Accession Number: pdtdbd00012

Details of the Target and Disease

Target Name : Human Cytochrome P450 2D6
Target Keywords : Human Cytochrome P450 2D6, CYP2D6, Cholesterol
Target Description :

The cytochrome P450s (CYPs), a large diverse heme-containing enzyme superfamily with a large number of members, are found across all organisms in prokaryotic and eukaryotic worlds from animals, plants, fungi, protists, bacteria, and archaea to viruses. These proteins contain unusual reduced carbon monoxide difference spectrum that exhibits a Soret peak at 450 nm, thus called "Pigment at 450 nm" or "P450". The unique spectral peak is produced by a thiolate anion acting as the fifth ligand to the heme. This peak is a unique feature only observed in four classes of hemoproteins, namely, P450s, nitric oxide synthases, chloroperoxidases, and protein H450.

Cytochrome P450 2D6 (Cytochrome P450 family 2 subfamily D member 6) is an enzyme that in humans is encoded by the CYP2D6 gene. The gene is located near two cytochrome P450 pseudogenes on chromosome 22q13.1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. CYP2D6 is primarily expressed in the liver. It is also highly expressed in areas of the CNS, including the substantia nigra.

Human CYPs are primarily membrane-associated proteins located either in the inner membrane of mitochondria or in the endoplasmic reticulum of cells. CYPs metabolize thousands of endogenous and exogenous chemicals. Some CYPs metabolize only one (or a very few) substrates, such as CYP19 (aromatase), while others may metabolize multiple substrates. Both of these characteristics account for their central importance in medicine. Cytochrome P450 enzymes are present in most tissues of the body, and play important roles in hormone synthesis and breakdown (including estrogen and testosterone synthesis and metabolism), cholesterol synthesis, and vitamin D metabolism. Cytochrome P450 enzymes also function to metabolize potentially toxic compounds, including drugs and products of endogenous metabolism such as bilirubin, principally in the liver.

Target Sequence :

Disease Name : Cholesterol
Disease Description :

Cholesterol is a waxy, fat-like substance that's found in all cells of the body. Your body needs some cholesterol to make hormones, vitamin D, and substances that help you digest foods. Your body makes all the cholesterol it needs. However, cholesterol also is found in some of the foods you eat.

Cholesterol travels through your bloodstream in small packages called lipoproteins. These packages are made of fat (lipid) on the inside and proteins on the outside.

There are several types of lipoproteins in the blood. In order of increasing density, they are Ultra Low Density Lipoproteins (ULDL) or Chylomicrons, Very Low Density Lipoproteins (VLDL), Intermediate Density Lipoproteins (IDL), Low Density Lipoproteins (LDL), and High Density Lipoproteins (HDL).

LDL cholesterol sometimes is called "bad" cholesterol. A high LDL level leads to a buildup of cholesterol in your arteries. (Arteries are blood vessels that carry blood from your heart to your body.)

HDL cholesterol sometimes is called "good" cholesterol. This is because it carries cholesterol from other parts of your body back to your liver. Your liver removes the cholesterol from your body.

Disease Symptoms :

High blood cholesterol is a condition in which you have too much cholesterol in your blood. By itself, the condition usually has no signs or symptoms. Thus, many people don’t know that their cholesterol levels are too high. A blood test is the only way to detect high cholesterol. People who have high blood cholesterol have a greater chance of getting coronary heart disease, also called coronary artery disease.

Most diabetics with high blood pressure have no symptoms. However, very high blood pressure or rapidly rising blood pressure can cause:

  • Headaches
  • Vision problems
  • Nose bleeds
  • Trouble breathing
  • Fits
  • Black-outs

Similar to high blood pressure, the symptoms of low pressure may not always be apparent. If you do get symptoms, they may be identified as any of the following:

  • Feeling dizzy, light headed or fainting
  • Blurred vision
  • A rapid or irregular heartbeat
  • Feeling nauseous
  • Confusion
Target Related Dockings :
Human Cytochrome P450 2D6

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Details of the Plant and Ligand

