Add time:08/30/2019         Source:sciencedirect.com

Neem seed preparations contain not only azadirachtin as the active insect antifeedant or growth regulator but also a variety of other limonoids, some of which are cytotoxic to N1E-115 neuroblastoma (mouse), 143B.TK− osteosarcoma (human) and Sf9 (insect) cultured cell lines. The most potent of these limonoids is nimbolide with an IC50 ranging from 4 to 10 μM and averaging 6 μM for the three cell lines. Other limonoids of decreasing potency and their average IC50 values (μM) are epoxyazadiradione (cas 18385-59-6) 27 μM, salannin 112 μM, and nimbin, deacetylnimbin and azadirachtin each > 200 μM (practically nontoxic). Nimbolide at 10 μM acts rapidly in the neuroblastoma cells to induce blebbing associated with disruption of plasma membranes almost instantaneously and 50% loss of cell viability within 30 min. At 5 μM nimbolide, the cells become elongated and assume a neuronal shape accompanied by spikes and lamellipodia within 1–2 hr followed shortly thereafter by extensive cytological changes and vacuolization associated with irreversible processes leading to cell death. Calcium is apparently not involved in the cytotoxic effect since a calcium-free medium, leading to profound morphological changes, does not alter the sensitivity to nimbolide. In contrast, epoxyazadiradione requires higher concentrations and a few hr for 50% viability loss without major morphological changes, indicating a difference in mode of action for nimbolide and epoxyazadiradione.

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