Abstract / Summary
Beta-amyloid peptide (Aβ), the key pathogenic factor of Alzheimer’s disease (AD), induces oxidative stress-mediated neuronal damage, eventually leading to death. Madecassic acid (MAD), a natural triterpenoid isolated from Centella asiatica, has been reported for many biological activities, including neuroprotective effects. The low solubility and poor bioavailability of MAD are major limitations; hence, the present study focused on formulating MAD in a nanostructured lipid carrier (NLC-MAD) and evaluating its protective effect against oxidative stress induced by Aβ (25–35) in Neuro-2A cells. NLC-MAD, made of 7.5% total lipid, 50% liquid oil, and 6% surfactant with desirable qualities, was selected for further studies. NLC-MAD exhibited potent free radical scavenging activity (IC50 value 80.20 ± 0.05 μg/mL), reducing power, total antioxidant power, and metal chelating activity (IC50 value 120.12 ± 0.02 µg/mL). NLC-MAD showed a dose-dependent inhibition of acetyl and butyrylcholinesterase with IC50 values of 12.5 ± 0.001 and 30 ± 0.02 µg/mL, respectively. NLC-MAD attenuated Aβ peptide aggregation and disaggregated the preformed mature fibrils. NLC-MAD pretreated Neuro-2A cells attenuated Aβ-induced toxicity dose-dependently and attenuated oxidative stress-mediated toxicity. Safety evaluation studies revealed that NLC-MAD is neither cytotoxic nor hemolytic under in vitro conditions and exhibited no adverse effects under in vivo conditions, indicating a non-toxic nature. The results warrant further studies on the stability of NLC-MAD and preclinical studies before consideration to clinical trials.