Orthosiphon aristatus (Blume) Miq. Extracts attenuate Alzheimer-like pathology through anti-inflammatory, anti-oxidative, and β-amyloid inhibitory activities

Ethnopharmacological relevance: Orthosiphon aristatus (Blume) Miq. (OA) is a traditional folk-herb, which is usually used to treat acute and chronic nephritis, epilepsy, cystitis, and other diseases. Phenols and flavonoids are the main active compound compounds of OA, with proven anti-inflammatory and antioxidant activities. Aims of this study: Based on evidenced therapeutic activities, we aimed to investigate the impact of OA on Alzheimer's disease (AD) which is the most common age-related neurodegenerative disease, and the pathological features include accumulation of beta-amyloid (Aβ) and neurofibrillary tangles (NFT). Materials and methods: OA was extracted with water, methanol, chloroform, and ethyl acetate, and determined its total flavonoid and phenolic contents. Initially, Aβ_1-42 based cytotoxicity was induced in BV2 cells and C6 cells to investigate the therapeutic impact of OA therapy by MTT, RT-PCR, Western blot, and ELISA. Further, Aβ₁₋₄₂ Oligomer (400 pmol)-induced AD mice model was established to evaluate the impact of OA extract on improving learning and memory impairment. Results: The results showed that the extract of OA could increase cell survival, inhibit the expression of TNF-α, IL-6, IL-1β, COX-2, and iNOS, and increase BDNF levels. We infer that the OA extract may attenuate Aβ-induced cytotoxicity by retarding the production of inflammatory-related factors. In the animal behavior test, the number of mice entering darkroom and the time of arriving at the platform were significantly reduced, indicating the learning and memory-improving ability of OA extract. Conclusions: These findings imply that the OA ethanolic extract demonstrated an improving effect on memory and hence could serve as a potential therapeutic target for the treatment of neurodegenerative diseases like AD.