Evaluation of selected indigenous medicinal plants from the western Himalayas for cytotoxicity and as potential cancer chemopreventive agents

Abstract

The western Himalayas in the northern areas of Pakistan have significant potential for ethnomedicinal research. In the current study, indigenous informants were interviewed using open-ended questionnaires and a free-listing of knowledge related to native medicinal plants. Information patterns indicated that over 100 local plant species were in frequent medicinal use for a variety of conditions, including inflammation and cancer. Several field surveys were conducted in community forests and meadows, with the aim of exploration, collection, taxonomic identification, and finally, in vitro analysis. Organic extracts of eight species were tested for inhibition of nuclear factor-kappaB (NF-κB), activation of retinoic acid X receptor alpha (RXR), induction of quinone reductase (QR), and inhibition of aromatase, along with assessment of cytotoxicity with four human cancer cell lines. Mellia azedarach, Ajuga bractiosa, Figonia cretica and Swertia chirata inhibited both tetradecanoylphorbol-13-acetate (TPA) and tumor necrosis factor (TNF) activated NF-κB activity, whereas Silybum merianum and Rumex dentatus were only active against TNF activation. The lowest IC50 values for inhibition of TPA activated NF-κB activity were 0.41 and 0.44 μg/mL for A. bractiosa and S. chirata, respectively. Extracts from three plant species, A. bractiosa, R. dentatus and R. hastaus, were active in the RXR assay. Results from the QR assay showed five active samples (with induction ratios >2) belonging to four species: A. bractiosa, R. dentatus, S. merianum and S. chirata. Most of the plant extracts were not cytotoxic (IC50 values >20 μg/mL) with HepG2, MCF7, LNCaP and LU cell lines. Only two plants, R. dentatus and R. hastaus, demonstrated moderate cytotoxic responses (IC50 values 5-15 μg/mL) with HepG2, MCF7 or LNCaP cells. None of the plant extracts was found to inhibit aromatase activity. Based on these data, it may be suggested that the plants under investigation contain potential chemopreventive compounds. Additional testing is required. However, the positive responses observed in these bioassays illustrate the high potential of local medicinal plants.