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  • The Kaempferia parviflora extract met the criteria for a

    2021-07-22

    The Kaempferia parviflora extract met the criteria for a non-competitive interaction with CYP1A1 based on the decrease of Vmax and unchanged Km. The high Ki value and low IC50, as well as the high Km value was indicative of the weakness of the interaction between the Kaempferia parviflora extract and CYP1A1. In the in vivo study, CYP1A1 activity was markedly induced by the short-term Kaempferia parviflora extract treatments. This finding was similar to previous reports on Andrographis paniculata extract (Jarukamjorn et al., 2006), and Curcuma comosa extract (Kittichanun et al., 2010), both of which increased CYP1A1 activity. However, the enzyme activity was induced slightly after long-term treatment and may indicate a recovery of the induction of this enzyme. Kaempferia parviflora extract may have hepatoprotective activity following long-term treatment. In addition, the induction of Kaempferia parviflora extract on CYP1A1 may impact the activation of carcinogenesis due to its ability to activate certain procarcinogens including benzo[a]pyrene and other polycyclic hydrocarbons (Guengerich and Shimada, 1991). With respect to CYP1A2, the Kaempferia parviflora extract presented a mixed-type interaction pattern with an increase in both Vmax and Km suggesting that it might bind to both the active site of the enzyme and an allosteric site. Interference with the allosteric site of CYP1A2 could modify the conformation of the enzyme and prevent the binding and subsequent UNC 0642 of concomitantly administered drugs (Volak et al., 2008). The high Vmax and low Ki values were indicative of a potent interaction between the Kaempferia parviflora extract and CYP1A2. In addition, short-term treatments with the Kaempferia parviflora extract resulted in the induction of CYP1A2 activity; this returned to baseline levels after prolonged administration. However, the induction was lower than that of β-naphthoflavone, positive control. Since, CYP1A2 is the main metabolic enzyme for many drugs, e.g., paracetamol, caffeine, ondansetron, phenacetin, tacrine, tamoxifen, and theophylline (Lin and Lu, 1998), the co-administration of Kaempferia parviflora extract with these drugs raises concerns about possible drug interactions. Moreover, CYP1A2 enzyme plays an important role in the activation of procarcinogens to carcinogens such as 2-aminoanthracene, 2-aminofluorene, quinoline derivatives, quinoxaline derivatives, 2-amino-1-methyl-6-phenylimidazole[4,5-b]pyridine (PhIP), and imidazole derivatives (Guengerich and Shimada, 1991). Hence, the Kaempferia parviflora extract may have an influence on carcinogenesis. The observations that the Kaempferia parviflora extract affects CYP1A1 and CYP1A2 activities are in accordance with the report of Walle and Walle (2007) on the effect of the methoxyflavones DMF and 5-methoxyflavone on CYP1A1 and CYP1A2 activities. Regarding the effect of Kaempferia parviflora extract on CYP2B, a competitive interaction in which the substrates may bind with the active site of the enzyme with low Km values are reflective of high potency. The in vivo study demonstrated that the Kaempferia parviflora extract markedly induced CYP2B activity, similar to that observed for Andrographis paniculata (Jarukamjorn et al., 2006) and Curcuma comosa (Kittichanun et al., 2010). CYP2B is an isoform that plays an important role in the metabolism of various drugs including bupropion, coumarins, cyclosphosphamide, mephenytoin, methadone, ketamine, and efavirenz, as well as the pesticide methoxychor (Coleman, 2010). It has also been reported that diabetic rats have markedly increased CYP2B activity (Ioannides et al., 1996). Thus, the consumption of Kaempferia parviflora extract by diabetic patients raises concerns for the possibility of herbal–drug interactions. The interaction of the Kaempferia parviflora extract on CYP2E1 was uncompetitive with low Vmax and Km values. When compared to vehicle group, Kaempferia parviflora extract significantly induced CYP2E1 activity only after long-term treatment. CYP2E1 is an enzyme that metabolizes many commonly used drugs and xenobiotics including ethanol, paracetamol, caffeine, chlorzoxazone, enflurane, and theophylline (Lin and Lu, 1998). This enzyme also plays a key role in the activation of procarcinogens such as carbon tetrachloride, ethylene dichloride, ethylene dibromide, vinyl chlorine, vinyl bromide, and ethyl carbamate (Guengerich and Shimada, 1991). Furthermore, CYP2E1 generates reactive oxygen species that may interact with DNA to induce mutations that involve in the etiology of many diseases including diabetes and rheumatoid arthritis, as well as in the process of aging. As a result of CYP2E1 induction, diabetic animals are sensitive to carcinogens that are activated by this enzyme (Ioannides et al., 1996). The induction of CYP2E1 at an advanced stage of alcoholic liver disease also increases basal lipid peroxidation and carbon tetrachloride-induced peroxidation (Castillo et al., 1992). Therefore, the induction of CYP2E1 by the Kaempferia parviflora extract might cause herbal–drug interactions and promote carcinogenesis.