Withania somnifera: Progress towards a Pharmaceutical Agent for Immunomodulation and Cancer Therapeutics

Abstract

Chemotherapy is one of the prime treatment options for cancer. However, the key issues with traditional chemotherapy are recurrence of cancer, development of resistance to chemotherapeutic agents, affordability, late-stage detection, serious health consequences, and inaccessibility. Hence, there is an urgent need to find innovative and cost-effective therapies that can target multiple gene products with minimal adverse reactions. Natural phytochemicals originating from plants constitute a significant proportion of the possible therapeutic agents. In this article, we reviewed the advances and the potential of Withania somnifera (WS) as an anticancer and immunomodulatory molecule. Several preclinical studies have shown the potential of WS to prevent or slow the progression of cancer originating from various organs such as the liver, cervix, breast, brain, colon, skin, lung, and prostate. WS extracts act via various pathways and provide optimum effectiveness against drug resistance in cancer. However, stability, bioavailability, and target specificity are major obstacles in combination therapy and have limited their application. The novel nanotechnology approaches enable solubility, stability, absorption, protection from premature degradation in the body, and increased circulation time and invariably results in a high differential uptake efficiency in the phytochemical's target cells. The present review primarily emphasizes the insights of WS source, chemistry, and the molecular pathways involved in tumor regression, as well as developments achieved in the delivery of WS for cancer therapy using nanotechnology. This review substantiates WS as a potential immunomodulatory, anticancer, and chemopreventive agent and highlights its potential use in cancer treatment.

Keywords: Withania somnifera; Withanolide D; Withanolides; ashwagandha; nanoformulation.

Figure 1

Various phytochemicals present in Withania somnifera.

Figure 2

Various molecular targets of Withania somnifera in cancer cells. WS influence the apoptosis, cell cycle, ER stress, and paraptosis while involving reducing metastasis, EMT, stemness, autophagy, and inflammation.

Figure 3

Different type of Withania somnifera nanoparticles. (A) inorganic nanoparticles and (B) organic nanoparticles. Red stars represent Withania somnifera.