Ashwagandha / Withania somnifera

W. somnifera, also known as Ashwagandha, is an important herb that has been used for over 3000 years. The important constituents of the root are steroidal alkaloids and steroidal lactones referred to as withanolides. It is used for anxiety, inflammation, Parkinson’s disease, cognitive and neurological disorders, and as a supportive adjunct for people undergoing radiation and chemotherapy. It is also considered an important adaptogen, an herb that helps manage the body’s response to stress, for people with nervous exhaustion, insomnia, debility due to stress, and as an immune stimulant in people with low white blood cell counts ^[1].

Withanolides are important hormone precursors that can convert into human physiologic hormones as needed and are therefore used to regulate important physiological processes. One theory for its mechanism of action is that when there is an excess of a particular hormone, the plant-based hormone precursor occupies the receptor sites thereby effectively blocking the binding of the actual hormone and preventing it from exerting its effects. However, if the hormone level is low, this plant-based hormone can exert a small effect ^[1,2]. W. somnifera modulates the oxidative stress markers of the body, reduces lipid peroxidation, and increases the superoxide dismutase (SOD) and catalase activity. It has also been reported to modulate GABAergic or cholinergic neurotransmission. Its GABA agonism has been linked to the prevention of anxiety and therefore this plant is beneficial in anxiety disorders. It has been proposed that the cholinesterase inhibitory potential along with calcium antagonistic ability could make the use of withanolides a possible treatment for Alzheimer's disease and associated problems. Withaferin A has been reported to be an inhibitor of angiogenesis, the generation of new blood vessels, and therefore protective in certain types of cancers. Two glycowithanoloids (sitoindoside IX or sitoindoside X) exhibit antistress activity and have been shown to augment learning acquisition and memory retention in both young and old rats ^[3].

Anxiolytic and Antidepressant effects

Anxiety disorders are extremely common in the general population with over 15% of people being affected at some point in their lives. W. somnifera possesses GABA mimicking properties and therefore helps reduce anxiety and contributes to its antidepressant effect ^[3,6]. One study demonstrated that W. somnifera was superior to placebo in treating anxiety ^[4]. One animal study compared the anxiolytic and antidepressant actions of W. somnifera compared to commonly prescribed pharmaceuticals, lorazepam and imipramine. W. somnifera and lorazepam both reduced brain levels of a marker of clinical anxiety and W. somnifera exhibited an antidepressant affect comparable to that of imipramine ^[5,6].

Antistress effect

Chronic stress has various negative impacts on the body, including cognitive deficit, sexual dysfunction, gastric ulceration, immunosuppression, abnormal glucose balance, and changes in plasma corticosterone levels ^[5]. W. somnifera is capable of increasing the capacity to tolerate non-specific stress in experimental animals due to its ability to restore multiple parameters while not interfering with normal physiological functions of the body ^[7]. It attenuated the following stress parameters: cortisol levels, mental depression, and sexual dysfunction in a study done on rats ^[5]. W. somnifera has been shown to decrease the number and severity of chronic stress-induced ulcers, reverse chronic stress-induced inhibition of male sexual behaviour as well as immunosuppression, and inhibit the adverse effect of chronic stress on retention of learned tasks in the same rat study ^[8].

Immunomodulatory and Anticancer effects

W. somnifera has the potential to increase tumor sensitization to radiation and chemotherapy while reducing common side effects to these treatments. It has an antiproliferative effect but not an antioxidant effect on human tumor cells. Animal research on W. somnifera confirms that it is useful in slowing tumor growth and increasing survival time. It exhibits both antioxidant and pro-oxidant activity and can repair oxidative damage caused by tumor growth and inflammation thereby reducing disease progression. W. somnifera does not up- or down-regulate Phase 1 of the detoxification pathway or p450 enzymes and therefore can be combined with drugs and herbs that affect these systems without interacting ^[7]. W. somnifera has been shown to increase hemoglobin levels, red blood cell counts and decrease serum cholesterol and ESR, a marker of inflammation. It can reduce leucopenia, enhance bone marrow cellularity, and increase the ratio of normochromatic to polychromatic erythrocytes in mice treated with gamma radiation. It can also enhance total white blood cell count and bone marrow cellularity in mice treated with cyclophosphamide, a common chemotherapeutic agent. Since immunity is suppressed in cancer, especially for those undergoing chemotherapy and radiation therapy, it is important to support the immune system ^[9]. Animal studies have shown that W. somnifera has a profound effect on the hematopoietic system since it acts as an immunoregulator and chemoprotective agent. A study in mice found that it enhances total white blood cell count and increases nitric oxide production in macrophages, which is important for people undergoing cancer treatment. W. somnifera exhibits stimulatory effects on cytotoxic T cells in vitro and in vivo and therefore has potential to reduce tumor growth due to the role that these cells play in targeting and killing cancer cells. An in vitro study showed that withanolides inhibited growth of human breast, lung, central nervous system, and colon cancer cell lines comparable to doxorubicin, a chemotherapeutic drug ^[2].

Thyroid stimulatory effect

The main circulating thyroid hormone is T4, which is synthesized in the thyroid gland. In one animal study, an increase in serum T4 concentration was seen following the administration of W. somnifera. It appears that it may stimulate the synthesis and/or release of T4 at the glandular level. In an animal study, the W. somnifera treated group had a significant decrease in hepatic lipid peroxidation and an increase in catalase activity. These observations suggest that it likely increases the effectiveness of the antioxidant system of the cells by stimulating the enzymes. Carbohydrate metabolism is also influenced by thyroid hormones. W. somnifera increased the activity of hepatic glucose-6-phosphatase (G-6-Pase), which coincided with increased thyroid hormone concentrations. This may have occurred due to the increase in T4 concentration since exogenous T4 is known to enhance the activity of G-6-Pase ^[10]. Therefore, W. somnifera may be useful in the treatment of hypothyroidism.

Cognitive effects

Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder and is characterized by the presence of confusion, mood swings, and memory loss. The beta-amyloid peptide (BAP) plays a significant role in the development of AD and is a main target for drug treatment. Withanamides potently inhibit lipid peroxidation, which is involved in the development of several disease states. Reducing this process can help maintain healthy cells and tissues. An animal study showed that withanamides reduce reactive free radicals that cause oxidative stress on neuronal cell membranes. This oxidative stress results in the fibrillation of tau proteins within the cells and ultimately leads to cell death. Therefore, preventing this stress is important for people with AD. W. somnifera also protects neuronal cells from death by plaque forming BAPs. Therefore, W. somnifera can be used to reduce neuronal cell death in patients with AD, may be useful as a prophylaxis, and can improve the quality of living of AD patients ^[11].

Safety

W. somnifera is considered safe and nontoxic in a wide range of reasonable doses. It has the potential to interact with other herbs and drugs so it is important to consult a healthcare provider with training in these interactions before taking W. somnifera ^[3]. Additionally, W. somnifera can cause miscarriages at high doses and therefore should be avoided in pregnancy. Due to its mild central nervous system depressant activity people should avoid alcohol, sedatives, and other anxiolytic agents when taking W. somnifera ^[2].

Conclusion

W. somnifera can be used to effectively reduce anxiety, depression, and the negative effects of stress. Additionally, it has been demonstrated to have anticancer, thyroid stimulating, and potent antioxidant effects that can benefit cognition. Due to its various benefits, excellent safety profile, and low potential to interact with other drugs and herbs it is used frequently in naturopathic practice.