Withania somnifera root extract ameliorates hypobaric hypoxia induced memory impairment in rats

Baitharu, Iswar; Jain, Vishal; Deep, Satya Narayan; Hota, Kalpana Barhwal; Hota, Sunil Kumar; Prasad, Dipti; Ilavazhagan, G.

doi:10.1016/j.jep.2012.10.063

Cited by 78 publications

(37 citation statements)

References 43 publications

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“…Like green tea and turmeric root, use of ashwaganda ( Withania somnifera ) is widely known to treat anxiety, depression and neurodegeneration (Ahmad et al, 2005, Baitharu et al, 2013, Bhattacharya et al, 2000, Jain et al, 2001), not only in research literature, but also historical documents and ancient medical texts pertaining to Ayurvedic medicine. Ashwaganda has beneficial effects on diseases of cardiovascular nature (Ravindran et al, 2015a), obesity, diabetes, infection, cancer (Choi and Kim, 2015, Khazal et al, 2014, Rai et al, 2016), arthritis (Gupta and Singh, 2014, Khan et al, 2015) and gastric inflammation (Kim et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Natural product HTP screening for attenuation of cytokine-induced neutrophil chemo attractants (CINCs) and NO2− in LPS/IFNγ activated glioma cells

Mazzio

Bauer

Mendonca

et al. 2017

Journal of Neuroimmunology

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Chronic or acute central nervous system (CNS) inflammation is carried out by glial cells, which can contribute to neurological injuries associated with head trauma, stroke, and infection, Parkinson’s or Alzheimer ’s disease. The process of aging combined with inflammation are also risk factors for developing glioblastoma multiforme (GBM) as well as perpetuating its malignant aggression. With growing public curiosity in complementary and alternative medicines (CAMs), in this work we conduct a high throughput (HTP) screening of >1400 natural herbs, plants and over the counter (OTC) products for anti-inflammatory effects on lipopolysaccharide (LPS)/interferon gamma (IFNγ) activated C6 glioma cells. Validation studies suggest a pro-inflammatory profile mediated by LPS [3μg/ml/IFNγ 3ng/ml] is consistent with elevation [> 8.5 fold] of MCP-1 and cytokine-induced neutrophil chemo-attractants (CINC) 1, CINC 2a and CINC3. The data show no evidence of changes to the following, IL-13, TNF-a, fracktaline, leptin, LIX, GM-CSF, ICAM1, L-Selectin, activin A, agrin, IL-1α, MIP-3a, B72/CD86, NGF, IL-1b, MMP-8, IL-1 R6, PDGF-AA, IL-2, IL-4, prolactin R, RAGE, IL-6, Thymus Chemokine-1, CNTF,IL-10 or TIMP-1. The data also show a LPS/IFNγ mediated rise in iNOS and NO2− as often reported. A HTP screening was conducted, where we employ an in vitro efficacy index (iEI) defined as the ratio of toxicity (LC50)/anti-inflammatory potency (IC50) to ensure biological effects were occurring in fully viable cells (ratio > 3.8). Using NO2− as a guideline molecule, the data show that 1.77 % (25 of 1410 tested) (at <250μg/ml) had anti-inflammatory effects with an iEI ratio >3.8. These include reference drugs (hydrocortisone, dexamethasone N6-(1-iminoethyl)-L-lysine and NSAIDS : diclofenac, tolfenamic acid), a histone deacetylase inhibitor (apicidin) and the following natural products; Ashwaganda (Withania somnifera), Elecampagne Root (Inula helenium), Feverfew (Tanacetum parthenium), Green Tea (Camellia sinensis), Turmeric Root (Curcuma Longa) Ganthoda (Valeriana wallichii), Tansy (Tanacetum vulgare), Maddar Root (Rubia tinctoria), Red Sandle wood (Pterocarpus santalinus), Bay Leaf (Laurus nobilis, Lauraceae), quercetin, cardamonin, fisetin, EGCG, biochanin A, galangin, apigenin and curcumin. The herb with the largest iEI was Ashwaganda where the IC50/LC50 was 11.1/>1750.0 μg/mL, and the compound with the greatest iEI was quercetin where the IC50/LC50 was 10.0/>363.6 ug/mL. These substances also downregulate the production of iNOS expression and attenuate CINC-3 release. In summary, this HTP screening provides guideline information as to efficacy of natural products that in the long term, could prevent inflammatory processes associated with neurodegenerative disease and aggressive glioma tumor growth.

