as spinach, kale, and yellow carrots. In green plants, lutein can regulate light energy and act as a non-photochemical quencher to treat the excessive production of triplet chlorophyll (the excited state of chlorophyll) during photosynthesis under high light intensity. It has been reported that lutein is found in Rhodiola rosea (Erythrophleum fordii), Nephrolepis cordifolia, and several other organisms with relevant data. Lutein (pronounced "lutein") is an oxygen-containing carotenoid found in vegetables and fruits. Lutein is present in the macula of the eye and is believed to act as a yellow filter there. Lutein has antioxidant properties, protecting cells from free radical damage. Lutein is one of the lutein compounds in the major photosynthetic protein complex of plants. Dietary lutein accumulates in the macula. See also: Calendula (part); Corn (part); Chicken; Lutein (ingredient)... See more...

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Pharmacological Indications
Lutein is used as a nutritional supplement and can also be used to treat dietary deficiencies or imbalances.

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Mechanism of Action
Lutein has antioxidant activity, reacting with reactive oxygen species to produce bioactive degradation products. They also inhibit the peroxidation of membrane phospholipids and reduce the formation of lipofuscin, both contributing to their antioxidant properties. Lutein is naturally found in the macula of the human retina. It can filter out blue light and near-ultraviolet radiation that can cause phototoxicity to the macula. This protective effect is partly attributed to the ability of these carotenoids to scavenge reactive oxygen species. Compared to other carotenoids such as β-carotene and lycopene, lutein is more stable and less susceptible to degradation by pro-oxidants. Lutein is abundant in the fovea region and is the main pigment at the outermost edge of the macula. Zeaxanthin is fully bound (unlike lutein), and may be more effective than lutein in protecting against phototoxic damage caused by blue light and near-ultraviolet radiation. Lutein is one of only two carotenoids currently found in the human lens, and it may help prevent age-related increases in lens density and the formation of cataracts. Furthermore, the protective effects that lutein may provide are partly attributed to its ability to scavenge reactive oxygen species. Carotenoids also have anti-cancer effects. One mechanism is through increased expression of connexin 43, which stimulates gap junction communication and prevents excessive cell proliferation. Pharmacodynamic studies have found that lutein is highly enriched in specific areas of the macula (a small area on the retina responsible for central vision). The hypothesis of this natural enrichment is that lutein helps protect against oxidative stress and high-energy light. Multiple studies have shown that increased macular pigmentation can reduce the risk of eye diseases such as age-related macular degeneration (AMD).
Lutein is a naturally occurring carotenoid with established health benefits, particularly for eye health and prevention of age-related macular degeneration (AMD). It is available as a dietary supplement and is added to foods as a nutrient. Lutein is one of the two major carotenoids found in the human retina (macula). It functions as a blue light filter and antioxidant in the eye. Clinical trials have demonstrated its efficacy in improving visual function and reducing the risk of AMD progression. It is approved as a Generally Recognized as Safe (GRAS) substance and is widely used in nutritional supplements.

C40H56O2

568.886

568.428

127-40-2

5281243

Orange to red solid powder

1.0±0.1 g/cm3

702.3±60.0 °C at 760 mmHg

183℃

269.1±27.5 °C

0.0±5.0 mmHg at 25°C

1.583

11.78

2

2

10

42

1270

3

CC1=C(C(C[C@@H](C1)O)(C)C)/C=C/C(=C/C=C/C(=C/C=C/C=C(\C)/C=C/C=C(\C)/C=C/[C@H]2C(=C[C@@H](CC2(C)C)O)C)/C)/C

KBPHJBAIARWVSC-RGZFRNHPSA-N

InChI=1S/C40H56O2/c1-29(17-13-19-31(3)21-23-37-33(5)25-35(41)27-39(37,7)8)15-11-12-16-30(2)18-14-20-32(4)22-24-38-34(6)26-36(42)28-40(38,9)10/h11-25,35-37,41-42H,26-28H2,1-10H3/b12-11+,17-13+,18-14+,23-21+,24-22+,29-15+,30-16+,31-19+,32-20+/t35-,36+,37-/m0/s1

(1R)-4-[(1E,3E,5E,7E,9E,11E,13E,15E,17E)-18-[(1R,4R)-4-hydroxy-2,6,6-trimethylcyclohex-2-en-1-yl]-3,7,12,16-tetramethyloctadeca-1,3,5,7,9,11,13,15,17-nonaenyl]-3,5,5-trimethylcyclohex-3-en-1-ol

Xanthophyll; Lutein

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

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

DMSO : ~50 mg/mL (~87.89 mM)

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.)