Inhibition of glutathione S-transferases by some Malvaceae flowers

Glutathione S-transferase (GST) enzymes have important roles in detoxification and have been implicated in resistance of tumor cells against chemotherapeutic agents. Exhibiting inhibitory potential on GST activity by plant extracts will be crucial in increasing the efficiency of cancer chemotherapeutics. Eight Malvaceae plant extracts were evaluated for their inhibitory effects on different mammalian GST isoenzymes along with their polyphenol, flavonoid, anthocyanin contents and antioxidant efficiencies. Hibiscus subdriffa extracts exhibited the highest phenolic contents (60.74 ± 7.1 mg gallic acid/g dry tissue). The highest flavonoid content was obtained with Hibiscus cannabinus (17.38±2.12 mg rutin/g dry tissue). H. subdriffa and H. cannabinus extracts showed high antioxidant activities (IC50 equal 0.79 ± 0.09 and 0.820 ±0.04 mg /ml, respectively), also had high phenolic, flavonoide and anthoyanin contents. Among the plant extracts studied for GST inhibition activity, Gossypium hirsutum (cotton) was the most efficient inhibitor for all studied GSTs (rat liver & kidney and human erythrocytes & placenta). Erythrocyte hGSTP1-1 only inhibited by G. hirsutum extracts with IC50 value equal 0.35 mg/g dry tissue, correlating with its relatively high phenolic contents. Inhibition of hGSTP1-1 by gossypol (major constituent of G. hirsutum) in vitro indicates the potential use of these compounds both as an in vivo inhibitor for GST P1-1. G. hirsutum extracts inhibited the purified erythrocyte hGSTP1-1 competitively, while, non-competitive inhibition was observed when gossypol (the major constituent of cotton flower) was used as inhibitor for both GST substrates, GSH and CDNB.