Novel botanical drug DA-9803 prevents deficits in Alzheimer’s mouse models

Abstract

BackgroundAlzheimer’s disease (AD) is a neurodegenerative disorder characterized by deposition of amyloid plaques and disruption of neural circuitry, leading to cognitive decline. Animal models of AD deposit senile plaques and exhibit structural and functional deficits in neurons and neural networks. An effective treatment would prevent or restore these deficits, including calcium dyshomeostasis observed with in-vivo imaging.MethodsWe examined the effects of DA-9803, a multimodal botanical drug, in 5XFAD and APP/PS1 transgenic mice which underwent daily oral treatment with 30 or 100 mg/kg DA-9803 or vehicle alone. Behavioral testing and longitudinal imaging of amyloid deposits and intracellular calcium in neurons with multiphoton microscopy was performed.ResultsChronic administration of DA-9803 restored behavioral deficits in 5XFAD mice and reduced amyloid-β levels. DA-9803 also prevented progressive amyloid plaque deposition in APP/PS1 mice. Elevated calcium, detected in a subset of neurons before the treatment, was restored and served as a functional indicator of treatment efficacy in addition to the behavioral readout. In contrast, mice treated with vehicle alone continued to progressively accumulate amyloid plaques and calcium overload.ConclusionsIn summary, treatment with DA-9803 prevented structural and functional outcome measures in mouse models of AD. Thus, DA-9803 shows promise as a novel therapeutic approach for Alzheimer’s disease.Electronic supplementary materialThe online version of this article (10.1186/s13195-018-0338-2) contains supplementary material, which is available to authorized users.

Potential Protective Role of Thymoquinone on Experimentally-induced Alzheimer Rats

“…The results of this study showed a significant decrease in SAP% in the AD group compared to the control group. This finding was in agreement with Pagnier et al [29] who found a decrease in alteration behavior at Y-the maze in an AD mice model.…”

Novel botanical therapeutic NB-02 effectively treats Alzheimer’s neuropathophysiology in an APP/PS1 mouse model

“…1o, Mann Whitney test, p<0.001). Since we had verified that neither NB-02 nor vehicle interfered with methoxy-X04 binding to individual plaques [13], decreases in plaque intensity signaled bona fide plaque clearance in NB-02 condition.…”

“…All the studies complied with Massachusetts General Hospital Animal Care and Use Committee as well as NIH guidelines for the use of laboratory animals. APP/PS1 mice underwent intracortical virus injections followed by cranial window installations over the right hemisphere [15] on the same day starting at 7 months of age similar to earlier reports [11,13,16,17]. Following anesthesia induction, animals were secured in a stereotaxic apparatus.…”

“…Restoration of neuronal calcium to control levels and normalization of neuroinflammatory response would indicate treatment efficacy [11,12]. NB-02, previously known as DA-9803, is a novel proprietary botanical cocktail containing extracts from Morus alba L. and Poria cocos [13]. The extract is reproducibly prepared according to a standardized recipe.…”

“…The extract is reproducibly prepared according to a standardized recipe. Currently in preclinical development by NeuroBo Pharmaceuticals, it is a multimodal therapeutic that has been shown to prevent deposition of amyloid plaques in young APP/PS1 [14] mice, an animal model of Alzheimer's disease [13]. In addition, it was effective at preventing neuronal calcium elevations, thus maintaining circuit integrity in these mice.…”