Andrographis paniculata: a review of aspects of regulatory mechanisms of hepatic CYP1A enzymes
Titel:
Andrographis paniculata: a review of aspects of regulatory mechanisms of hepatic CYP1A enzymes
Auteur:
Kanokwan Jarukamjorn
Verschenen in:
Boletín latinoamericano y del Caribe de plantas medicinales y aromáticas
Paginering:
Jaargang 7 (2008) nr. 2 pagina's 100-107
Jaar:
2008
Inhoud:
Cytochrome P450 (CYP) enzymes are involved in the biotransformation of a plethora of structurally diverse compounds of both endogenous and exogenous as well as numerous interactions between drugs and food, herbs and other drugs. CYP1A participates in the metabolic activation of chemical mutagens from daily exposure to tobacco smoke, cooked food, automobile exhaust, and industrial processes, in which its mechanism of transcriptional regulation has been postulated through an arylhydrocarbon receptor (AhR) and the AhR nuclear translocator. The activity of CYP1A is thus suspected to be not only a critical aspect for risk assessment when determining carcinogenicity, but also a considerable safety criterion for drug development testing. Andrographis paniculata, a folklore remedy employed as an herbal supplement for an alternative medicinal therapy or for health promotion including its major diterpenoid constituent andrographolide has been reported to possess several pharmacological activities. Besides the potentials for the treatment of ailments, the crude extract of Andrographis paniculata has exhibited capability to increase hepatic CYP1A enzymes including ethoxyresorufin and methoxyresorufin activities, in accord with the inductive effects conveyed by andrographolide. Strong synergistic induction of CYP1A1 by co-treatment with andrographolide and a typical CYP1A inducer as well as a robust increase of CYP1A1 by andrographolide in which the induction was blocked by an AhR antagonist resveratrol, affirmed participation of AhR-mediated transcription activation on andrographolide-induced CYP1A1 expression. Therefore, some advice and precautions for rational use of Andrographis paniculata and/or andrographolide including some associated risks are of clear concern. Moreover, investigations not restricted to the AhR-mediated pathway revealing the synergistic mechanism of andrographolide on CYP1A1 induction as well as influences of other confounding substances in this herb and andrographolide analogues, which
Uitgever:
Sociedad Latinoamericana de Fitoquímica (provided by DOAJ)
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