Black pepper (Piper nigrum) dried fruits, also known as peppercorns, are commonly used as a spice in ground form and are often simply referred to as black pepper.
Black pepper contains a large collection of piperidines, with piperine found in high quantities.
Piperidines Found In Black Pepper | Amount |
---|---|
9-(1,3-benzodioxol-5-yl)-1-pyrrolidin-1-ylnon-8-en-1-one | Unspecified [1] |
Dipiperamide D | Unspecified [7] |
Dipiperamide E | Unspecified [7] |
Pipercyclobutanamide A | Unspecified [1] |
Piperidine | 0.5-5% [2] |
Piperine | 10% |
Piptigrine | Unspecified [8] |
Wisanine | Unspecified [8] |
Using Black Pepper Medicinally
Piperidine From Black Pepper Tea
To brew a piperidine rich drink from black pepper without extracting much of the piperine, mix course ground black pepper in cold water. Let it steep overnight in the refrigerator. Filter out the solids and discard them. The piperine in the black pepper is very poorly soluble in cold water and most remains in the black pepper grounds.
One 8 ounce cup of tea prepared in this way from 8 grams of black pepper will contain up to 400 mg of piperidine, and up to only 9.4 mg of piperine.
Piperine From Whole Black Pepper
To use black pepper for its piperine content efficiently the black pepper should be consumed whole in capsules, and not brewed as filtered tea.
Doses of up to 8 grams of black pepper have been used orally. However, if brewed as filtered tea, you would need at least 8 1/2 cups of water to hold this level of piperine. Piperine's solubility in water is extremely low (40 mg/L @18 C). 1 cup of water at @18 C can only hold up to 9.4 mg of piperine, the amount of piperine in about 94 mg of black pepper.
Separating Piperidine from Piperine in Black Pepper
Black pepper contains substantial amounts of piperineand piperidine.
Piperine is a very weak base and practically insoluble in water (40 mg/L @ 18 C), and less so in cold water. It does not form salts with weak acids. Piperine hydrochloride is not stable and is practically insoluble in water because it decomposes into hydrochloric acid and piperine on contact with water. Most piperidine salts are very stable, and extremely soluble in water. Piperidine freebase is also highly water soluble..
The boiling point of freebase piperidine (106.3 C) is close to that of water (100 C). In freebase form it distills along with water. It's salt forms boil at much higher temperatures and cannot be distilled along with water. Piperine melts at 130 C and decomposes at higher temperatures. No form of piperine will distill with water.
These highly different characteristics allow these two amines to be easily separated from each other after extraction from black pepper.
Effects on Enzymes and Transporters
Piperine is often wrongfully identified as the active ingredient in black pepper that inhibits CYP2D6. While black pepper inhibits CYP2D6, isolated piperine is a proven selective inhibitor of CYP3A4 with almost no effect on CYP2D6.[6] Other components in black pepper have been identified as potent inhibitors of CYP2D6.[1]
P450 Enzyme | Effects | Strength | Dosage | Verified In Humans |
---|---|---|---|---|
CYP1A1 | Unspecified Inhibition | ? | ? | ? |
CYP2A6 | Unspecified Inhibition | ? | ? | ? |
CYP2C9 | Potent Inhibition | ? | ? | ? |
CYP2D6 | Potent Inhibition | 72.8% inhibition at high doses[3] | IC50=315 μg/ml | ? |
CYP2D6 | Potent inhibition from 9-(1,3-benzodioxol-5-yl)-1-pyrrolidin-1-ylnon-8-en-1-one1 | >50 % inhibition | 10 mM[1] | ? |
CYP2D6 | Potent inhibition from Pipercyclobutanamide A2 | >50 % inhibition | 10 mM[1] | ? |
CYP3A4 | Potent Inhibition | 84.0% Inhibition[3] | IC50=29 μg/ml | ? |
CYP3A4 | Potent inhibition from piperine | 184% increase in substrates[9] | 15 mg for three days[9] | Yes[9] |
Transporters | Effects | Strength | Dosage | Verified In Humans |
P-gp | Unspecified Inhibition[5] | ? | ? | ? |
Aldehyde Dehydrogenase Enzyme | Effects | Strength | Dosage | Verified In Humans |
Unspecified | Unspecified Induction | ? | ? | ? |
Aldose Reductase Enzyme | Effects | Strength | Dosage | Verified In Humans |
hrALR2 | Potent Inhibition | 0.22 mg/ml[4] | ? | ? |
MAO Enzyme | Effects | Strength | Dosage | Verified In Humans |
MAO-B | Inhibition | ? | ? | ? |