Ashwagandha & Nanotechnology in Cancer Therapy

Advancements in research and medicine have significantly influenced cancer therapies thus enhancing the life expectancy of numerous individuals. Notwithstanding technological advancements, the condition continues to impact many persons worldwide and ranks among the primary reasons of mortality. Moreover, drug resistance is a significant challenge that influences cancer cell viability and recurrence. Consequently, the discovery of effective treatments that can influence tumor growth and cancer cell proliferation is of paramount significance. Ashwagandha Withaferin, a phytochemical extracted from the plant Withania somnifera, has garnered significant attention for its anticancer effects demonstrated in several murine models and tumor cell investigations.

Recent years have witnessed significant breakthroughs in nanotechnology aimed at improving the efficacy of phytochemicals. Nanotechnology enhances the bioavailability and stability of therapeutic plants, hence increasing targeted administration and addressing the limitations associated with traditional herbal preparations. The synergistic therapeutic potential of ashwagandha with nanoformulations enhances the treatment efficacy and offers an innovative strategy in cancer management, while also mitigating the long-term impacts of malignancy.

The Power of Ashwagandha

Withania somnifera, an evergreen shrub, commonly referred to as ashwagandha, is extensively utilized in ayurvedic medicines. Patients with various musculoskeletal diseases are prescribed for ashwagandha in different formulations. It is also taken as a general health tonic to boost energy and improve overall health and wellbeing. It is also recommended to the patients having bone diseases like arthritis, and during pregnancy. An extensive number of pharmacological studies have been conducted to investigate the properties of Withania somnifera in an attempt to substantiate its usage as a multifaceted medicinal agent. Various researches have documented its anti-cancer, anti-inflammatory, hemopoietic, and immunomodulatory properties. These rejuvenating characteristics of ashwagandha exerts beneficial effects on body’s endocrine, central nervous system and cardiovascular system.

Withania somnifera contain several bioactive compounds such as withanolides like Withaferin A. Theses bioactive substances exerts strong anti-cancer potential and demonstrate significant effectiveness against various types of cancers, including breast, ovarian, cervical and endometrial malignancies. It not only provides prevention against reproductive system but also prevents cancers of urinary system and digestive system such as prostate, renal, colorectal, hepatic and gastric carcinomas. Ashwagandha treats cancer by inducing apoptosis, preventing angiogenesis, and suppressing metastasis. It suppresses pro-survival pathways like Akt/NF-κB/Bcl-2, cell proliferation, migration, and cancer stem cells, further suppressing angiogenesis and generating cell cycle arrest, autophagy, apoptosis and ferroptosis.

The Limitations of Traditional Herbal Use

Notwithstanding the extensive anti-cancer properties of Withaferin Ashwagandha (WA), there are several limitations, such as possible toxicity, inadequate oral bioavailability, and limited production. Withaferin A extract is the primary bioactive component of Withaferin Somnifera, and studies have shown that it is safe for all tested groups. The utilization on WA has shown some hazardous side effects in mice, with an LD50 of 54 mg/kg body weight. In order to mitigate these toxicity issues, scientists have investigated structural alterations to produce WA derivatives with similar but less hazardous action. For example, ASR488, 2-thiophene ester-linked derivative of WA, selectively suppressed bladder cancer cells without harming healthy cells. After oral administration, the compound often undergoes first-pass hepatic metabolism, significantly reducing its systemic circulation and, therefore, its effectiveness increase at the tumor site. According to a recent study published in Pharmaceuticals, WA's low solubility hinders its pharmacological efficacy in vivo by causing poor absorption and bioaccumulation.

