Cucurbitacin: As a candidate against Cytokine Storm in Severe COVID-19 Infection

Abstract

The severity of SARS-CoV-2 infection is marked by elevated cytokines and chemokines levels like interleukin 6 (IL-6), interferon-gamma (IFN-γ),  tumour necrosis factor (TNF), IL-2 and monocyte chemotactic protein 1. This hyperactive pro-inflammatory response identified as the Cytokine Storm (CS) complicates the disease leading to extensive damage of the host tissue, Acute Respiratory Distress Syndrome (ARDS), which further result in multiple organ failures. CS is very critical for the disease progression and is responsible for high death rate in an infected patient. Accordingly, various therapeutic modalities are currently investigated for their effectiveness in subsiding the hyper-inflammatory syndrome either using immunomodulatory agents or anti-inflammatory therapies. Phytochemical (herbal) compounds are demonstrated to possess anti-inflammatory, antimicrobial or antioxidants properties. Various signalling pathways and molecules exacerbating the inflammation state complicate the pathophysiology of COVID-19.  Cucurbitacins are tetracyclic bioactive phytochemical compounds found in cucurbitaceous plants. More than 100 species of cucurbitacins possess various pharmacological properties, including anti-inflammatory. Cucurbitacin E and R have shown to be down-regulated the expression of TNF alpha and IL-1beta. Cucurbitacin II B also alleviates the expression of TNF-α as well as IFN-γ and IL-6. Cucurbitacin1 has the potential to reduce the oxidative stress-induced with the reactive oxygen species, and thus prevents cardiovascular damage. Thus cucurbitacins may be pharmacologically manipulated to establish its clinical efficacy in minimizing the disease state and improvising the prognosis of the patients.