Abstract
The effects of Andrographis paniculata and Orthosiphon stamineus extracts on the in vitro glucuronidation of 4-methylumbelliferone (4MU) by recombinant human UGTs, UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A10, UGT2B7 and UGT2B15 were determined. The potential inhibitory effects of both of the extracts on the activity of each of the UGT isoforms were investigated using 4MU as the substrate. Incubations contained UDP-glucuronic acid (UDPGA) as the cofactor, MgCl2, cell lysate of respective isoform, and 4MU at the approximate apparent Km or S50 value of each isoform. Final concentrations of Andrographis paniculata and Orthosiphon stamineus extracts used were 0.025, 0.25, 2.5, 25 and 50 μg/mL and 0.01, 0.10, 1.0, 10 and 50 μg/mL respectively. Both extracts variably inhibited the activity of most of the isoforms in a concentration dependent manner. Andrographis paniculata extract was the better inhibitor of all the isoforms studied (IC50 1.70 μg/mL for UGT1A3, 2.57 μg/mL for UGT1A8, 2.82 μg/mL for UGT2B7, 5.00 μg/mL for UGT1A1, 5.66 μg/mL for UGT1A6, 9.88 μg/mL for UGT1A7 and 15.66 μg/mL for UGT1A10). Both extracts showed less than 70% inhibition of UGT2B15, so the IC50 values were >50μg/mL. The inhibition of human UGTs by Andrographis paniculata and Orthosiphon stamineus extracts in vitro suggests a potential for drug-herbal extract interactions in the therapeutic setting.
Highlights
It is becoming more common to consume drugs with medicinal herbs, and studies that evaluate the potential or possible interactions of therapeutic drugs and herbal medicines are much needed
Andrographis paniculata extract contained as its primary constituents lactones such as andrographolide, neoandrographolide and deoxyandrographolide, along with flavonoids
We studied the effects of andrographolide on all isoforms except UGT2B15 since the extract had minimal effect on UGT2B15 (Figure 2)
Summary
It is becoming more common to consume drugs with medicinal herbs, and studies that evaluate the potential or possible interactions of therapeutic drugs and herbal medicines are much needed. In Malaysia, two of the most commonly used medicinal herbs are Andrographis. F.) Nees from the Acanthaceae family, indigenous to China, India and South East Asia has been traditionally used in Asia for gastric disorders, colds, influenza and other infectious diseases [1]. For the last two decades, a standardized extract of Andrographis paniculata has become popular in Scandinavia in treating the common cold [2]. There are reports on Andrographis paniculata’s effectiveness as an immunostimulant [3] and as an anti-HIV drug [4]
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