A notable disadvantage is that when Withaferin Ashwagandha and other herbal compounds are administered using normal methods, their distribution is non-specific. Owing to their lack of specificity in targeting cancer cells, these chemicals often permeate healthy organs, resulting in unintended adverse consequences. The absence of tailored delivery necessitates higher doses, hence increasing the risk of systemic toxicity. Moreover, herbal formulations diminish in efficiency owing to enzymatic degradation in the intestines or physiological variables such as an acidic gastric pH. The cytotoxic efficacy of withaferin A against malignant cells cannot be fully harnessed without inflicting damage to normal tissues. This is attributable to the narrow therapeutic window of withaferin A. This underscores the need of developing contemporary drug delivery techniques, such as nanoencapsulation, to bridge the divide between traditional herbal wisdom and contemporary cancer treatments, given the pharmacological and delivery-related problems.

Nanoencapsulation: A Modern Solution

Nanoencapsulation involves enclosing compounds within diminutive structures using nano-emulsification, nano-structuration, or nano-composites to facilitate the regulated release of the core material. Various nano-encapsulation methods, including liposomes, nanoparticles, micelles, nanospheres, nanoemulsions, and nanocochleates, have been employed depending on the applications. These can be employed as nutritional supplements to conceal undesirable flavors, enhance bioavailability, and facilitate the efficient distribution of insoluble supplements without the need for emulsifiers or surfactants. It has emerged as an innovative approach to overcome the limitations of conventional herbal compositions. Encapsulating bioactive compounds in nanocarriers improves their solubility, protects them from degradation, and facilitates targeted delivery to tumor sites. Various nanocarriers, including polymeric nanoparticles, liposomes, and solid lipid nanoparticles, have been explored for the administration of Withaferin A. For instance, Withaferin A-loaded nanosponges have demonstrated enhanced anticancer efficacy against MCF-7 human breast cancer cells, exhibiting effectiveness comparable to cisplatin in reducing tumor volume. Similarly, PEGylated nanoliposomes including WA have exhibited significant tumor growth suppression and improved survival in mice with Dalton Lymphoma Ascites tumors. These nanoformulations improve the pharmacokinetic profile of WA and promote its accumulation in tumor tissues, hence enhancing its therapeutic index.

Unlocking Therapeutic Potential of Ashwagandha Through Nanoformulation Techniques

Modern pharmaceutical advancements, especially nano-encapsulation techniques, have evolved as a game changer in the history of traditional herbal treatment. Nanoencapsulation of ashwagandha, enhance stability, solubility and effective administration. There are various delivery methods of nanotechnology that enhance the bioavailability and anti-tumor potential of Withaferin Ashwagandha such as nanostructured lipid carriers (NLCs), liposomal encapsulation, solid lipid nanoparticles (SLNs), polymeric nanoparticles, and nanoemulsions. These delivery techniques enables effective administration and release the bioactive compound at the specific tumor site. Nanoencapsulation enhance the residence time in the blood and at the tumor site and provide a shield against premature breakdown. For instance, PLGA-based nanoparticles (polylactic-co-glycolic acid) loaded with Withaferin A have shown promising results in both in vitro and in vivo cancer models by ensuring enhanced absorption in malignant cells while maintaining healthy tissues.

To deliver phytochemicals in the body, two major nanoformulation techniques i.e. liposomes and polymeric nanoparticles are commonly used to deliver bioactive compounds due to their ability to modify their surfaces and bioavailability. These two techniques allow for active targeting to cancerous cells. The process involves further improving site-specific accumulation and decreasing off-target toxicity by functionalizing nanoparticles with ligands such as monoclonal antibodies or folic acid. In one study, the scientists developed folate-functionalized WA-loaded PLGA nanoparticles; when compared to free WA, this showed a dramatic reduction of cell growth in breast cancer cells in vitro and enhanced apoptosis. One of the possible approaches is through the application of solid lipid nanoparticles, which ensure increased physical stability and scalability to commercial production. These nanoformulations increase therapeutic potency and open up new avenues for oral, intravenous, or transdermal delivery modalities in the near future pharmaceutical landscape. With these advanced technologies, Ashwagandha can be shifted from a traditional adaptogen to a scientifically validated nutraceutical or adjunct anticancer therapy.

