Ashwagandha

Description
Ashwagandha is an ancient Indian herb often times called Indian Ginseng. Although stimulatory in nature, the mechanism of action is different than Panax ginseng.


Benefits

"...results from various studies indicate ashwagandha possesses many qualities, including anti-inflammatory, antitumor, and immunomodulatory properties, as well as exerting an influence on the endocrine, nervous, and cardiopulmonary systems."^[2]

"Subsequent treatment with WL-A (1 microM) induced significant regeneration of both axons and dendrites, in addition to the reconstruction of pre- and postsynapses in the neurons. WL-A (10 micromol kg(-1) day(-1), for 13 days, p.o.) recovered A beta(25-35)-induced memory deficit in mice. At that time, the decline of axons, dendrites, and synapses in the cerebral cortex and hippocampus was almost recovered. WL-A is therefore an important candidate for the therapeutic treatment of neurodegenerative diseases, as it is able to reconstruct neuronal networks."^[3]

Mechanism of Action

"The withanolides serve as important hormone precursors that can convert into human physiologic hormones as needed. Ashwagandha is thought to be amphoteric; i.e., it can help regulate important physiologic processes. The theory is that when there is an excess of a certain hormone, the plant-based hormone precursor occupies cell membrane receptor sites so the actual hormone cannot attach and exert its effect. If the hormone level is low, the plant-based hormone exerts a small effect. Ashwagandha is also considered to be an adaptogen, facilitating the ability to withstand stressors, and has antioxidant properties as well. Other studies have shown ashwaganda to have an immunostimulatory effect."^[1]

"The drug-induced increase in cortical muscarinic acetylcholine receptor capacity might partly explain the cognition-enhancing and memory-improving effects of WS extracts in animals and in humans."^[2]

"The compounds slightly enhanced acetylcholinesterase (AChE) activity in the lateral septum and globus pallidus, and decreased AChE activity in the vertical diagonal band. These changes were accompanied by enhanced M1-muscarinic-cholinergic receptor-binding in lateral and medial septum as well as in frontal cortices, whereas the M2-muscarinic receptor-binding sites were increased in a number of cortical regions including cingulate, frontal, piriform, parietal, and retrospinal cortex. The data suggest the compounds preferentially affect events in the cortical and basal forebrain cholinergic-signal-transduction cascade."^[2]

"We investigated whether withanolide A (WL-A), isolated from the Indian herbal drug Ashwagandha (root of Withania somnifera), could regenerate neurites and reconstruct synapses in severely damaged neurons. We also investigated the effect of WL-A on memory-deficient mice showing neuronal atrophy and synaptic loss in the brain. Axons, dendrites, presynapses, and postsynapses were visualized by immunostaining for phosphorylated neurofilament-H (NF-H), microtubule-associated protein 2 (MAP2), synaptophysin, and postsynaptic density-95 (PSD-95), respectively. Treatment with A beta(25-35) (10 microM) induced axonal and dendritic atrophy, and pre- and postsynaptic loss in cultured rat cortical neurons. Subsequent treatment with WL-A (1 microM) induced significant regeneration of both axons and dendrites, in addition to the reconstruction of pre- and postsynapses in the neurons. WL-A (10 micromol kg(-1) day(-1), for 13 days, p.o.) recovered A beta(25-35)-induced memory deficit in mice. At that time, the decline of axons, dendrites, and synapses in the cerebral cortex and hippocampus was almost recovered. WL-A is therefore an important candidate for the therapeutic treatment of neurodegenerative diseases, as it is able to reconstruct neuronal networks."^[3]

Withania somnifera root extract improves catecholamines and physiological abnormalities seen in a Parkinson's disease model mouse.

"ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera root extract (Ws)/Ashwagandha/Indian ginseng is a traditional herbal medicine, used over 4000 years in India, shown to have effect on neural growth and locomotor function. Although catecholamines and oxidative stress resulting in neurodegeneration and locomotor disorder are the main events in Parkinson's disease (PD), efficacy of the drug on these molecules and physiological abnormality are not clear. AIM OF THE STUDY: The objective of the study was to examine effect of Ws on catecholamines and physiological abnormalities seen in PD using PD model mouse.

MATERIALS AND METHODS: Mouse were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 4 days to show biochemical and physiological abnormalities similar to patients with PD. PD mice were treated with Ws 100mg/kg body weight for 7 or 28 days. Catecholamines: dopamine (DA), 3,4-dihydroxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA); antioxidants: glutathione (GSH) and glutathione peroxidase (GPx); and lipid peroxidation marker (TBARS) were analyzed in the Ws treated and untreated PD mouse striatum.

RESULTS: Mouse treated with MPTP showed reduced levels of DA, DOPAC, HVA, GSH and GPx and induced thiobarbituric acid reactive substance (TBARS) level compared to the control. Physiological abnormalities were seen in the mouse as determined by hang test and rotarod test. Oral treatment of PD mouse Ws root extract (100mg/kg body weight) for 7 days or 28 days increased DA, DOPAC and HVA levels and normalized TBARS levels in the corpus striatum of the PD mouse. The 7 days Ws treated mice showed improved motor function as determined by hang test and rotarod test. Treatment with Ws for 28 days increased GSH and GPx levels in the striatum compared to the Ws untreated PD mouse striatum.

CONCLUSION: These data suggest that Ws is a potential drug in treating catecholamines, oxidative damage and physiological abnormalities seen in the PD mouse."^[4]

References
^[1] Ashwagandha Monograph

^[2] Scientific basis for the therapeutic use of Withania somnifera (ashwagandha) zeidoros.com [PDF]

^[3] Neuritic regeneration and synaptic reconstruction induced by withanolide A.

^[4] Withania somnifera root extract improves catecholamines and physiological abnormalities seen in a Parkinson's disease model mouse.