Table 1.
Summary of the results of selected research studies on Ashwagandha (Withania somnifera).
| Disease | Target | Likely Mechanism of Action | Type of Study | Observed Activity | Reference |
|---|---|---|---|---|---|
| Alzheimer’s disease | The use of MTM to investigate how it affected the expression of the genes involved in neural plasticity and HDAC2 in an Alzheimer’s disease cell culture model. | An sp1 inhibitor called MTM prevented HDAC2 overexpression and resulted in much lower HDAC2 gene and protein expression, which restored the expression of synaptic plasticity genes in SH-APP cells. | In vitro model system | Inhibition of amyloid-beta production and activated B cells (NF-κB)-associated neuroinflammatory molecules’ gene expression—prevention of neuroinflammation and neurodegeneration | [10] |
| Removal of toxic Aβ peptide in the brain | Decreased expression of RAGE and clusterin. Selective down-regulation of liver LRP and degradation of Aβ. | In vivo mouse model | Increased levels of sLRP in plasma, enhanced expression of LRP and NEP in the liver, concomitant increase in plasma Aβ42/40 and decrease in brain Aβ monomer levels—reversal of behavioural dysfunctions | [11,12] | |
| The ability of Withania somnifera derivatives to improve the fibril formation of amyloid-β 42 in Alzheimer’s disease | Interaction with the hydrophobic core of amyloid-β 1–42 during the oligomeric stage, thus inhibiting further interaction with the monomers and reduces aggregation | In vitro studies | Decrease in apoptotic cells and reactive oxygen species. | [15] | |
| Neuroprotective effect of Withaferin A | Cell toxicity signaling pathway inhibition involving PI3K/mtor pathway | In vitro studies | Protection of dopaminergic and cortical neurons. Increase in cell survivor. | [17] | |
| Withanolide A’s ability to penetrate the brain and protect against cerebral ischemia-reperfusion damage | Inhibition of matrix metalloproteinases-2 (MMP-2). Lowered elevated levels of glutamate and GABA. However, more studies required to properly elucidate the mechanism of action. | In vivo mouse model | Decrease in apoptotic and necrotic cell death. Reduction in morphological damage of brain tissues. Reduced cerebral infarction and oedema. Restored blood-brain barrier disruption. | [18] | |
| Parkinson’s disease | Protection of neuronal injury in Parkinson’s disease and physiological abnormalities | Upregulation Of DA receptors after lesioning. Use of gpx which uses H202 to oxidize GSH in order to defend against hydrogen peroxide toxicity and detoxify free radicals and lipid peroxides. Further studies required for description of mechanism especially for dosage form. Interference with oxidative damage. |
In vivo mouse model | Reversal of toxic effects of 6-OHDA, muscle, and locomotive activity. Increase in striatal content and dopaminergic D2 receptor populations in striatum. Improvement of enzyme activity hence physiological functions | [22,26] |
| W. somnifera root extract, protective effects against 6-OHDA-induced toxicity in the human neuroblastoma SH-SY5Y cell line | Increase in glutathione peroxidase activity and thioltransferase activity. Modulation of oxidative response proteins and the control of redox regulation via S-glutathionylation | In vitro cell lines | Increase in ATP levels and decrease in protein-glutathionylation levels in the cells. | [23] | |
| Effect of W. somnifera on catecholamines and physiological abnormalities | Induction of catecholamines, antioxidants, and translation of proteins hence Cell growth |
In vivo mouse model | Increased DA, DOPAC and HVA levels and normalized TBARS levels in the corpus striatum. Improved motor function | [24] | |
| Evaluation of the neuroprotective effects of W. somnifera extract on the LRRK2 loss-of-function | Decrease in PSP amplitude and suppression of mutation by reversal of mutation-related loss of mitochondrial structural integrity | In vivo Drosophila melanogaster model | Improved motor and muscle activity. Protection against mitochondria degeneration | [25] | |
| Huntington’s disease | Restoration of biochemical alterations caused by 3-NP | Not yet fully understood and require further research | In vivo mouse model | Restoration of mitochondrial enzyme activity and antioxidant enzymes in striatum and cortex of the brain, reversal of muscle impairment, reduction of lipid peroxidation, nitrate, and dehydrogenase enzymes | [28] |
| Elongation of lifespan with administration of Withaferin A | Activation of HSF1 and induction of HSR chaperones | In vivo mouse model | Decrease in inflammatory process and mutant huntingtin aggregates. Improvement of striatal function | [29] | |