Ashwagandha in Cancer Research: Global Progress

The discovery of effective tumor therapies is a tremendous challenge since cancer is the top cause of death globally and poses a huge danger to human health. In 2020, there were over 10.0 million cancer-related deaths and 19.3 million new cases worldwide, according to cancer statistics. It is anticipated that by 2040, there would be 28.4 million instances of cancer. The use of natural compounds in drug development is still highly important. Significant anti-tumor effectiveness is demonstrated by Withaferin A (WA), the most potent phytocompound that was isolated from the well-known nutritional supplement named as Withania somnifera Dunal commonly known as Ashwagandha.

The anticancer effects of ashwagandha and its nanencapsulation has drawn increasing attention from the global scientific community. The pre-clinical research on cancer has demonstrated that Withaferin Ashwagandha is effective against different cancer types, including breast, prostate, and lung cancers. Epithelial-mesenchymal transition is a crucial step in inducing cancer metastasis and ashwagandha obstructs the epithelial-mesenchymal transition (EMT) by controlling the signaling pathways such as TGF-β and NF-Κb. Withaferin ashwagandha has the ability to inhibit the synthesis of vascular endothelial growth factor (VEGF) and exhibits strong anti-angiogenic properties. The inhibition of VEGF prevents the formation of new blood vessels that promotes tumor growth. The increasing preclinical data provides a strong argument for moving WA-based nano-formulations to clinical trials, even if clinical studies are still in the early stages.

Opportunities for Nutraceutical and Pharmaceutical Industries

The growing public preference for food and drug are continuously changing and their inclination towards natural and plant-based medicines with advancements in nanotechnology, creates a favorable environment for the development of ashwagandha based products. Nanoencapsulation technology can benefit both pharmaceutical and nutraceutical industries. Pharmaceutical companies can develop more tailored and effective anti-cancer medications by employing nanoencapsulation technology. Nutraceutical industries can utilize technique of nanoencapsulation for the development of dietary supplements designed to mitigate the risk of developing cancer and to support cancer treatment. In order to enhance the field of nanotechnology and their incorporation into traditional herbal treatments, there is a strong need of collaboration between researchers, medical professionals and industrial stakeholders. Collaborative efforts are essential for transforming preclinical findings into clinically approved therapies, especially the therapies for chronic diseases. The effective utilization of nanotechnology in the field of science can benefit patients globally.

Conclusion

The combination of traditional herbal medicine with contemporary nanotechnology offers a promising opportunity for improving cancer therapy. The bioactive compound present in Ashwagandha, Withaferin A, demonstrates this interaction. Withaferin Ashwagandha possesses strong anti-cancer potential, and its pharmacological characteristics have exhibited considerable anti-tumor potential across various types of cancer. Despite its notable anti-tumor activity, ashwagandha has some limitations, including possible toxicity and poor oral bioavailability, which must be addressed when evaluating it as an anti-tumor candidate drug. Nanoencapsulation technique not only alleviates the limitations but also improve the overall therapeutic effectiveness of withaferin A. Various oncologists have illustrated the intricate anticancer mechanism of Withaferin Ashwagandha and its nanoencapsulation, demonstrating a promising positive results in standard cancer therapies. By implementing this nanoencapsulation technique, we may enhance the development of patient-centered cancer medicines with more efficient and targeted approach. Nevertheless, owing to its potential anti-tumor characteristics, Withaferin Ashwagandha remains an intriguing candidate for further pharmacological investigation. As research in this field progresses, we expect a more precise understanding of the exact mechanisms of WA's effect, its toxicity profile, and enhancements in delivery methods.

Please note that the views expressed in this article are of the author and do not necessarily reflect the views or policies of any organization.

The writers are affiliated with National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan. For correspondence, please contact Mian Kamran Sharif at mks@uaf.edu.pk

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