Herbal products may alter the
Herbal products may alter the metabolism of certain drugs and, likewise, the metabolism of components of herbal products may be altered by some drugs, specifically those that affect cytochrome P450 ryanodine receptor (CYP). These can bring about an alteration of the pharmacokinetics and pharmacological activity of drug or herbal product components leading to adverse reactions following their co-administration (Gonzalez, 1990, Ogu and Maxa, 2000). CYP is a superfamily of isozymes in which CYP1, CYP2, and CYP3 play major roles in the metabolism of many drugs (Randic and Di-Carlo, 1997). The induction or inhibition of some of these isoforms can lead to clinically significant manifestations (Cupp and Tracy, 1998). While drug candidates are routinely evaluated for their effect on drug-metabolizing enzymes during the development process, this is not the case for many herbal medicines. Recently, some herbal medicines were administered for the purpose of measuring the inhibition or induction of hepatic CYP enzymes. For example, andrographalide from Andrographis paniculata was shown to alter CYP1A1 activity and mRNA expression in mice hepatic microsomes (Jarukamjorn et al., 2006, Jarukamjorn et al., 2010, Chatuphonprasert et al., 2009). Pueraria candollei induced CYP2B9 activity and mRNA expression in mouse liver (Udomsuk et al., 2010), while Curcuma comosa extracts increased CYP1A1 and CYP2B1/2B2 activities in rat liver (Kittichanun et al., 2010). In addition, Yahom Ampanthong (combination of traditional medicines) inhibited CYP1A1, CYP1A2, and CYP2E1 activities in mice (Sirisangtrakul and Sripanidkulchai, 2011). Nevertheless, there are no reports regarding the hepatic metabolism of Kaempferia parviflora extract, neither the contribution of CYP450 enzymes to its metabolism nor the effect of the extract on various liver CYP450 isoforms. Therefore, the aim of this study was to investigate the effects of Kaempferia parviflora extract on the in vitro and in vivo activity of pivotal isoforms of mouse hepatic CYP enzymes involved in drug metabolism including CYP1A1, CYP1A2, CYP2B, CYP2E1, and CYP3A. This is expected to raise awareness of possible metabolic interactions with concomitant administered traditional and herbal medicines.
Materials and methods
Discussion Kaempferia parviflora has been long used as a herbal medicine. Methoxyflavones, which are the major components in this plant, can be used as standards for the characterization of Kaempferia parviflora extract. They can be identified and quantified by HPLC analysis with high sensitivity and precision over linear concentration ranges. Although, there are several studies on its pharmacodynamic characteristics and safety, information on the effect of Kaempferia parviflora extract on metabolic enzymes has not been established. Therefore the goal of this study was to investigate the effect of Kaempferia parviflora extract on CYP450 enzyme activities in mouse hepatic microsomes both in vitro and in vivo. The in vitro studies measured a direct effect of Kaempferia parviflora extract on CYP through binding the enzymes, while the in vivo study demonstrated its influence on CYP regulation, both of inhibition and induction. The results showed for the first time that Kaempferia parviflora extract had a significant impact on CYP-metabolizing enzymes. The positive controls used in this study were 3-methylchrolanthrene, β-naphthoflavone, phenobarbital, ethanol, and dexamethasone and were shown to significantly induce CYP1A1, CYP1A2, CYP2B, CYP2E1, and CYP3A activities, respectively, compared to that of the untreated control group. Similarly, the vehicle (2% carboxymethyl cellulose) that was used to suspend the Kaempferia parviflora extract did not affect the CYP450 contents, CYP1A1 and CYP3A activities in all durations of treatment, and CYP1A2, CYP2B, and CYP3A activity in 7- and 14-day of treatments. However, the vehicle slightly affected on CYP1A2, CYP2B, and CYP2E1 activities at 21-day of treatment. This is consistent with the findings of Cantoni et al. (2003) who reported that using 1.6% carboxymethyl cellulose as a vehicle for St. John's wort (Hypericum perforatum) extract for 12-day treatment, did not affect CYP450 enzymatic activity. These findings implied the possible effect of long-term utilization of carboxymethyl cellulose as the vehicle. Moreover, the hepatic microsomal CYP450 contents of the mice after 7 and 21 days Kaempferia parviflora extract treatment were not significantly different from the vehicle control groups. However, the elevated levels of CYP 450 after 14 days of treatment suggested a time-dependent induction.