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Sunday, 2 July 2023

5-methoxypsoralen (5-MoP) Found in #FennelSeedExtract Shows A Strongest Inhibition of Toxins Induced by Drug Interaction , Scientists Show

Kyle J. Norton

Fennel seeds may have the potential to act as liver antitoxins enzymes in removing xenobiotics from our body, some scientists suggested.

Liver cytochrome P450 3A4 (abbreviated CYP3A4) is an important enzyme, mainly found in the liver with the function of stimulating the removal of toxins from our body through the oxidation of small foreign organic molecules (xenobiotics).

Acute drug toxicity is a condition characterized by having too much of a drug in the body at once caused by overdoses of a certain medicine.

Otherwise, drug toxicity is a condition of toxin accumulation caused by long-term intake of medicine which has a strong and negative impact on the liver or kidneys enzymes that are responsible for toxin removals.

The signs and symptoms of toxicity differ depending on the medication. However, most common symptoms may include diarrhea, dizziness, nausea, stomach pains, vomiting, and weakness.

Untreated drug toxicity may induce complications of ataxia, muscle twitches, slurred speech, nystagmus, seizures, coma,....... and, in rare cases, heart problems and death.

Dr. ALASDAIR BRECKENRIDGE, in the article " A clinical pharmacologist's view of drug toxicity" wrote, "Our ability to understand the basis of adverse drug reactions has improved progressively, and with it, the ability to prevent their occurrence; one aim of the clinical pharmacologist is to identify patients at special risk" and " With a fair degree of certainty one can also predict that advances in bioinformatics, genomics, and combinatorial chemistry will progressively contribute to clinical toxicology in the future"(6).

Fennel (Foeniculum vulgare) is a plant species of the genus, belongings to Apiaceae (Umbelliferae), native to the Mediterranean


The herb or food has been used in traditional and herbal medicine as a warming, carminative, antispasmodic, and depressant agent and to stimulate the appetite, ease indigestion, soothe coughing, reduce intestinal spasms, regulate the menstrual cycle, and relieve PMS,...

In the study to compare the effectiveness of herbal compounds isolated from fennel against toxins that are mediated by human liver cytochrome P450 3A4, researchers found that 13 compounds process a strong inhibitory activity(1).

Among these compounds, 5-methoxypsoralen (5-MoP) showed the strongest inhibition of toxins induced by drug interaction with an IC50 value of 18.3 μm and with a mixed type of inhibition(1).

According to the Brescia University Hospital, 5-methoxypsoralen (5-MOP) may be considered an alternative to 8-methoxypsoralen (8-MOP) for photochemotherapy of psoriasis, proven by the study in compared the clinical efficacy and tolerability of 5-MOP (1.2 mg/kg)-UVA versus 8-MOP (0.6 mg/kg)-UVA therapy in 25 patients of skin type III and IV(5).


The University of Toyama conducted an experiment to examine whether methanolic extract of fennel showed a characteristic of mechanism-based inactivation on erythromycin N-demethylation mediated by human liver microsomal cytochrome P450 3A4 (CYP3A4), suggested, 5-methoxypsoralen (5-MOP) showed the strongest inhibition with an IC50 value of 18.3 microM and a mixed type of inhibition, similar to those of above study.

With the preincubation time of 20 min only, 5-MOP showed preincubation time dependency with the IC50 value decreased from 18.3 microM with a preincubation time of 0 min to 4.6 microM with a preincubation time of 20 min(2).

These results suggested that 5-MOP acts as a human Liver Cytochrome P450 3A4 in the inhibition of toxins caused by drug interaction in a time-dependent manner.

Additionally, in the examine the antitoxic effect of 30 sample plants of Indonesia, caused by injection of xenobiotics, researchers showed that methanol extracts isolated from fennel seed exerted time-dependent inhibition toxins oxidized similarly to those of cytochrome P450 3A4 (CYP3A4) and CYP2D6.


In comparing the experimental injection to another plant with the same volume, fennel seeds extract should contain mechanism-based inhibitors on CYP3A4.

Mechanism-based inhibition or suicide inhibition, also known as suicide inactivation is an irreversible form of enzyme inhibition. If you need more information about the definition, please click the link provided by the Evidence Based Medicine

Taken together, fennel may be considered a functional food in protect liver detoxed enzymes against overexpression of toxins caused by small foreign organic molecules.


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Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the Karate GB Daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as the international journal Pharma and Bioscience, ISSN 0975-6299.

Sources
(1) Foeniculum vulgare Mill: A Review of Its Botany, Phytochemistry, Pharmacology, Contemporary Application, and Toxicology by Shamkant B. Badgujar,* Vainav V. Patel, and Atmaram H. Bandivdekar(PMC)
(2) Inhibition on human liver cytochrome P450 3A4 by constituents of fennel (Foeniculum vulgare): identification and characterization of a mechanism-based inactivator by Subehan1, Zaidi SF, Kadota S, Tezuka Y(PubMed)
(3) Mechanism-based inhibition of CYP3A4 and CYP2D6 by Indonesian medicinal plants by Subehan1, Usia T, Iwata H, Kadota S, Tezuka Y.(PubMed)
(4) Antimicrobial and P450 Inhibitory Properties of Common Functional Foods by San Nguyen1 , Huang Huang2 , Brian C. Foster1,3, Teresa W. Tam1 , Tim Xing2 , Myron L. Smith2 , John T. Arnason1 , Humayoun Akhtar(J Pharm Pharm Sci (www.cspsCanada.org) 17(2) 254 - 265, 2014)
(5) A reappraisal of the use of 5-methoxypsoralen in the therapy of psoriasis by Calzavara-Pinton P1, Ortel B, Carlino A, Honigsmann H, De Panfilis G(PubMed)
(6) A clinical pharmacologist's view of drug toxicity by ALASDAIR BRECKENRIDGE(PMC)

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