INVOLVEMENT OF PHARMACOGENETICS IN PHARMACOLOGICAL ACTIONS OF MEDICINAL PLANTS (A NARRATIVE REVIEW)

Abstract

Actuality. Pharmacogenetics (PGx) and pharmacogenomics (PGx) involve variations of human genome sequencing amongst individuals, which may influence drug response. The application of PGx and personalized medicine may assist health care providers in administering optimal medication and doses to avoid adverse effects of treatment for specific patients. However, the impact of genetic variability on the pharmacokinetics of natural products and their influence on gene expression regulation is not fully understood. The purpose of the work. This narrative review aims to demonstrate the effects of genetic heterogeneity on the pharmacokinetics of natural products and their role in the modulation of specific genes involved in the treatment of mental disorders and cancer, as well as herb-drug interactions. Material and methods. A narrative review was conducted using PubMed, Google Scholar, and Scopus databases. 22 articles aligned with the inclusion criteria for this review. Research results. Flavonoids, stilbenes, coumarins, quinones, and terpenes have been reported to impede UDPglucuronosyltransferase (UGT) enzymes. Inhibition of UGT1A1-mediated bilirubin glucuronidation by herbs rich in certain polyphenolic acids, may lead to a high bilirubin-related adverse drug reactions. Silybins, the main component of milk thistle, may cause herb-drug interactions by inhibiting UGT1A1*1 and UGT1A1*6 genotypes. Tulbaghia violacea leaves extractions upregulate p53 and p21 gene expression, leading to a suppression of tumor development in HeLa cells. Resveratrol concomitant with other agents downregulates expression of the multi-drug resistance (MDR1) gene and the apoptosis-suppressing gene (Bcl-2). The MDR modulation function of Traditional Chinese Medicine components (flavonoids, alkaloids, terpenoids, coumarins, quinonoids) and extracts (Bufo gargarizans, Salvia miltiorrhiza, and Schisandra chinensis) is achieved by decreasing the P-glycoprotein expression. In silico analyses have demonstrated the potential of some active ingredients of herbal antidepressants for inhibition of CYP2D6 WT and CYP2D6*53. In vivo administration of Carthamus tinctorius extract revealed a significantly different gene expression pattern associated with major depressive disorder, anxiety, and neurobehavior. Conclusion. The application of PGx may support personalized administration of natural products, as well as provide opportunities to choose the most beneficial concomitant herb-conventional therapy to prevent drug toxicity or synergism.