Ashwagandha (Withania Somnifera, WS), belonging to the family Solanaceae, is an Ayurvedic herb known worldwide for its numerous beneficial health activities since ancient times. This medicinal plant provides benefits against many human illnesses such as epilepsy, depression, arthritis, diabetes, and palliative effects such as analgesic, rejuvenating, regenerating, and growth-promoting effects. Several clinical trials of the different parts of the herb have demonstrated safety in patients suffering from these diseases. In the last two decades, an active component of Withaferin A (WFA) has shown tremendous cytotoxic activity suggesting its potential as an anti-carcinogenic agent in treatment of several cancers. In spite of enormous progress, a thorough elaboration of the proposed mechanism and mode of action is absent. Herein, we provide a comprehensive review of the properties of WS extracts (WSE) containing complex mixtures of diverse components including WFA, which have shown inhibitory properties against many cancers, (breast, colon, prostate, colon, ovarian, lung, brain), along with their mechanism of actions and pathways involved.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel coronavirus that emerged from Wuhan, China in late 2019 causing coronavirus disease-19 (COVID-19). SARS-CoV-2 infection begins by attaching to angiotensin-converting enzyme 2 receptor (ACE2) via the spike glycoprotein, followed by cleavage by TMPRSS2, revealing the viral fusion domain. Other presumptive receptors for SARS-CoV-2 attachment include CD147, neuropilin-1 (NRP1), and Myeloid C-lectin like receptor (CLR), each of which might play a role in the systemic viral spread. The pathology of SARS-CoV-2 infection ranges from asymptomatic to severe acute respiratory distress syndrome, often displaying a cytokine storm syndrome, which can be life-threatening. Despite progress made, the detailed mechanisms underlying SARS-CoV-2 interaction with the host immune system remain unclear and are an area of very active research. The process’s key players include viral non-structural proteins and open reading frame products, which have been implicated in immune antagonism. The dysregulation of the innate immune system results in reduced adaptive immune responses characterized by rapidly diminishing antibody titers. Several treatment options for COVID-19 are emerging, with immunotherapies, peptide therapies, and nucleic acid vaccines showing promise. This review discusses the advances in the immunopathology of SARS-CoV-2, vaccines and therapies under investigation to counter the effects of this virus, as well as viral variants.

There is currently a growing interest in the use of cannabidiol (CBD) to alleviate the symptoms caused by cancer, including pain, sleep disruption, and anxiety. CBD is often self-administered as an over-the-counter supplement, and patients have reported benefits from its use. However, despite the progress made, the mechanisms underlying CBD’s anti-cancer activity remain divergent and unclear. Herein, we provide a comprehensive review of molecular mechanisms to determine convergent anti-cancer actions of CBD from pre-clinical and clinical studies. In vitro studies have begun to elucidate the molecular targets of CBD and provide evidence of CBD’s anti-tumor properties in cell and mouse models of cancer. Furthermore, several clinical trials have been completed testing CBD’s efficacy in treating cancer-related pain. However, most use a mixture of CBD and the psychoactive, tetrahydrocannabinol (THC), and/or use variable dosing that is not consistent between individual patients. Despite these limitations, significant reductions in pain and opioid use have been reported in cancer patients using CBD or CBD+THC. Additionally, significant improvements in quality-of-life measures and patients’ overall satisfaction with their treatment have been reported. Thus, there is growing evidence suggesting that CBD might be useful to improve the overall quality of life of cancer patients by both alleviating cancer symptoms and by synergizing with cancer therapies to improve their efficacy. However, many questions remain unanswered regarding the use of CBD in cancer treatment, including the optimal dose, effective combinations with other drugs, and which biomarkers/clinical presentation of symptoms may guide its use.

Treatment of late-stage lung cancers remains challenging with a five-year survival rate of 8%. Immune checkpoint blockers (ICBs) revolutionized the treatment of non-small cell lung cancer (NSCLC) by reactivating anti-tumor immunity. Despite achieving durable responses, ICBs are effective in only 20% of patients due to immune resistance. Therefore, synergistic combinatorial approaches that overcome immune resistance are currently under investigation. Herein, we studied the immunomodulatory role of Withaferin A (WFA)—a herbal compound—and its effectiveness in combination with an ICB for the treatment of NSCLC. Our in vitro results show that WFA induces immunogenic cell death (ICD) in NSCLC cell lines and increases expression of the programmed death ligand-1 (PD-L1). The administration of N-acetyl cysteine (NAC), a reactive oxygen species (ROS) scavenger, abrogated WFA-induced ICD and PD-L1 upregulation, suggesting the involvement of ROS in this process. Further, we found that a combination of WFA and α-PD-L1 significantly reduced tumor growth in an immunocompetent tumor model. Our results showed that WFA increases CD-8 T-cells and reduces immunosuppressive cells infiltrating the tumor microenvironment. Administration of NAC partially inhibited the anti-tumor response of the combination regimen. In conclusion, our results demonstrate that WFA sensitizes NSCLC to α-PD-L1 in part via activation of ROS.