Parvalbumin interneurons in Alzheimer's disease: Physiological insights and pathophysiological mechanisms.

Positive symptoms, negative symptoms, and chronic cognitive impairment are the hallmarks of schizophrenia, a severe and diverse neuropsychiatric illness with significant functional disability. The positive symptoms of schizophrenia are successfully managed by antipsychotic medications, but the negative and cognitive symptoms constitute a significant unmet therapeutic need. The main targets of antipsychotics are the dopaminergic receptors and, to a lesser degree, serotonergic receptors indicating single- or limited-target focus. Dopaminergic targets remain central in schizophrenia treatment because brain imaging shows that overactive presynaptic dopamine neurons in the striatum lie at the heart of psychosis. The role of dopaminergic targets in schizophrenia is limited to the positive symptoms, while its effect is weak on the negative and cognitive symptoms. The complex and multifaceted neurobiology of schizophrenia, which involves the dysregulation of several interrelated pathways, such as glutamatergic transmission, neuroinflammation, oxidative stress, and neurotropic signalling, is not sufficiently addressed by this reductionist approach. Multi-target therapeutic approaches that concurrently modulate several biological networks have great value in schizophrenia. In this regard, a promising yet unexplored source of poly-pharmacological agents is medicinal plants and their bioactive components. Among these, (L.) Wettst., a medicinal plant widely used in traditional ayurvedic medicine, has drawn a lot of interest for its neuroprotective and cognition-enhancing qualities. Preclinical and clinical research has shown that has antioxidant, anti-inflammatory, and neuro-modulatory properties in addition to improving learning, memory, and attention. These pharmacological effects of Brahmi coincide with biological mechanisms linked to the pathophysiology of schizophrenia, especially those that underlie negative symptoms and cognitive impairment. The main bioactive components of contributing to its therapeutic value are bacosides, a type of triterpenoid saponins. Analytical hurdles in quantification and analysis of bacosides, due to their structural complexity, various isomeric and glycosylated forms, pose significant challenges. In addition, diversity in Brahmi formulations, such as extracts, tablets, capsules, and composites and their bacoside concentrations, further complicates accurate reproducible measurement. Existing bacoside quantification methods show limitations in accuracy, reproducibility and application to therapeutic formulations (Brahmi tablet, Brahmi ghrita and Saraswatarishta), as they are limited to crude extracts.