| Treatment of obsessive-compulsive disorder, alcohol withdrawal syndrome | Alleviating symptoms of obsessive-compulsive disorder | Not yet fully understood and require further research—likely impact on the serotonin system | Randomized double-blind placebo-controlled trial | Significantly greater effect of W. somnifera in alleviation severity of OCD assessed using Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) in a randomized double-blind placebo-controlled trial | [35] |
| In vivo rat model | Decrease in marble hiding behaviour activity behavioural activity without affecting motor activity in rats |
[36] | |||
| In vivo rat model | Beneficial effects on controlling behavioural changes, anxiety and seizures in alcohol withdrawal symptoms in rats, and improve locomotor activity. | [38] | |||
| In vivo rat model | Alleviation of withdrawal anxiety due to chronic alcohol consumption, | [37] | |||
| Anti-inflammatory/immunomodulatory effects mi |
Alleviating inflammation and improving immunity | Not yet fully understood and require further research—likely Inhibition of lipopolysaccharide (LPS)-activated NFκB, P38 and JNK/SAPK MAPK pathways, regulating cytokines | In vivo mouse model | Inhibition of the NF-κB and MAPK (mitogen-activated protein kinase) pathways by de-creasing the expression of pro-inflammatory cytokines, including interleukin (IL)-8, IL-6, tumour necrosis factor (TNF-α), IL-1β, and IL-12, and increasing the expression of anti-inflammatory cytokines | [41] |
| In vivo mouse model | Potent inhibitory effect on proteinuria, nephritis, and other inflammatory markers such as cytokines including interleukin (IL)-6 and tumour necrosis factor (TNF)-α, nitric oxide (NO), and ROS in a mouse model of lupus | [133] | |||
| In vivo rat model | Changes in the concentrations of a number of serum proteins such as α2 glycoprotein, acute phase protein α1 and prealbumin were demonstrated, along with a significant reduction in inflammation | [40] | |||
| In vivo mouse model | Increase in the total number of white blood cells and bone marrow cells, as well as to increase the titre of circulating antibodies and antibody-producing cells, and to stimulate the production of immune cells and phagocytosis of macrophages | [44] | |||
| In vivo rat model | Changes in the concentrations of serum proteins such as α2 glycoprotein, acute phase protein α1 and prealbumin with a significant reduction in inflammation | [40] | |||
| In vivo rat model | Inhibition of reactive gliosis, production of inflammatory cytokines such as TNF-α, IL-1β, IL-6, and expression of nitrooxidative stress enzymes | [60] | |||
| Randomized double-blind placebo-controlled trial | Significantly increased natural killer cell activity and cytokine levels compared to placebo | [45] | |||
| Randomized double-blind placebo-controlled trial | Significant increase in natural killer cell activity and cytokine levels in a randomized, double-blind, placebo-controlled trial | [45] | |||
| Antibacterial properties | Inhibiting the growth pathogenic bacteria | Not yet fully understood and require further research–likely disrupting bacterial cell membranes—more research needed | In vitro | Inhibition of the growth of methicillin-resistant Staphylococcus aureus and Enterococcus spp. | [46] |
| In vitro | Effective inhibition the growth of Staphylococcus aureus, Proteus mirabilis, Escherichia coli and Pseudomonas aeruginosa. | [122] | |||
| In vitro | Effective inhibition the growth of Escherichia coli, Salmonella typhi, Citrobacter freundii, Pseudomonas aeruginosa and Klebsiella pneumoniae. | [49] | |||
| In vitro | Effective treatment for salmonellosis, as it significantly alleviates the course of infection following infection with this pathogen | [51] | |||
| In vitro | Significantly slowness the growth of bacteria present in the oral cavity, such as Streptococcus mutant and Streptococcus sobrinus | [52] | |||
| In vitro | Induction of cell death (acts on promastigotes) of Leishamania donovani by activating the process of apoptosis | [53] | |||
| In vitro | Antifungal properties against some fungal species; it inhibits Candida albicans | [48] | |||
| In vitro | Antifungal properties of Withania somnifera glycoprotein from its root tubers, against Aspergillus flavus, Fusarium oxysporum, Fusarium verticilloides, and antibacterial properties against Clavibacter michiganensis subsp. michiganensis | [54] | |||
| In vivo mouse model | Effective in the treatment of malaria, significantly reducing parasitaemia | [56] | |||
