Herb-Drug Interactions Essay

Herb-Drug Interactions:

The use of herbs as a complementary and alternative medicine has increased steadily over the last decade. The WHO (2002) report stated that more than 80% of the world market depending on herbal medicinal products. In Asian countries, approximately 80% population use herbal medicine for promoting health conditions and healing several diseases (Young et al., 2011).

In India and China, traditionally herbs are widely used in Ayurveda and Traditional Chinese medicines (TCM) systems, respectively. Ayurveda (Ayur, life; Veda, science or knowledge) is an ancient medical science of India. It is included several herbs viz., aloe-vera, garlic, ginger, brahmi, ashoka, neem and tulsi. In Traditional Chinese medicines (TCM), several

The first major concern of herb-drug interactions was recognized in 1989, when grapefruit juice was reported to increase the blood concentrations of felodipine (anti-hypertensive calcium channel antagonist). Afterward in 1996, a similar interaction of grapefruit was observed with terfenadine (a non-sedative antihistamine). Consecutive studies reported that inhibitory effect of grapefruit juice was primarily, due to the inhibition of intestinal CYP3A4 and P-glycoprotein (P-gp) by furanocoumarins (e.g. 6’, 7’-dihydroxybergamot-tin, bergamottin and bergapten). Due to the inhibition of CYP3A4 enzyme, blood concentration of terfenadine increases which leads to prolonged QT intervals and following cardiac arrhythmias. This was one of the main reasons for withdrawal of terfenadine from the market in 1998. Grapefruits showed significant CYPs mediated interaction with several drugs (specifically CYP3A4 substrates) (Wanwimolruk et. al., 2014).

St. John's wort (Hypericum perforatum L.; family Clusiaceae) is a popular medicinal herb, widely used for the treatment of depression and anxiety. On chronic use, It affect the pharmacokinetic of several drugs (cyclosporine, theophyllin, warfarin, oral contraceptives, digoxin, indinavir and clopidogrel) by inducing CYP 3A4, 2C9 and 1A2 enzymes; results in treatment failure. Also, it has been reported to inhibit the CYP 3A4 isoform, increased

Whereas, some drugs simultaneously modify both the apoprotein and the prosthetic heme group of CYP enzymes. For example, spironolactone (antihypertensive drug) is irreversible inhibitor of the CYP2C and CYP3A subfamilies (Juinn et. al., 1998).

1. Heme Alkylation: Drugs containing terminal double-bond (olefins) or triple-bond (acetylenes) can oxidized by CYPs to potent radical intermediates, which alkylate the prosthetic heme group and inactivate the enzyme. For example, allyl-isopropylacetamide (AIA) and ethinylestradiol.

2. Covalent Binding to Apoprotein: Covalent bonding of few drugs to apoprotein causes covalent modification of protein which results in loss of catalytic activity, only if essential amino acids are modified (Kamel et. al., 2013). For example, chloramphenicol, tienilic acid and cyclopropylamines inhibit CYP enzymes by generating reactive species that modify the protein. In case of chloramphenicol, the dichloroacetamido group is oxidized to an oxamyl moiety that acylates a lysine residue in the CYP active site; leads to CYPs enzyme inhibition (Juinn et. al., 1998).

Quasi-Irreversible