Phytoconstituents as modulator of inflammatory pathways for COVID-19: A comprehensive review and recommendations.

SARS-CoV-2 infection causes disruptions in inflammatory pathways, which fundamentally contribute to COVID-19 pathophysiology. The present review critically evaluates the gaps in scientific literature and presents the current status regarding the inflammatory signaling pathways in COVID-19. We propose that phytoconstituents can be used to treat COVID-19 associated inflammation, several already formulated in traditional medications. For this purpose, extensive literature analysis was conducted in the PubMed database to collect relevant in vitro, in vivo, and human patient studies where inflammation pathways were shown to be upregulated in COVID-19. Parallelly, scientific literature was screened for phytoconstituents with known cellular mechanisms implicated for inflammation or COVID-19 associated inflammation. Studies with insufficient evidence on cellular pathways for autophagy and mitophagy were considered out of scope and excluded from the study. The final analysis was visualized in figures and evaluated for accuracy. Our findings demonstrate the frequent participation of NF-κB, a transcription factor, in inflammatory signaling pathways linked to COVID-19. Moreover, the MAPK signaling pathway is also implicated in producing inflammatory molecules. Furthermore, it was also analyzed that the phytoconstituents with flavonoid and phenolic backbones could inhibit either the TLR4 receptor or its consecutive signaling molecules, thereby, decreasing NF-κB activity and suppressing cytokine production. Although, allopathy has treated the early phase of COVID-19, anti-inflammatory phytoconstituents and existing ayurvedic formulations may act on the COVID-19 associated inflammatory pathways and provide an additional treatment strategy. Therefore, we recommend the usage of flavonoids and phenolic phytoconstituents for the treatment of inflammation associated with COVID-19 infection and similar viral ailments.