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.

Pharmacological potential of Withania somnifera (L.) Dunal and Tinospora cordifolia (Willd.) Miers on the experimental models of COVID-19, T cell differentiation, and neutrophil functions

“…In the current study, we used well-characterized extracts of WS and TC two commonly used Asian traditional medicines to investigate their protective effect against COVID-19 by using hamster and hACE2.Tg mice model. WS contains a large number of phytoconstituents including steroids, alkaloids, saponins, glycosides, volatile oils, sitoindosides, and others with various pharmacological activities ( 60 ). Various chemical constituents such as diterpenoid lactones, glycosides, steroids, sesquiterpenoid, phenolics, aliphatic compounds, essential oils, fatty acids, and polysaccharides are present in TC with known biological activities ( 61 )…”

Withania somnifera Alter BCL2/Bax signaling and trigger apoptosis of MCF-7 and MDA-MB231 breast cancer cells exposed to γ-radiation

“…Further, it might increase the susceptibility of cancer cells to ionizing radiation. 27 Withaferin A (WA), a promising anticancer constituent of the Ayurvedic medicinal plant Withania somnifera, inhibits growth of MDA-MB-231 and MCF-7 human breast cancer cells in culture and xenografts in association with apoptosis. 28 Besides, the results of the present study indicated that WS-treated breast cancer cells were arrested in the G2/M phase whereas, the Survivin, a protein inhibitor of apoptosis expressed in a large number of malignancies 29 is expressed highly at G2/M phase and declines rapidly in the G1 phase of the cell cycle.…”

Phyto‐therapeutic potential of Withania somnifera: Molecular mechanism and health implications

“…In HepG2 cells, extract arrested cell cycle at G0/G1 phase with 61.9% and the G2/M phase with 1.3%. In osteosarcoma cells, WA was found to regulate cell cycle, cell Kashyap et al, 2022;Khalil et al, 2023 proliferation and G2/M phase cell cycle arrest and in MCF-7 breast cancer cells causes cell development restraint and cell cycle arrest in the G2/M phase (Figure 6) (Atteeq, 2022;Chen et al, 2014).…”

“…It was shown that leaf had more powerful antitumor effects than other plant parts exerted against prostate and colon cancer by preventing the genetic activation of nuclear factor kappa B (NF-κB). The anticancer effect is caused by a slowing down of cyclooxygenase enzymes, tumor cell proliferation, and lipid peroxidation (Kashyap et al, 2022). Studies have likewise upheld the use of WFA in nanosponges to treat disease models and sent off additional opportunities for growing the viability of regular item-based prescriptions (Shah et al, 2021).…”