Ligand Name : beta-Sitosterol
Systematic Names : beta-Sitosterol; Cupreol; Sitosterol; Quebrachol; Cinchol; 22,23-Dihydrostigmasterol
Molecular Formula : C29H50O
Molecular Weight : g/mol
IUPAC Name : (3S,8S,9S,10R,13R,14S,17R)-17-[(2R,5R)-5-ethyl-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol
Ligand Description :
  1. β-Sitosterol is a substance found in plants. Chemists call it a "plant sterol ester." It is found in fruits, vegetables, nuts, and seeds. It is used to make medicine.
  2. β-Sitosterol is used for heart disease and high cholesterol. It is also used for boosting the immune system and for preventing colon cancer, as well as for gallstones, the common cold and flu (influenza), HIV/AIDS, rheumatoid arthritis, tuberculosis, psoriasis, allergies, cervical cancer, fibromyalgia, systemic lupus erythematosus (SLE), asthma, hair loss, bronchitis, migraine headache, and chronic fatigue syndrome.
  3. Some men use β-Sitosterol for enlarged prostate (benign prostatic hyperplasia or BPH). Some women use it for symptoms of menopause.
  4. It is also used for enhancing sexual activity.
  5. Marathon runners sometimes use β-Sitosterol to reduce pain and swelling after a run.
  6. Some people apply β-Sitosterol to the skin for treating wounds and burns.
  7. In foods, β-Sitosterol is added to some margarines (Take Control, for example) that are designed for use as part of a cholesterol-lowering diet and for preventing heart disease. The federal Food and Drug Administration (FDA) allows manufacturers to claim that foods containing plant sterol esters such as β-Sitosterol are for reducing the risk of coronary heart disease (CHD). This rule is based on the FDA's conclusion that plant sterol esters may reduce the risk of CHD by lowering blood cholesterol levels. Although there is plenty of evidence that β-Sitosterol does lower cholesterol levels, there is no proof that long-term use actually lowers the risk of developing CHD.
  8. Don’t confuse β-Sitosterol with Sitostanol, a similar substance contained in the product called Benecol. Both Sitostanol and β-Sitosterol are used for lowering cholesterol levels in people with high cholesterol and appear to be equally effective.
Other Related Plants :
Ligand Related Dockings :

Plant Name : Ivy gourd
Alternative Names : Coccinia indica, Scarlet gourd, Kowai, கோவை, கோவைக்காய், கோவைப்பழம்
Scientific Name : Coccinia grandis
Medicinal Parts : Fruit, Leaf, Stem, Root
Plant Category : Vegetable, Herb
2° Metabolites (3/11) :
β-Amyrin, Cephalandrine A, Cephalandrine B, Cephalandrol, Cucurbitin B, Lupeol, β-Sitosterol, Stigma-7-en-3-one, Taraxerol, Taraxerone, Tritriacontane
Phytochemical IDs : pdtdbl00231, pdtdbl00027, pdtdbl00230
Plant Keywords : Ivy gourd, Coccinia grandis, Coccinia indica, Scarlet gourd, Kowai, கோவை, கோவைக்காய், கோவைப்பழம்
Plant Description :

The different medicinal utilities of Ivy gourd are attributed to its various parts such as leaves, fruits, root and stem. Some household uses and remedies of different part of Ivy Gourd are:

Leaves have been used in

  • Skin diseases such as ring worm, itching, skin eruptions as seen in small pox, scabies.
  • Sinus which has been there for a long time
  • Various gastro-intestinal disturbances
  • Causing cooling effects to the eyes
  • In fever to alleviate body temperature
  • Gonorrhea
  • Diabetes or increased glucose in urine
  • Expectorant
  • Urinary tract infection
  • Problems related with respiratory tract

Fruits have been known to cure

  • Sores on tongue
  • Eczema

Stems have been used as home remedy for treatment of

  • Asthma and bronchitis
  • Diabetes and increased blood in urine (a condition known as glycosuria)
  • Gastro-intestinal disturbance
  • Skin disease
  • Urinary tract infection

Roots of Ivy gourd have been shown to be useful in the treatment of

  • Joint pains
  • Painful mouth ulcers
  • Wheezing and phlegm
  • Skin diseases
  • Diabetes and glycosuria

In India, it is eaten as a curry, by deep-frying it along with spices, stuffing it with masala and sauteing it, or boiling it first in a pressure cooker and then frying it. It is also used in sambar, a vegetable and lentil-based soup.


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Ivy gourd

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Details of Docking Evaluation

Docking Score : -52.09 kcal/mol
Number of Interactions : 2
Herbal Recipe :
Extract 20-30 ml juice from Ivy Gourd leaves and consume it early morning on an empty stomach without mixing anything in it. This process will reduce sugar levels in blood within 3 months.
Drug Action :

β-Sitosterol in Ivy gourd inhibits the enzyme glucose-6-phosphatase of Cytochrome P450 2D6. This glucose-6-phosphatase is one of the key liver enzymes involved in regulating sugar metabolism.

Ivy gourd is a powerful anti-diabetic agent. By regulating the breakdown of starch, it helps to prevent a sudden surge of blood sugar after consuming carbohydrates. It could also protect the vital organs from the adverse effect of high blood sugar level. Abnormal changes in the fatty acid composition in diabetics could be prevented by consuming Ivy gourd leaves. By raising the plasma vitamin C level and reducing oxidant agents, Ivy gourd leaves protect diabetics from oxidative stress.

Author(s) : Members of PDTDB team.
Submitted Date : 23-Nov-2016
Docking Keywords : Human Cytochrome P450 2D6, CYP2D6, Cholesterol, beta-Sitosterol, Ivy gourd

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