Dietary Vitamin D Mitigates Coronavirus-Induced Lung Inflammation and Damage in Mice.

The COVID-19 pandemic caused by the SARS-CoV-2 (ß-CoV) betacoronavirus has posed a significant threat to global health. Despite the availability of vaccines, the virus continues to spread, and there is a need for alternative strategies to alleviate its impact. Vitamin D, a secosteroid hormone best known for its role in bone health, exhibits immunomodulatory effects in certain viral infections. Here, we have shown that bioactive vitamin D (calcitriol) limits in vitro replication of SARS-CoV-2 and murine coronaviruses MHV-3 and MHV-A59. Comparative studies involving wild-type mice intranasally infected with MHV-3, a model for studying ß-CoV respiratory infections, confirmed the protective effect of vitamin D in vivo. Accordingly, mice fed a standard diet rapidly succumbed to MHV-3 infection, whereas those on a vitamin D-rich diet (10,000 IU of Vitamin D3/kg) displayed increased resistance to acute respiratory damage and systemic complications. Consistent with these findings, the vitamin D-supplemented group exhibited lower viral titers in their lungs and reduced levels of TNF, IL-6, IL-1ß, and IFN-γ, alongside an enhanced type I interferon response. Altogether, our findings suggest vitamin D supplementation ameliorates ß-CoV-triggered respiratory illness and systemic complications in mice, likely via modulation of the host's immune response to the virus.

cis-Aconitic Acid, a Constituent of Echinodorus grandiflorus Leaves, Inhibits Antigen-Induced Arthritis and Gout in Mice.

cis-Aconitic acid is a constituent from the leaves of Echinodorus grandiflorus, a medicinal plant traditionally used in Brazil to treat inflammatory conditions, including arthritic diseases. The present study aimed to investigate the anti-arthritic effect of cis-aconitic acid in murine models of antigen-induced arthritis and monosodium urate-induced gout. The possible underlying mechanisms of action was evaluated in THP-1 macrophages. Oral treatment with cis-aconitic acid (10, 30, and 90 mg/kg) reduced leukocyte accumulation in the joint cavity and C-X-C motif chemokine ligand 1 and IL-1ß levels in periarticular tissue. cis-Aconitic acid treatment reduced joint inflammation in tissue sections of antigen-induced arthritis mice and these effects were associated with decreased mechanical hypernociception. Administration of cis-aconitic acid (30 mg/kg p. o.) also reduced leukocyte accumulation in the joint cavity after the injection of monosodium urate crystals. cis-Aconitic acid reduced in vitro the release of TNF-α and phosphorylation of IκBα in lipopolysaccharide-stimulated THP-1 macrophages, suggesting that inhibition of nuclear factor kappa B activation was an underlying mechanism of cis-aconitic acid-induced anti-inflammatory effects. In conclusion, cis-aconitic acid has significant anti-inflammatory effects in antigen-induced arthritis and monosodium urate-induced arthritis in mice, suggesting its potential for the treatment of inflammatory diseases of the joint in humans. Additionally, our findings suggest that this compound may contribute to the anti-inflammatory effect previously reported for E. grandiflorus extracts.

Effect of the Hydroethanolic Extract from Echinodorus grandiflorus Leaves and a Fraction Enriched in Flavone-C-Glycosides on Antigen-Induced Arthritis in Mice.

The leaves of Echinodorus grandiflorus are traditionally used in Brazil to treat several inflammatory conditions, including arthritis. This study aimed to investigate the antiarthritis activity of the 70% ethanol extract of E. grandiflorus leaves and a standardized flavonoid-rich fraction in an antigen-induced arthritis model in mice. Previously immunized mice were treated per os with saline (control group), 70% ethanol extract (100-1000 mg/kg), or a flavonoid-rich fraction (0.7-7.2 mg/kg) 40 minutes before and 3 and 6 hours after the challenge with antigen into the knee joint. The administration of the 70% ethanol extract and flavonoid-rich fraction to mice significantly reduced neutrophil recruitment to the joint cavity and in periarticular tissue. The levels of chemokine (C-X-C motif) ligand 1, tumor necrosis factor-α, and interleukin-1ß quantified by the enzyme-linked immunosorbent assay (ELISA) in the periarticular tissue were also diminished in mice treated with the 70% ethanol extract and flavonoid-rich fraction, as well as mechanical hypernociception. Histological analysis confirmed that both the 70% ethanol extract and flavonoid-rich fraction suppressed joint inflammation and inhibited cartilage and bone destruction when compared to the control group. Our results demonstrate, for the first time, that E. grandiflorus has anti-inflammatory activity in an experimental arthritis model and highlights the role of flavonoids in the observed response.