Ultradiluted Eupatorium perfoliatum Prevents and Alleviates SARS-CoV-2 Spike Protein-Induced Lung Pathogenesis by Regulating Inflammatory Response and Apoptosis

Background/Objectives: SARS-CoV-2 provokes acute oxidative stress in the lungs via cytokines, inflammatory mediators, and apoptotic factors, which might cause alveolar injury followed by severe respiratory syndrome during COVID-19 infection. The lack of particular antivirals for SARS-CoV-2 has opened novel avenues of complementary and alternative medicine as a potential remedy. The current study explored the mechanistic role of the ultradiluted formulation of Eupatorium (UDE) against SARS-CoV-2 recombinant S protein-mediated oxidative stress and mitochondriopathy. Methods: Cell line and BALB/c mice were used to report that SARS-CoV-2 S protein caused an inflammatory response and subsequent cytokine storm via the NF-κB pathway in the lung along with oxidative damage. Morphological examination was performed using DAPI staining and histology for treated cells and lung tissues of animals, respectively. The molecular mechanism of action of UDE was investigated through qRT-PCR for the genetic expressions of various cytokines, inflammatory, and apoptotic mediators; ELISA, immunofluorescence, immunohistochemistry, and Western blot for the translational expression of the same molecules assayed for genetic expressions; and biochemical assays for various enzymes and ROS. Results: UDE treatment suppressed the inflammatory cell infiltration and tissue-level oxidative stress and safeguarded mitochondrial integrity from free radical-mediated oxidative damage. Additionally, UDE played a direct role in restoring cellular redox homeostasis and reducing the inflammatory response by suppressing NF-κB, IL-1β, IL-18, caspase-1 expression, and ROS formation. Further, a plausible mechanism of action of UDE against S protein-induced damage was proposed. Conclusions: This study described a novel therapeutic approach against S protein-mediated hyperinflammation, apoptosis, and oxidative damage. Hence, UDE may be considered as a prospective alternative to combat life-threatening consequences of SARS-CoV-2 infection.