Abstract
Murraya koenigii is a well-known Indian medicinal herb, and a carbazole alkaloid (mahanine) from this plant causes apoptosis in cancer cells. Here, we investigated how seasonal and geographical variations influence carbazole alkaloids composition and medicinal property of this plant against cancer cells in vitro and in vivo. Leaflets were collected from various places in different seasons for three years. A mahanine-enriched fraction (MEF) was prepared in two steps using ethanol and water. The best plant was selected based on the highest percent of mahanine. MEF prepared from leaflets of nine different locations showed a different concentration of identified markers (mahanine, mahanimbine, and koenimbine) which exhibited differential reduced metabolic activity against ovarian cancer, mahanine being the best. Our systematic study revealed that mahanine content was highest during September–December. Interestingly, MEF from southern part (tropical zone) exhibited 43 ± 2.5% mahanine compared to 2.7 ± 1.3% in northeastern part (subtropical zone) with five folds higher activity against PA1. Moreover, MEF reduced metabolic activity of sixteen cancer cell lines from nine different origins and significantly reduced tumor mass in lung and ovarian cancer xenograft models. Taken together, this is the first report demonstrating the marker's content in these leaflets is highly dependent on location/season. A positive correlation between biological activity and mahanine concentration was established in MEF. Such a comprehensive study suggests that the selection of location and suitable season for collection of any plant materials with biologically active stable markers in sufficient quantity play a decisive role in determining the fate of their medicinal property.
Highlights
Natural products, especially from plants, are important medicinal source for many diseases as documented in Charaka Samhita, a comprehensive text on ancient Indian medicine written during 200–400 B.C., known as “Encyclopedia of Ayurveda” [1]
Such ecological factors varied based on different seasons and diverse geographical regions. erefore, it is worthwhile to prepare a detailed document for the optimization of the conditions for the collection of plant material and in-depth investigation for the best utilization of such herbal product for a specific disease
Our systematic study (Figure 7) reveals that the percent of mahanine is highest in leaflets collected from Tamil Nadu (MEFTN) from September to December
Summary
Especially from plants, are important medicinal source for many diseases as documented in Charaka Samhita, a comprehensive text on ancient Indian medicine written during 200–400 B.C., known as “Encyclopedia of Ayurveda” [1]. The medicinal value of these plants depends upon several ecological factors which include climatic factors like rainfall, atmospheric humidity, wind, gases, temperature, and light; physiographic factors (altitude and sunlight); and biotic and abiotic factors (soil microorganisms and nutrients) [3] Such ecological factors varied based on different seasons and diverse geographical regions. We observed that mahanine is a pro-oxidant molecule It induced death receptor-mediated apoptosis in leukemia, acts as mTORC1/2 inhibitor in glioblastoma multiform [5] and regulation of hedgehog pathway [6] and, acts as Hsp inhibitor in pancreatic [7] and enhanced tumor suppressor proteins in colon cancers, inhibited autophagy and LC3-mediated anoikis in ovarian cancer [8]. It exhibited antileishmanial activity through immunomodulation [9]
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