| Support for infertility treatment | Improve the quality of semen | Not yet fully understood and require further research—likely effect on the GABA receptors, thus facilitating the expression of GnRH expression; structural similarity to testosterone and thus imparted the benefits of male steroidal hormones; regulation of oxidative stress |
In vivo study | Decrease in stress, improved the level of antioxidants and improved overall semen quality | [58] |
| Randomized, double-blind, placebo-controlled study | Statistically significant increase in the total DISF-M (the derogatis interview for sexual functioning-male) scores | [65] | |||
| Triple-blind randomised clinical trial | Increased mean sperm count and progressive motility and improved sperm morphology compared to the baseline | [59] | |||
| Clinical trial | Repair of disturbed plasma concentrations of lactate, alanine, citrate, GPC, histidine and phenylalanine and restores semen quality | [60] | |||
| A randomized controlled trial | Significant subjective perception of sexual well-being and assisted in increasing serum testosterone levels in the participants. | [65] | |||
| Anticancer effects | Inhibition of cancer cell proliferation | Not yet fully understood and require further research | In vitro | Activation by withaferin A the TRIM16 protein, leads to the degradation of cancer-related proteins and ultimately induces cell death in melanoma cells | [68] |
| In vitro | Effectiveness of withaferin a in the treatment of melanoma by compound induces apoptosis reduction cell proliferation and inhibits melano-ma cell migration | [69] | |||
| In vitro/In vivo | Inhibited GBM growth in vitro and In vivo and triggered intrinsic apoptosis of GBM cells | [70] | |||
| In vitro | Inhibition of proliferation of human endometrial cancer cells by Withaferin A through the modulation of TGF-β signaling and the inhibition of TGF-β dependent Smad2 phosphorylation | [134] | |||
| In vitro | Withaferin A alone or in combination with standard chemotherapy is a potential treatment option for EGFR (epidermal growth factor receptor) wild-type lung cancer and may decrease the occurrence of cisplatin resistance by inhibiting lung CSCs (cancer stem-like cell). | [135] | |||
| In vitro/In vivo mouse model | combination of extract and intermittent fasting decrease cancer cell proliferation through apoptosis induction, while also reducing cisplatin-induced toxicity in the liver and kidney. | [71] | |||
| In vivo rat model | protective effect against acute and chronic gamma radiation-induced damage to the liver and spleen tissues of rats | [72] | |||
| Antidiabetic activity | Lowering blood sugar levels | Not yet fully understood and require further research—likely Improving insulin sensitivity, stimulating beta cells, reducing inflammation, and protecting against oxidative stress, inhibition of α-glucosidase | In vivo rat model | Decrease in fasting blood glucose levels in rats with STZ-induced hyperglycaemia | [73] |
| In vivo rat model | Improvement diabetes-induced testicular dysfunction in pre-adolescent rats. | [74] | |||
| In vivo rat model | Efficacy against elevated plasma glucose, insulin and cortisol levels and changes in adrenal and spleen weights in diabetic animals | [80] | |||
| Double-blind randomized control trial | Improve antioxidant parameters and lipid profile, and demonstrate the tolerability and safety | [84] | |||
| Treatment of sleep disorders | Improve the quality and length of sleep | Not yet fully understood and require further research—likely effect on GABAergic activity | In vivo mouse model | Significant induction of NREM (Non-Rapid Eye Movement) sleep in research on mice | [93] |
| In vivo rat model | significant reduction in the levels of free radicals, lipid peroxidation, and an increase in the levels of antioxidant enzymes in the sleep-deprived rat group | [102] | |||
| Randomized, double-blind, placebo-controlled study | Improvement in the general wellbeing, sleep quality, and mental alertness in a prospective, randomized, double-blind, placebo-controlled study | [92] | |||
| Randomized, double-blind, placebo-controlled study | Significantly improved the quality of sleep and easier and faster to falling asleep | [84] | |||
| Randomized, double-blind, placebo-controlled study | Sleep efficiency, sleep duration and total sleep time improvements in physical, psychological, and environmental areas were also noted | [98] | |||
