Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

Pharmacogenomics and Alternative Medicine
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Pomegranate Juice
Pomegranate juice (PJ) was previously reported to have anti-atherogenic and antioxidative
properties. This antioxidant effect may be due to PJ phenolic, which can
stimulate PON2 expression via PPAR and AP-1 pathway activation. 49,50 It may also
reduce cellular cholesterol accumulation and foam cell formation, and even lessen
chemoprevention and chemotherapy effects of cancers. 51 Studies have been conducted
by researches to find whether PJ could involve the pharmacokinetic pathways
to influence drug responses. Faria et al. found that male mice that consumed PJ
decreased hepatic CYP content by 43%, mainly CYP1A2 and CYP3A. 52 Studies by
Hidaka et al. showed that components of pomegranate inhibited enteric CYP3A,
therefore inhibiting CYP3A-mediated metabolism of carbamazepine and further
altered the carbamazepine pharmacokinetics (the AUC of carbamazepine increased
by 1.5-fold). 53 PJ is also reported to influence the pharmacokinetics of nitrendipine.
The increase in AUC of nitrendipine in coadministered and pretreated groups was
1.8- and 4.99-fold, and in C max was 1.4- and 4.1-fold, respectively. This effect may
due to the chronic inhibition by PJ on intestinal P-gp-mediated efflux and CYP3Amediated
metabolism of nitrendipine. 54
Cinnamon
The Chinese herb medicine cinnamon is known to have antidiabetic effects. It can
improve both insulin resistance and glucose metabolism. The antidiabetic effect of cinnamon
may work by activating AMP-activated protein kinase pathways, upregulating
mitochondrial uncoupling proteins-1 (UCP-1), and enhancing the production and translocation
of glucose transporter 4 (GLUT4). 55,56 Currently, there is a lack of genetic variation
study on the differences in cinnamon treatment response. Studies have reported
that functional polymorphisms rs5435 (C→T) of the GLUT4 gene is associated with
diabetes, with the odds ratio for the C/T + T/T genotype being 1.26 when taking the
C/C genotype as reference. 57 Whether the cinnamon treatment effect is affected by this
glucose transporter gene polymorphism still remains to be validated.
Butterbur
Butterbur or Petasites hybridus is a herbal remedy for add-on therapy of asthma
because of its anti-allergic and anti-inflammatory effects. 58 Its preventive treatment
of migraine has also been widely reported to be effective. 59 A bioactive compound,
S-petasin, isolated from butterbur, is reported to inhibit adrenocorticotropin or
cAMP production and decrease the activities of cytochrome P450 side-chain cleavage
enzyme (P450scc). 60 In vitro study discovered that butterbur extracts can inhibit
COX-2 and PGE2 release by direct interaction with the enzyme and by preventing
p42/44 MAP kinase activation. 61
Together with the above-mentioned herbs, artichoke, PJ, and cinnamon are wellknown
CAM for diseases. Pharmacogenomic mechanisms are proved to involve
drug response and affect herb–drug interactions via regulating pharmacokinetic and
pharmacodynamics gene expressions. In these four herbs, however, there is still a