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Section: Discussionmentioning

confidence: 99%

Natural product HTP screening for attenuation of cytokine-induced neutrophil chemo attractants (CINCs) and NO2− in LPS/IFNγ activated glioma cells

Mazzio

Bauer

Mendonca

et al. 2017

Journal of Neuroimmunology

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“…There is evidence that WS inhibits acetylcholine esterase (AchE), while enhancing GPCR M1muscarinic receptor binding in the basal forebrain area and prefrontal cortex [12,13]. In vitro and in vivo, AchE inhibition by various fractions (specifically aqueous extract) and crude extracts of WS has been measured in the cortical and basal areas of rat brains, and supplementation by WS notably reduced levels of hypobaric hypoxia induced AchE levels [12][13][14]. The cholinergic signaling system within the cerebral cortex plays an important role in cognition, memory formation and retention and successful learning of new information [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Effects of Withania somnifera on Cholinergic Signaling in the Cerebral Cortex and Memory Function in the Aging Rat Brain

Chen¹

2018

JONAM

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Objectives: Withania somnifera Dunal (WS, ashwagandha) has been traditionally used as an adaptogen in Ayurveda.Administered over a long-term, it has demonstrated its potential as a remedy against age-and stress-related cognitive dysfunction. Aims of the Study:In this long-term study, the effects of WS alone and WS combined with whole food diet and voluntary wheel-running on age-related alterations in acetylcholine esterase (AchE) levels and in the density of the cholinergic muscarinic receptor subtype 1(M₁GPCR), combined with the downstream transcription factor phospho-CREB (P-CREB) were evaluated. Additionally, index of memory function of the animals (measured by Novel object recognition test, NOR) and spatial learning ability (Barnes Maze) was correlated to the aforementioned molecular outcomes.Methods: WS root powder was tested in the live rats by oral administration of 100mg/kg for 19 months, followed by novel object recognition (NOR) and Barnes Maze tests at 20 months of age. AchE activity in frontal cortex was measured via colorimetric assay; M₁-GPCR and P-CREB/total CREB density via Western blot (WB).Results: WS herbal supplement alone or in combination with additional lifelong lifestyle interventions did not lead to an increase in the levels of muscarinic acetylcholine receptor in the frontal cortex of the aged rats, did not affect AchE activity significantly, nor did it alter expression of P-CREB in the frontal cortex of the aged rat. However, aerobic exercise and healthy diet treatments led to significant decrease in AchE activity combined with an increase in P-CREB and M₁GPCR immuno reactivity. In addition, via NOR Discrimination Index (DI), WS-treated rats have the best object memory, have above average hippocampus-dependent spatial memory and frontal-cortex mediated learning flexibility; combined intervention did not improve object discrimination while it preserved comparable spatial memory. Additionally, exercised rats showed adequate mental flexibility in special tasks, but their object memory was below average. Linear regression analysis revealed a significant correlation between M1 receptor density and memory index; between M1 receptor density and AchE activity in WS and Combo-treated rats, but failed to reach significance for inverse correlation with latency to complete Barnes Maze spatial navigation task.

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“…30 Earlier, it has been reported that leaf juice constituents of WS inhibit acetylcholinesterase (AChE) directly and nicotinamide adenine dinucleotide diaphorase (NADPH-d) activity indirectly, 31 as well as WS root extract ameliorated HH-induced memory impairment and neurodegeneration in hippocampus through NO-mediated modulation of corticosterone levels. 32 Therefore, the present structural-based in silico study was carried out to search potent and selective inhibitor for human nNOS from a set of 40 W. somnifera phytochemical structure.…”

Section: Introductionmentioning

confidence: 99%

Withania somniferaphytochemicals confer neuroprotection by selective inhibition of nNos: Anin silicostudy to search potent and selective inhibitors for human nNOS

Kumar

Paliwal

Patnaik

et al. 2017

J. Theor. Comput. Chem.

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Neuronal nitric oxide synthase (nNOS or NOS1) is an important therapeutic target for the treatment of various neurological diseases. A major challenge faced in the design of nNOS inhibitors emphasizes on potency in humans and selectivity over other NOS isoforms À À À eNOS and iNOS. The present structural-based in silico study was carried out to search potent and selective inhibitor for human nNOS from a set of 40 Withania somnifera phytochemicals structure. Ten phytochemicals appear as dual-selective inhibitors of nNOS over both iNOS and eNOS. Here we report¯ve potent and selective human nNOS inhibitors, namely, Chlorogenic Acid, Withanolide B, Withacnistin Pelletierine, and Calystegine B2 based on their selectivity, binding energy and nNOS active site residues interaction pro¯le. These phytochemicals have nNOS selectivity higher than 4-methyl-6-(2-(5-(3-(methylamino)propyl)pyridin-3-yl)-ethyl) pyridin-2-amine inhibitor and have potential as an oral neurotherapeutic agent to combat neurological disorders mediated by nNOS activation.

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Withania somnifera root extract ameliorates hypobaric hypoxia induced memory impairment in rats

Cited by 78 publications

References 43 publications

Natural product HTP screening for attenuation of cytokine-induced neutrophil chemo attractants (CINCs) and NO2− in LPS/IFNγ activated glioma cells

Natural product HTP screening for attenuation of cytokine-induced neutrophil chemo attractants (CINCs) and NO2− in LPS/IFNγ activated glioma cells

Effects of Withania somnifera on Cholinergic Signaling in the Cerebral Cortex and Memory Function in the Aging Rat Brain

Withania somniferaphytochemicals confer neuroprotection by selective inhibition of nNos: Anin silicostudy to search potent and selective inhibitors for human nNOS

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