The convolution associated with memory is being resolved with advancement in neuroscience. According to the concurrent assumptions, synaptic plasticity forms one of the basis of memory formation, stabilization and strengthening. In Alzheimer's disease (AD), which is generally characterized by memory dysfunction, connections amongst the cells in the brain are attenuated or lost leading to degeneration of neural networks. Numerous attempts have been made to find new therapies for memory dysfunction with increasing attention and investments being laid on herbal drugs. Many herbal plants and extracts have already documented beneficial results when tested for antiamnesic effects. Brahmi (Bacopa monniera) is one such common herbal drug, which is employed for a long time in the Indian and Chinese medical system in order to treat several disorders. Previous research has shown that Brahmi exerts many pharmacological effects including memory boosting capacity in the treatment of Alzheimer's disease and Schizophrenia, exhibiting antiparkinsonian, antistroke, and anticonvulsant potentials. The present review discusses the chemical constituents of Brahmi along with in vitro and in vivo studies based on the pharmacological effects exerted by it. The efficacy of Brahmi in treating various disorders has evoked sufficient research in recent years and now it is a time to launch multiple clinical trials.

The treatment of brain diseases has been a major challenge since a long time. Although there are several potent drugs, which are highly therapeutic yet their efficiency is marred due to the presence of the Blood Brain Barrier (BBB). The BBB, which is present at the capillary level regulates and monitors the entry of all small and large molecules entering into the brain. Although this barrier is of immense importance to the brain in terms of safety, it becomes a hindrance when it comes to therapy because the drug molecules are unable to reach the brain. Various biomaterial-based strategies are being developed to overcome the BBB and deliver the drug into the brain. These include polymeric nanoparticles, liposomes, solid-lipid nanoparticles (SLNPs), nanogels, implants, etc. This review provides an overview on CNS disorders, BBB, and various delivery strategies available for biologists engaged in translational neuroscience, to target CNS.

In the present study, engineered lactoferrin (Lf)-conjugated pH and redox-sensitive polymersomes derived from the triblock copolymer polyethylene glycol-S-S-polylactic acid-polycaprolactone (PEG-S-S-PLA-PCL-OH) have been used to deliver bacosides to the brain. Bacosides are classified as triterpenoid saponins and are used in Indian Ayurveda for reversal of amnesia; however, no study has extensively demonstrated their efficacy as a nano-formulation in an animal model. The polymer was synthesized by ring opening polymerization of lactide and ε-caprolactone. The nanoparticles obtained by nanoprecipitation showed a core-shell morphology, with an average size of 110 nm, by transmission electron microscopy (TEM). The colloidal stability, hemocompatibility and cytocompatibility of the polymersomes proved their biocompatibility. pH and disulfide linkages in the polymeric chain accelerated the disintegration of the polymersomes at pH 6.6 and at pH 6.6 with glutathione (GSH) in comparison to pH 7.4, supporting their degradation behavior. Supermagnetic iron oxide nanoparticles (SPIONs, 74.99 μg mg-1 polymer) encapsulated into the polymersomes demonstrated their uptake in a mouse model by MRI. Furthermore, bacosides encapsulated in the polymersomes (10% loading) showed significant memory loss reversal in chemically induced amnesic mice, supported by the gene expression profiles of Arc, BDNF and CREB as well as by histopathology.

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Despite decades of rigorous scientific endeavors for Alzheimer’s disease (AD) drug development, massive failures in clinical trials is continuously posing healthcare and societal burden. Currently recommended single targeted drugs including rivastigmine with limited bioavailability can alleviate AD symptoms only for a limited period of time but unable to reverse the disease progression. Recent evidences consider poly-pharmacological and multi-targeted agents aiming at amyloid and tau burden, neuroinflammation, neuroprotection and cognitive enhancement as potential treatment options. In this regard, bioactive herbal compounds with holistic action and minimal adversities have gained prominence, though lacunae in their scientific validation and limited bio-permeability to cross BBB represent major hurdles. Previously, we showed that lactoferrin conjugated PEG-S-S-PLA-PCL-OH efficaciously delivered herbal compounds to brain and such nano-herbal formulation of bacosides-lauric acid (BAN-LAN) attenuated neuronal damages induced by scopolamine in vitro. Here, we tested the preclinical potential of BAN-LAN in reversal of AD pathologies in 5XFAD transgenic mice. Our nano-herbal formulation substantially reduced amyloid burden by clearing Aβ plaques in the hippocampus of 5XFAD mice and also attenuated aβ42 induced alterations in AD associated gene expression in hippocampal neurons in vitro. It showed neuroprotection by rescuing neuronal damage and promoting neurogenesis in the hippocampus of AD transgenic mice. Anti-neuroinflammatory properties were also exhibited by the formulation as evident from inhibition of hippocampal astrocytic and microglial activation in 5XFAD mice. BAN-LAN showed cognitive efficacy by restoring memory impairment in AD transgenic mice and effects were more pronounced than unconjugated natural form and rivastigmine. These findings suggest that BAN-LAN may serve as a promising therapeutic agent for AD with better brain penetration and targeting multiple AD pathways.