Gender-associated modulation of inducible CYP1A1 expression by andrographolide in mouse liver

Abstract We previously observed a strong synergistic effect on polycyclic aromatic hydrocarbon (PAH)-induced CYP1A1 expression by andrographolide, a major constituent of an herbal medicine derived from the plant Andrographis paniculata , in mouse hepatocytes in primary culture. The present paper describes confirmation of an enhancing effect of andrographolide on the CYP1 family in vivo in the PAH-responsive C57BL/6 mouse. Andrographolide did not alter CYP1 expression in the PAH-nonresponsive DBA/2 mouse. The enhanced expression induced by andrographolide was observed in male C57BL/6 mice, but not in intact or ovariectomized females, or in orchiectomized male mice. However, treatment with testosterone restored the effect in both orchiectomized males and ovariectomized females. These observations indicate a male hormone-related system to be a crucial mediator of the modulation of CYP1 expression by andrographolide. Precautions should be taken regarding the use of A. paniculata as an alternative medication or health promotion, according to its distinctive characterization on sexually dimorphic modulation of CYP1A1 expression.