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Inhibition of caspase-3 by isolates from Lonchocarpus haberi from Monteverde, Costa Rica
Caspase-3 plays a pivotal role in apoptosis as an executioner caspase when cells are damaged due to UV, oxidative stress, and disease. By inhibiting caspase-3 it allows the cells to remain alive. This is particularly useful for neurological diseases since there is already a decrease in proliferating nerve cells, by inhibiting cell death, it will keep more of the cells alive.
Lonchocarpus haberi M. Sousa (Fabaceae, Papilionoideae) was collected from Monteverde, Costa Rica. Crude bark extracts were obtained by Soxhlet extraction using acetone. The crude extract was initially separated using preparative flash chromatography on silica gel. Those fractions were then dissolved in methanol and subjected to HPLC analysis.
Human caspase-3 was cloned into pET28b and purified using FPLC. The activity was analyzed using a colorimetric assay comparing the inhibition of novel compounds with the known inhibitor DEVD-fmk.
Two isolated compounds showed notable inhibitor activity against caspase-3. Preliminary results show a decrease in caspase-3 activity as much as 35%-45% depending on the chemical environment of the inhibitor.