Unveiling the potential of medicinal herbs as the source for screening toward the inhibition of Nrf2.

Background: Drug resistance is one of the leading causes attributed to the failure of cancer treatment by chemotherapy. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor regulating gene expression in cell defense against oxidative stress or hazardous factors. Taking advantage of this feature, Nrf2 also serves as the bodyguard for both normal and cancer cells. Many pieces of evidence have reported that inhibiting Nrf2 activity in cancer cells can reverse chemotherapy drug resistance. In addition, secondary metabolites from medicinal plants have been reported to inhibit Nrf2 activity in the study. This study aimed to preliminarily investigate fractions from medicinal herbs that inhibit Nrf2 activity in Huh7 liver cancer cells, thereby establishing a basis for subsequent isolation and extraction processes.

Materials And Methods: Sub-fractions from five medicinal plants have been evaluated the Nrf2 inhibitor activity on Huh7 cells through luciferase-reported genes assay. Thin-layer chromatography (TLC) was also performed to quantify the extracts' main phytochemistry components. Combining the half-maximal inhibitory concentration (IC) and half-maximal cytotoxicity concentration (CC) enables us to determine which extracts have the potential for further isolation steps.

Results: Ten over 30 crude extracts and sub-fractions showed the inhibition of Nrf2 activity with the percentage ranging from 30 to 97 %. The methanol and -hexane sub-fractions from Lour. leaves showed the strongest inhibition ability on Nrf2 activity with the IC = 20.98 ± 3.67 and 42.22 ± 2.10 μg/mL, respectively. The TLC results showed the presence of steroids and terpenoids in the promising sub-fractions.

Conclusions: Combining the TLC results with the screening on Nrf2 activity screening of medicinal plants, the outcomes suggest the steroids and terpenoids in the methanol extract and hexane sub-fraction from Lour. leaves show promise towards inhibiting Nrf2 activity in liver cancer cell lines without toxicity in the normal cells.