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  • phosphodiesterase inhibitor On the other hand the interactio

    2019-12-02

    On the other hand, the interaction of the Kaempferia parviflora extract with CYP3A was uncompetitive with a low Vmax value. In the in vivo study, the Kaempferia parviflora extract did not interfere with CYP3A activity throughout the entire duration of treatment. This is fortunate as CYP3A isoforms are important phosphodiesterase inhibitor involved in the metabolism of many drugs and xenobiotics including clarithromycin, codeine, cyclosporin, dapsone, diazepam, erythromycin, indinavir, lovastatin, nifedipine, carbamazepine, losartan, quinidine, taxol, terfenadine, and verapamil (Lin and Lu, 1998). There were several reports of commercial methoxyflavones affecting CYP450 activity. Wen et al. (2005) reported that DMF and 5-hydroxy-7-methoxyflavone inhibited CYP1A1 activity. Walle and Walle (2007) also demonstrated that DMF and TMF affected on CYP1A1, CYP1A2, and CYP3A4 activity. In addition, 2′-methoxyflavone, 3′-methoxyflavone, 4′-methoxyflavone, and 3′,4′-dimethoxyflavone inhibited CYP1A1, CYP1A2, and CYP2A6 activities (McKendall et al., 2008). Our results revealed that Kaempferia parviflora crude extract, which is a traditional used preparation that contains more than 11 methoxyflavones (Sutthanut et al., 2007), modulated CYP450 metabolizing enzymes. However, to better understand the modulatory effect of methoxyflavones of the Kaempferia parviflora, each ingredient should be further studied.
    Conclusions Kaempferia parviflora extract had a marked effect on CYP450 metabolizing enzymes in both in vitro and in vivo studies. These enzymes are responsible for metabolizing many drugs and herbs. Therefore, drug–herb interactions need to be considered when concomitantly administering other medications. This also points to the importance of fully characterizing the Kaempferia parviflora extract in terms of methoxyflavone content in order to bring about an effective utilization of the herb and to better predict the potential for interactions. In addition, the induction of CYP1A1, CYP1A2, CYP2B, and CYP2E1 enzymatic activity by the Kaempferia parviflora extract might cause an activation of carcinogenesis. However, the mechanism of these effects needs to be investigated further. Moreover, the effect of certain methoxyflavones as inhibitors or inducers should be further identified.
    Acknowledgements The research fund of this study was obtained from the Office of National Research Council of Thailand, the Royal Golden Jubilee PH.D. Program (Grant No. PHD/0072/2549) to Catheleeya Mekjaruskul and Bungorn Sripanidkulchai, the National Research Council of Thailand, Graduate School, Khon Kaen University, Thailand, and Center for Research and Development of Herbal Health Products, Khon Kaen University, Thailand.
    Introduction Oxysophocarpine (OSC) and sophocarpine (SC), which are major phosphodiesterase inhibitor active and toxic quinolizidine alkaloids, are highly valued and are important in traditional Chinese medicine (TCM). These TCMs include Sophora flavescentis radix (Kushen) and Subprostrate sophora Root (Shandougen), which are widely distributed in Asia, Oceanica, and the Pacific islands. These medicines are commonly used for the treatment of inflammation, hepatitis, and cardiac diseases for thousands of years in China. In recent years, they have held impressed attraction in the scientific field because of their neuroprotective, anti-viral, anti-hepatitis B virus, antioxidant, cardioprotective, and anti-tumor activities [33]. “Kushen” injection and capsule, derived from the TCM and mainly composed of Kushen, had been clinically used in China for the treatment of chronic hepatitis or oligoleukocythemia caused by liver cancer. In addition, Kushen was used to improve liver function and ameliorated the degree of liver injury. Quinolizidine alkaloids, which have powerful and wide pharmacological activities, have been proven to be the main bioactive components in S. flavescens. OSC showed significant anti-HBV activity with inhibitory potency against HBsAg secretion [4] and has significant neuroprotective effects that can be attributed to the inhibition of endoplasmic reticulum stress-induced apoptosis [33]. OSC administration is also suggested to have anti-nociceptive effects on the central and peripheral nervous systems [27]. SC is an effective agent for treating colonic inflammation; SC can significantly decrease myeloperoxidase activity and ameliorate dextran sulfate sodium induced colitis by regulating the production of anti-inflammatory cytokines IL-6 and IL-1 [26].