Modulatory effects of Benjakul extract on rat hepatic cytochrome P450 enzymes

Abstract

Benjakul, a traditional Thai formulation, has been used as a carminative and adaptogenic drug. It consists of five plants, Piper chaba Hunter, Piper sarmentosum Roxb., Piper interruptum Opiz., Plumbago indica Linn., and Zingiber officinale Roscoe, in equal ratios. Some individual herbs present in Benjakul were reported to modulate cytochrome P450 (CYP) enzymes. This study aimed to investigate the effects of Benjakul extract on the activities and mRNA expression levels of hepatic CYP2C11 and CYP3A1 in rats. Adult male rats were orally administered 200, 400, or 600 mg/kg BW Benjakul extract for 28 days. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine levels were assayed. CYP2C11 and CYP3A1 activities were analyzed using cytochrome P450 assay kits. The mRNA expression of CYP2C11 and CYP3A1 was measured using a quantitative real-time PCR assay. Benjakul treatment significantly increased the serum ALT and BUN levels. At doses of 200, 400, and 600 mg/kg BW, Benjakul treatment increased hepatic CYP3A1 activity and CYP3A1 mRNA expression. CYP2C1 1 mRNA expression was unchanged by treatment with Benjakul extract; however, treatment with the high and middle doses of Benjakul extract increased CYP2C11 activity. Treament with Benjakul extract induced CYP2C11 and CYP3A1 activity in rats. Concurrent use of Benjakul with conventional drugs should be considered to potentially induce herb-drug interactions.

Lysiphyllum strychnifolium (Craib) A. Schmitz Extracts Moderate the Expression of Drug-Metabolizing Enzymes: In Vivo Study to Clinical Propose

“…The most regular mechanisms of herb extracts imply the induction or inhibition of CYP450 expression, which correlates with protein synthesis [ 34 ] and enzyme activity [ 2 ]. The stimulation of CYP450 enzymes enhances drug clearance, leading to a decrease in the therapeutic effect, while inhibition results in a decrease in drug excretion and increases the drug plasma concentration, causing toxicity and therapeutic failure [ 2 , 15 ]. In this study, we reported the Que and GA derived from LS-SE and LS-LW.…”

“…Rat CYP2C11 is functionally similar to human CYP2C9 [ 2 ]. CYP2C11 has a proportion of 60% of the total; it metabolizes approximately 15% of all drugs [ 45 ] and is considered the main enzyme for the anti-coagulant warfarin [ 46 ], the anti-diabetic agent tolbutamide, the nonsteroidal anti-inflammatory drug diclofenac [ 45 ], angiotensin II blockers, and antiepileptics [ 47 ].…”

“…The use of herbal medicines as complementary or alternative medicines has become increasingly common in many countries worldwide due to scientific support for their therapeutic effectiveness and fewer harmful side effects than conventional therapies [ 1 , 2 ]. Lysiphyllum strychnifolium (Craib) A. Schmitz (Fabaceae family) (LS) is also known as Ya nang daeng or Khayan [ 3 ].…”