Neuroprotective effects of Centella asiatica against LPS/amyloid beta-induced neurodegeneration through inhibition of neuroinflammation

Abstract

Protein aggregation and microglia-mediated neuroinflammation are the major contributors to the progression of neurodegeneration. Currently, available drugs for neurodegenerative diseases have limited efficacy and are associated with several side effects; suggesting a need to discover novel therapeutic agents. Therefore, we aim to evaluate the neuroprotective effects of C. asiatica against amyloid beta (Aβ) and lipopolysaccharides (LPS)-induced neurodegeneration using human microglia and neuronal cell-based models. To identify potential molecular targets of C. asiatica, network pharmacology-based approaches were used along with molecular docking, followed by experimental validation via indirect ELISA, Western blotting, and indirect immunofluorescence assays. Our results from network pharmacology, molecular docking, and cell-based models, exhibited that AKT1, TNF-α, STAT3, CASP3, PTGS2, MAPK1, APP, and NF-κB are the potential molecular targets of C. asiatica. Further, we have found that C. asiatica treatment reduces LPS/Aβ-induced cell death, NO production, and LDH release in microglia and neuronal cells. The anti-neuroinflammatory effect of C. asiatica was further observed via the reduction of LPS, Aβ, and LPS+Aβ-induced neuroinflammatory markers; TNF-α, IL6, IL-1β, AKT1, INOS, NF-κB, MAPK3, and PTGS2 in microglia cells. Moreover, neurodegenerative and apoptotic markers; APP, α-syn, P-tau STAT3, and CASP3 were reduced upon C. asiatica treatment in neuronal cells, suggesting its neuroprotective properties. For the first time, we have shown the neuroprotective effects of C. asiatica against LPS, Aβ, and LPS+Aβ −induced neurodegeneration via inhibition of neuroinflammation and neurodegenerative markers. The outcomes of the study suggested that C. asiatica could be a promising candidate for neuroinflammation-mediated neurodegenerative diseases like Parkinson’s and Alzheimer’s.