The 7+ Benefits of Rubiscolins (Opioid Peptide From Rubisco)

The 7+ Benefits of Rubiscolins (Opioid Peptide From Rubisco)

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Rubiscolins are naturally occurring opioid peptides that come from Spinach.

In this post, we will discuss the benefits of Rubsicolin (-5 and -6) and their mechanism of action.


  1. Basics Of Rubiscolin

  2. Benefits Of Rubiscolin

  3. My Experience With Rubiscolin

  4. Sources And Where To Get Rubiscolin

  5. Mechanism Of Action

  6. More Research

Basics Of Rubiscolin


Rubiscolin is one reason why you should eat your dark leafy greens.

Consisting of approximately 30–50% of soluble protein in green leaves of plants, rubiscolin is known to be the most abundant protein on earth. R

Rubiscolin is an opioid peptide derived from d-ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), a major protein found in green leaves which is responsible for carbon dioxide fixation and photorespiration of plants. R R

Rubiscolin-5 and Rubiscolin-6 can bind to both δ-opioid receptor (DOR) and μ-opioid receptor (MOR), while rubiscolin-6 shows higher affinity to the DOR compared to the MOR. R R R


Benefits Of Rubiscolin

1. Combats Pain

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Rubiscolin-6 has an analgelsic effect and may help with pain. R

2. Improves Glucose Tolerance And Diabetes

Opioid receptors can control glucose homeostasis in skeletal muscle independent of insulin action. R

For example, in cell cultures, addition of rubiscolin-6 has shown to increases glucose uptake in skeletal muscle, potentially (by increasing AMPK and GLUT4 translocation) dependently of opioid receptors. R

Therefore, rubiscolin-6 may be useful for treating Diabetes. R

3. Enhances Memory

In contrast to other opioids, Rubiscolin-6 may improve memory (opioids are mostly reported to impair learning and memory). R

For example, mice eating rubiscolin-6 (100mg/kg) from spinach had enhanced memory consolidation (via DOR) after oral administration. R

4. May Reduce Anxiety

By activating Sigma1 (σ1R) and Dopamine D1 (DRD1) receptors, rubiscolin (at 100 mg/kg in mice) can reduce anxiety. R

5. Improves Food Intake And Ghrelin Resistance

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By acting on opioid receptors, rubiscolin-6 can act as an orexigenic compound and improve food intake (increases COX-2 and PGDS), while reducing intake of a high-fat diet. R R

Rubiscolin-6 may also combat ghrelin resistance. R

For example, in mice with ghrelin resistance, rubiscolin-6 could stimulate food intake (via NPY and ghrelin). R

6. Protects The Liver

Rubiscolin can protect liver cells from excess oxidative stress and increase Glutathione (GSH), Catalase (CAT) and Superoxide Dismutase-1 (SOD-1). R

7. May Prevent Proteopathy

Rubiscolin-5 may help with Endoplasmic Reticulum (ER) stress and prevent proteopathies. R

My Experience With Rubiscolin

I will eat handfuls of spinach as a snack and I do notice it improves my overall mood.

I’ve also been adding spinach powder to my smoothies and italian dishes.

Sources And Where To Get Rubiscolin


Rubisoclin-6 is a protein of green leaves so eating and green leafy veggies would be a good source:

  • Soybeans R

  • Spinach (although watch out as it can be high in oxaltes) R

Mechanism Of Action


  • Increases AMPK R

  • Increases CAT R

  • Increases COX-2 R

  • Increases DRD1 R

  • Increases DOR R R R

  • Increases Ghrelin R

  • Increases GLUT4 R

  • Increases GSH R

  • Increases MOR R R R

  • Increases NPY R

  • Increases PGDS R

  • Increases σ1R R

  • Increases SOD1 R

  • Reduces ROS R


  • The anxiolytic-like activity of rubiscolin-6 is mediated as follows: rubiscolin-6 → d opioid receptor → endogenous s1 ligand → s1 receptor → dopamine → D1 receptor → anxiolyticlike effect. R

  • YPMDLV was nearly 20 times more potent than rubiscolin-6 in MVD assay (see study for amino acid chain). R

  • Rubiscolin–5 and –6 activate G-protein signaling at δ opioid receptors. R

  • Rubiscolin–5 and –6 only weakly recuits β-arrestin 2. R

More Research

  • Rubiscolin can inhibit forskolin induced cAMP. R