| Cardioprotective properties | Protection of heart cells against harmful agents | Not yet fully understood and require further research—likely anti-apoptotic properties due to an increase in AMP-activated protein kinase (AMPK) phosphorylation and an increase in the Bcl-2/Bax ratio (AMPK) and by restoring oxidative balance | In vivo rat model | A decrease in glutathione levels, a decrease in the activity of superoxide dismutase, catalase, creatinine phosphokinase, and lactate dehydrogenase albino rats in which myocardial necrosis treated with Withania Somnifera. | [85] |
| In vivo rat model | Reduction of the damage to the heart caused by ischemia induced in rats | [86] | |||
| In vivo rat model | In this study in rats, low doses of withaferin A were shown to have a cardioprotective effect by upregulating the mitochondrial anti-apoptotic pathway due to an increase in AMP-activated protein kinase (AMPK) phosphorylation and an increase in the Bcl-2/Bax ratio (AMPK). | [87] | |||
| Anxiolytic and anti-stress effects | Calming and stress-relieving effect | Not yet fully understood and require further research—likely moderating effect on the hypothalamus-pituitary-adrenal axis (HPA); antioxidant and anti-inflammatory effects | A randomized, double-blind, placebo-controlled study | Reduction in the HAM-A (Hamilton Anxiety Rating Scale) IN A randomized, double-blind, placebo-controlled study | [103] |
| A double-blind, randomized, placebo-controlled clinical study | Reduction in PSS (perceived stress scale) scores I A Double-blind, Randomized, Placebo-controlled Clinical Study | [108] | |||
| A randomized, double-blind, placebo-controlled study | A reduction in stress levels, improvement in memory and attention, sleep quality, and overall psychological well-being. | [112] | |||
| Randomized double-blind placebo-controlled trial | Potentially support SSRI therapy in patients diagnosed with GAD syndrome | [107] | |||
| Randomized, placebo-controlled clinical trial | Medium effect sizes over placebo for depression single-item and anxiety-depression cluster scores. Adverse events were mild and transient | [114] | |||
| Double-blind randomized control trial | Increased of college students’ perceived well-being through supporting sustained energy, heightened mental clarity, and enhanced sleep quality | [104] | |||
| Double-blind randomized control trial | Improvements in attention and working memory, as well as reductions in symptoms of anxiety and stress, as a result of Withania somnifera supplementation in adults | [119] | |||
| Adaptogenic effect | ability to adapt and maintain homeostasis in response to various stressors, both physical and emotional | Not yet fully understood and require further research—likely regulation of the HPA axis, antioxidant effects, immunomodulatory effects, and modulation of neurotransmitter signaling. | In vivo equine model | Adaptogenic and immunomodulatory activity in an equine model, potentially improving the health and performance of horses | [136] |
| In vivo rat model | Significant anti-stress effects, including the modulation of the HPA axis, increased levels of antioxidant enzymes, and reduced levels of lipid peroxidation, | [121] | |||
| Hypothyroidism | Increase in the concentration of thyroid hormones | Not yet fully understood and require further research | A double-blind, randomized placebo-controlled trial | Effective normalisation of serum thyroid indices during the 8-week treatment period | [123] |
| In vivo rat model | Significant parameter improvements in serum TSH level, serum glucose, Il-6, body weight gain, hepatic and renal MDA and NO, the values of GSH, gpx and Na+/K+-atpase, and improvement in thyroid histology | [124] | |||
| In vivo mouse model | Significant reduction of hepatic lipid peroxidation, whereas the activity of antioxidant enzymes such as superoxide dismutase and catalase were increased | [125] | |||
| Increase muscle strength | Not yet fully understood and require further research, likely increase in testosterone levels, reductions in muscle damage and inflammation, and antioxidant and anti-inflammatory effects. | A double-blind, randomized placebo-controlled trial | Ashwagandha supplementation association with increased muscle strength and endurance in older adults who performed resistance training. | [126] | |
| A double-blind, randomized placebo-controlled trial | Increase in cardiorespiratory endurance and an improvement in quality of life | [128] | |||
| A double-blind, randomized placebo-controlled trial | Extract of Ashwagandha on muscle strength, power, and recovery in healthy men who engaged in resistance training. | [129] | |||
| A double-blind, randomized placebo-controlled trial | Significant improvements in cardiorespiratory endurance measures of the elite Indian cyclists | [127] |