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.

Keywords::

• Traditional medication
• chemoprevention
• ethnobotany
• anticancer
• medicinal plants
• nuclear factor-kappaB
• retinoic X receptor
• quinone reductase
• cytotoxicity

Acknowledgements

The authors are grateful for funding support by the Higher Education Commission Pakistan, under “International Research Support Initiative Program” for field survey. We also acknowledge all the local people, herbalists and field staff for their help during plant collection. This work was supported by Program Project P01 CA48112 USA, awarded by the National Cancer Institute, USA.

This work was presented in part as an abstract at the 31st Annual Conference of the American Society of Ethnobiology, University of Arkansas, Fayetteville, Arkansas, USA, 16–19 May 2008.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.