Effects of the extract of Ginkgo biloba L. on inflammatory response and mitochondrial dynamics in microglia in Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disorder that lacks disease-modifying therapies. This study investigated the effects of Extract of Ginkgo biloba L. (EGb) on mitochondrial fission machinery and inflammatory responses in an Aβ 1−42 -stimulated BV2 microglial model. The chemical profile of EGb was qualitatively analyzed using HPLC-MS. BV2 microglial cells were exposed to Aβ 1−42 . Mitochondrial morphology was observed using high-resolution microscopy; DRP1-MFF and DRP1-FIS1 associations were assessed by co-immunoprecipitation (Co-IP); dynamin-related protein 1 (DRP1), mitochondrial fission 1 protein (FIS1) and mitochondrial fission factor (MFF) were evaluated using image-based phenotypic metrics and Western blotting; interleukin-1 beta (IL-1β) levels were measured by ELISA; p38 mitogen-activated protein kinase (p38), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) were assessed via high-content screening; mitochondrial membrane potential (ΔΨm), oxidative stress and apoptosis-associated changes were detected by fluorescence and spectrophotometry. Fifty-eight compounds, including ginkgolides, flavonoids and phenolic acids, were tentatively identified. EGb alleviated Aβ 1−42 -induced mitochondrial structural abnormalities, increased MFF expression, and decreased DRP1 and FIS1 expression. Co-IP analysis indicated the association of DRP1 with MFF and FIS1. EGb also reduced IL-1β release and altered the expression levels of p38, JNK, and ERK, while mitigating ΔΨm loss, alleviating oxidative stress-related changes, and partially reducing apoptosis-associated TUNEL staining. EGb attenuated Aβ 1−42 -induced injury and modulated mitochondrial fission-related changes in BV2 microglial cells, suggesting a cellular-level protective effect in AD-related microglial dysfunction.