Piper Longum's Neuroprotective Role Against Amyloid-β and Okadaic Acid-Induced Toxicity in U87MG Cells Through the Lipocalin-2 Pathway.

OBJECTIVES: Alzheimer's disease (AD) is a neurological disorder that causes symptoms such as cognitive impairment and memory loss. The number of AD patients keeps escalating throughout the world leading to various social problems, meanwhile no practical treatment for the disease has been proposed. Some of the well-known causes of AD are excessive amyloid-β (Aβ) accumulation and tau hyperphosphorylation. Lipocalin-2 (LCN2) is a proinflammatory mediator in astrocytes that increases Aβ aggregation and tau pathology accumulation. However, Piperine, a plant-derived siderophore found in Piper longum disrupts the function of LCN2. This study aimed to investigate the effect of P. longum on U87MG cell line under administration of Aβ and Okadaic acid (OKA) with LCN2-related mechanism. METHODS: Aβ and OKA were administered to the U87MG cell lines. PLE (Piper Longum Extract) was administered to see the therapeutic affect against the toxins. WST assay and Western blot were used to compare cell viability and relative intensity of p-Tau (AT8), p-Tau (AT180), and LCN2. RESULTS: PLE showed neuroprotective effects in U87MG cells on Aβ and OKA each. The group treated with PLE showed increased cell viability and the decreased level of LCN2 compared to the Aβ group. Also, the group treated with PLE recovered cell viability and showed significantly decreased p-Tau (AT8)/p-Tau (AT180) levels compared to the group treated with OKA. Upon administration of PLE, there was a considerable decrease in the relative level of LCN2 compared to the OKA treated group. CONCLUSION: These findings demonstrate that P. longum exerts neuroprotective effects against Aβ- and tau-induced toxicity in an astrocyte cell model by alleviating the damage from Aβ and OKA that induce neuroinflammation and decreasing LCN2 levels in astrocyte cells. Additionally, there is need to investigate other underlying mechanisms for novel use of P. longum that may contribute to AD recovery in the future.