Protective role of root-derived betulinic acid from Artocarpus heterophyllus against arsenic-induced neurotoxicity in Drosophila melanogaster

Exposure to arsenic (As) has several adverse health effects, including cognitive deficits in humans and animals. In
the present study, neuroprotective effect of Artocarpus heterophyllus root derived purified (98 %) betulinic acid
powder (BAP) was examined against As induced neurotoxicity in Drosophila melanogaster (Oregon K, wild type).
BAP was well characterized using HPTLC and LC-MS. Adult flies treated with As alone showed significant
behaviour deficits, enhanced oxidative stress, neurotoxicity, and mortality. Further, flies were co-fed with BAP
along with As (0.5 mM) for 7 days. As a result, BAP decreased the mortality rate in a concentration dependent
manner against As toxicity (36–77 %). Behavioural studies indicated that flies treated with BAP had an improved
locomotor phenotype and increased survival potential (18 days) for As induced flies. The biochemical analysis
revealed that BAP restored As induced elevation of oxidative markers in both head and body regions of flies. BAP
enhanced the activity of membrane-bound enzymes such as succinate dehydrogenase and NADH-cytochrome c
reductase. Additionally, it was found that BAP alleviated cholinergic disturbances and dopamine depletion,
which are associated with As and bring down abnormal brain architecture to normal. Overall, data suggests that
BAP may provide neuromodulatory effects against As-induced neurotoxicity by suppressing oxidative stress and
attenuating mitochondrial dysfunction.