RESUMEN
Background: Silymarin is a polyphenolic flavonoid complex extricated from dried fruits and seeds of the plant Silybum marianum L. Chemically, it is a mixture of flavonolignan complexes consisting of silybin, isosilybin, silychristin, silydianin, a minor quantity of taxifolin, and other polyphenolic compounds, which possess different bio medicinal values. Purpose: This review critically looks into the current status, pharmaceutical prospects and limitations of the clinical application of Silymarin for treating neurological disorders. In particular, Silymarin's medicinal properties and molecular mechanisms are focused on providing a better-compiled understanding helpful in its neuro-pharmacological or therapeutic aspects. Methods: This review was compiled by the literature search done using three databases, i.e., PubMed (Medline), EMBASE and Science Direct, up to January 2023, using the keywords-Silymarin, neurological disorders, cognitive disorders, Type 2 Diabetes, pharmaceutical prospects and treatment. Then, potentially relevant publications and studies (matching the eligible criteria) were retrieved and selected to explain in this review using PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) study flow chart. Result: Since its discovery, it has been widely studied as a hepatoprotective drug for various liver disorders. However, in the last 10-15 years, several research studies have shown its putative neuroprotective nature against various brain disorders, including psychiatric, neurodegenerative, cognitive, metabolic and other neurological disorders. The main underlying neuroprotective mechanisms in preventing and curing such disorders are the antioxidant, anti-inflammatory, anti-apoptotic, pro-neurotrophic and pro-estrogenic nature of the bioactive molecules. Conclusion: This review provides a lucid summary of the well-studied neuroprotective effects of Silymarin, its underlying molecular mechanisms and current limitations for its usage during neurological disorders. Finally, we have suggested a future course of action for developing it as a novel herbal drug for the treatment of brain diseases.
RESUMEN
Our earlier report on scopolamine-induced amnesia and its improvement by pre-treatment with i-Extract (alcoholic extract of Ashwagandha leaf) suggested that the i-Extract mediated nootropic effect may involve neuronal immediate early gene, Arc. With a hypothesis that the i-Extract induced expression of Arc protein may cause augmentation in Arc function, we examined the effect of i-extract on a major function of Arc protein, i.e. F-actin expansion, using Arc antisense oligodeoxynucleotides (ODN). Stereotaxic infusion of Arc antisense ODN in the CA1 region of hippocampus decreased the level of Arc protein as demonstrated by immunoblotting. However, this decrease was attenuated when treated with i-Extract prior to infusion of Arc antisense ODN. We noted a significant decrease in the polymerization of F-actin during scopolamine-induced amnesia as well as Arc antisense ODN infusion that was restored rather enhanced when pre-treated with i-Extract in both the cases. We also compared the corresponding changes between CA1 (the infusion site) and CA3 (neighbouring site of infusion) regions of hippocampus, and found more pronounced effects in CA1 than in the CA3 region. The extent of F-actin polymerization, as revealed by changes in the dendritic spine architecture through Golgi staining, showed that both scopolamine as well as Arc antisense ODN disrupted the spine density and mushroom-shaped morphology that was again regained if pre-treated with i-Extract. In conclusion, the findings reveal that the Arc helps in polymerization of F-actin and subsequent changes in the morphology of dendritic spines after pre-treatment with i-Extract in scopolamine-induced amnesic mice, suggesting an important role of Arc in scopolamine-induced amnesia and its recovery by i-Extract.
Asunto(s)
Alcoholes/química , Amnesia/tratamiento farmacológico , Amnesia/metabolismo , Proteínas del Citoesqueleto/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Actinas/metabolismo , Animales , Western Blotting , Espinas Dendríticas/efectos de los fármacos , Espinas Dendríticas/patología , Regulación hacia Abajo/efectos de los fármacos , Técnica del Anticuerpo Fluorescente , Hipocampo/patología , Masculino , Ratones , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Polimerizacion , Coloración y Etiquetado , Técnicas EstereotáxicasRESUMEN
Preclinical studies on animal models have discerned the antiamnesic and memory-enhancing potential of Bacopa monniera (Brahmi) crude extract and standardized extracts. These studies primarily focus on behavioral consequences. However, lack of information on molecular underpinnings has limited the clinical trials of the potent herb in human subjects. In recent years, researchers highlight plasticity markers as molecular correlates of amnesia and being crucial to design therapeutic targets. In the present report, we have investigated the effect of a special extract of B. monniera (CDRI-08) on the expression of key neuronal (BDNF and Arc) and glial (GFAP) plasticity markers in the cerebrum of scopolamine induced amnesic mice. Pre- and postadministration of CDRI-08 ameliorated amnesic effect of scopolamine by decreasing acetyl cholinesterase activity and drastically upregulating the mRNA and protein expression of BDNF, Arc, and GFAP in mouse cerebrum. Interestingly, the plant extract per se elevated BDNF and Arc expression as compared to control but GFAP was unaltered. In conclusion, our findings provide the first molecular evidence for antiamnesic potential of CDRI-08 via enhancement of both neuronal and glial plasticity markers. Further investigations on detailed molecular pathways would encourage therapeutic application of the extract in memory disorders.
RESUMEN
Arc (Activity-regulated cytoskeletal-associated protein) is a member of the immediate-early gene (IEG) family protein. Because of its critical role in learning and memory, it is widely considered to be an important protein in synaptic plasticity and related neurobiological functions. Alcoholic extract of Ashwagandha leaves (i-Extract) was recently shown to have preventive and therapeutic potential for scopolamine-induced amnesia and glutamate-induced excitotoxicity. In the present study, we investigated the involvement of Arc in scopolamine-induced amnesia and its recovery by i-Extract with particular focus to the changes in Arc expression in the hippocampus and cerebral cortex of mice. Morris water maze test showed that spatial learning and memory of mice were drastically reduced by scopolamine administration but improved with i-Extract treatment as compared to control and scopolamine-challenged mice. Molecular analysis revealed a remarkable decline in Arc expression in both hippocampus and cerebral cortex of amnesic mice, which was recovered after i-Extract treatment. Interestingly, Arc expression showed better recovery in the hippocampus than the cerebral cortex and the pre-treatment with i-Extract was more effective than the post-treatment. These findings suggest that Arc may be involved in i-Extract mediated recovery from amnesia.