What are Withanolides?
Withanolides are natural compounds first found in the plant, Ashwagandha, also known as Withania Somnifera. They are steroid-like in structure and contain 28 carbon atoms. Figure 2 below shows the structure of two important groups of withanolides. Of note, Ashwagandha is in the GRAS category of plants, which stands for generally regarded as safe, if used for therapeutic purposes. There has been a huge amount of research with withanolides for a wide variety of biologic uses.
Anti-tumor effects
Multiple laboratory studies have shown that withanolides can stop the growth of some tumor cell lines. This effect is partly due to withanolides’ ability to stop DNA synthesis in tumor cells, as well as make them more sensitive to the effects of radiation therapy. Withanolides work by blocking certain proteins that cancer cells use to stay alive and by creating oxidants that are toxic to cancer cells. These lab studies, however, do not prove that withanolides can be used to treat real patients with cancer, and therefore much further research is needed.
Anti-inflammatory effects
Lab studies have shown that withanolides can inhibit the enzyme cyclo-oxygenase 2, which is also blocked by commonly used over the counter agents such as ibuprofen (Advil, Motrin) and naproxen (Aleve). Withanolides also block an important inflammatory cellular factor called NFkB, which is responsible for revving up inflammation in tissues. These lab studies, however, do not prove that withanolides have the same level of anti-inflammatory and pain-relieving effects as ibuprofen and naproxen, and therefore much further research is required.
Immune system enhancing effects
Withanolides have been studied in stressed animals with reduced immune system cells known as T-cells. It was shown that withanolides were able to boost the number of T cells in these stressed animals, while also reducing levels of stress related substances found in the blood such as glutathione and glycogen. Once again, although encouraging in the lab settings, the immune enhancing effects of withanolides need more study in humans to determine whether this can really help people with reduce immune system function (e.g. cancer or HIV/AIDs).
Increased nerve cell growth and function
Withanolides have been shown to increase the growth of neurites from experimental nerve cell lines. This has sparked interest in testing a withanolides based drug in patients with neurogenerative diseases such as Alzheimer’s and Parkinson’s disease. In addition, withanolides have been shown to block an enzyme known as acetylcholinesterase. This enzyme breaks down a molecule known as acetylcholine, which is important to normal nervous system function. Therefore, blocking the enzyme increases the levels of acetylcholine, which can result in enhanced nerve cell signaling and possible benefits in patients with Alzheimer’s disease.
What part of withanolides is important for its biologic effects?
Figure 6 below highlights the portions of the withanolides structure that are important for these biologic effects. This knowledge may lead to the development of prescription drugs that can be used to treat patients with the conditions mentioned above.
Summary of withanolides’ biologic effects
Ashwagandha has been used for centuries in traditional Indian herbal (Ayurvedic) medicine for a variety of conditions. Laboratory research shows some biologic effects that are plausible (but not proven) explanations for some of these conditions, as outlined above. These findings have sparked renewed interest in Ashwagandha herbal supplement sales. Ashwagandha is generally regarded as safe, but consumers should know that claims of benefit for actual health conditions are largely not supported by high quality clinical evidence. We do not recommend that patients with very serious medical conditions such as cancer, inflammatory conditions, HIV/AIDs, Alzheimer’s disease, and Parkinson’s disease take ashwagandha supplements without first speaking to a healthcare professional. There is some limited research in support of Ashwagandha for stress and insomnia, but we believe this also requires confirmation in larger studies.
References
- Chen et al. Natural withanolides: an overview. Nat. Prod. Rep., 2011,28, 705-740.
Disclaimer: The information provided in this blog post is for educational purposes only and should not be considered as a substitute for professional medical advice, diagnosis, or treatment. As a clinical pharmacist, I strive to provide accurate and up-to-date information, but the field of herbal supplements is constantly evolving. Individual responses to herbal supplements may vary, and it is important to consult with a qualified healthcare professional before starting any new herbal supplement regimen. Additionally, it is crucial to carefully read and follow the instructions, warnings, and precautions provided by the manufacturers of herbal supplements. The author and the website disclaim any liability for any adverse effects or consequences resulting from the use or misuse of the information contained in this blog post.
