Central nervous system (CNS) diseases are a significant health burden globally, with the development of novel drugs lagging behind clinical needs. Orchidaceae plants have been traditionally used to treat CNS diseases, leading to the identification of therapeutic leads against CNS diseases from the Aerides falcata orchid plant in the present study. The study isolated and characterized ten compounds, including a previously undescribed biphenanthrene derivative, Aerifalcatin (1), for the first time from the A. falcata extract. The novel compound 1 and known compounds, such as 2,7-dihydroxy-3,4,6-trimethoxyphenanthrene (5), agrostonin (7), and syringaresinol (9), showed potential activity in CNS-associated disease models. Notably, compounds 1, 5, 7, and 9 demonstrated the ability to alleviate LPS-induced NO release in BV-2 microglial cells, with IC50 values of 0.9, 2.5, 2.6, and 1.4 μM, respectively. These compounds also significantly inhibited the release of pro-inflammatory cytokines, IL-6 and TNF-α, reflecting their potential anti-neuroinflammatory effects. Additionally, compounds 1, 7, and 9 were found to reduce cell growth and migration of glioblastoma and neuroblastoma cells, indicating their potential use as anticancer agents in the CNS. In summary, the bioactive agents isolated from the A. falcata extract offer plausible therapeutic options for CNS diseases.
