Solving a long standing puzzle as to how  ayurvedic medicine Ashwagantha attenuates cognitive dysfunction and prevents neurodegeneration: Mechanistic insights into how  Withaferin A, derived from Ashwagantha, attenuates cognitive dysfunction and neurodegeneration: Withaferin A, isolated from Ashwagantha,  decreases vascular cell adhesion molecule 1 (VCAM 1), inhibits microglia activity, increases hippocampal neural precursor activity, ameliorates cognition, & attenuates age-related neurodegeneration, through up regulation of its target genes, 8/July/2019, 10.47 am

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Introduction: What they say

A study from the Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA, VA Palo Alto Health Care System, Palo Alto, CA, USA, Palo Alto Veterans Institute for Research, Palo Alto, CA, USA, Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA shows that “Aged blood impairs hippocampal neural precursor activity and activates microglia via brain endothelial cell VCAM.” This research paper was published, in the 13 May 2019 issue of the journal “Nature Medicine” [One of the best research journals in General medicine with an I.F of 32.261] by Prof.Tony Wyss-Coray’s (One of TIME Magazine’s 50 Most Influential People in Health Care) research team.


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Solving a long standing puzzle as to how  ayurvedic medicine Ashwagantha attenuates cognitive dysfunction and prevents neurodegeneration: Mechanistic insights into how  Withaferin A, derived from Ashwagantha, attenuates cognitive dysfunction and neurodegeneration: Withaferin A, isolated from Ashwagantha,  decreases vascular cell adhesion molecule 1 (VCAM 1), inhibits microglia activity, increases hippocampal neural precursor activity, ameliorates cognition, & attenuates age-related neurodegeneration, through up regulation of its target genes


What is known?

A number of studies suggests that circulatory environment in older people can: a) induce microglia; b) decrease neural precursor cell activity; and c) reduce cognition. However, the mechanistic details of this remains largely unknown.

Prof.Tony Wyss-Coray’s research team has recently shown that: 1. brain endothelial cells (BECs) in the hippocampus express increased levels of vascular cell adhesion molecule 1 (VCAM1) protein, which promotes vascular-immune cell interactions; 2. increased levels of VCAM1 is found in the plasma of aged humans and mice; 3. plasma from aged mice can increase the levels of VCAM1 in young mice; and 3. Anti-VCAM1 antibody counteracts the detrimental effects of plasma from old mice and attenuates cognitive defects, suggesting that decreasing the expression of brain endothelial VCAM1 in aged individuals may attenuate age-related neurodegeneration.


From Research findings to Therapeutic opportunity:

Withania somnifera (also known as Ashwaganthaa) is used in India, in ayurvedic medicine, for centuries, however, the mechanistic basis of its therapeutic effect, in promoting cognition, learning and memory  among others, remains largely obscure for decades. This study provides, for the first time, mechanistic insights into how Ashwagantha attenuates cognitive dysfunction and neurodegeneration, in the aged population. 

This study suggests, for the first time, with detailed mechanistic insights,  Withaferin A , derived from Ashwagantha roots/oils, aids in the treatment of age-associated decline in memory and cognitive function in hippocampus.

Withaferin A, by increasing the expression of its target gene, it may decrease the levels of VCAM1. Thereby, it may: (1) increase the levels of a number of proteins essential for learning, memory and cognition; (2) attenuates inflammatory transcriptional profile; (3) inhibit microglia activity; (4) increase neural precursor cell activity; (5) increase cognition, memory, and learning; (6) improve spatial memory; (7) promote hippocampal function; and (8) attenuate age-related neurodegeneration (Figs.1-3).

Figure 1. Mechanistic insights into how Withaferin A  attenuates age-related neurodegeneration and improves cognitive function in aged individuals. Withaferin A, by increasing the expression of its target gene, it may decrease the levels of VCAM1. Thereby, it may increase cognition, memory, and learning, promote hippocampal function; and attenuate age-related neurodegeneration.

Figure 2. Withaferin A  attenuates the expression of VCAM1 and rescues cognitive decline in aged population.

Figure 3. While Anti-VCAM1 or genetic deletion of VCAM1 attenuates cognitive deficits, Withaferin A  attenuates the expression of VCAM1 and rescues cognitive decline in aged population.

Figure 4.  Withaferin A  attenuates the expression of VCAM1, increases the expression of genes that promote cognition, learning and memory, and rescues cognitive decline in the  aged population.

Figure 5. While Anti-VCAM1 antibody or genetic deletion of VCAM1 attenuates cognitive deficits, Withaferin A  attenuates the expression of VCAM1 and rescues cognitive decline in the aged population.

Thus, a pharmaceutical mixture encompassing Withaferin A or its analogs, either alone or in combination with other drugs,  can be used to suppress age-associated overall physiological decline of hippocampal function, improve cognition,learning and memory, and attenuate age-related neurodegeneration (Fig.4).

Given the mechanistic basis as to  how  Withaferin A  can suppress age-associated overall physiological decline of hippocampal function, and attenuate age-related neurodegeneration, allopathic practitioners may consider putting this interesting finding into a clinical trial. 


Details of the research findings:

Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Undisclosed mechanistic information: How does  Withaferin A  decrease VCAM1?

Amount: $750

For purchase and payment details, you may reach us at info@genomediscovery.org

* Research cooperation


References:

Web: http://genomediscovery.org

Citation: Boominathan, L.,  Solving a long standing puzzle as to how  ayurvedic medicine Ashwagantha attenuates cognitive dysfunction and prevents neurodegeneration: Mechanistic insights into how  Withaferin A, derived from Ashwagantha, attenuates cognitive dysfunction and neurodegeneration: Withaferin A, isolated from Ashwagantha,  decreases vascular cell adhesion molecule 1 (VCAM 1), inhibits microglia activity, increases hippocampal neural precursor activity, ameliorates cognition, & attenuates age-related neurodegeneration, through up regulation of its target genes, 8/July/2019, 10.47 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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